TW200400972A - Biocompatible polymers and use as imaging probes - Google Patents

Abstract

The present invention relates to fluorinated and paramagnetic biocompatible polymers and proteins useful as imaging probes, diagnostic agents, contrast agents, pharmaceutical formulation ingredients, encapsulating agents, implants, surface active agents and emulsifiers. Additionally, the present invention relates to methods of using the polymers such as for example use as imaging agents, contrasting agents, encapsulating agents and implants.

Description

200400972 (1) Description of the invention: [Technical field to which the invention belongs] The present invention relates to a novel development probe and a method for measuring physiological functions by using the probe in a diagnostic development program and other development programs. In addition, the present invention relates to a developing method and an implant covered with a developing probe of the present invention. [Prior art] Fluorocarbon compounds and their formulations have various applications in medicine, as therapeutic and diagnostic agents, and as blood substitutes. Fluorine is characterized by a van der Waals radius (1.2A) similar to hydrogen (1.35A). Therefore, hydrogen substitution (using F) does not cause significant configurational changes, and fluorination can lead to increased lipophilicity, enhancing the bioavailability of many drugs. Fluorinated substances are often biologically inert and are generally expected to reduce the side-effect profile of the drug. The carbon-fluorine bond strength (460 kilojoules / mole in CH3F) exceeds the equivalent C-H bond strength. Perfluorocarbons (PFCs) are highly chemically and biologically inert and have the ability to dissolve significant amounts of gases per unit volume, especially oxygen, carbon dioxide and air. PFC can dissolve about 50% oxygen by volume at 37 ° C and pure oxygen atmosphere. Fluorocarbon compositions are useful in wound treatment, such as those described in U.S. Patent 4,366,169. Fluorocarbon formulations can also be used in diagnostic procedures, for example as a contrast agent (Riess, JG, f Xirong · # f and attack: f. · 遽 向 2 / 世 · / 2 之 # #, Technomics PubL Co, Lancaster, Pa USA, Chapter 14 (1991); 61: 225-239, 1991). Nuclear magnetic resonance (NMR) technology allows the evaluation of biochemical, functional, and physiological information from patients. Tissue water magnetic resonance imaging (MR1) can be used to measure perfusion and diffusion with sub-millimeter resolution. Magnetic resonance spectroscopy can be used to evaluate tissue metabolites containing protons, phosphorus, fluorine, or other nuclei. Development 84865 200400972

The combination of spectroscopy technology and spectral development technology has led to the mapping of proton metabolism products at resolutions as low as 0.25 cubic centimeters (Zakian KL

Koutcher JA; Ballon D > Hricak H; Ling CC, Semin Radiat Oncol .; 11 (1): 3-15, 2001). In magnetic resonance angiography (MRA), contrast agents are used to visualize arteries and veins in order to diagnose heart and vascular disease and related conditions. Of particular interest is the diagnostic value of fluorine in non-invasive imaging applications. The polar oxygen system imparts a paramagnetic relaxation effect on the 19F nucleus, which is related to the spin-lattice relaxation rate (RD and chemical shift. This effect is proportional to the partial pressure (p02) of 0. Therefore, 19FNMR can detect cells and Oxygen environment for specific fluorinated species in other biological structures. Ideally, PFC developers should combine the following characteristics: non-toxic, biocompatible, chemically pure and stable, low vapor pressure, high fluorine content, reasonable cost, and Commercial availability. In addition, it should meet several 19 F-NMR standards, including the maximum number of chemically equivalent fluorines, which resonate at one or only a few frequencies, preferably from trifluoromethyl functional groups. Some others Spectral standards have been discussed elsewhere in detail (CH Sotak, PS Hees, ΗN. Huang, M. H. Hung, C. G. Krespan, S. Raynolds, Mei /., 29, 188-195, 1993). For MRI, it is further desired to have control over the amount of magnetically responsive materials for special applications, and to use temperature-responsive and pH-dependent developers for special applications. It may have applicability, and individual MRI-based temperature monitoring 'On' for tumors General fever treatment (see 'for example sL · Fossheim ·' κ. Α · n'yasov, J. Heraiig, A. Bjomemd, AW.iW0 /., 7 (12), 1107-15, 2000) 'and for monitoring The efficacy of chemotherapy (see, for example, NH Rhagunand, R. Martinez-Zagulan, SH Wright, 84865 200400972 RJ Gilles, Biochem. Pharmacol., 57, 1047-1058, 1999; I. F Tannock, D. Rotin, 49, 4373-4383, 1989). Furthermore, the solubility of water will increase the functionality of PFC in many biomedical environments, so it will eliminate the need for emulsifiers. Although selected efforts have been directed towards the development of novel fluorinated MRI probes , But none of them are water-soluble compounds [such as perfluoro- [15] -crown-5 ether]], and some are not available on the market [such as perfluoro-2,2,2 ', 7-tetramethyl- 4,4'-bis (1,3-dioxolane)]. It seems that so far no attempt has been made to focus on screening available PFCs from thousands of commercially available fluorinated products to identify potentially more appropriate MRI probes for biomedical use. Furthermore, no research seems to have attempted to establish a structure-activity relationship (SAR) of related PFCs for MRI purposes. It is also worth noting the fact that all PFCs tested so far have molecular weights below 1,000, typically between 400-600 Da. This partly reflects the special requirements for blood substitutes, and is due to the widely held belief that higher molecular weight or polymeric fluorinating agents will not be measured by 19F-NMR, which is due to expectations Excessive lines become wider and therefore will not fit. Therefore, with the exception of the polymer-coated PFCs indicated above, this important type of material has so far been excluded from consideration. Paramagnetic ions, such as gadolinium (Gd3 +), reduce the protons of water near them, thereby providing enhanced contrast. The long electron relaxation time and high magnetic moment of radon make it highly effective perturbation. Since unconjugated osmium is extremely toxic, it does not chelate probes, such as acetoethylene triamine pentaacetic acid (GdDTPAMw570Da), albumin-GdDTPA (Gadomer-17, Mw35 or 65 kDa), has been widely used in MRI of tumors and other affected organs and tissues. Several other chelating agents for development 84865 200400972 have also been reported, including dual-labeling agents, oligonucleotide-derived, dextran-derived GdDTPA and TAT, and other peptide-derived chelating agents. However, currently approved MRI contrast agents are either tissue-specific, such as GdDTPA, or target only normal tissues, which may limit their utility in the diagnosis of metastasis or tumor formation. For example, MRI studies using GdDTPA did not correlate with vascular cause or vascular endothelial growth factor (VEGF). Attempts have also been made to overcome the low relaxation properties of small GdDTPA chelates by preparing Gc ^ DTPA / 2 "polymer conjugates [see, for example, MRA. Duarte MG; Gil MH; Peter JA; ColetJ.M .; ElstL Vander; Muller RN; Geraldes CFGC, Bioconjug. Qiem ·, 21, 170-177, 2001]. However, the relaxation properties of these polymeric conjugates are only slightly improved, and they are eliminated very quickly from the blood of rats, which indicates that they have limited value as blood bank contrast agents for MRI. Although there are many things that can be achieved with currently available contrast and contrast agents, there is still unmet need for new diagnostic agents, especially those that develop biological specificity. The imaging agent suitable for metastasis or tumor formation will substantially improve the sensitivity and availability of MRI for tumor detection and prevention. Similarly, it is suitable for developers that target receptors that involve bioactive proteins, such as the production and use of insulin, which substantially improves our understanding of the diabetes process and the function of anti-diabetic drugs. Although selected efforts have been directed towards the development of such novel probes, more extensive research on these agents is urgently needed. Likewise, novel development probes are needed as non-invasive devices to detect and visualize cells, tissues and organs undergoing cell decay. [Summary of the Invention] 84865 200400972 The present invention relates to fluorinated and paramagnetic polysaccharide uronic acid (formula I-IV) and fluorinated protein, which can be used as imaging probes, diagnostic agents and contrast agents. In addition, the present invention relates to a development method using a compound of formula I-IV of the present invention and a fluorinated protein described herein. The fluorinated and chemically modified polyuronic acid glycosides of the present invention include compounds of the following general formulae I to IV:

Wherein with respect to formula I:

RfOH '0X, X; r2 = 0h, OX, X, NHCOX; R3 = OH, 0γ, OX' NHX, alkyl, alkoxyalkyl; r4 means c = 0, CH2, CNX, CF2; The best case is that R1 is 0H or 0x, r2 is 0H or ox, particularly preferably one of & and R2 is OH, and the other is οχ Formula II: R! = OH 'OX' X ^ OR4; R2 = 0H'OX'X'OR4; R3 = Oh, Y, X, r4; r4 = fluorenyl, alkyl or aryl; preferably, & is or OX, R2 is oh or ox, R3 Is OH, R4 is C = 0, particularly preferably, one of R and R2 is OH, and the other is οχ About Formula III:

RfOH, ox, X; r2 = 0h, ox, X; R3 = H, N (X) 3, and preferably, & is OH, R2 is OH, and R3 is H or N (X) 3 -10- 84865 200400972 About formula IV:

Ri = OH, OX, X, R2 = OH, OX, X, -〇-Α (χ) -0- or -0-A (R_3) -〇-, R3 = burning group or test group M is a transition metal or Any paramagnetic ion of the lanthanide, including europium (III), iron (III), manganese (II and III), chromium (III), copper (II), europium (III), europium (ΠΙ), “(III ), Bait (III) and plutonium (III); the most preferred are plutonium (III), plutonium (III), iron (III), and manganese (II), and the ionic valence is a = l, b = l; a = 2 , B = l / 2; a = 3, b = l / 3; a = 4, b = l / 4, etc., and A is any non-paramagnetic ion, including ammonium fluoride salts, such as ammonium heptafluorate ( V), ammonium hexafluorogermanate, ammonium hexafluoroniobate, ammonium hexafluorophosphate, ammonium hexafluorostannate, ammonium tetrafluoroborate, antimony (III) or (V) fluoride, barium fluoride, boron fluoride salts , Including boron trifluoride and its derivatives, fluorine-based lithium compounds, including lithium tetrafluoroborate and lithium fluoride, iron (II) fluoride, magnesium fluoride, potassium fluoride, sodium fluoride, and tetraalkane fluoride Ammonium salts, including tetrabutylammonium tetrafluoroborate. Where X is a fluorine-containing moiety. Appropriate fluorine moieties include fluoroalkyl, fluoroaryl, fluorenyl, perfluoroalkyl, perfluoroaryl, perfluorofluorenyl, perfluoropolymer, fluoroamine, fluoroaminocarbamate , Fluoro-three cultivating, Fluoro-sulfonyl alkyl derivative acryl, 0 卩 3, 0) (:} ^) ?, € 3 <: 02, (: 33 / min, ([012] 1110 to 012 €? 20: ^-(CF2CF20) z (CF2) 2CF2CH20 (CH2) p0H, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz [CxFzO] mF, CH2C (CH3) C02CxHz (CF2) mCF3 'CH2 x (CF2 CF2 0) y (CF2 0) z CF2 CH2 OH, NHCxFyHzOp, CH2CF20 [CF2CF20] mCF20CF2CH20H, C0CxHz (CF2) mCF3, C0-CF20 [CF2CF20] nCF20CF2C02H, C0-CF (CF3) CF20 (CF3) ] mF, 84865 -11-200400972 ([ch2] m 〇) x (ch2 cf2 o) y (cf2 cf2 o) z CF2 CH2 o (ch2) p OH, so2 [CF2] x

, CF3 S〇3, N [cx Fy Hz] p, cx Hz C02 cx Hz (CF2) m CF3, COCx Fy [cp Fz 0] mF, luminescent residue, fluorescent residue, fluorinated luminescent residue or Fluorinated fluorescent residue, Y = CH2C (OH) CH3, and m 'p, x, y, z = 0_150, and its middle claw is more preferably 10-100, and most preferably 10_50, and its x, p, y and z are more preferably from 10 to 75, and still more preferably from 10 to 50, and most preferably from 10 to 20 ', and among them, n is more preferably from 10 to 10, and ⑻ is even more preferably from 10 to 1,000, and most preferably 10_250. Preferred compounds of formula IV are those in which both & and & The residues of the formulae I to IV include residues of lipophilic phosphonium groups, including saturated and unsaturated aliphatic residues, having a q chain, of which 2 100, more preferably 2-5, and most preferably It is 2-20, and the aryl residue therein includes aromatic partial groups, including benzyl, biphenyl, phenyl, polycyclic aromatic compounds, and heteroatom-containing aromatic compounds. The novel phantom fluorinated and paramagnetic polyuronic acid glycosides include analogs of polyuronic acid, wherein the polyuronic acid is selected from the group consisting of acacia, alginate, gellan, glucosaminoglycan, Hyaluronic acid esters, polymannuronic acid, polyguluronic acid, pectin, propylene glycol alginate, carboxyalkyl polysaccharides, including carboxymethyl sol starch, chitomethyl cellulose, and demethyl dextran , $ Methyl glutamate, dian powder, ethyl ethyl starch, penta-starch, dextran, tragacanth gum and Sancan gum. The aforementioned pharmaceutically acceptable salts of the degraded polysaccharide uronic acid are also intended to be encompassed by the present invention. When more than one of the named substituents or partial details such as X) appear in the chemical formula of a compound, the substituents in the chemical formula of the compound may be the same or different at different positions of the substituent. Disclosed is a novel composition comprising fluorinated and chemically modified 84865 -12- 200400972. Cells, cell surfaces, cell membranes, cell surface receptors and regulators

The control of the biofilm channel, the, / / bite < has activity or affinity. Fluorinated and / or cis- and d-protein males can be used as imaging probes and diagnostic agents. Exemplary proteins include fluorescein analogs of epitaxin V with conjugate protoplasmin Σ and superparamagnetic addendin ν with conjugate protoplasm I iron oxide conjugate.

This month is also about the fluorinated and paramagnetic analog of the antidiabetic agent, AL AXVII) ′, which can be used as a radiographic needle, diagnostic agent and contrast agent. In addition, the present invention relates to a developing method using the compound of the present invention 彳 monthly formula AI-AXVII. Mt coat of the antidiabetic agent of the present invention Bing Liu < Rolled and paramagnetic analogs, including AI to AXVII compounds:

ΝΗ—Ri (R3) 3〒

Ri (R4) 3C ΊΓ 丫 ΝΗ ΝΗ

84865 -13- 200400972

AVill

9 Η Η

II I I

Rl-I-Νγ-Ν-R2

〇 O AX

AXiii AXiV

AXV

> \ T 'R3 T—r2— 〇 o AXV " 84865 14- 200400972 where formula AI:

Ri = H 'X; R2 = H >X; R3 = H >X; R4 = H' X. About the formula All:

RfH, X; R2 = H, X; R3 = H, X; R4 = H, X; R5 = H, X About formula AIII:

RpH, X; R2 = H, X; R3 = H, X; R4 = H, X; R5 = H, X; R6 = H, X; R7 = H, X; R8 = H, X; R9 = H, X X; R10 = CO, CHF, CF2, CNX, X; Rn = H, C (R7) 3, X About formula AIV:

RfH, X; R2 = H, X; R3 = H, X; R4 = H, X; R5 = H, X; R6 = H, X

RfH, X; R2 = H, X; R3 = H, X; R4 = H, X; R5 = H, X; R6 = H, X; R7 = H, X

RfH, X; R2 = H, X, NH2, NHX, NX2; R3 = H, X; R4 = H, X About formula AVII:

RfH, X; R2 = H, X; R3 = H, X; R4 = H, X; R5 = H, X; R6 = H, X About formula aviii:

RfH, X; R2 = H, X; R3 = H, X; R4 = H, X; R5 = H, X; R6 = H

, X; r7 = h, X 84865 -15-200400972 With regard to the formula AIX:

R! = H 'X; R2 = H' X '(CH2) 2NHCONHX; R3-H' X 'ox; r4 = h, X About formula AX:

Ri = X; R2 = CvHkFh; CvHkFhOd; C6HkFhR3; R3 = X where v is 6-9, k is 0-11, h is 1-12, d is 0-4. About formula AXI:

RfH, X; R2 = H, X, NH2, NHX, NX2; R3 = H, X; R4 = H

, X; r5 = h, x; r6 = h, x; r7 = h, x; r8 = oh, X About formula AXII:

Ri = H, X; R2 = H, X, NH2, NHX, NX2; R3 = H, X; R4 = H

, X; r5 = h, X; r6 = h, X; r7 = h, X; r8 = oh, X About formula AXIII:

Ri = H, X; r2 = h, X; r3 = h, X; r4 = h, X; r5 = h, X; r6 = h, X; R7 = H, X; R8 = H, X; R9 = H, X; R10 = H, CH2X, X 'NHX >CH2NHX; Rn = H'X; R12 = OH'OX'X > NHX About formula AXIV:

Ri = H, X; r2 = h, X; r3 = h, X; r4 = h, X; r5 = h, X; r6 = h, X; R7 = H, X; R8 = H, X; R9 = H, X; R10 = H, X; Rn = H, CH3, CH2X, X, NHX, CH2NHX; R12 = CH3, CH2X, X, NHX, CH2NHX About formula AXV:

= H, X, NH2, NHX, NX2; R2 = H, X; R3 = H, X; R4 = H, X, NH2, NHX, NX2; RS = H, X; R6 = H, X; R7 = H , X 84865 -16- 200400972 About formula AXVI:

RfH, X, NH2, NHX, NX2; R2 = H, X; R3 = H, X; R4 = H, X; R5 = H, X; R6 = h, X; R AI-AXVI and the following formula AXVII: X = fluoroalkyl, fluoroaryl, fluorofluorenyl, perfluoroalkyl, perfluoroaryl, perfluorofluorenyl, perfluoropolymer, F, CF3, COCxFy 'CxFyHz, ((CH2) m 0) x (CH2 cf2 0) y (CF2 CF2 0) z (CF2) 2 cf2 CH2 0 (CH2) p OH, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz [CxFzO] mF, CH2C (CH3) C02CxHz (CF2) mCF3, CH2 (CF20) x (CF2CF20) y (CF20) z-CF2CH2OH, NHCxFyHzOp, CH2CF20 [CF2CF20] m (CF20CF2CH20H > COCxHz (CF2) mCF3 'C0-CF20 [CF2CF2] 20 CO-CF (CF3)-[CF (CF3) CF20] mF, ([CH2] m0) x (CH2CF20) y (CF2CF20) z- CF2CH20 (CH2) pOH, N [CxFyHz] p, CxHzC02CxHz (CF2) mCF3, COCxFy [CpFzO] mF, luminescent residue, fluorescent residue, fluorinated luminescent residue or fluorinated fluorescent residue, and m, x, p, y, z are integers from 1 to 150, and m is more preferably 10-100, and most preferably 10-50, and among them X, p, y, and z are more preferably 10-75, still more preferably 10-50, and most preferably 10-20. And alkyl residues The system contains lipophilic moieties, including saturated and unsaturated aliphatic residues, with a Ck chain, where k is 2 to 100, more preferably 2-50, and most preferably 2-20, and aryl residues It contains aromatic moieties, including fluorenyl, biphenyl, phenyl polycyclic aromatic compounds, and heteroatom-containing aromatic compounds; and the formula AXVII: -17- 84865 200400972 κ = χΟ, X , XNH, R4 [0 (CH2) 2] m0, YM; T = CH2NH, C02, O, S2, CONH, NHCO, X, NHCOX, R4 [0 (CH2) 2] m0, CH2CO (CH2) 2; r2 = (ch2) 2c6h6, ch2nh (ch2) 2c6h6, conh (ch2) 2c6h6, X, NHX; R3 = cyclohexyl, aryl, X, YM; R4 = H, OH, YM, R !, and M = transition metal Or any of the paramagnetic ions of the lanthanide, including chaotic (III), iron (III), manganese (II and III), chromium (III), copper (II), plutonium (III), plutonium (III), "( III), bait (III) and plutonium (III); the most preferred are plutonium (III), plutonium (III), iron (III) and manganese (II). x = fluoroalkyl, fluoroaryl, fluorofluorenyl, perfluoroalkyl, perfluoroaryl, perfluorofluorenyl, perfluoropolymer, fluoroamine, fluoroaminocarbamate, fluorotris Well, fluorosulfofluorenyl alkyl derivative, CF2C1, S02 [CF2] xCF3, F, cf3, COCxFy, CF3C02, CxFyHz, ([CH2] m0) x (CH2CF20) y (CF2CF20) z- (CF2) 2CF2CH20 (CH2) p OH, QFy ^ Op, COCxFyHz, 0CH2CxFz [CxFz0] mF, CH2C (CH3) C02CxHz (CF2) mCF3, CH2 (CF20) x- (CF2CF20) y (CF20) zCF2CH20H, COCxHz (CF2) m NHCxFyHzOp, CH2 CF2 0 [CF2 CF2 0] m (CF2 OCF2 CH2 OH, C0-CF20 [CF2CF20] n-CF20CF2C02H, C0-CF (CF3)-[CF (CF3) CF20] mF ([CH2] m0) x ( CH2CF20) y- (CF2 CF2 0) z CF2 CH2 0 (CH2) p OH, CF3 S03, N (CxFyHJp,

