CN106986951A - A kind of hydrophobic polysaccharide and its preparation method and application - Google Patents
A kind of hydrophobic polysaccharide and its preparation method and application Download PDFInfo
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- CN106986951A CN106986951A CN201610038059.9A CN201610038059A CN106986951A CN 106986951 A CN106986951 A CN 106986951A CN 201610038059 A CN201610038059 A CN 201610038059A CN 106986951 A CN106986951 A CN 106986951A
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- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 68
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 68
- 150000004676 glycans Chemical class 0.000 title claims abstract description 66
- 230000002209 hydrophobic effect Effects 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229960005486 vaccine Drugs 0.000 claims abstract description 14
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 12
- 229920001503 Glucan Polymers 0.000 claims abstract description 11
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229940079593 drug Drugs 0.000 claims abstract description 6
- 150000001413 amino acids Chemical class 0.000 claims abstract description 5
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000002994 raw material Substances 0.000 claims abstract description 3
- 229940014800 succinic anhydride Drugs 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- 241000894006 Bacteria Species 0.000 claims description 15
- 241000700605 Viruses Species 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000843 powder Substances 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002105 nanoparticle Substances 0.000 claims description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 4
- -1 ethoxy dextran Chemical compound 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- 241000233866 Fungi Species 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000012535 impurity Substances 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000001384 succinic acid Substances 0.000 claims description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 230000000890 antigenic effect Effects 0.000 claims description 2
- 239000008367 deionised water Substances 0.000 claims description 2
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- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000003995 emulsifying agent Substances 0.000 claims description 2
- 229920000669 heparin Polymers 0.000 claims description 2
- 229960002897 heparin Drugs 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims 3
- TWNIBLMWSKIRAT-RWOPYEJCSA-N (1r,2s,3s,4s,5r)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol Chemical compound O1[C@@]2([H])OC[C@]1([H])[C@@H](O)[C@H](O)[C@@H]2O TWNIBLMWSKIRAT-RWOPYEJCSA-N 0.000 claims 1
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 claims 1
- 229920000945 Amylopectin Polymers 0.000 claims 1
- 229920000856 Amylose Polymers 0.000 claims 1
- 229920002101 Chitin Polymers 0.000 claims 1
- 229920001661 Chitosan Polymers 0.000 claims 1
- 229920002307 Dextran Polymers 0.000 claims 1
- 229920002472 Starch Polymers 0.000 claims 1
- 229920002000 Xyloglucan Polymers 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- 230000002429 anti-coagulating effect Effects 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
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- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000008014 freezing Effects 0.000 claims 1
- 238000007710 freezing Methods 0.000 claims 1
- 238000005342 ion exchange Methods 0.000 claims 1
- 229940118199 levulan Drugs 0.000 claims 1
- 239000007908 nanoemulsion Substances 0.000 claims 1
- 239000003755 preservative agent Substances 0.000 claims 1
- 230000002335 preservative effect Effects 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000000523 sample Substances 0.000 claims 1
- 239000008107 starch Substances 0.000 claims 1
- 235000019698 starch Nutrition 0.000 claims 