CxHzC02CxHz (CF2) mCF3, COCxFy [CpFzO] mF, luminescent residue, fluorescent residue, fluorinated luminescent residue or fluorinated fluorescent residue, y = ch2c (oh) ch3, and m, p, X, y , Z = 1-150, and among them, m is more preferably 10-100, and most preferably 10-50, and among them, X, p, y, and z are more preferably 10-75, and more preferably 10-50, and The best is 10-20. Among them, η is more preferably 10-10,000, still more preferably 10-1,000, and most preferably 10-250. The fluorenyl and alkyl residues of the formula XX contain a lipophilic moiety group 84865 200400972, including saturated and unsaturated aliphatic residues, with a fluorene chain, where is 2 to ι〇〇, more preferably 2-50 , And preferably 2-20, and the aryl residue system includes aromatic partial groups, including benzyl, biphenyl, phenyl, polycyclic aromatic compounds, and aromatic compounds containing heteroatoms. γ = polydentate ligand metal complex residues' for example, 4,7,10_tetraazacyclododecane · 1,4,7,10-tetraacetic acid mono (p-aminofluorenylaniline ), 5-Aminotomethoxyphenyl_ 1,4,7,10-tetraazacyclo-dodecyl-1,4,7,10-tetraacetic acid, 2-p-aminofluorenyl 4,4 , 7,1〇_ Tetraazacyclo-dodecyl-1,4,7,10-tetraacetic acid, p-aminobenzyl_diethylenetriaminepentapic acid, p-isothiocyanatofluorenyl-1 , 4,7,10-tetraazacyclododecane_M, 7,10_tetraacetic acid 'p-isothiocyano-benzyl diethylenetriamine pentaacetic acid, p-isothiocyanatofluorenyl diethyl Triamine pentaacetic acid, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-hydroxysuccinyl erysimimine ester), 1,4,7 , 10-tetraazacyclododecane_M, 7 ^ (acetic acid_third-butyl ester) -10-acetic acid, diethylenetriamine pentaacetic acid, 1,4,7,10-tetraazacyclododecane Alkanes, 丨 4 7_ — · azepines, 1,4,7,10-tetrazol-1,4,7,10- (methylenephosphonic acid) and 10- (2- Ethyl-3,4-diketo-1-cyclobutenyl) -i, 4,7,10-tetraazacyclododecyl 1,4,7-triacetic acid. The invention also relates to novel imaging procedures to measure the course of diabetes, and the function or lack of antidiabetic agents. This imaging procedure involves administering a fluorinated or paramagnetic antidiabetic agent to the patient and then subjecting the patient to MRI. The MRI is then explained in comparison with a baseline MRI study to determine the mechanisms subordinate to the diabetic process and the functionality of the antidiabetic agent. This procedure can be conveniently used to monitor the progress of the disease state in the patient and the anti-diabetic agent over time. Sustained pharmacological activity. In addition, the present invention relates to a fluorinated biopolymer and a polymer derivative (formula 84865 200400972 bi-bxx) 'which can be used as a development probe, a diagnostic agent, and a contrast agent. In addition, the present invention relates to a developing method using the compound of formula BI_BXX of the present invention. The novel composition comprising the modified biopolymer of the present invention is a bayu / B! ™ compound, and its use as a novel biological substance, development detection tool and contrast agent: ^

OR〇

BIV

OR ^ ORs R50

B V 0¾ R6nr7

B VII

Of which about Formula BI:

Ri = H, X; R2 = H, X; R3 = h, 〇H, 〇Υ, OX, NHX About formula BII:

r1 = H, X; R2 = H, X; R3 = h, 〇Y, 〇X, NHX 84865 -20- 200400972 About the formula Bill:

Rj = Η, X, R2 = Η, X, R3 = Η, Y, X About formula BIV:

Ri = H, X; R2 = H, X; R3 = C02H, C02X, CH2X, CH2NHX; R4 = h, X; R5 = H, X; R6 = H, X; R7 = X, coCH3, COX About Formula BV:

Ri = H 'X; R2 = H' X; R3 = C02H 'C02X' CH2X 'ch2nhx; R4 = H, so3h, X; r5 = h, so3h, X; r6 = h, X; r7 = coch3, (: ox, X on formula BVI:

Ri = H, X; r2 = h, x; r3 = co2h 'co2x, CH2X, CH2NHX; R4 = H, X; R5 = S03H, X; R6 = H, X; r7 = coch3, COX, X About formula BVII :

Ri = H, X; R2 = H, x; r3 = h 'X; r4 = so3h, X; r5 = so3h, X; R6 = H, X; ~ = Η, X; R7 = COCH3, cox, X About Formula BVIII:

Ri = H, X; R2 = h, x; r3 = co2h, co2x, ch2x, ch2nhx; R4, X, r_5 = h, X, Rg = H, X; R7 = h, X;

R8 = COCH3, cox, X where all the above chemical formulas x = fluoroalkyl, fluoroaryl, fluorenyl, perfluoroalkyl, perfluoroaryl, all-air brewing group, perfluoropolymer 'fluoro group Amine, Fluorocarbamate, Fluoro Mitsui, Fluoro-continuous thiol derivative, CF2C1, so2 [cf2] xcf3, F, cf3, CoCxFy, cxFyHz, ([CH2] m0) x ( CH2CF20) y (CF2CF20) z (CF2) 2CF2-84865 -21-200400972 CH20 (CH2) pOH, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, 0CH2CxFz [CxFz0] mF, CH2C (CH3) C02CxHz (CF2) (CF20) x- (CF2 CF2 0) y (CF2 0) z CF2 CH2 OH, COF (CF3)-[CF (CF3) CF20] mF, NHCxFyHzOp, CH2CF20 [CF2CF20] m (CF20CF2CH20H, COCxHz- (CF2) mCF3 , C0CF20 [CF2CF20] nCF20CF2C02H, ([CH2] mO) x- (CH2 CF2 0) y (CF2 CF2 0) z CF2 CH2 0 (CH2) p OH, N [CxFyHz] p, CxHzC02CxHz (CF2) mCF3, COCxFy [ CpFzO] mF, luminescent residue, fluorescent residue, fluorinated luminescent residue or fluorinated fluorescent residue, and m, x, p, y, and z are integers from 1 to 150, and m is more preferably 10 -100, and the best is 10-50, and among them, x, p, y, and z are more preferably 10-75, more preferably 10-50, and most preferably 10-20. The sulfonyl and alkynyl residues in the chemical formula include lipophilic moieties, including saturated and unsaturated aliphatic residues, with a Ck chain, where k is 2 to 100, more preferably 2-50, and most It is preferably 2-20, and the aryl residue system includes aromatic partial groups, including benzyl, biphenyl, phenyl polycyclic aromatic compounds and aromatic compounds containing hetero atoms. Y = sugar branching Residues, including mono-, di-, oligo-, or polysaccharides, and fluorinated sugar branching residues, including mono-, di-, oligo-, or poly-. This novel composition is made of modified biopolymers Composition, wherein the biopolymer is selected from the group consisting of sol starch, cellulose, dextran, dextrin, polygalactose, / 3-polyglucose, glucosaminoglycans, including chondroitin sulfate, thiodermatin, Heparin sulfate, heparin, hyaluronate and keratan sulfate, maltodextrin, mannan, polytriglucose, starch, xylan and its copolymers, linear or cyclic oligomers, mixtures, salts and derivatives 84865 -22-200400972 A novel composition comprising a modified biopolymer of the present invention, comprising a general formula BIX to BXII compounds and disclosed herein as novel biological substances, imaging probes, diagnostic tools and contrast agents:

B IX

0-

-R5 K. m π q

BXII where about formula BIX:

RpH, X, Z; R2 = H, X, Z; R3 = H, X; R4 = H, X, Z; R5 = H, X; R6 = H, X; r7 = h, X, z About Equation 6 also:

RfH, x, ch2ogoco2h, ch2ogco2x, CH2OGCONX, CH2OGCH2NX; R2 = H, X, z; R3 = H, X, ch2ogoco2h, CH20GC02X, CH2OGCONX, CH2OGCH2NX; R4 = H, COCH3, coxgo2, x2, x2, x2 CH2OGCH2NX About Formula BXI:

RfH, OH, X, OX, oz, CH20G0C02H, CH2OGC02X, -23-84865 200400972 CH2OGCONX, CH2OGCH2NX; R2 = H, OH, X, ox, oz, CH20G0C02H, CH20GC02X, CH2OGCONX, CH2OGCH2NX, CH2OX CH2OZ, CH2X, CH2NHX, co2h, co2x, CONX, ch2ogoh, ch2ogox, ch2ogoco2h, ch2ogco2x, ch2ogconx, ch2ogch2nx; r4 = oh, Z, OX, X; G = alkyl, Weife group About formula BXII: K = Η, OH, X 'OX, 〇Z; L = Η, OH, X, OX, oz; W = Η, OH, X, OX, OZ; T = H, OH, X, OX, oz; V = dehydration Glycosyl, anhydro 11 glycosyl, and m, n, p, q, r = 1-500 (inclusive); η = 1-8 (inclusive). Among them, all of the above chemical formulas are fluorenyl, aryl, fluorenyl, perfluorocarbon, perfluoroaryl, perfluorofluorenyl, perfluoropolymer, fluoroamine, fluorocarbamate , Fluoro-Three Cultivation, Fluorosulfosulfanylalkyl Derivatives, F, cf2ci, so2 [cf2] xcf3, cf3, COCxFy, CxFyHz, ([CH2] m0) x (CH2CF20) y (CF2CF20) z (CF2) 2-CF2CH20 (CH2) pOH, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz (CxFzO) mF, CH2C (CH3) C02CxHz (CF2) mCF3, CH2 (CF20) x- (CF2 CF2 0) y (CF2 0) z CF2 CH2 OH, COCF (CF3)-[CF (CF3) CF2 0] mF, NHCxFyHzOp, CH2CF20 [CF2CF20] m (CF2OCF2CH2OH, COCxHz- (CF2) mCF3, C0CF20 [CF2CF20] nCF20CF2C02Hm, (x2 -(CH2 CF2 0) y (CF2 CF2 0) z CF2 CH2 0 (CH2) p OH, N [CxFyHz] p,

CxHzC02CxHz (CF2) mCF3, COCxFy [CpFzO] mF, luminescent residue 'fluorescent residue, Itized luminescent residue or fluorinated fluorescent residue, and m, x, p, y, z 84865 -24- 200400972 are Integer 1 to 150, and among them, m is more preferably 10-100, and most preferably 10-50, and among them x, p, y, and z is more preferably 10-75, and more preferably 10-50, and most preferably 10-20. The fluorenyl and alkyl residues in the above formula include lipophilic moieties, including saturated and unsaturated aliphatic residues, with a Ck chain, where k is 2 to 100, more preferably 2-50, and The most preferred is 2-20, and the aryl residue system contains aromatic partial groups, including benzyl, biphenyl, phenyl polycyclic aromatic compounds and aromatic compounds containing hetero atoms; and Z = The base and pit basic invention composition is composed of modified biopolymer, wherein the biopolymer is selected from linear, branched, cyclic, ionic or neutral glycans, such as gum arabic, agar , Alginate, arabinogalactan, arabinoxylan, carrageenan, cyclodextrin, fructo-oligosaccharide, seaweed polysaccharide, gum life, galactomannan, glucomannan, inulin, pectin, Polytriglucose, tragacanth gum, xanthan gum and xylose polyglucose, carboxyalkyl polysaccharides, such as carboxymethyl cellulose, carboxymethyl chitosan and carboxymethyl dextran, poly Sugar esters, such as cellulose acetate, cellulose phosphate, cellulose sulfate and starch acetate, amino glycans, Such as chitin, chitosan, bitter almond and poly (galactosamine), hydroxyalkyl polysaccharides, such as hydroxyethyl cellulose, hydroxypropyl cellulose, alkyl polysaccharides, such as ethyl fiber And methyl cellulose, polysialic acid and its oligomers, mixtures, salts and derivatives. The novel compounds of the present invention include compositions containing modified biopolymers of the general formula BXIII as novel biological substances, imaging probes, diagnostic tools and contrast agents: 84865 -25- 200400972

ΒΧΠΙ Where the formula ΒχΠΙ: κ = Η, OH, X, 〇χ, 〇Z, (Y) f; L = H, OH, X, 〇χ, 〇Z, ⑺f; W = H, (CH2) d, C02H, CH, CX, X; T = Η, OH, X, OX, OZ; V = (CH2) d, CH2OX, CH2OZ, CH2X, CH2NHX; S = Η, 〇, X, NHX, (Y) f; T = Η, Ο, X, NHX, (Y) f; R! = H, X 'JLd = 1-3; f, n = 1-1,500, preferably f, n = 100-1, 000, where all of the above Cultural formula X = Fluoro'fluoroaryl, fluoric acid, all-it fluorenyl, perfluoroaryl, perfluorofluorenyl, perfluoropolymer, fluoroamine, fluorinated 1-aminocarbamate, fluoro group San 11 well, fluorosulfofluorenyl alkyl derivative, F, CF3, CF2C1, so2 [cf2] xcf3, C0CxFy, CxFyHz, ([CH2] m0) x (CH2CF20) y (CF2CF20) z (CF2) 2- CF2CH20- (CH2) pOH, CH2C (OH) CxFyHz 'CxFyHzOp, COQFyt ^, OCH2CxFz [CxFzO] mF, CH2 C (CH3) C02 Cx Hz (CF2) m CF3, CH2 (CF2 0) x (CF2 CF2 0) y (CF2 0) z CF2 CH2 OH, NHCxFyHzOp, CH2CF20 [CF2CF20] m (CF20CF2CH20H, COCxHz (CF2) mCF3, C0-CF20 [CF2CF20] nCF20CF2C02H, C0CF (CF3)-[CF (CF3) CFCH2) mF, ] m0) x (CH2CF20) y (CF2 CF20) zCF2CH20 (CH2) p0H, N [CxFyHz] p, CxHzC02CxHz (CF2) mCF3, COCxFy [CpFzO] mF, luminescent residue, fluorescent residue, vaporized luminescent residue, or fluorinated fluorescent residue 'and m , X, p, y, 84865 -26- 2UU4UU972 z is an integer from 1 to 150, beans', middle m is more preferably 10-100, and most preferably 10-50, and: XP, /, Z is more preferably 1〇_75 'and more preferably 10-50, and most preferably 10-methylated, wherein the fluorenyl and alkyl residues in the formula contain a lipophilic moiety, including saturated and unsaturated aliphatic residues, Has a Ck chain, where 2 :: 〇t is preferably 2-50 'and most preferably 2_20' and the aryl residue system contains an aromatic knife group, including fluorenyl, biphenyl, and phenyl polycyclic Aromatic compounds and aromatic compounds containing heterogen. γ-amino acid residue, fluorinated amino acid residue. z = _base, burning base. The new composition is composed of modified biopolymers, wherein the biopolymers and polymers are selected from the group consisting of collagen, elastin, gelatin, poly (amino acids) 'including poly (aspartic acid), Poly (glutamic acid) and poly (lysine), biological poly (a), including poly (glycolic acid), poly (xianganic acid) and poly (lactic acid), copolymers, oligomers, mixtures, Salts and derivatives. The novel composition of the present invention comprises a compound comprising a modified polymer of the general formula BXIV to BXX < and its use as a novel biological substance, a development probe, a diagnostic tool and a contrast agent:

B XVII B XVIII 84865 -27- 200400972

Among them, about formula BXIV:

RfH, X; R2 = H, Z, X. About formula BXV:

RfH, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R2 = H, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R3 = H, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R4 = H, CH3, (CH2) m CH3, CF3, (CF2) m CF3; R5 = H, CH3, (CH2) m CH3, CF3, (CF2) mCF3, CH2X, CH2NHX; R ^ H, CH3 , (CH2) mCH3, CF3, (CF2) mCF3, CH2X, CH2NHX; m = 1-10; n = 1-3,000. About Formula BXVI:

RfOH, X, OX, OZ; R2 = OH, X, OX, OZ; m, n = 1-15,000, preferably m, n = 500-2,000. About Formula BXVI:

Ri = 0, CH2X, CH2NHX, OZ; R2 = CH3, (CH2) mCH3; R3 = CH3, (CH2) mCH3, CF3, (CF2) mCF3; R4 = (CH2) n; R5 = (CH2) q; R6 = H 'OH, OX, X; R7 = H, OH, OX, X; m, n = 1-30; p, q = 0-3,000; preferably p, q = 50-500. About formula BXVII: & = 0, OX, CF3, (CF2) mCF3; R2 = CH3, (CH2) nCH3, CF3, (CF2) nCF3; R3 = CH3, (CH2) nCH3, CF3, (CF2) nCF3; R4 = (CH2) m; R5 = (CH2) q; R ^ OH, OX, X; R7 = H, X; m = l-2; n = l-10; p, q = l-3,000 84865 -28 -200400972, preferably p, q = 100-1,000. About formula BXVIII:

Ri = H, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R2 = H, OH, OX, X; R3 = H, OH, OX, X; m = 1-30; n = 1-3,000, Preferably, n = 500-1,000. About the formula: 6 乂 1

Ri = CH2, CH2CH2, CF2, CF2CF2; R2 = CH2, CF2; R3 = OH, OX, OZ; R4 = H, X, Z; where Z = Y [(OCH2CH2) m] q; Y = polydentate fit The somatic core, such as a trivalent or tetravalent residue; m, η = 1-80,000, preferably m, n = 1,000-20,000; q = 1-10. About formula BXX:

RpH, X; R2 = H, X, (CH2CH2N) m, (CH2CH2NX) m; R3 = H, X βΗ2 CH2 N) m, (CH2 CH2 NX) m; R4 = Η, X, (CH2 CH2 N) m CH2 CH2 NH2, (CH2CH2N) mCH2CH2NHX; m = 1-3,000; n = 5-80,000, preferably n = 500-15,000. Of all the above formulas, fluoroalkyl, fluoroaryl, fluorofluorenyl, perfluoroalkyl, perfluoroaryl, perfluorofluorenyl, perfluoropolymer, fluoroamine, fluorocarbamate , Fluoro-Three Cultivation, Fluoro-Sulfoalkyl Derivatives, F, CF3, COCxFy, CxFyHz, ([CH2] g0) x (CH2CF20) y (CF2CF20) z (CF2) 2CF2CH20 (CH2) p0H, CH2C ( OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz [CxFzO] gF, CH2 C (CH3) C02 Cx Hz (CF2) g CF3, CH2 (CF20) x (CF2CF20) y- (CF2〇) zCF2CH2OH, CF2C02, SCF2C02 xCF3, NHCxFyHzOp, CH2CF20 [CF2CF20] g (CF20CF2CH20H, COCxHz (CF2) gCF3, CO- 84865 • 29- 200400972 CF2 [CF2 CF2 0] n CF2 OCF2 C02 H, CO-CF (CF3)-[CF (CF3) CF2 0] g-F ([CH2] g 〇) x (CH2 cf2 〇) y (CF2 cf2 0) z cf2 ch2 0 (CH2) p oh, NRFyHJp, CxHzC02CxHz (CF2) gCF3 'COCxFy [CpFzO] mF, luminescence residue Group, fluorescent residue, fluorinated luminescent residue or fluorinated fluorescent residue, and g, x, p'y, z are integers from 1 to 150, and g thereof is more preferably from 10 to 100, and The best is 10-50, and among them, x, p, y, and z are more preferably 10-75, more preferably 10-50, and most preferably 10-20. The fluorenyl and alkyl residues in the chemical formula include lipophilic moieties, including saturated and unsaturated aliphatic residues, which have a (^ chain, where k is 2 to 100 ', more preferably 2-50, and The most preferred is 2-20, and the aryl residue system contains aromatic partial groups, including fluorenyl, biphenyl, phenyl polycyclic aromatic compounds, and aromatic compounds containing hetero atoms; and fluorenyl, Alkyl. The novel composition consists of a modified polymer, wherein the polymer is selected from biocompatible polymers including poly (acrylate), poly (propylamine) water, Ok—alcohol) , Including poly (ethylene glycol), poly (ethylene oxide), and poly (propylene glycol), = (allylamine), poly (butadiene), poly (caprolactone), poly (acetimide), Poly (methacrylate), poly (orthoester), poly (tetrahydrofuran), poly (ethynyltetrahydropyrrolidone), poly (ethyl ethyl acetate) and poly (ethinyl alcohol), their copolymers, Polymers, mixtures, salts, and derivatives, and the contents of which are disclosed in the following-Wyl & residue system, including lipophilic moieties, & Saturated and unsaturated ^ Residue residues "having a Ck chain" where k is 2 to 100, more preferably 2 to 50, and preferably 2 to 20, and the aryl residue system includes an aromatic moiety Groups, such as amyl, phenyl, polycyclic aromatic compounds, and aromatic compounds containing heteroatoms. 84865 -30- 200400972 Detailed description of the invention In the practice of the present invention, the polymer, antidiabetic compound, polyuronic acid, or protein bound to the receptor are affiliated with a fluorine-containing moiety and / or cis Magnetic ions are modified to produce analogs that can be used as imaging probes, diagnostic agents, and contrast agents in MRI imaging procedures.

In a specific embodiment, alginate is used as the polyuronic acid glycoside. Alginic acid is a linear 1,4-linked block copolymer composed of / 5-D-mannuronic acid (M) and α-L-guluronic acid (G) residues. Alginates can have different mannuronic acid / guluronic acid ratios and compositions. The alginate with high G content shows the strongest gel-forming ability, and is based on its biaxial configuration compared to the bi-equator bond in the poly M sequence. The typical M: G ratio of alginates obtained from different biological sources can be changed from 1.40-1.95 to 0.45-1.00, compared with ~ 38-41% of regular alginates, where " G "alginate contains the highest 69% G residues. For example, alginic acid derived from brown seaweed Macrocystis pyrifera, with 18% poly G segments, 41% poly M segments, and 42% mixed G / M segments, while Laminaria hyperborean alginic acid The ester has 61% poly G segment, 13% poly M segment, and 27% mixed G / M segment. In addition, epimerase can be used to change the alginate monosaccharide composition. For use in this The preferred alginate of the invention is a high-g alginate with at least about 50% G residues. A high-g alginate is preferred, especially in applications that require gelled form of alginate, such as beads Or capsules, which are derived from the mismatch of calcium, barium, or similar ions that are known to cause higher gel strength or allow gel formation at lower alginate concentrations. These high G alginic acids Esters are fluorinated as described herein to produce fluorinated high G alginates. When 84865 -31-200400972 are not gummed When the alginate composition is desired, propylene glycol alginate or high M alginate can be used as the starting material as described herein. Due to the solubility of propylene glycol alginate in organic solvents, Alkylation is also preferred when it involves highly hydrophobic and incompatible agents that are incompatible with aqueous solutions. When compositions without or with limited water solubility are desired, alginic acid itself is the preferred starting material, or The final product can be converted into a comparable free form alginic acid form by appropriate ion exchange procedures. Various other derivatives and variants in the above method can be used for alginate and other polysaccharide aldehydes known to those skilled in the art Acid acid. Some 200-grade alginic acid and its various salts are manufactured and commercially available. In another specific embodiment, for the purpose of the present invention, the epitoxin V is passed through its N-terminal region. Modification in order to retain its cell membrane binding affinity intact. Appropriate modification procedures have been described by Tait et al. (See Tait, JF, Gibson, D., Fujikawa, K., J. Biol. Chem., 264, 7944-9 , 1989; Tanaka, K ., Einaga, K. Tsuchiyama, H. Tait, JF FujikawaK, Biochemistry., 35, 922-9, 1996; Tait, JF, Brown, DS, Gibson, D., Blankenberg, FG Strauss, HW, Bioconjugate Chem., 11, 918-925, 2000). Similar procedures can be used to prepare other biologically active proteins under appropriate conditions to retain receptor binding activity. The fluorinated addendin V can then be used as a diagnostic tool to identify cell decay in tissues, tumors or other affected organs, and to evaluate the effectiveness of individual therapeutic interventions. A similar procedure is used to make other fluorinated bioactive polymers by fluorinating the starting material protein using standard fluorination techniques. Paramagnetic proteins are produced by reacting proteins with desired paramagnetic ions. 84865 -32- ΙΑ Paramagnetic compounds of the present invention

"Development and magnetic Α 粝 a 其 ν 忠 忠 月" is used for live dazzle MR Jinwa: & radiography. This contrast agent is physiologically buffered, = other physiologically acceptable carriers known to those skilled in the art: Instrument: Configuration = or intraperitoneal administration. The dosage is determined by the sensitivity and composition of the contrast agent. Therefore, a contrast agent containing a high-yield substance such as rhenium usually requires a lower dose compared to a contrast agent with a lower magnetic moment. Generally, & the dosage is about 0.001-1 millimole jp / eight ΛΛ1Λ1 „Bi Moer / kg" in the garden, more preferably about 0.01-0.1 hammer / kg. In one ..., chastity 1 ^ xiao In her case, the product is dispersed in an injection medium, such as distilled water or physiological saline, to form a dispersion. It is introduced into the patient's vascular system by intravenous injection. After cooking, the particles are passed through the vascular system. Carry it to the target organ, where it is absorbed. When administered intravascularly, 'the paramagnetic compound is preferentially absorbed by organs that normally function to cleanse blood impurities, especially the liver, spleen and lymph nodes' And is absorbed by other organs that are prone to accumulate such impurities: especially bones and nerve tissues, and lungs, to a certain extent. In each of these organs and tissues, it is absorbed into copper 舳 FREE Ik 丄 „soil homoendothelial cells It occurs by phagocytosis, where the compound enters individual cells in the cell membrane-bound vesicles; this allows longer half-lives in the cell, due to the paramagnetic compounds bound by the cell membrane. Easy agglomeration or aggregation (aggregation system from the microbial metabolism and the rapid removal of Et / tissue). Other absorption mechanisms are possible, such as puffing. Other liver cells (liver cells) may also absorb paramagnetic compounds. Because cancerous tumor cells may lack the ability of 呑 嗟 cells to absorb them, the paramagnetic compounds of blood vessels 84865 -33- 200400972 and 弋 Xi Yu can be used in cancer organs in the organs mentioned above. With the 彳 Λ value tool, tumors will be immediately distinguishable on any image acquired. Tian Wan, a In another specific embodiment, the paramagnetic compound is administered as a dispersion: the intestine, including the esophagus, stomach, and small and large intestines, whether orally, by insertion: or fine enema, where appropriate Medium towels, such as steamed hall water, or any suitable, medical wood sword. The particle system is preferentially absorbed by the cells of the channel, especially the intestinal y, field cells and similar particles introduced by intravascular methods, which will have an effect on the organ or group 2. In this way, cancer and other debilitating diseases of the digestive system, such as ulcers, can be diagnosed and pinpoint the affected area. 3 The novel fluorocompounds of the present invention with a carbohydrate, polymer or protein backbone or matrix, use routine fluorination chemistry, such as those described herein, by treating individual starting materials (mains with a fluorine moiety) Chain or matrix moiety). Novel fluorinated polymers are made into probes. One target substrate is alginate 'which can be fluorinated by a variety of methods. — This series of fluorine-containing water-soluble alginates can be made to have a wide range of fluorine content. The fluorine content can be changed from 5% to more than 40%, and can easily be further maximized. More importantly, although two kinds of line widening effects of the fluorine-soluble water-soluble seawater and alginic acid have been found, the bF_nmr spectrum can show a very high signal-to-noise (STN) ratio, which has superior diagnostic value. This is true even at moderate fluorine levels. Figure "shows an example of sevoflurane alginate derivative (Example 1, F ~ 10%), and its i9F_NMR spectrum in a dilute aqueous solution (~ 3W / V%), only 100 instants are obtained Figures la and b show six well-dispersed (~ 45ppm) trifluoro 84865 • 34- 200400972 of this derivative. The methyl group resonates with difluoromethylene and has a high STN. Furthermore, 'When alginic acid heptafluoro When the butyl ester is converted into beads by addition to an aqueous calcium solution, the BpNMR spectrum (Figure lc) formed is acceptable, even at a relatively low overall concentration (04%) of this material. Of course, various other examples of these MRI probes are made using alginate and other fluorination treatments (see Examples 2-17). The i spectra of some formed substances are shown in Figure 2. It is obvious that Yes, in all cases, the bath salt probe will produce a very suitable spectrum with high STN, and its "heart resonance" is tailored to appear in a wide range of spectral regions, depending on the fluorinated residue Type and ^. Therefore, Fig. 2e shows the W-NMR spectrum of the perfluoroaniline alginic acid derivative of Example 4, in which all its main resonances appear between about 175 ppm. Example 9 The main resonance of the perfluoropolymer alginate derivative (Figure 2a) is at -60 to -80 ρρπχ, and * / 丨! In the case of PPm, the derivatives of Example 11 (Figure 2b) are at _55 to -85 ppm, individually. The ability to customize the spectral properties of polymer developers by exhausting and optimizing the substituents of the Tiantian Roller < Tongdang Selection >

'This force has obvious advantages, especially when the MRI test needs to resonate in the specific light 4 and zone φ cω You Yang E domain to provide a selective pulse sequence. Another benefit is that these new | combined figures turn around, ~, pump pump shirts allow the combined use of standard PFCs (such as in the form of coatings), without the possibility of 4 θ ^ about the possibility of individual fluorine resonance Concerns about spectral overlap. This multiple i9F 熘 4+ needle system can be designed to assist in the simultaneous evaluation of several environmental conditions. The fluorinated residues described in this paper are linked to polyuronic acid, and are linked by & _ 丄 * agglutinin V and other matrix 4, and can be refined by a variety of conventional reactions, many of which have been generally described in common Vehicle chemistry (guan ΓTM η) (for review, see, for example:

GT Hermanson, Lan # 异 无 #Chemical Girl A 'Yu Publishing House, New York, 1996; 84865 200400972 SS Wong, Protein: f1 is a must learn to compete with, CRC Publishing House, Boca Raton, 1993; RL Lundblad , 蛋 冷 # ## 犮 婚, CRC Press, Boca Raton, 1994; CF Meares (ed.), 祎 祎 兰 # 异 无 #Chemistry, American Chemical Society, Washington, 1993) 0 Polysaccharide aldehydes described in this article Acid glycosides, proteins (epixin V), and other terminal hydroxyl groups on the substrate are allowed to react with bromoacetamidine to form bromoacetamidate, which is then reacted with the amine precursor to form -nh-ch2 -c (o) -link. The terminal hydroxyl group may also be allowed to react with 1, Γ-carbonyl-bisimidazole, and this intermediate may be allowed to react with the amine precursor in turn to form a -NH-C (0) 0-chain (see, Bartling et al., IVaiwa 243, 342, 1973). It can also allow terminal hydroxyl groups to react with cyclic anhydrides such as succinic anhydride to produce half-esters, which in turn are allowed to react with the precursor of formula CxFyHz-NH2, using conventional peptide condensation techniques such as dicyclohexylcarbodiimide, chlorophosphonic acid Phenyl ester or 2-chloro-4,6-dimethoxy-1,3,5-tricotine (see, for example, Means et al., Chemical Remnants of Protein Deficiency: T, Holden-Day, 1971). The terminal hydroxyl group may also be allowed to react with 1,4-butanediol diglycidyl ether to form an intermediate, having an epoxide functional group, and linked to the end of the polymer through an ether bond. This terminal epoxide functional group is allowed to react with amine or hydroxy precursors in turn (Pitha et al., Ugly ... / csoem, 94, 11, 1979; Elling and Kula, oiec /? · / 4 邵 /. 历 _oc / zem., 13, 354, 1991; Stark and Holmberg, oiec / i. Li oeng ·, 34, 942, 1989). The hydroxylation allows subsequent reactions with alkanediamines such as 1,6-hexanediamine. Then, the formed product is allowed to react with carbon disulfide in the presence of potassium hydroxide, followed by the addition of propyl chloride to produce isothiocyanate, which in turn reacts with the amine precursor to produce -NC (s) -N-(CH2) 6-NH-link (see, for example, 2 34 84865 -36- 200400972, for example Means et al., Egg Cold # 之 化 梦遗 Holden-Day, 1971). The polysaccharide uronic acid glycosides, proteins (epixin V) and other substrates described herein can use N, N'-dicyclohexylcarbodiimide, 1- (3-dimethylaminopropyl (Yl) -3-ethylcarbodiimide or equivalent carbodiimide is activated and then individually reacted with an amine or light group to form amidine or ether. Livers and amidines will produce the same linkages as amines and alcohols. Alcohols can be activated by carbonyldiimidazole and then linked to amines to produce carbamate linkages. Alkyl halides can be converted into amines or reacted with amines, diamines, alcohols or glycols. The hydroxyl group can be oxidized to form its corresponding aldehyde or ketone. This aldehyde or ketone is then allowed to react with the precursor bearing a terminal amine group to form an imine, which is sequentially reduced with sodium borohydride or sodium cyanoborohydride to form a secondary amine (see Kabanov et al., / · 22, 141 (1992); Lu Xun Cai Fa, XLVII, edited by Hirs & Timasheff, Acad. Press, 1977). The precursor terminated with an amine group may also be reacted with an alkanoic acid or a fluorinated alkanoic acid, preferably an activated derivative thereof, such as osmium chloride or anhydride, to form a linking group -CONH-. Alternatively, the amine precursor can be treated with α-ω-diisocyanoalkane to produce -NC (0) NH (CH2) 6NHC (0) -N-linkage (see Means, protein # 之 必 荸 砹 #, Holden-Day, 1971). Furthermore, asymmetric links, such as -CONH- or -NHCOO-, can exist in reverse orientation; for example, -NHCO- and -OCONH-. Examples of activated carbonyl groups include anhydrides, ketones, p-nitrophenyl esters, N-hydroxysuccinimide imide, pentafluorophenyl ester, and europium chloride. Suitable fluorinated starting materials for making the novel compositions of the present invention include organic and inorganic fluorinating agents. Representative fluorinating agents include trifluoromethyl hypofluorite, sulfur tetrafluoride, CF2C1, S02 [CF2] XCF3, potassium fluoride, organic fluorinating agents, such as 84865 -37- 200400972 such as fluoroamines, fluoro groups Carbamate, fluorotrifluorene, fluorosulfoalkyl alkyl derivative, SelectfluorTM, fluoroalkylcarboxylic acids, fluoroalkylaldehydes, anhydrides of fluoroalkylcarboxylic acids, esters, ketones, Samarium chlorides, such as monofluoroacetic acid, difluoroacrylic acid, difluoroacrylic acid, pentafluoropropionic acid, heptafluorobutyric acid, heptafluorobutyric acid, heptafluorobutanyl chloride, nonafluoropentanoic acid, thirteen Fluoroheptanoic acid, pentafluorooctanoic acid, heptafluorononanoic acid 'nonadecafluorodecanoic acid, perfluorododecanoic acid, perfluorotetradecanoic acid; fluoroalkanols, such as 2,2,3,3, 4,4,4-Heptafluorobutanol, 2.2.3.3.4.4.5.5.6.6.7.7.8.8.8- Pentadeca-1-octyl || '2,2,3,3,4,4 , 5,5,6,6,7,7,8,9,9,9- Heptafluoro-1-nonanol: Phantom "" Canyi Yi Canfengfeng melon nineteen fluorine- 丨 -decanol Krytox and Zonyl derivatives, fluoroaryl vinegars, fluoroarylamines, fluoroarylamines, 2,2,3,3,4,5,5,6,6,7,7,8 , 8,9,9,10,10,11,11,11-hexafluoro-1-undecanol, containing trans Fluorinated polymers with reactive end groups, fluorinated halogen halides, such as Qihua whole mouse acetamidine,? Canonization of full gas propane, desertification of full gas hexane, brominated full gas heptane 'brominated perfluorooctane, iodized perfluorodecane, iodized perfluorooctane, 1,1,1,2, 2,3,3,4,4,5,5,6,6,7,7,8,8-Heptadecyl-based, broken base decyl, 1.1.1.2.2.3.3.4.4.5.5.6. 6.7.7.8.8- Heptamethynyl-10-decadecylhydrazone, polyoxytetrakiethylene-co-oxidized difluoromethylene-α, ω-bis (methyl amylate), perfluoropoly Dioxanyl propoxyfluorenyl derivative, perfluoropolyoxyfluorene light-weight polyethoxyl derivative, etc. Appropriate modification procedures have been described in several monographs (JJ Clark, D. Walls. TW Bastock, Mao's consent, CRC Press Boca Raton, FL, 1996; M. Hudlicky, AE Pavlath, # Mule Deer Compound Chemistry, ACS, Washington, DC 1995; edited by M. Howe-Grant.

Wiley, New York, 1995; edited by G. A. Olah, G. K. Sarya Prakash, R. D. Chambers, Synthesis Yuhua #, Wiley, New York, 1992). 84865 • 38- 200400972 Special examples of formula I IV ports * may require the use of protecting or blocking groups 乂 to make it successful and sophisticated enough to become the desired structure. The protecting group can be referred to ‘et al.’ Cai Tiehe's poor protection, John Wiley & Sons, 1991 for selection. The blocking group can be easily removed, meaning that it can be removed, if desired, by a procedure that does not cause the rest of the molecule to split or otherwise disintegrate. Such private sequences include chemical and enzymatic hydrolysis, chemical reduction or oxidizing agents, treatment under mild conditions' treatment with fluoride ions, treatment with transition metal catalysts and nucleophiles, and catalytic hydrogenation. Examples of suitable protecting groups are: trimethyl nightmyl, triethylsulfanyl o-nitrofluorenyloxycarbonyl, p-nitrofluorenyloxycarbonyl, tert-butyldiphenyl Silyl, tertiary dimethylsilyl, benzyloxycarbonyl, tertiary oxoyl 2'2'2 ·: chloroethoxycarbonyl and allyloxycarbonyl. Appropriate kilysyl groups are exemplified by benzyl, o-nitrobenzyl, p-nitrobenzyl, L-naphthylmethyl, #propyl, 2-chloromethylpropyl, and propyl , 2-bis-2-trichloroethyl, trimethyl sulfanyl, tertiary-butyldimethyl, tertiary. Butyldiphenylsilyl, 2- (trimethylsilyl) ethyl Group, benzamidinemethyl, p-methoxyfluorenylacetone, p-methoxybenzyl, 4-p-pyridinylfluorenyl and tert-butyl. Paramagnetic polyuronic acid glycosides can be prepared by contacting a polyuronic acid glycoside that is suitably salt-forming with an appropriate molar amount of a suitable metal ion under a strip sufficient to form a polyuronic acid salt. For example, paramagnetic alginate beads can be formed by slowly adding sodium alginate with gluturonic acid content to a stirred aqueous solution of gadolinium (111) acetate at approximately equal molar ratios. . The beads formed are separated by centrifugation and can be washed with calcium chloride to remove excess plutonium. Similarly, 'superparamagnetic polyuronic acid bead can be produced by the same procedure as above 84865 -39- 200400972' but using superparamagnetic particles, such as a suspension of iron oxide particles, instead of the chaotic water solution. The superparamagnetic protein common system is prepared by mixing superparamagnetic nanoparticles with a buffered protein solution. Superparamagnetic nanoparticles can be optionally oxidized in fish protein. Then, the reaction mixture was centrifuged, and the supernatant was discarded to obtain the desired protein conjugate. Two or more specific implementations, the present invention is a method for diagnosing the functionality of an anti-diabetic drug in a diabetic patient, which includes: a. Administering a therapeutic amount of the anti-diabetic drug to a patient in a gas-containing or paramagnetic similar manner B. Allow the patient to receive tissues / organs, this is the place where the anti-diabetic drugs act; c. Evaluate the functionality of anti-diabetic drugs from MRI images. Another specific example of this month is a method for monitoring the progress of diabetes in a patient, which includes: a. Administering a therapeutic amount of a fluorine-containing or paramagnetic analog of an anti-diabetic drug to the patient; b. Patients are subjected to MRI of tissues / organs, which is the site of action of anti-diabetic drugs over time; and c. MRI images obtained over a long period of time to assess the progress of diabetes. Those skilled in the art can easily evaluate MRI results by comparing current < images with previous images obtained from the same patient or standard images used as diagnostic aids. It is known that the novel fluorinated antidiabetic drug 84865 -40- 200400972 of the present invention can be prepared by a general processing method: ^. ^ W J is known to replace the compound with a murine chemical unit for & anti-diabetes The agent is not fluoridated by fluoridation (as shown in Example 32-40); (2) Antidiabetic agents are linked by fluorinated reagents and ⑶ polyfluorinated residues. (Shown); and m ^ a few urinary agents, such as the use of functional wholes as shown in Examples 29 and 49). The above treatment allows the preparation of… urinary agents and their analogs, with a wide range of fluorine Substituent type and incorporation content (5_40% or more, as shown in the examples below), and can be suitable for either diagnostic or therapeutic #. Higher fluorine incorporation can be achieved by synthetic strategy For example, for the sulfonylurea compound of structural formula AX, where R1 is perfluorooctane, and R2 is pentafluorophenyl (according to the procedure in the example below, 'perfluorinated phase' compounds and isopentanoic acid Made from the precursor of flufenate), the fluorine content is more than 60%. The most suitable fluorine content is determined in each case by the diagnostic requirements for sensitivity, and the maximum degree of fluorine substitution will not interfere with the biological or physicochemical properties of the probe, such as its solubility or receptor binding capacity. Those skilled in the art can easily perform routine binding and solubility studies to determine the effect of fluorine substituents. An important parameter in these tests is the type of fluorine substitution and its location on the probe matrix. In general, the F content is preferably from 10 to 40%, and more preferably from 20 to 40%. The preparation of paramagnetic SU analogs can be achieved by a similar synthetic process, using either paramagnetic polymer-coated superparamagnetic iron oxide particles (SPIO) or macrocyclic chelating residues containing functionalized paramagnetic ions, For example, europium chelates are attached to appropriate SU analogs (as shown in Examples 40-48). The linking of fluorinated residues to antidiabetic agents described herein can be achieved through a variety of conventional responses of 84865 -41- 200400972, many of which have been described generally in conjugate chemistry (for a review _, see For example: GT Hermanson, Nothingness is chemistry, University Press, New York, 1996; SS Wong, Egg Cold # is the alternative to itching with cold mat #, CRC Press, Boca Raton, 1993; R. L · Lundblad, protein f #f, CRC Press, Boca Raton, 1994; CF Meares (ed.), Yuan Bangli # 为 与 # / 6 #, American Chemical Society, Washington, 1993). The terminal hydroxyl groups on the anti-diabetic agents described herein may be allowed to react with bromoacetamidine chloride to form bromoacetamidate, which is then reacted with an amine precursor to form -NH-CH2-C (O )-link. It is also possible to allow the terminal end to react with 1, Γ-carbonyl-bisimidazole, and in turn allow this intermediate to react with the amine precursor to form a -NH-C (0) 0-link (see Bartling et al., Apply re, 243, 342, 1973). It can also allow terminal hydroxyl groups to react with cyclic anhydrides such as succinic anhydride to produce half-esters, which in turn are allowed to react with the precursor of formula CxFyHz-NH2, using conventional peptide condensation techniques, such as dicyclohexylcarbodiimide, chloro Diphenyl phosphonate or 2-chloro-4,6-dimethoxy-1,3,5-tri (1 well (see, for example) ^ & 118 et al. Improve poverty, Holden-Day, 1971). The terminal groups can also be allowed to react with ι, 4-butanediol diglycidyl ether to form an intermediate, which has an epoxide functional group and is linked to The end of the polymer. Next, the terminal epoxide function is reacted with an amine or hydroxy precursor (Pitha et al., Five Mr. So ocAem., 94, 11, 1979; Elling and Kula, 5⑹ec / z. Calendar 13 , 354, 1991; Stark and Holmberg, oied Li Shen, 34, 942, 1989). The halogenation of hydroxyl groups allows subsequent reactions with alkanediamines such as 1,6-hexanediamine. Then 'make the formed The product is reacted with carbon disulfide in the presence of potassium hydroxide, followed by the addition of propyl chloride 'to produce isothiocyanate, and then

84865 -42- 200400972 which reacts with amine precursors to produce -NC (S) -N- (CH2) 6-NH- links (see, e.g. Means et al., Protein # 的 化学 遗 #, Holden-Day , 1971). The carboxylic acid group of the anti-diabetic agent described herein may be N, N'-dicyclohexylcarbodiimide, 1- (3-diamidinopropyl) -3-ethylcarbodiimide or equivalent The carbodiimide is activated and then individually reacted with an amine or hydroxyl group to form amidine or ether. Anhydrides and rhenium chlorides will produce the same linkages as amines and alcohols. Alcohols can be activated by carbonyldiimidazole and then linked to amines to produce carbamate linkages. Alkyl compounds can be converted to amines or reacted with amines, diamines' alcohols or glycols. Hydroxyl groups can be oxidized to form their corresponding aldehydes or ketones. This aldehyde or ketone is then reacted with a precursor bearing a terminal amine group to form an imine, followed by reduction with sodium borohydride or sodium cyanoborohydride to form a secondary amine (see Kabanov et al., Co.ra // et / and e / eose, 22, 141 (1992); You # method, XLVII, Hirs & TTimasheff, Acad. Press, 1977). It is also permissible to react with an amine-terminated precursor with an alkanoic acid or a fluorinated alkanoic acid, preferably an activated derivative thereof, such as a chlorinated turtle or alkaloid, to form a linking group -CONH-. Alternatively, the amine precursor can be treated with a diisocarbyl fe to produce a -NC (0) NH (CH2) 6NHC (0) -N-chain (see Means, Protein # 之 化学 政 #, Holden-Day , 1971). In addition, asymmetric links, such as -CONH- or -NHCOO-, can exist individually in reverse orientation; for example, -NHCO- and -OCONH-. Examples of activated carbonyl groups include anhydrides, ketones, p-nitrophenyl esters, N-hydroxysuccinimide, pentafluorophenyl esters, and europium chloride. The paramagnetic sulfonylurea complex of the present invention can be made using suitably activated metal complex residues, such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracycline Acetic acid mono (p-aminofluorenylaniline) [DOTA-p-NH2-acylaniline], 5-amino-2-methoxyphenyl-84865 -43-200400972 1,4,7,10-tetrazine Cyclododecane_ι, 4,7,10-tetraacetic acid, 2-p-aminobenzyl_; ι, 4,7,10-tetraazacyclododecane-1,4,7,10 -Tetraacetic acid, p-aminobenzyl-diethylenetriaminepentaacetic acid, p-isothiocyanato-1,4,7,10-tetraazacyclododecyl-1,4,7,1. -Tetraacetic acid, p-isothiocyanatofluorenyl-diethylenetriamine pentaacetic acid, p-isothiocyanatobenzyl_diethylenetriamine pentaacetic acid [p-SCN-Bz-DTPA], 1, 4, 7 , 10-tetraazacyclododecane-μ,?, 10-tetraacetic acid mono (N-#-based succinimide fluorenyl ester), κιο-tetraazacyclododecane_ 丨, 4,7_reference (Acetic acid-tertiary-butyl ester) -10-acetic acid [D0TA_ginseng (third-butyl ester)], diethylenetriaminepentaacetic acid (DTPA) dianhydride or other metal complex residues reported in the literature Groups such as squaric acid derivatives, 10- (2-ethoxy · 3,4-diketo Xi-yl-butyl) _ 1,4,7,10-tetraaza cyclododecane _ι, 4,7_ triacetate (Aime et al., Blue # field carry flute Chemistry, 10, 192-199, 1999). Amine functionalized residues can be condensed with synthetic units containing appropriate carboxyl groups, and DTPA dianhydrides or residues with a single free-state carboxyl group, such as DOTA-Ginseng (third-butyl ester), can be easily activated It also reacts with a variety of nucleophiles (see, for example, the attachment of DOTA to amine residues; Bhorade et al., # 关 无 # 必 学,: 11,301305, 2000). Likewise, an isothiocyanate or a Sa-metal complex derivative, such as p_SCN-Bz_DTPA, can be used to prepare a sulfonylurea core, as exemplified in Example 29 below. Then, the thus-prepared sulfonylurea common product of the present invention is processed in a buffered aqueous solution having a stoichiometric paramagnetic ion such as Gd (0AC) 3 or Dycl3 to obtain the desired paramagnetic sulfonylurea.组合。 The compound. This co-operation can be conveniently monitored by NMR measurement of the 1H relaxation rate (1/11) of the solvent. The novel gasification biopolymer (Formula BI-BXX) of the present invention can be prepared by the following methods: (1) Low molecular weight fluorinated substituents (such as π in the example), (2) high molecular weight Fluorinated residues, such as the use of functional perfluorinated 84865 -44-200400972 polymers; and (3) fluorinated monomers can be incorporated into polymeric materials by chemical or enzymatic methods. The above-mentioned processing methods allow the preparation of fluorinated biopolymers, with a wide range of fluorine substituent types, and incorporation levels (5-40% or more, as shown in the examples below), which can be suitable for either diagnosis or treatment use. The optimum fluorine content is on the one hand, in each case determined by the diagnostic requirements for sensitivity, and the maximum degree of fluorine substitution will not interfere with the biological or physicochemical properties of the probe, such as its solubility or receptor-binding ability. An important parameter in these considerations is the type of fluorine substitution and its position on the probe matrix. In general, the F content is preferably 10-40%, and more preferably 20-40%. Other fluorination methods described herein with respect to polyuronic acid and fluorinated anti-diabetic compounds are also used to make fluorinated biopolymers. Certain compounds of formula BI-BXX may require the use of protecting or blocking groups to allow them to successfully and delicately become the desired structure. Protective groups can be selected, refer to Greene, T. W., et al., UI Synthesizer, John Wiley & Sons, 1991. The blocking group can be easily removed, meaning that it can be removed, if desired, by a procedure that does not cause the rest of the molecule to split or otherwise disintegrate. Such procedures include chemical and enzymatic hydrolysis, chemical reduction or oxidants, treatment under mild conditions, treatment with fluoride ions, treatment with transition metal catalysts and nucleophiles, and catalytic hydrogenation. Examples of suitable hydroxy-protecting groups are: trimethylsilyl, triethylsilyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, third-butyldiphenylsilyl, third- Butyldiamidylsilyl, benzyloxycarbonyl, tert-butoxycarbonyl, 2,2,2-trichloroethoxycarbonyl and allyloxycarbonyl. Examples of suitable carboxy-protecting groups are benzhydryl, o-nitrofluorenyl, p-synylfluorenyl, 2-theylmethyl, 84865 -45-200400972 fluorenyl, 2-chlorodipropyl, benzyl Base, 2,2,2-trichloroethyl, trimethylsilyl 'third-butyldimethylsilyl, third-butyldiphenylsilyl, 2- (trimethylsilyl) Ethyl, phenylmethyl, p-methoxybenzyl, acetone, p-methoxyphenyl, 4-pyridylmethyl, and tert-butyl. The compounds of the present invention can be easily prepared according to the examples detailed below using readily available starting materials, reagents and conventional synthetic procedures. Other variations known to those skilled in the art are generally possible, but are not mentioned in more detail. The following examples illustrate the practice of the invention, but should not be construed as limiting its scope. Alginic acid, sodium alginate, high G alginate, propylene glycol alginate, 3,5,5'-ginseng (trifluoromethyl) octafluorohexanoic acid, 3,5,5'-ginseng (trifluoro (Methyl) octafluorohexanoic acid, 3,5,5'-ginseno (trifluoromethyl) octafluorohexanol, perfluoro-3,6,9-trioxadecanoic acid methyl ester, perfluorohexadecane Methyl ester, dextran, poly (ethylene glycol) and superparamagnetic iron oxide nanoparticles (3 nm), obtained from CarboMer Company (Westborough, MA and San Diego, CA); Sodium, high-g alginate, and propylene glycol alginate starting materials have molecular weights of ~ 600,000, ~ 500,000, ~ 450,000, and ~ 700,000 Da, respectively. Hexafluoropropane oxide and heptafluorobutane chloride were obtained from Lancaster Synthesis (Windham, NH). Deoxo-Fluor [bis (2-methoxyethyl) aminosulfur trioxide] is available from Air Products Corporation (Allentown, PA). Polytetrafluoroethylene-co-difluoromethylene-α, ω-bisdifluoroacetic acid, gadolinium (II) acetate, polytetrafluoroethylenefluorene-co-difluoromethylene oxide-α, ω -Bis (methyl carboxylic acid ester), polytetrafluoroethylene-co-dioxymethylene- < 2, ω-diisocyanate, and aniline V, obtained from Aldrich (St. Louis, ΜΟ ). The chemical formulas in the following examples and the scope of the patent application include 84865 -46- 200400972 under m and η, which are added as the ratio of the designated repeating unit {column. The sum (m + n) with η in each chemical formula is one unit. [Embodiment] Example 1 Heptafluorobutyroyl alginic acid A solution (0.6 equivalent) of ticated heptafluorobutyric acid in DMS0 was added to the alginic acid and stirred for 6 hours at a temperature of J. This product was allowed to settle with acetone, filtered, washed with acetone, dialyzed, and dried to produce heptafluorobutyryl alginic acid with F9.07%.

r \ r " = h, (cf2) 3ch2f; ft; hm = 0,70-0.3 n = 0.3-0.7 where m + η = 1 sevoflurane alginate (example 1) biocompatibility results, The line was tested in human cell culture and was found to be non-toxic at a concentration of 0 2-10%. Example 2 6- [3- [2- (Perfluorohexyl) -2-ethoxy] _2-isopropyl] marine acid 3- [2- (perfluorohexyl) -2-ethoxy]- A solution of propylene oxide in dichloromethane (0-6 equivalents) was added to the alginic acid and stirred at ambient temperature for 6 hours. This suspension was washed with dichloromethane, washed with dichloromethane and acetone, dialyzed, and dried 'to give 3- [2- (perfluorohexyl) -2-quinyl] alginate with f 20.41%.

R1, R " = H, CF2〇F (〇H) (CF2) 3Cfr3 m = 0.70-0.3 η = 0 · 3-0.7 where m + η = 1 Example 3 Perfluorotri-n-butylamine alginate 84865 -47 · Zhi'li (1.1 equivalents) was added to alginic acid, and the whole gas tri-n-butylamine was in water, and stirred at ambient temperature for 6 hours. This product was precipitated with acetone, filtered, washed with acetone, lysed, and dried with F9.41%

R4 H, N [(CF2) 3CF3] 3 m = 0,70-0.3 n = 0.3-0.7 where m + n = j ^ L Example of perfluorotris-n-butylamine alginic acid 4 Polytetrafluoroethylene oxide _ Gaipi Yibang /, emulsified monofluoromethylene-α-methyl-carboxylic acid ester-ω-chinoate alginic acid propylene glycol brewed a solution of propylene glycol alginate in methanol and polytetrafluoroethylene -Co-difluoromethylene oxide-bis (methyl metabolite XMw ~ 2, _Da, 0.6 equivalent) was treated and the resulting thick paste was stirred at ambient temperature for 6 hours. The reaction mixture was immersed in acetone, acetone, filtered, dialyzed, and dried to produce a perfluoropolymer-labeled alginate with F 27.66% ^

m = 0.70-0.3 η = 0.3-0.7 where m + n = i Example 5 6- [2- (Perfluorohexyl) -2-kisyl] dimethylaminosulfonyl alginic acid alginic acid 6- [ Solution of 2- (perfluorohexyl) -2-quinyl] ester (Example 2, 0.6 equivalents) in DMSO 'as 5-N, N-dimethylamino 4-benzenesulfonium chloride (DANSYL) (0.1 eq.) Treatment 'Dissolved in anhydrous acetone and carbonic acid noodles (0.1 eq.) And stirred at ambient temperature for 3 hours. The reaction mixture was precipitated with acetone, washed with acetone, filtered through 84865 -48-200400972, dialyzed, and dried to produce dimethylaminonaphthalenesulfonylated alginic acid 6_ [2_ (full gas hexyl) g.

R1, RM = H, CH2CH (0H) CH20 (CH2) 20 (CF2) 6CF3, r- '·

πί-0.70-0.3 π = 0.3-0.7. where m + η = 1 Example 6 3-[(Hexafluoropropyl > 2-acid] Alginic acid solution of hexafluoropropylene oxide in dichloromethane ( 0.8 equivalent) was added to sodium alginate with a high guluronic acid content (68%) and stirred at ambient temperature for 6 hours. This suspension was filtered, washed with dichloromethane and acetone, dialyzed 'and dried 'Produced alginic acid 3-[(hexafluoropropyl) -2-¾yl], with ρ 12.50%.

Example 7 Perfluorophenylarsine alginic acid> Wholesaling of Wang Qidong Jieng in Erqijiakeng> Valley (0,6 equivalents) was added to an aqueous copper alginate solution with high guluronic acid content (68%), Stir at ambient temperature for 6 hours. The reaction mixture was precipitated with acetone, washed with acetone, filtered, dialyzed 'and dried to produce perfluorophenylhydrazone alginate with F 10.35%. 84865 -49- 200400972

R = co2h, c = nnhc6f5 m = 0.70-0.3 n = 0.3-0 7 where ⑺ + n = (Example 8 polytetrafluoroacetic acid _co-difluoromethylene π difluoroacetic acid 仏 ^ digas Fermented fluorescein alginate will be a solution of sodium alginate with a high guluronic acid content (68%) to polyoxytetrafluoroacetamidine-co-oxidized bis-methylene_α, ω-acetic acid (Mw ~ 500, 0.6 equivalents), and the formed viscous paste was stirred at ambient temperature for 6 hours. One part was treated with fluorescein isothiocyanate (0.1 equivalents) for 4 hours. The reaction mixture was precipitated with acetone, washed with acetone, filtered, dialyzed, and dried to produce a perfluoropolymer and a labeled alginate with 64

Dioxin ::: Alcohol: Difluoro Oxide "in the methanol

Difluoromethylene-β-Gas / Cl-I, bis-diacetic acid (Mw ~ 2,000, 0.6 equivalent) Chutan 84865 -50- 200400972, and a thick paste formed with y at the ambient temperature Take it off for 6 hours. The reaction / m compound was reacted with acetonitrile and was washed with acetone, washed with dialysis, and dialyzed, and dried to produce alginate labeled with fluoropolymer, having F 33 〇4%.

m = 0,70-0.3 η = 0.3-0,7 where m + n = 1 Example 10 Perfluorobenzylamine alginate A solution of perfluoroaniline (0.6 equivalents) in dichloromethane was added to Gulose in sodium alginate aqueous solution (68%) and stirred at ambient temperature for 6 hours. The reaction mixture was precipitated with acetone, washed with acetone, filtered, dialyzed, and dried to produce perfluorobenzamide alginate with F 19.35%.

R = C02H, CONHC6F5 m = 0.70-0.3 π = 0.3-0.7 where m + n = 1 Example 11 Perfluoroaniline alginate A solution of perfluoroaniline (0.6 equivalent) in dichloromethane was added to a solution with high gulo An uronic acid content (68%) in an aqueous sodium alginate solution. Add sodium cyanoborohydride (8,6 equivalents) and stir at ambient temperature for 6 hours. The reaction mixture was precipitated with acetone, washed with acetone, filtered 'dialyzed' and dried to produce perfluoro

84865 -51-200400972 aniline alginate with F 22.65%.

R ^^ HC ^ NHCqFs m = 0.70-0.3 _.3--0.7 where m + n = i Example 12 Alginic acid 3-[(hexafluoropropyl) -2-hydroxy] propylene glycol ester Hexafluoroepoxypropylene The solution (0.7: the amount) in dichloromethane was added to propylene glycol alginate, and stirred at ambient temperature for 24 hours. This suspension was filtered, washed with acetonitrile and acetone, dialyzed, and dried to produce alginic acid 3, [(fluorofluoropropyl > 2-meryl) propylene glycol ester, having F204i%.

R " '= H, CH% 2H (〇S) CH3F3, CH2CHi〇H) CH20 (CH2) 2OCF2CF (〇H) CF3; m = 〇.7〇-0.3 n = 〇.3_〇7 where + Example 3 & Tetrafluoroacetamidine · co-dioxymethylene methylene ester di 6 > Tolyl isocyanate propylene glycol alginate A solution of propylene glycol alginate A field f H 2 O 3 in methanol Oxidation of monofluoromethylene-field with polytetrafluoroacetamidine j, ω--aryl esters (Mw ~ 3,00,0.6 equivalents) and the formation Place the reaction mixture to precipitate, ^ even with propane, ^ wash with acetone, filter, dialyze, and dry to produce the fluoropolymer label, > ,, ## △ Mother bath bismuth ester, with F 29.99 % 84865 -52- 200400972

R: __. R "= H, -NHC0C6H3 [CH3lNHC02 [CF2CF2〇] x (CF20) yC0NHC6H3 (NC0) CH3; RM, s H, CH2CH (OH) CH3 m = 0.70-0,3 n = 0.3-0.7 where m + n = 1 Example 14 Perfluoro-3,6,9-trioxadecanate alginate will be an alginate aqueous solution with a high guluronic acid content (68%), with perfluoro-3, Treated with methyl 6,9-dioxodecanoate (1.6 equivalents), and the resulting thick paste was stirred at ambient temperature for 16 hours. The reaction mixture was precipitated with acetone, washed twice with acetone, filtered, and dialyzed. And dried to produce perfluoroM · trioxadecanate alginate with F 30.25%.

m = 0.70-0.3 n = 0.3-0.7 where m + η = 1 Example 15 3,5,5L Ginseng (trifluoromethyl) octafluorohexanoate alginate will have a high guluronic acid content (68 %) Of alginate in acetone was hard to disperse, treated with 1,3-diisopropylcarbodiimide (08 equivalents) for 1 hour, and then treated with 3,5,5- (3-fluoromethyl) (difluoromethyl) Octafluorohexanol (06 equivalents) was treated and the resulting thick paste was stirred at ambient temperature for 16 hours. The reaction mixture was allowed to settle with acetone, washed twice, filtered, dialyzed, and dried to produce perfluorinated 3,5,5-dimethylhexanol alginate with a pH of 24.73%. 84865 • 53- 200400972

R = H, C〇CF2CF (CF3) CF2C (CF3,3 m = 0.70-0.3 ㈣.3.0.7 where m + n = i Example 16-3, S, 5'_ (trifluoromethyl) octafluoro Alcoholic acid propylene glycol alginate propylene glycol alginic acid propylene glycol @ aims to the solution in methanol with W ,. ginseng (trifluoromethyl) octafluorohexamethylene bismuth (0.4 field) and the resulting thick paste The agent was stirred at ambient temperature for 16 hours. The reaction mixture was precipitated with acetone, washed with acetone and filtered / analyzed by both, and dried to produce a seawater labeled with perfluoro-3,5,5'-trimethylhexanoate. Sour cool, with F 14.71%.

R '; (R " = H, COCF2CF (CF3) CF2C (CF3) 3 = H, CH2CH (OH) CH3. CH2CH (CH3) OCOCF2CF (CF3) CF2C (CF3) 3 m = 0.70-0.3 n = 0.3-0.7 Where m + n = 1 Example 17 Methyl perfluorohexadecanoate alginate An aqueous alginate solution having a high guluronic acid content (68%) is methyl perfluorohexadecanoate (0.4 equivalent) Treatment and stirring the formed viscous paste at ambient temperature for 6 hours. The reaction mixture was precipitated with acetone, washed twice with acetone, filtered, dialyzed, and dried to produce perfluorohexadecanoate alginic acid. Ester with F 32.36%. -54-84865 200400972

1 Example 18 Paramagnetic magnetic alginate beads were added in a rapidly agitated aqueous solution of ferric acid (111) (1.1 equivalents). After injection, the dilute solution with a high guluronic acid content (68%) was added dropwise. Alginate water '4 solution. The formed gel beads were centrifuged, the supernatant was discarded, and the beads were washed and centrifuged twice with a dilute chloride solution to remove excess milk. The magnetization curve shows that the alginate beads are paramagnetic. Sterile preparations were obtained through filtration through a 0.22 micron filter by filtering the bactericidal ingredient solution before their combination. Paramagnetic osmium alginate beads (Example 18) have been found to be non-toxic in cell cultures. Example 19 Superparamagnetic iron oxide alginate beads containing superparamagnetic iron oxide nanoparticles (3 nm, u equivalent) containing poly (ethylene glycol) at 10 mmol (NF grade, Mw400, 25%) The calcium chloride aqueous solution was rapidly stirred into the suspension, and a dilute sodium alginate aqueous solution having a high gulose jun acid content (68%) was added dropwise by a syringe. The formed gel beads were centrifuged, the supernatant was discarded, the beads were washed, and centrifuged twice with a dilute calcium chloride solution. The magnetization curve shows that the alginate beads are superparamagnetic. Sterile preparations were obtained by filtering the bactericidal component solution and suspension through a 0.22 micron filter prior to their combination. Example 20 Superparamagnetic iron oxide alginate-coated nanoparticles in a rapidly stirred 10 millimolar calcium chloride aqueous solution, dropwise via a syringe 84865 • 55- 200400972 Add superparamagnetic iron oxide nanoparticles (3 nanometers) ) Suspension in a dilute aqueous solution of sodium alginate with a high guluronic acid content (68%). The formed coated nanoparticles were centrifuged, the supernatant was discarded, the nanoparticles were washed 'and centrifuged twice with a dilute chlorinated J-bow solution. Example 21 Superparamagnetic iron oxide alginate-coated nanoparticles were slowly added to a dilute aqueous sodium alginate solution with a high guluronic acid content (68%), and the superparamagnetic iron oxide nanoparticles were slowly added ( 3 nm) in poly (ethylene glycol) (NF grade, Mw400, 25%). The resulting suspension was stirred for 10 minutes, then heated at 70 ° C for 30 minutes, and centrifuged. The supernatant was discarded and the coated nanoparticles were dialyzed. Example 22 Superparamagnetic iron oxide dextran-coated nanoparticles were slowly added to a rapidly agitated dilute dextran (Mw 10,000) aqueous solution, and superparamagnetic iron oxide nanoparticles (3 nm) were slowly added to poly (ethylene glycol) Alcohol) (NF grade, Mw 400, 25%). The resulting suspension was stirred for 10 minutes, then heated at 70 ° C for 30 minutes' and centrifuged. The supernatant was discarded and the coated nanoparticles were dialyzed. Example 23 Superparamagnetic iron oxide addin conjugate In a rapidly stirred aqueous solution of the superparamagnetic iron oxide glucan-coated nanoparticle obtained from Example 22, sodium paraperiodate (0.05 equivalent) was added And the resulting mixture was stirred for 1 hour. Add ethylene glycol and centrifuge the mixture. The supernatant was discarded and the oxidized coated nanoparticles were washed and centrifuged twice with pBS buffer. The oxidized coated nanoparticles were added to a buffer solution of addin V. The resulting mixture was stirred for 25 minutes at 4 ° C, followed by centrifugation. Discard the supernatant and get all the cars you want. 84865 -56- Example 24: Paramagnetic Iron Oxide Additives A total of 1-According to the procedure outlined in Example 23, the seaweed acid prepared in accordance with Example 20 or 21 is coated with 4 tablets of $ 彳, whether accompanied by The oxidation step or directly use 'to obtain the desired car. Example 25: Light superparamagnetic iron oxide addin co-light product. Follow the procedure outlined in Examples 22 and 23 to use luciferin isochloric acid to make labeled addendin V instead of the unlabeled protein to obtain the desired Co-fluorescence of coated superparamagnetic iron oxide halo particles. Alternatively, fluorescent alginate (e.g., Examples 5 and 8) can be used. Example 26 Heptafluorobutyryl hydroxyethyl starch A solution (0.6 equivalent) of heptafluorobutyryl chloride in DMS0 was added to hydroxyethyl starch and stirred at ambient temperature for 12 hours. This product was precipitated with two ketones, filtered, washed with acetone, dialyzed, and dried to give heptafluorobutyryl hydroxyethyl starch with F 16.75%. Example 27 Perfluorotri-n-butylamine alginate An aqueous acidic dispersion of alginic acid was treated with perfluorotri-n-butylamine (16 equivalents) at ambient temperature for 12 hours. This product was allowed to sink in acetone, over-extended, washed with propidium dialysis and dried to produce perfluorotri-n-butylamine alginate with F 11.50%. Example 28 Glipipiride difluorodexoxo-Fluor (C6H14F3N02S, 6 equivalents) was added dropwise in a solution of glimepiride in anhydrous toluene at ambient temperature. The reaction mixture was stirred for 2 hours, concentrated, and then added to acetone. The resulting brown solid was washed with ether, dried, and chromatographed on silica gel to yield 84865 -57- 200400972 and 3-ethyl-2,5-dihydro-4-Tyl-N- [2 {4 -[[[(Trans_4-methylcyclohexyl) aminobenzyl] amino] continyl] phenyl] ethyl] -2,2-dimer-1H-pyrrole-1-N-carboxyl Lamine. C24H34F2N4〇4S Molecular weight: 512.61 Calculated value C, 56.23; H, 6.69; F, 7.41; N, 10.93; S, 6.26 Found C, 56.01; H, 7.05; F, 7.18; N, 10.71; S, 6.23

Example 29 Polyemulsified tetrafluoroethylene-co-oxidized difluoromethylene · α-tolyl carbamate-ω-tolyl isocyanate Glimepirid is obtained from a solution of Glimepirid in anhydrous toluene At ambient temperature, polytetrafluoroethylene-co-oxidized difluoromethylene_α, ω diisocyanate (Mw ~ 2,000, 0.2 equivalent) was added dropwise. The reaction mixture was stirred for 2 hours, concentrated, and then added to acetone. The white solid formed was washed with osmium and dried to produce 3-ethyl-2,5-dihydro-4-methyl_N_ [2 {4-[[[(trans 4 -Methylcyclohexyl) amino] carbonyl] amino] ceramic group] phenyl] ethyl] keto-1 ^^ biha-1-fermenting amine. C53H48F24N7O17S Molecular weight: 1543.01 Calculated value C, 41.25; H, 3.14; F, 29.55; N, 6.35; S, 2.08 Found C, 40.90; H, 3.34; F, 29.67; N, 6.23; S, 1,98

y = ~ 40 84865 -58- 200400972 Example 3 Heptafluorobutanyl metformin in a solution of metformin in anhydrous toluene, slowly add heptafluorobutyric anhydride (1.2 equivalents) And stirred at ambient temperature for 4 hours. The reaction was terminated by adding water 'and the reaction mixture was precipitated in acetone. The crude metformin fluoride was chromatographed on silica gel to produce N-heptafluorobutyridinyl N, N, -dimethylamidinodicarbodiimide diamidine.

CsH1 () F7N50 Molecular weight: 325.19 Calculated value C, 29.55; H, 3.10; F, 40.90; N, 21.54 Found C, 29.35; H, 3.42; F, 40.65; N, 21.18

Example 31 7-Amino-4- (trifluoromethyl) -coumarin Glimepirid is obtained from a solution of Glimepirid in dichloromethane, and 7-amino- is added at ambient temperature 4- (trifluoromethyl) -coumarin (1.2 equivalents) and sodium cyanoborohydride (7.2 equivalents). The reaction mixture was stirred for 12 hours and concentrated. After chromatography on silica gel, 3-ethyl-2,5-dihydro-4-methyl-N- [2 {4-[[[(trans--4- Methylcyclohexyl) _amino] carbonyl] amino] sulfofluorenyl] phenyl] -ethyl] -2- [7-amino-4- (trifluoromethyl) _coumarin] -1H- Pyrrolidine. C34H42F3N506S Molecular weight: 705.79 Calculated value C, 57.86; H, 6.00; F, 8.08; N, 9.92; S, 4.54 Found C, 57.61; H, 6.05; F, 8.18; N, 9.71; S, 4.23

84865 -59- 200400972 Example 32 Heptafluoroglybide analogue Step 1: 4-carboxy_2,3,5,6-tetrafluorophenylcyclohexylamino] amino]- Sulfo) -phenyl] ethyl] benzylamine in 2,3,5,6-tetrafluoroterephthalic acid and dicyclohexylcarbodiimide (1.2 equivalents) in dichloromethane In the solution, 4- (2-aminoethyl) amine besylate (L0 equivalent) was added at ambient temperature over 16 hours. The reaction product was then treated with cyclohexyl isocyanate (U equivalent) and a base (15 M NaOH) for 12 hours to provide the desired intermediate A. ^ 2 3 H23F4N306S Molecular weight: 545.50 Calculated value C, 50.64; H, 4.25; F, 13.93; N, 7.70; S, 5.88 Found C, 50.32; H, 4.35; F, 13.55; N, 7.41; S, 5.75

Step 2: Ke 4- (2,2,2-trifluoroethyl) melamine-2,3,5,6-tetrafluorophenyl] | [2_ (4_ [[[(cyclohexyl-amino)] Carboxyl] amino] pyridyl) _2,3,5,6-tetrafluorophenyl] ethyl] _2_methoxybenzylamine will be obtained from the intermediate of step 1 as 2,2,2-tris Fluoroethylamine (1.0 equivalent) and dicyclohexylcarbodiimide (1.2 equivalent) were treated for 16 hours, and the product was obtained after chromatography on silica gel. C25H25F7N4O5S Molecular weight: 626.54 Calculated C, 47.92; H, 4.02; F 21.23; N, 8.94; S, 5.12 found C, 47.65; H, 3.78; F, 2U1; Ν, 8.76; S, 5.02 84865 -60-

Example 33 23,4,5,6-pentafluorophenyl_N_ [2_ (4 _ [[[(cyclohexylamino) carbonyl] amino] _sulfofluorenyl) phenyl] ethyl] benzamide is used The method outlined in Example 32, step 1, using pentafluorobenzoic acid in place of 2,3,5,6-tetrafluoroterephthalic acid provided the desired analogue of Grambride. C2 2% 2 F5 N3. 4 S Molecular weight: 519.49 Calculated C, 50.86; H, 4.27; F, 18.29; N, 8, 09; S, 6.17 Found C, 50.64; H, 4.05; F, 18.05; N, 7.63; S, 5.78

^ > 7 \ νΤνΌ Example 34 3,5-bis (trifluoromethyl) phenyl-meaning 丨 Cyclohexylamino group carbonyl} amino group-amino group) -phenyl 1ethyl] benzene Formamidine uses the method outlined in Example 32 to replace the 2,3,5,6-tetrafluoroterephthalic acid 'with 3,5_bis (trifluoromethyl) phenylarsinic acid' to provide the desired gramb cloth Lay analogs. C24H25F6N304S Molecular weight: 565.53 Calculated value C, 50.97; H, 4.46; F, 20.16; N, 7.43; S, 5.67 Found C, 50.68; H, 4.17; F, 20.00; N, 7.21; S, 5.27

Example 35 2,3,4,5,6-Pentafluoro 2- (4-[[[((23,4-trifluorophenyl] carbonyl) amino] amino group __trans 84865 -61-200400972 fluorenyl) phenyl group 】 Ethyl 1 benzamidine uses the method described in Example 32 to replace cyclohexanone isocyanate with 2,3,4-trifluorophenyl vinegar isochloride to provide the desired analogue of Glybride C22H13F8N304S Molecular weight: 567.05 Calculated value C, 46.57; H, 2.31; F, 26.79; M,? &Quot;; s, 5.65 Found C, 46.14; H, 2.05; F, 26.46; N, 7.14; S 5.35

Example 36 2,3,4,5,6-Pentafluoroyang_ (4_ [丨 丨 (2,3,4 s, 6_pentafluorophenyl 丨 carbonyl) amino] sulfonyl) phenyl] ethyl ] Benzamide uses the method outlined in Example 35, replacing pentafluorophenyl isocyanate with 2,3,4-difluorophenyl isocyanate 'to provide the desired analogue of Glybride. 603.39 Calculated value C, 43.79; H, 1.84; F, 31.49; N, 6.96; S, 5.31 Found C, 43.43; H, 2.02; F, 31.33; N, 6.66; S, 5.36

Example 37 Heptafluorofluorosulfonylurea (grebbride) analogue A solution of the intermediate obtained in Example 32 in DMSO was prepared with 7-aminopyridine (trifluoromethyl) coumarin (1.0 (Equivalent) treated with dicyclohexylcarbodiimide (1.2 equivalents) for 18 hours. After chromatography on silica gel, N_ [7_amino-based (trifluoromethyl) coumarin] -Spanamine-2 , 3,5,6-tetrafluorophenyl] -N- [2- (4-[[[(cyclohexylamino] -jinyl] amino]] 84865 -62- 200400972 sulfonyl) -2,3, 5,6-tetrafluorophenyl] ethyl] -2-methoxybenzamide. C33H29F7N407S Molecular weight: 758.66 Calculated C, 52.24; H, 3.85; F, 17.53; Ν, 7.38; S, 4.23 Found C, 52.12;., 3.59; F, 17.39; N, 7.12; S, 4.14

Example 38 2,3,4,5,6-pentafluorophenyl with [[[(4-trifluoromethylphenyl] carbonyl] _amino] sulfonamido) -4-trifluoromethylphenyl 1 Ethylamine used the method outlined for Example 32, using α, α, α-trifluoro-p-tolyl isocyanate in place of cyclohexyl isocyanate 'to produce the desired Glybride analogue. C23H15F8N304S Molecular weight: 581.44 Calculated value C, 47.51; Η, 2.60; F, 26_14; N, 7.23; S, 5.51 Found C, 47.19; Η, 2.55; F, 26.25; N, 7.21; S, 5.39

F

Example 39 [1,1-Diketo-6- (trifluoromethyl) -1,2,3,4-tetrahydro · 1 fork-6-2-4 · benzopyrene-7-continyl ) H3,5-bis (trifluoromethyl) phenyl] carboxamide will be 1,1-diketo-6- (trifluoromethyl) -1,2,3,4-tetrahydro-1; 1__6 -2-4-benzophenone Erqian-7-sulfonamide in DMSO 'with 3,5-bis (trifluoroamidino) phenyl isocyanate (1,1 equivalent) and base (1.5MNaOH ) Treatment for 12 hours to provide the desired product. Molecular weight: 586.41 84865 • 63- 200400972 Calculated value C, 34 · 82; Η, 1.89; Found C, 34.54; Η, 1.55; F, 29 · 16; Ν, 9.55; S, 10.94 F >29.15; Ν, 9.29 ; S, 10.56

Example 4 Ν- [4_ (1,4,7, ΐ〇_Tetraazacyclododecane-1,4,7,10 Shoulder: ^ ,, 1 \ ,,, 1 ^ ,,-tetraacetic acid

) (P-Aminophenylaniline) jiminamine_2,3, s, 6-tetrakiphenyl] [2 (4 丨 [丨 (cyclohexylamine N-[[(cyclohexylamino) carbonyl ] Amine] Sulfomethyl] phenyl] ethyl] benzylamine in dichloromethane burning solution 'Add tetraazacyclododecane_1,4,7,10-tetraacetic acid at ambient temperature Mono (p-aminoamidoaniline) (11 equivalents) and dicyclohexylcarbodiimide (1.2 equivalents), after π hours of chromatography on silica gel, produce the desired fluorinated DOTA product. C4 4H55F4N90i2S Molecular weight: 1010.02 Calculated value C, 52 · 32; H, 5.49; F, 7.52; N, 12.48; S, 3.17 Found C, 52 · 14; 52, 5.55; Ν, 12.29

84865 -64- 200400972 Example 41 N- 丨 1 · (Diethylenetriamine-N, N, N ,, N ,,, N "-pentaacetic acid) Carboxamide-] · ν- [2- (4_ [[ [(Cyclohexyl-amino) carboxyl] amino] continyl) ethyl] -2-methoxybenzylamine was obtained from 4- (2-aminoethyl) benzene as outlined in Example 32 In a dichloromethane solution of sulfonamide and cyclohexyl isocyanate in dichloromethane, diethylene triamine pentaacetic acid (DTPA) dianhydride (1.05 equivalent) was added at ambient temperature over 16 hours on silica gel After chromatography, the desired DTPA product was produced. C29H45N6012S Molecular weight: 701.77 Calculated value C, 49.63; Η, 6.46; N, 11 _98; S, 4.57 found C, 49.34; H, 6.24; N, 11.45

Example 42 1 ^ [2,3,4,5,6-pentafluorophenyl) carboxamidine + 2- (4- 丨 丨 丨 < cyclohexylaminocarbonyl) amine 1sulfonyl) Ethyl] -2-p-phenylmethyl (diethylenetriamine-N, N, N ,, N ,,, N ,,-S acetic acid) at 2,3,4,5,6-pentafluorobenzene In a solution of formic acid and dicyclohexylcarbodiimide (. 2 equivalents) in dichloromethane, at ambient temperature, 4- (2-aminoethyl) benzenesulfonamide (1.0 equivalent) was added. 16 hours. The reaction product was then treated with p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (0.05 equivalents) and base (1 · 5M NaOH) for 12 hours' to provide the desired DTPA product. C37H4〇F5N6014S Molecular weight: 919.80 84865 -65- 200400972 Calculated -C, 48.31; H, 4.38 'F, 10.33; N, 9.H; S, 3.49 Found C, 48.12; H, 4.22' N, 9.05

h〇2o / ^ c〇2H V-N

Examples 43-48 Paramagnetic continuum diurea complex The individual preparations of the sulfonylurea conjugate described in Examples 40-42 in a pH 6.5 buffered aqueous solution were individually cultured with stoichiometric Gd (OAc) 3 or Dyci3 4 hours 'then purified by HPLC' or after adjusting the pH to 8, purified by centrifugation to obtain the desired paramagnetic sulfonylurea complex. By measuring the 1 错 relaxation rate (1 / Ti) of the solvent, the co-operation was monitored. Example 49 6-carboxyamido- {4- [1-amidoamino-1,6-hexanediamine] -6-amidoamino]-2,3,5,6-tetrafluorophenyl ΓΗ [[(cyclohexylamino) carbonyl] amino] _sulfofluorenyl) _phenyl] ethylbenzidine}}-polytetrafluoroethylene · co-difluoromethylenetolylamine Carbamate-ω-tolyl isocyanate alginic acid propylene glycol ν% 1 · Polytetrafluoroacetamidine-co-dioxymethylene oxide_tolylamino formate-ω-tolyl isocyanate alginate propylene glycol A solution of propylene glycol alginate (Mw ~ 700,000Da) in methanol was prepared by using polytetrafluoroacetamidine-co-difluoromethylene_α, ω_diisocyanate (Mw ~ 3,00). (0,6 equivalents), and the resulting thick paste was stirred at ambient temperature for 24 hours.使 _The reaction mixture was precipitated 'was washed with propane, filtered, infiltrated 84865 -66- 200400972, and dried to produce a perfluoropolymer-labeled alginate with F 29 99%. Step 2: 6-carboamido- "M1 · amido- [N, N-1,6-hexanediamine] -6-acidamino] · 2,3,5,6-tetrafluorophenyl _N _ [[[(Cyclohexylamino) condensyl] amino]]-term fluorenylphenyl] ethyl] benzamidine) -polytetrafluoroethylene_co-difluoromethylenetolyl Aminophosphonate-ω-fluorenyl isocyanate propylene glycol alginate 4-carboxy-2,3,5,6-tetrafluorophenyl_N _ [[[(cyclohexylamino) carbonyl] amino] _ Sulfonyl) phenyl] ethyl] benzamide (step i, Example 32) in acetone, treated with 丨, 3-diisopropyl condensed diimine (U equivalent) for 1 hour, and then treated with 6-hexanediamine (1.1 equivalents) was treated for 6 hours. This material was purified by silica gel chromatography, and the formed aminated glaebride product was condensed with a perfluoropolymer labeled sea han vinegar (1.1 equivalents) obtained in step 1 in an aqueous methanol solution. 16 After dialysis, a polymer fluorinated glebride was obtained after dialysis, with F 21.45%.

C02Rm \ j n

x = ~ 25 m = 0.3-0.7 y = ~ 40 n = 0.7-0.3 1¾ where m + n = 1. Example 50 N- [3_ [2_ (perfluorohexyl) -2-ethoxy] -2-light Propyl] polyamino acid A solution (0.6 equivalent) of 3- [2- (perfluorohexyl) -2-ethoxy] -1,2-propylene oxide in dichloromethane was added to T- Polyglutamic acid 'and stirred at ambient temperature for 6 hours • 67- 84865 200400972 hours. This suspension was filtered, washed with dichloromethane and acetone, dialyzed, and dried to produce 3- [2- (perfluorohexyl) -2-ethoxy; j_2_hydroxypropyl r_polyglutamic acid, having F 13.38%. CF3 (CF2) 6〇 (CH2) 2〇CH2CH (〇H) CH2

m = 1-70, 〇〇〇η = 70,00 (Μ Example 51 (full gas hexyl) " 2-ethoxy] · 2-¾propyl hyaluronic acid aqueous solution of hyaluronic acid to 3- [2- (perfluoro Hexyl) -2-ethoxy ^ glycidine (0.6 equivalent) treatment 'and the resulting thick paste was stirred at ambient temperature for 6 hours. The reaction mixture was precipitated with acetone, washed with acetone, and wiped with tears , Dialysis, and drying to produce 3- [2- (perfluorohexyl) -2-ethoxy] -2-hydroxypropyl hyaluronate with F33.12%.

n = 1-4,000 Example 52 3- [2- (Perfluorohexyl) -2-ethoxy] -2-carboxypropylmaltodextrin The aqueous maltodextrin solution was mixed with NaOH (1.3 equivalents) and then with DMS. It was treated with 3- [2- (perfluorohexyl) -2-ethoxy] -1,2-epoxypropane (0.6 equivalents), and the resulting thick paste was stirred at ambient temperature for 6 hours. The reaction mixture was settled with acetone, washed with acetone, filtered, dialyzed, and dried to produce 3_ [2_ (perfluorohexyl) -2-ethoxy] -2-chitopropyl maltodextrin, with F 21.52% . 84865 -68- 200400972

R = H, CF3 (CF2) 60 (CH2) 20CH2CH (0H) CH: n = 5-1,000 Example 53 Perfluorophenylphosphonium carboxymethyl cellulose A solution of perfluorophenylhydrazine in DMSO (0.6 equivalent) was added Into carboxymethyl cellulose aqueous solution, and stirred at ambient temperature for 6 hours. This suspension was filtered, washed with dichloromethane and acetone, dialyzed, and dried to produce a perfluorobenzene CMC, with F of 18.94%.

UK R = H, CH2C02H, CH2C = NNHC6F5 n = 20-10,000 Example 54 Di- (Heptafluorobutanyl) polyethylene glycol A solution of heptafluorobutane chloride in dioxolane (0.6 equivalents) ) Was added to polyethylene glycol (Mw 1,000) in dioxolane containing triethylamine (0.6 equivalents) and stirred at ambient temperature for 6 hours. The reaction mixture was precipitated in ether, and the crude fluorinated PEG product was chromatographed on silica gel to produce heptafluorobutyryl PEG with F 19.95%. CH2 F (CF2) 3 [OCH2 ch2] n 0 (CF2) 3 ch2 fn = 1-50,000 Example 55 Perfluoroaniline hyaluronate 84865 -69- 200400972 Add a solution of perfluoroaniline (1.6 equivalents) in DMSO to hyaluronic acid Sodium hydroxide solution and stirred at 40 ° C for 4 hours. The reaction mixture was allowed to cool, treated with sodium cyanoborohydride (10 equivalents) for 9 hours, precipitated with acetone, washed with acetone, filtered and dialyzed, and dried to give perfluoroaniline hyaluronate with F 17.75%. -^ 〇H 〇 ^ OH ^ 〇H ^ .NHC6F5

• NHAc OH NHAc OH n = 1-4,000 Example 56 Perfluorohexanoate hyaluronate Sodium hyaluronate was dissolved in water, and the pH of the solution was adjusted to pH 4.75 by adding o.l NHC1. EDC (1.5 equivalents) was then added, followed by methyl methyl perfluorohexanoate (1.05 equivalents). The pH of the reaction mixture was then raised to 6.2 within two hours. The reaction mixture was kept at room temperature for five hours, and then it was formed into a thick insoluble hydrogel. This hydrogel was dialyzed against a 1 M NaCl solution and lyophilized to obtain perfluorohexanoate hyaluronate, F 29.52%.

Example 57 Trifluoroacetate hydroxypropylcellulose A solution of ethyl trifluoroacetate in Edo (1.6 equivalents) was added to a pyridine solution of several propylcellulose and stirred at ambient temperature for 9 hours. This solution was immersed in ice water ', filtered, washed with methanol and propyl dialysis, and dried' to produce trifluoroacetate hydroxypropyl cellulose, which had F 34.56%. 84865 -70- 200400972

OR R = H, OCOCF3, CH2CH (OCOCF3) CH3 n = 3 = 10,000 Example 58 3- (Perfluoro-n-octyl) -2-hydroxypropyl hyaluronic acid Base) -1,2-propylene oxide (1.2 equivalents), and the resulting thick paste was stirred at ambient temperature for 6 hours. The reaction mixture was precipitated with acetone, washed with acetone, filtered, dialyzed, and dried to give 3- (perfluoro-n-octyl) -2-hydroxypropyl hyaluronic acid with F31.52%.

R = H, CF3 (CF2) 7CH2CH (〇H) CHr n = 1-4,000 Example 59 Perfluoro-2,5,8,11-tetramethyl-3,6,9,12-tetraoxypentadecane The hyaluronic acid aqueous solution is treated with perfluoro-2,5,8,11-tetramethyl-3,6,9,12-tetraoxypentadecanate (1.2 equivalent) and a catalytic amount of sulfuric acid, The resulting thick paste was stirred at ambient temperature for 14 hours. The reaction mixture was washed with acetone, filtered, dialyzed, and dried to produce perfluoro-2,5,8,11-tetramethyl-3,6,9,12-tetraoxypentadecanate hyaluronate, having F 34.65%.

R DiH, CoCF (CF3) [〇CF2CF (CF3)] 3〇 (CF2) 2CF3 n = 1-8,000 84865 -71-200400972 Example 60 4,4,4-Difluorotrifluoromethyl Butyric acid propylcellulose 3 acidifies 4,4,4_trifluorohydroxy-3_ (trifluoromethyl) butyric acid aqueous solution (M equivalent) to P 4.75 and EDC (3.5 equivalent) followed by water Hexapropyl cellulose was treated and the resulting viscous was stirred at ambient temperature for M hours. The reaction mixture was dialyzed and lyophilized to produce 4,4,4_trifluoro-hydroxy-3_ (trifluorofluorenyl) butyric acid propylcellulose with F.

Ο

OR R = H, 0C〇CH (〇H) (CF3) 2, CH2CH [〇C〇CH (OH) (CF3) 2] CH3 n = 3-l 0,000 Example 61 4,4,4-trifluoro- 3-Chino-3- (trifluoromethyl) butyrate dextran acidifies 4,4,4-trifluoro-3-hydroxy-3- (trifluoromethyl) butanoic acid in water (42 equivalents) To pH 4.75, and treated with EDC (4.5 equivalents), followed by Gluco-Lion Shoulder in water, and the resulting paste was stirred at ambient temperature for 14 hours. The reaction mixture was precipitated with acetone, filtered, re-dissolved in water, concentrated, and dried to produce 4,4,4-trifluoro-3-hydroxy-3- (trifluorofluorenyl) butyrate dextran, Has F 24.57%.

R = H, o [coch (oh) (cf3) 2] ch3 n = 2-25,000 Example 62 Trifluoroacetate collagen 84865 -72- 200400972 Add a solution of ethyl trifluoroacetate in pyridine (1.6 equivalents) to Collagen in Evan solution, and stirred at ambient temperature for 6 hours. This solution was dialyzed, and Donggan 'produced trifluoroacetate collagen' with F23.16%.

0 R = H, COCF3; Ri = H, OH, OCOCF3; R2 = H, CH3; R3 = OH, OCOCF3, NHRt m = 0.1-0.2 n = 0.25-0.4 p = 0.1-0.2 m + n + p = ~ 0.5 Example "Trifluoroacetate poly (vinyl alcohol) A solution of trifluoroacetic anhydride in pyridine (u equivalent) is added to a poly (ethylene alcohol) pyridine solution (Mw30,000) and stirred at ambient temperature 6 hours. This solution was precipitated with ice water, dialyzed, and lyophilized to produce trifluoroacetate pVA with F39.98%.

ococf3 m = 20-1 〇〇〇〇〇 Example 64 Heptafluorobutylfluorenyl polyethylenimine A solution of heptafluorobutanyl chloride in DMSO (2.6 equivalents) was added to the solution containing diethylamine (2.6 ounces) The solution is acetonitrile (Mw 70,000) in DMSO and stirred at ambient temperature for 6 hours. The reaction mixture was dialyzed to produce heptafluorobutyryl PEI with F 45.35%. 84865 -732004200972

^ N (CF2) 3CH2F 'NH (CF2) 3CH2F

c, [n (cf2) 3ch2fj2: N (CF2) 3CH2F] 2 _〆〆m = 0-0.3 n = 0.1-1 p = 〇-〇.3 v = 0-0.3 m + n + p + v = l Example 65 Superparamagnetic iron oxide hyaluronate particles were added to an ultrafine iron oxide particle (3 nm, 0.5 g) in a stirred dispersion of water (50 ml), and sodium hyaluronate aqueous solution (50 mg, 5 ml) was added. . The knife solution was sonicated, centrifuged, and the supernatant was filtered through a 0.22 micron filter. The magnetization curve shows that the hyaluronate particles are superparamagnetic. Example 66 Paramagnetic hyaluronate beads In a rapidly stirred aqueous solution of gadolinium acetate (1 μm x 1 equivalent), an aqueous sodium hyaluronate solution was added dropwise via an injector. The formed gel beads were centrifuged, referenced, and dried. The magnetization curve shows that the particles of uric acid g are paramagnetic. Uses of novel developers

… 1 ~ The machine is deeply defeated. It shows the sensitivity of J to different oxygen partial pressures, and produces a linear correlation at a range of p0 2. This is a note of the CPM as a sensitive development | slave exploitability. This fluorinated alginic acid vinegar also shows chemical properties and temperature characteristics, which indicates its applicability as a temperature-sensitive development probe. Today, these new drugs are suitable for a variety of diagnosis

^ / Oh use, and provide in vivo I heart or non-k-intensive monitoring tissues, organs and Λ fat implants are incapable, such as female Yueyi Island F cells, which is based on the fluorine of the present invention

Paper coated with uronic acid, J

The fluorinated water that you have invented. You can never lose it. 84865 ----------- -74 »200400972 A measure of their quality, function, viability, or inflammation. In addition, after transplantation of isolated islets, it is possible to use

Island monitoring for inductive fluorinated probe identification. With these new medicaments! 9 F_MRI allows monitoring of other conditions, such as cancer, normal or affected cells, organs or tissues. When these fluorinating agents are specific to the target tissue, it is the viability of the transplanted cells or other tissues. This novel method is instrumental in clinical examinations to monitor disease progression and response to treatment in people with diabetes, and among individuals at risk for diabetes and other patients. F or superparamagnetic residues and fluorescent moieties are incorporated into polyuronic acid or polymer medicaments at the same time, and diagnostic probes can be obtained that can be used in MRI and fluorescent studies. Examples of such bifunctional diagnostic probes are glycuronic acid glycosides or proteins, where I has a fluorine moiety group 1 a fluorescent moiety group or a fluorinated fluorescent moiety group as described herein, such as: 4_trifluoromethyl_difluoromethyl-7-hydroxycoumarin (or its acetate or butyrate-7-amine-fluorenyl-benzofurol) Some BODIpY dyes 5,7 -Dimethyl-4-boron-3a, 4a-diaza-spiro per tea_3_even, |

As described in the case study of the mechanism of action of the parent molecule, the diagnostic tool permitted by the method of the present invention is used. For example, by using difluoromethyl-7-aminocoumarin, 4-

84865 • 75- 200400972 permits the preparation of bifunctional diagnostic agents. Therefore, the simultaneous incorporation of Bp or superparamagnetic residues and fluorescent moieties into an anti-diabetic agent makes it possible to obtain diagnostic probes that can be used in MRI and calorimetry research. An example of such a dual-function diagnostic probe is an anti-diabetic compound that contains a fluorine moiety and a fluorescent moiety or a fluorinated fluorescent moiety, such as trifluorofluoride, as described herein. Methyl-7-aminocoumarin, 4-trifluoromethyl-7-hydroxycoumarin (or its acetate or

Butyric acid la derivative), 4-fluoro-7-amine-continyl-benzo-benzoic acid, some BODIpY 'materials such as N (4,4_monofluoro-5,7-dimethyl_4_ · _3a, 4a-diaza-spiro-mangal-3-yl) methyl acetochlor, N- (4,4'-difluoro_ι, 3,5,7-tetramethyl-4-boron -3a, 4a-diaza-spiro_indo-2-yl) -acetamidine and 4,4, _difluoro_5_phenyl pipeboron_eg, such as -diazo-spiro_burial · 3-propanoic acid, 3-chloroyl (3-chloroyl (trifluoromethyl) _2 · pyrimidinyl) _5_ (trifluoromethyl), 2-metaimidine, 6-side methylthio_2, , 4,5,7 | _tetrabromo_4,5,7_trifluorofluorescein (Eosm F3S) and Oregon green carboxylic acid. These are potentially important bifunctional slave needles' It is enough to correlate the development results with those obtained from a fluorescent microscope. For example, the probe-labeled continuous urea of these probes can be added to the cells, and the knots can be confirmed under the microscope, so the MRI will be understood. The developmental research will truly correlate with the binding situation, which is something that cannot be easily achieved without fluorescence. [Simplified illustration of the figure] Figure 1 shows you 丨 1 5, p < mother bath red sevoflurane NMR spectrum of methyl ester. Figure 2 shows an example NMR spectra of fluorinated polymers of 4, 7, and 9. Figure 3 shows the NMR spectrum of perfluorocarbon-based hyaluronic acid of Example 51. In addition, 'the fluorinated anti-diabetic agent of the present invention can be used because of its unusual gas substitution. Not too low blood sugar is $, which is different from the non-fluorinated analog, and is superior / bad than its 84865 • 76- 200400972. Generally skilled artists will perform routine dose adjustment experiments to find the efficacy of the fluorine analog of the present invention. And adjust the dose accordingly. -77- 84865

Claims (1)

WU972 I. Application for patent scope: L ~ fluorinated or paramagnetic polyuronic acid polymer, which contains polymer of formula I, π, m or rv For a polymer capable of forming a salt, it includes a pharmaceutically acceptable salt thereof, with respect to the formula I: \ represents OH, OX, X; R2 represents 0Η, 0χ, X; r3 represents 〇Η, 〇γ, Νχχ,丨 yuan radical, dry oxygen radical; r4 represents c = 〇 ,, CNX, CF2; About formula II: 1 represents OH, OX'X, OR4; r2 represents 0H, 〇χ, χ, 〇R4; & represents OH , Y, X; R4 = brewing group, alkyl group or aryl group; About formula III: Heart represents OH, OX, X; R2 represents 0H, 0X, χ; R3 represents H, wind; About formula IV: Rl represents OH , OX, X ′ · R2 represents 0H, 0X, χ, depending on whether or not 〇_ or〇HER) 〇; Rs represents an alkyl or fluorenyl group, and A represents a non-paramagnetic ion; a where M is a transition metal or steel element Any of the paramagnetic ions, and is an integer, and " b " is 1 / a; 84865 200400972 where all formulas I-IV X Table π fluorine-containing moiety group, luminescent residue, fluorescent residue, fluorination Luminescent residue or fluorinated fluorescent residue; Υ represents CH2C {PH) C: H3; m, P, X, y, Z represents 0-150; and 11 is 1 (MO, 〇〇〇 (inclusive) According to Shen The patentable scope of Item 1 glucuronide polysaccharide polymer which comprises a compound selected from the group comprising the group of the formula a · heptafluoro butyric alginic acid acyl hydantoin b · The following formula 6- [3_ [2_ (perfluorohexyl) -2-ethoxy] -2-hydroxypropyl] alginic acid I C. Perfluorotri-n-butylamine alginate m + n = 1 d · polytetrafluoroethylene oxide-co-difluoromethylene oxide-α-methyl-84865 200400972 R *. R " = Η, C0CF2 (CF20) x (CF2CF20) y0CF2C02CH3; R- = H, CH2CH (OH) CH3 m + n = 1 e. The following formula 6- [2- (perfluorohexyl) -2- Hydroxy] dimethylaminonaphthalenesulfonyl alginic acid R .. R *. = H, CH2CH (OH) CH2〇 (CH2) 2〇 (ar2) 6CF3, FT m + n = 1 f. 3-[(hexafluoropropyl) -2-meryl] alginic acid R ', R *' = H, CF2CF (OH) CF3 m + n = l g. Perfluorophenylarsine alginic acid r = co2h, c = nnhc6f5 m + n = ί h. Polytetrafluoroethylene oxide-co-dioxidized difluoromethylene-α-difluoroacetic acid-ω-difluoroethylfluorenyl alginate 84865 200400972 co2h /-· / & \ A OR1 R ^ O / A OR 'A \ / / V_ / 〇- _-m R \ R "= H, C〇CF2〇 [CF2CF20] x (CF20) yCF2C〇 2H, R_ " i. Polyoxytetrafluoroethylene-co-oxidized difluoromethylene difluoroacetate-ω-difluoroethylenyl alginate propylene glycol R ·· R " = H, C〇CF20 [CF2CF2〇lx (CF2〇) yCF2C〇2H R, M = H. CH2CH (OH) CH3 m + n = 1 j. Perfluorobenzamide alginic acid of the following formula Ester R R = C02H, CONHC6F5 m + a ~ 1 R = C02H, CH2NHC6F5 m + n = l 4- 84865 200400972 1. 3-[(hexafluoropropyl) -2-hydroxy] propanediol alginate R *, R " = H, CF2Cfr (〇H) CF3, CH2CH (OH) CH2〇 (CH2) 2〇CF2CF (OH) CF3 m + n = l m. Polytetrafluoroethylene-co-dioxide Fluoromethylene-α-tolyl carbamate-ω-tolyl isocyanate propylene glycol alginate R ', R " = Η, -NHCOC6H3 (CH3) NHC〇2 (CF2CF2〇lx (CF2〇) yCONHC6H3 (NCO) CH3; R'-= H, CH2CH (OH) CH3 m + n = 1 n. Perfluoro-3,6,9-trioxadecanoic acid S alginate R ', R *' = H, COCF2〇 (CF2) 2〇 (CF2) 20 {CF2} 3CF3 m + n = i 〇. The following formula 3,5,5'-symbol (trifluoromethyl) octafluoro Caproate Alginate R = H, COCF2CF (CF3) CF2C (CF3) 3 m + n = 1 84865 ^ UU4〇9722 P. The following formula 3,5,5'-gins (trifluoromethyl) octafluorohexanoate alginic acid Propylene glycol ester R ； .R- = η, COCF2CF (CF3) CF2C (CF3) 3 R = H, CH2CH (OH) CH3, CH2CH (CH3) OCOCF2CF (CF3) CF2C (CF3) 3 m + n = 1 q Alcoic acid Γ · Heptafluorobutyryl hydroxyethyl starch, and s. Perfluorotri-n-butylamine alginate. 3. The fluorinated and / or paramagnetic polymer according to item 1 of the scope of the patent application, wherein M is selected from the group consisting of rhenium (III), iron (III), manganese (II and IΠ), chromium (III), copper ( II), 镝 (III), 铽 (III), '(III), bait (III), and 铕 (III) 04. The fluorinated and / or paramagnetic polymer according to item 1 of the patent application scope, wherein a In Formula I, the heart is 0Η or OX, R2 is 0Η or OX, R3 is 0Η, and R4 is c = o, b. In Formula II, it is OH or OX, R2 is OH or OX, and R3 is OH. , And R4 is c = o, c. In Formula III, Ri is OH, R2 is OH ′ and R3 is Η, N (X) 3, and d. In Formula IV, R! Is OH or -0A (X) 0-'R2 is OH or -0Α (Χ) 0- '84865-6-200400972 and M is rhenium (III), iron (III), manganese (II) or rhenium (III). 5. The fluorinated and / or paramagnetic polymer according to item 1 of the scope of patent application, wherein X is a fluoroalkyl group, a fluoroaryl group, a fluorenyl group, a perfluoroalkyl group, a perfluoroaryl group, a perfluorofluorenyl group, Perfluoropolymers, fluoroamines, fluoroaminocarbamic acids, fluoro-based sangen, fluorosulfofluorenyl alkyl derivatives, F, CF3, COCxFy, CF3C02, CxFyHz ^ ([CH2] m 0) x ( CH2 CF2 0) y (CF2 CF2 0) z (CF2) 2 CF2 CH2-0 (CH2) pOH, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz [CxFzO] mF, CH2C (CH3) C02CxHz (CF2) mCF CH2 (CF2 0) x (CF2 CF2 0) y (CF2 0) z CF2 CH2 OH, NHCxFyHzOp, CH2CF20 [CF2CF20] mCF20CF2CH20H, C0CxHz (CF2) mCF3, C0-CF2 0 [CF2 CF2 0] n CF2 OCF2 C02 H ' CO-CF (CF3) [CF (CF3) CF2 0] mF, ([CH2] m 〇) x (CH2 cf2 0) y (CF2 cf2 0) z cf2 ch2 0 (CH2) p OH, S02 [CF2] xCF3 , CF3S03, N [CxFyHz] p, CxHzC02CxHz (CF2) mCF3, COCxFy [CpFzO] mF, luminescent residue, fluorescent residue, fluorinated luminescent residue or fluorinated fluorescent residue; Y means CH2C (OH) CH3 ; m, ρ, X, y, and z are 0-150, and η is 10-10,000 (inclusive). 6. A paramagnetic alginate bead comprising paramagnetic osmium alginate beads or paramagnetic iron oxide alginate beads. 7. A paramagnetic particle comprising paramagnetic iron oxide alginate-coated particles, paramagnetic iron oxide alginate-coated particles, or paramagnetic iron oxide glucan-coated particles. 8. A bioactive protein paramagnetic co-monitor, which contains a bioactive protein that is co-located or mismatched with the paramagnetic ion of transition metal 84865 9 or a free element. The paramagnetic conjugate of biologically active protein according to item 8 of the patent 4 patent park, wherein the paramagnetic protein conjugate is an iron oxide addin conjugate, a super-member magnetic iron oxide addin, or a fluorescent superpara Magnetic iron oxide addin conjugate. 0. The fluorinated polyuronic acid aluminum polymer according to item 1 of the application, wherein the uronic acid is replaced by alginate, and the alginate has an α-L-gulose content of at least 50. weight%. 11 · —An implant for a mammalian host, comprising: a. Living cells that produce a desired biologically active compound, and b • one or more polymers according to item 1 of the scope of the patent application, wherein the polymer is Encapsulating the living cells and suppressing the host's immune response to the implant, and allowing the implant to be evaluated by MRI examination. 12. The implant according to item 11 of the application, wherein the polymer is a fluorinated or paramagnetic alginate. 13. The implant according to item 11 of the application, wherein the cells are human or porcine pancreatic B-islet cells that produce insulin. From the implant according to item 13 of the application, wherein the polymer is a fluorinated or paramagnetic alginate. 15. —A method for improving the effectiveness of magnetic resonance imaging (MRI), which comprises: (i) administering to a patient an effective amount of one or more fluorinated and / or paramagnetic polymers according to item 1 of the scope of patent application; b. subject the patient to an MRI of the tissue / organ, where it is expected that the polymer administered will accumulate there; and 84865 200400972 c. evaluate the tissue / organ from the MRI image obtained. 16. The method according to item 15 of the application, wherein the polymer is fluorinated polyuronic acid. 17. The method according to item 15 of the application, wherein the polymer is a paramagnetic polyuronic acid. 18. A fluorinated anti-diabetic compound comprising compounds of the general formulae AI to AXVII: NH-R (R3) 3? R2 (Can, W1 NH NH A1 84865 200400972 〇Ra AXI! AXV AXVI, r3 Ri-Ding-R7 --- Λ T 0 O 〇AVil iAl ·. X ^ H, X; R2 means H, X; R3 means H, X; R4 means H 84865 -10- 200400972 & means Η , X; R2 represents Η, X; R3 represents Η, X; R4 represents Η, X; R5 represents Η, X About formula AIII: Rn represents Η, X; R2 represents Η, X; R3 represents Η, X; heart represents Η, X; R5 means Η, X; R6 means Η, X; R7 means Η, X; R8 means Η, X; R9 means Η, X; &. Represents CO, CHF, CF2, CNX, X; i represents H, C (R7) 3, X About formula AIV: Ri represents Η, X; R2 represents Η, X; R3 represents Η, X; R4 represents Η, X; 115 means 11, 乂; 116 means 11, meaning about the formula AV: heart means Η, X; R2 means Η, X; R3 means Η, X; R4 means Η, X; R5 means Η, X; means Η, X; R7 represents Η, X with respect to the formula AVI: Ri represents Η, X; R2 represents Η, X, NH2, NHX, NX2; R3 represents H, X; R4 represents Η, X; Formula AVII: represents Η, X; R2 represents Η , X; R3 represents Η, X; R4 represents Η, X; 115 represents 11, and; 116 represents 11, and about formula AVIII: R! Represents Η, X; R2 represents H, X; R3 represents H, X; R4 Represents H, X; R5 represents Η, X; R6 = H, X; R7 represents Η, X; with respect to formula AIX: represents Η, X; R2 represents Η, X, (CH2) 2NHCONHX; R3 represents H 84865 200400972, X, OX; R4 represents Η, X. About the formula AX: & represents X; R2 represents CvHkFh; CvHkFhOd; C6HkFhR3; R3 represents X, where v is 6-9 (inclusive), k is 0-11 (inclusive), h Is 1-12 (inclusive), d is 0-4 (inclusive) About formula AXI: Ri represents Η, X; R2 table Η, X, NH2, NHX, NX2; R3 means Η, X; R4 means H, X; R5 means H, X; R6 means H, X; R7 means Η, X; R8 means OH, X About formula AXII: Ri Represents Η, X; R2 represents Η, X, NH2, NHX, NX2; R3 represents H, X; R4 represents Η, X; R5 represents Η, X; R6 represents Η, X; R7 represents Ή, X; R8 represents OH , X About formula AXIII: represents Η, X; R2 represents H, X; R3 represents H, X; R4 represents H, X 'l represents H, X; R6 represents H, X; R7 represents H, X; R8 represents H , X;% means H, X;. Represents H, CH2X, NHX, CH2NHX; i = H, X; R12 represents OH, OX, X, NHX 阚 in the formula AXIV: represents Η, X; R2 represents H, X; R3 represents H, x; R4 represents H, x X Han 5 means H, X, Rg means Η, X; R7 means Η, X; R8 means H, X; means Η, X;. Represents Η, X; Ru indicates H, CH3, CH2X, X, NHX, CH2NHX; R12 indicates CH3, CH2X, X, NHX, CH2NHX About formula AXV: 84865 200400972 & Represents Η, X, NH2, NHX, NX2; R2 Represents Η, X; R3 represents Η, X; R4 represents H, X, NH2, NHX, NX2; R5 represents Η, X; R6 represents Η, X; R7 represents Η, X; for formula AXVI: Ri represents Η, X, NH2, NHX, NX2; R2 means Η, X; R3 means H, X; R4 means Η, X; R5 means Η, X; Rg means Η, X; R7 means Η, X, where the above formula AI-AXVI: X = Fluoroamyl, Fluoroaryl, Fluoroyl, Perfluoroalkyl, Perfluoroaryl, Perfluorofluorenyl, Perfluoropolymer, Fluoroamine, Fluoroaminoformate, Fluoro , Fluorosulfonyl alkyl derivative, F, CF3, COCxFy, CxFyHz '([CH2] m 0) x (CH2 cf2 0) y (CF2 cf2 0) z (CF2) 2 cf2 ch2 0 (CH2) p oh, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz- [CxFzO] mF, CH2C (CH3) C02CxHz (CF2) mCF3, CH2 (CF20) x- (CF2 CF2 0) y (CF2 0) z CF2 CH2 S02 [CF2] xCF3, CF3 SO3NH-CxFyHz0p, CH2CF20 [CF2CF20] m (CF20CF2CH20H, C0CxHz- (CF2) mCF3, C0-C F20 [CF2CF20] nCF20CF2C02H, C0-CF (CF3)-[CF (CF3) CF20] mF ^ ([CH2] m0) x (CH2CF20) y (CF2CF20) zCF2CH2- 0 (CH2) p0H, N [CxFyHz] p, CxHzC02CxHz (CF2) raCF3, COCxFy [CpFzO] mF, luminescent residue, fluorescent residue, fluorinated luminescent residue or fluorinated fluorescent residue, and m, X, p, y, z are integers 1 to 150 ( Included): and where about formula AXVII: 200400972 & represents XO, X, XNH, R4 [0 (CH2) 2] m0, YM; T represents CH2NH, C02, O, S2, CONH, NHCO, X, NHCOX, R4 [0 (CH2) 2] m0 'CH2CO (CH2) 2; R2 means (CH2) 2C6H6, CH2NH (CH2) 2C6H6, CONH (CH2) 2C6H6, X, NHX; R3 means cyclohexyl, aryl, X, YM ; R4 represents europium, OH, YM, R !, and M represents any paramagnetic ion of transition metal or lanthanide; X represents fluoroalkyl, fluoroaryl, fluorenyl, perfluoroalkyl, perfluoroaryl , Perfluorofluorenyl, perfluoropolymer, F, CF3, COCxFy, CF3C02, CxFyHz, ((CH2) m 0) x (CH2 cf2 0) y (CF2 cf2 0) z (CF2) 2 cf2 ch2 0 (CH2 ) p oh, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz- [CxFzO] mF, CH2C (CH3) C02CxHz (CF2) mCF3, CH2 (CF20) x- (CF2 CF2 0) y ( CF2 0) z CF2 CH2 OH 'COCx Hz (CF2) m CF3 ^ NHCX Fy H, Op, CH2CF20 [CF2CF20] m (CF20CF2CH20H, C0-CF20 [CF2CF20] n-CF20CF2C02H, C0-CF (CF3)-[CF ( CF3) CF20] mF, ([CH2] m0) x- (CH2CF20) y (CF2CF20) zCF2CH20 (CH2) p0H, CF3S03, N [CxFyHz] p, CxHzC02CxHz (CF2) mCF3, COCxFy [CpFzO] mF, luminescent residue , Fluorescent residue, fluorinated light-emitting residue or fluorinated light residue, Y represents CH2C (OH) CH3, and m, p, x, y, and z represent 1-150 (inclusive), and η is 10-10,000 (inclusive), Y represents polydentate ligand metal complex residues, selected from the group consisting of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid Mono (p-aminoamidoaniline), 5-amino-2-methoxyphenyl-1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid, 2-p-aminobenzyl-l, 4,7,10-tetraazacyclo-dodecane-l, 4,7,10-tetraacetic acid, p-aminobenzyl-diethylenetriamine pentaacetic acid, P-Isothiocyanatobenzyl-l, 4,7,10-tetraazacyclododecane- 84865 -14- 200400972 1,4,7,10-tetraacetic acid, p-isothiocyanato_yl Ethylene triamine pentaacetic acid, p-isothiocyanatofluorenyl diethylene triamine pentaacetic acid, 丨, 4, 7, ι -Tetraazacyclododecane_ι, 4,7,1〇_tetraacetic acid monoequiyl succinimide fluorenyl ester), 1,4,7,10-tetraazacyclododecane-1,4, 7-ginseng (acetic acid-tertiary-butyl ester) -10-acetic acid, diethylenetriamine-pentaacetic acid 1'4,7,10_tetraazacyclododecyl, 1,4,7-triazacyclo Azalea, 1,4,7,10-tetraazacyclododecane-1,4,7,10-methyl (methylenephosphonic acid) and 10_ (2_ethoxy_3,4_dione Methylcyclohexylbutanyl) -1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid. 19. A fluorinated anti-diabetic compound according to item 18 of the scope of patent application, which is a compound selected from the group consisting of: a. 6-carboxyamido- {4- [l-amido-[- Ν, Ν-1,6-hexanediamine] -6-aminoamine] -2,3,5,6-tetrafluorophenyl-N-[[[(cyclohexylamino) carbonyl] amino]] Sulfonyl) _phenyl] ethyl] -benzidine amine} -polytetrafluoroethylene-co-difluoromethylene · α-methylbenzylamino phosphonate phenylphenyl isocyanate alginate propylene glycol ester b. The meaning of the following formula is [2,3,4,5,6-pentafluorophenyl) carboxamide +; ^ _ [2_ (4-[[[(cyclohexylamino) -carbonyl] amino] sulfonyl (Ethyl) ethyl] -2-p-phenylmethyl (diethylenetriamine-N, N, N ', NΠ, N " -pentaacetic acid) ~ 25: -4 0 84865 -15-200400972 And its paramagnetic complex; c. The following formula N- [l- (diethylenetriamine-N, N, N ', N ", N" -pentapic acid) benzamine_] · ν, [2 -(4-[[[(cyclohexyl-amino] carbonyl] amino] amino] ethyl) ethyl] -2-methoxybenzidine And its paramagnetic complex; d. The following formula N- [4- (l, 4,7,10-tetraazacyclododecane_i, 4,7,10_N, NVN ",; Nr- Tetra-acrylic acid p-amino-fluorenylaniline) carboxamidin-2,3,5,6-tetrafluorophenyl] _N_ [2_ (4 _ [[K cyclohexylamino] carbonyl] -amino] _ Sulfonyl)] ethyl] _2_methoxybenzylamine 84865 -16- And its paramagnetic complex; 200400972 e · The following formula [1,1-diketo-6- (trifluoromethyl) -1,2,3,4-tetrahydro-1 []-6-2- 4-Benzothiine-7-sulfofluorenyl)]-[3,5-bis (trifluoromethyl) phenyl] carboxamide f. The following formula 2,3,4,5,6-pentafluorophenyl-N-[[[(4-trifluoromethylphenyl] carbonyl] -amino] pyridyl) -4-trifluorofluorene Phenyl] ethylamine g. N- [7-amino-4- (trifluoromethyl) coumarin] -carboxamide-2,3,5,6-tetrafluorophenyl] -N- [2- (4 -[[[(Cyclohexylamino) amino] sulfofluorenyl) -2,3,5,6-tetrafluorophenyl] ethyl] -2-methoxybenzylamine 84865 -17- 200400972 h. The following formula 2,3,4,5,6-pentafluoro 4 [2- (4-[[[[(2,3,4,5,6-pentafluorophenyl] carbonyl] _amino] sulfonium ) Phenyl] ethyl] benzamide F i. The following formula 2,3,4,5,6-pentafluoro-N- [2- (4-[[[[(2,3,4-trifluorophenyl] carbonyl] amino] -sulfofluorenyl) Phenyl] ethyl] benzamide F j. Formula 3,5-bis (trifluoromethyl) phenyl-N- [2- (4-[[[(cyclohexylamino) carbonyl] amino] -sulfofluorenyl) -phenyl] ethyl Yl] benzamide k. The following formula 2,3,4,5,6-pentafluorophenyl-N- [2- (4-[[[(cyclohexylamino) carbonyl] amino] -phenylamino) phenyl] ethyl Yl] benzamide 84865 -18- 200400972 1. 乂 [4- (2,2,2-trifluoroethyl) carboxamide-2,3,5,6-tetrafluorophenyl] _N- [2- (4- [ [[(Cyclohexyl-amino] carbonyl] amino] sulfofluorenyl) _2,3,5,6-tetrakiphenyl] ethyl] -2-methoxybenzylamine 0 F Η Η m_ of the following formula 4-Ethyl-2,3,5,6-tetrafluorophenyl-N-[[; [(cyclohexylamino) carbonyl] amino] -continyl) -phenyl] Ethyl] phenylhydrazine〇F ΗΟ Ο Η Η The formula 'Amine ice (trifluoromethyl) -coumarin Glimepirid ° · Heptafluorobutyridinyl metforminΌNΗ, ... P. The following formula is used to oxidize tetrafluoroethylene-co-oxidized difluoromethylene- (3! _Tolylaminocarboxylic acid-0 > tolyl isocyanate Limepilide X S—N NHC02 [CF2CF20] x (CF20) yC0NHC6H3 (NC0) CH3 84865 -19- 72 and q · difluoroglimepiride 20. The fluorinated anti-diabetic compound according to item 18 of the patent application, wherein the magnetic ion M is selected from the group consisting of rhenium (ΠΙ), iron (ΠΙ), manganese (Π and III), chromium (III), steel (II), 镝 (III), 钺 (III), '(III), bait and 铕 ⑽. 21. The fluorinated anti-diabetic compound according to item 18 of the patent application, wherein the fluorenyl and alkyl residues contain a lipophilic moiety, including saturated and unsaturated aliphatic residues, with a ck chain, where k is 2 to 100, and the aryl residue system thereof includes an aromatic partial group selected from the group consisting of a fluorenyl group, a biphenyl group, a phenyl group, a polycyclic aromatic compound, and a hetero atom-containing aromatic compound. 2Z The fluorinated anti-diabetic compound according to item 18 of the scope of patent application, wherein each of x, p, y, z and m is an integer of 10-50 (inclusive). 23. —A method of assessing the course of diabetes in a patient, comprising: a. Administering to the patient a fluorinated anti-diabetic compound according to item 18 of the scope of the patent application; b. Subjecting the patient to an MRI procedure; and c -Assess the course of diabetes in a patient by comparing this MRI result to a MRI result or baseline MRI result previously obtained from the patient. 24. A method for evaluating the function of anti-diabetic drugs in a patient, comprising: a. Administering to the patient a fluorinated anti-diabetic compound according to item 8 of the patent application; 84865 -20- 200400972 b. The patient undergoes an MRI procedure; and c. Assess the function of the anti-diabetic drug by comparing this MRI result to a previous result obtained from the patient or a baseline MRI. 25. A method for monitoring the progress of diabetes in a patient, comprising: a. Administering to the patient a fluorine-containing anti-diabetic compound in accordance with item 18 of the scope of the application at a therapeutic amount; b. Subjecting the patient to a tissue / Organ MRI, which is the site of action of anti-diabetic drugs over time; and c. Evaluate the progress of diabetes by comparing MRI images with MRI images obtained over a long period of time. 26. A fluorinated biopolymer comprising any compound of formula BI-BVIII: r50 / OR.-or4 0, ReNR7 84865 BIV _ 〇R2 BV BV! BVIi 〇BVill -21-200400972 where formula BI: Ri represents Η, X; R2 represents Η, X; R3 represents Η, OH, 〇Υ, OX, ΝΗχ About formula BII: R! Represents Η, X; R2 represents Η, X ; R3 represents Η, 〇Υ, 〇Χ, ΝΗΧ with respect to the formula Bill: & represents Η, χ; R2 represents Η '×; R3 represents Η, Υ, χ with respect to the formula BIV: &represents;,X; R2 represents Η, X ; R3 represents C02H, C02X, CH2X, CH2NHX; R4 represents H, X; R5 represents H, X; R6 represents H, x; R7 represents X, COCH3, COX About formula BV: represents Η, X; R2 represents Η, X ; R3 means C02H, C02X, CH2X, CH2NHX; R4 means H, S03H, X; R5 means H, S03H, X; Rg means Η, X; R7 means COCH3, COX, X About formula BVI: & means Η, X ; R2 represents Η, X; R3 represents C02H, C02X, CH2X, CH2NHX; R4 represents Η, X; R5 represents S03H, X; R6 represents Η, X; R7 represents COCH3, COX, X. About formula BVII: represents Η, X R2 means Η, X; R3 means Η, X; R4 means S03 H, X; R5 means S03H, X; Rg means H, X; R6 means H, X; R7 means coch3, COX, X 84865 -2 2- 200400972 About formula Bvm: represents Η, X; R2 represents Η, X; R3 represents C02H, C02X, CH2X 'CH2NHX; R4 represents Η, X; R5 represents η' X; R6 represents η, X; R7 represents Η, X; R8 represents COCH3, COX, X. Among all the above formulas BI-B VIII X represents a fluorine-containing moiety group, and Y represents a branch residue that does not include early di-, oligo-, or how cool, or Vaporized branching residues, including mono-, di-, oligo- or polysaccharides. 27. A fluorinated biopolymer comprising any compound of formula BIX and BXII BIX Among them, the formula BIX: Ri means H, X, Z; R2 means H, X, Z; R3 means Η, X; Ruler 4 means H, X, Z; R5 means H, X; R6 means H, X; R7 means H, X, Z About formula BX: -23- 84865 200400972 I means Η, X, CH20G0C02H, CH20GC02X, CH2OGCONX, CH2OGCH2NX; R2 means H, X, Z; R3 means H, X, ch2ogoco2h, CH20GC02X, CH2OGCONX, CH2O R4 represents H, COCH3 'COX' X 'CH20G0C02H' CH20GC02X 'CH2OGCONX, CH2OGCH2NX About formula BXI: h represents H, OH, X, ox, oz, ch2ogoco2h, ch2ogco2x, ch2ogconx, ch2ogch2nx; r2ox, H, OH , OZ, CH2 OGOC〇2 H, CH2 0GC02 X, CH2 OGCONX, CH2 OGCH2 NX; r3 means ch2oh, ch2ox, ch2oz, ch2x, ch2nhx, co2h, co2x, conx, ch2ogoh, ch2ogox, ch2ogoco2h, CH2OGX, CH2OGX R4 represents OH, z, OX, X; G represents a calcined group and a lightly calcined group. With respect to the formula BXII: K represents Η, OH, X, OX, OZ; L represents Η, OH, X, OX, OZ; W represents H, OH, X, OX, OZ; T is H, OH, X, OX, OZ; V is anhydroanyl group Glycosyl, and m, n, p, q, r, and s represent integers from 1 to 500 (inclusive); where all of the above formula BIX-BXII X represents a fluorine-containing moiety group, a luminescent residue, and a fluorescent light Residues, fluorinated luminescent residues or fluorinated fluorescent residues; Y represents a sugar branching residue containing mono-, di-, oligo- or polysaccharides, or a fluorinated sugar branching residue containing mono-, di -, Oligo- or polysaccharide; z represents a radical or a radical. 84865 -24- 200400972 28. —Specification BXIII fluorinated biopolymer BXIII Among the formulas BXIII: K represents Η, OH, X, OX, OZ, (Y) f; L represents Η, OH, X, Οχ, ΟZO, (Y) f; W represents Η, (CH2) d, C02H , CH, CX, X; T represents H, OH, X, OX, OZ; V represents (CH2) d, CH2OX, CH2OZ, CH2X, CH2NHX; S represents Η, 〇, X, NHX, (Y) f; T Represents Η, Ο, X, NHX, (Y) f represents H, X, and D represents 1-3 (inclusive); f and n represent 1-1,500 (inclusive), and regarding all the above chemical formulas: X Represents a fluorine-containing moiety, a luminescent residue, a fluorescent residue, a fluorinated luminescent residue, or a fluorinated fluorescent residue; Y represents an amino acid residue or a fluorinated amino acid residue; and Z represents 醯Base, burning base. 29. A fluorinated biopolymer comprising any compound of formula BXIV-BXX 84865 -25-200400972 R4, WR3 • J η BXIX BXX where formula BXIV: X; Ri represents H, X; R2 represents Η, Z, and formula BXV: I represents Η, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R2 represents Η, CH3, (CH2 ) mCH3, CF3, (CF2) mCF3; R3 means Η, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R4 means H, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R5 means H, CH3, (CH2) m CH3, CF3, (CF2) m CF3, CH2 X, CH2 NHX; Re represents H, CH3, (CH2) m CH3, CF3, (CF2) m CF3, CH2 X, CH2 NHX; m represents 1-10 (inclusive); n represents 1-3,000 (inclusive); About formula BXVI: the heart represents OH, X, OX, OZ; R2 represents OH, X, OX, OZ; m and n represent 1-15,000; About formula BXVI: Heart represents O, CH2X, CH2NHX, OZ; R2 represents CH3, (CH2) mCH3; R3 represents CH3, (CH2) mCH3, CF3, (CF2) mCF3; R4 represents (CH2) n; R5 represents (CH2 ) q; R6 represents H, OH, OX, X; R7 represents H, OH, OX, X; m and n represent 1-30 (inclusive); p and q represent 0-3,000; 84865 -26- 200400972 BXVII: represents 0, OX, CF3, (CF2) mCF3; R2 represents CH3, (CH2) nCH3 CF3, (CF2) nCF3; R3 means CH3, (CH2) nCH3, CF3, (CF2) nCF3; R4 means (CH2) m; R5 means (CH2) q; Chemical means OH, OX, X; R7 means Η, X m represents 2; n represents 1-10 (inclusive); p and q represent 1-3,000 (inclusive); About the formula Bxvm: R! represents Η, CH3, (CH2) mCH3, CF3, (CF2) mCF3; R2 represents Η, OH, OX, X; R3 represents Η, OH, OX, X; m represents 1-30 (inclusive); n represents 1-3,000 (inclusive); About the formula BXIX: the heart represents ch2, ch2ch2, cf2, cf2cf2; r2 represents ch2, cf2; r3 represents 011, 0 乂, 02; 114 represents 11, again, 2; where 2 represents Y [(OCH2CH2) m] q; Y represents the core of the doze ligand, m And n represents 1-80,000 (inclusive); and q represents 1-10 (inclusive); regarding formula BXX: represents Η, X; R2 represents Η, X, (CH2CH2N) m, (CH2CH2NX) m; R3 represents Η , X, (CH2CH2N) m, (CH2CH2NX) m; R4 represents Η, X, (CH2CH2N) mCH2CH2NH2, (CH2CH2N) mCH2CH2NHX; m represents 1-3,000 (inclusive); n represents 5-80,000; of which all about the above culture The formula X represents a fluorine-containing moiety, a luminescent residue, and a fluorescent residue. Fluorinated or fluorinated fluorescence emitting residue residue; and Z represents an alkyl or acyl. 84865 -27- 200400972 30. The fluorinated biopolymer according to item 26 of the patent application is also paramagnetic. 31. The fluorinated biopolymer according to any one of claims 26-30 of the scope of the patent application, wherein X is a fluorocarbon group, a fluoroaryl group, a fluoric acid group, a perfluorocarbon group, a perfluoroaryl group, a perfluorofluorene Bases, perfluoropolymers, fluoroamines, fluorocarbamates, fluorosamakis, fluorosulfoalkyl derivatives, cf2ci, so2 [cf2] xcf3 ^ F > CF3 > COCxFy > CxFyHz ^ ([CH2] m0) x (CH2CF20) y (CF2CF20) z- (CF2) 2CF2CH20 (CH2) p0H, CH2C (OH) CxFyHz, CxFyHzOp, COCxFyHz, OCH2CxFz [CxFzO) mF, CH2C (C2Cx) CF2) mCF3, CH2 (CF2 0) x (CF2 CF2 0) y (CF2 0) z CF2 CH2 OH, COCF (CF3)-[CF (CF3) CF20] mF, NHQFyH.Op, CH2CF20 [CF2CF20] m- ( CF2OCF2CH2OH > COCxHz (CF2) mCF3 'COCF2 0 [CF2 CF2 0] n-CF20CF2C02H, ([CH2] m 0) x (CH2 cf2 0) y (CF2 cf2 0) z cf2 ch2 o- (CH2) pOH, N [CxFyHz] p, CxHzC02CxHz (CF2) mCF3, COCxFy- [CpFzO] mF, and m, x, p, y, and z are integers from 1 to 150 (inclusive). 32. A fluorinated biopolymer containing A polymer compound selected from the group consisting of: a. Formula 3- [2- (perfluorohexyl) -2-ethoxy] -2-propylpropyl-polyglutamic acid: m = 1-70,000 n = 70,000-1 where [m + n = l] qq = 5-70,000; 84865 -28- 200400972 b. Formula 3- [2- (perfluorohexyl) -2-ethoxy] -2-¾propyl hyaluronate R = H, CF3 (CF2) 6〇 (CH2) 2〇CH2CH (〇H) CH2-n = 1-4,000 c. The following formula 3- [2- (perfluorohexyl) -2-ethoxy] -2 -¾propyl maltodextrin R = H, CF3 (CF2) 60 (CH2) 20CH2CH (0H) CH2 n = 5-1 (000 d. Perfluorophenylphosphonium carboxymethyl cellulose R = H, CH2C02H (CH2C = NNHC6F5 n = 20-10,000 e. The following formula 2- (Heptafluorobutyryl) polyethylene glycol CH2 F (CF2) 3 [OCH2 ch2] n 0 (CF2) 3 ch2 f n- 1-50,000 f. perfluoroaniline hyaluronate n = 1-4,000 84865 -29- 200400972 g. Perfluorohexanoic acid vinegar hyaluronic acid formula n = 1-8,000 h. trifluoroacetate hydroxypropyl cellulose R = H, OCOCF3, CH2CH (OCOCF3) CH3 n = 3-10,000 i. The following formula 3- (Perfluoro-n-octyl) -2-Hydroxypropyl hyaluronic acid R = H, CF3 (CF2) 7CH2CH (OH) CH2-n = 1-4,000 and salts thereof; j. Perfluoro-2,5,8,11-tetramethyl-3,6,9,12- Tetraoxypentadecanate hyaluronic acid R = H, cocf (cf3) [ocf2cf (cf3)] 3o (cf2) 2cf3 n = 1-8,000 and its salt; -30- 84865 200400972 k. The following formula 4,4,4-trifluoro-3-hydroxy- 3- (trifluoromethyl) butyrate hydroxypropyl cellulose R = H, OCOCH (OH) (CF3) 2, ch2ch [ococh (oh) (cf3) 2] ch3 n = 3-10,000 1. The following formula 4,4,4-trifluoro-3-hydroxy-3- ( Trifluoromethyl) butyrate dextran R = H, 0 [C0CH (0H) (CF3) 2] CH3 n = 2-25,000 m. Trifluoroacetate collagen R = H, COCF3; Ri = H, OH, OCOCF3; R2 = H, CH3; R3 = OH, OCOCF3l NHR, m = 0.1-0.2 n = 0.25-0.4 p = 0.1-0.2 where m + n + p = ~ 0 · 5 n. Trifluoroacetic acid poly (vinyl alcohol) of the following formula + rt l J m OGOCF3 m = 20-10,000 -31-84865 200400972 〇 · Heptafluorobutynyl polyethylenimine of the following formula .N (CF2) 3CH2F [N (CF2) 3CH2F] 2 ^ NH (CF2) 3CH2F \ [n (cf2) 3ch2f] 2 m = 0-0.3 η = 0.1-1 · 0 p = 0-0.3 v = 0- 0.3 m + n + p + v = 1 P · q · superparamagnetic iron oxide hyaluronate particles; and paramagnetic holmium hyaluronate beads. 84865 32-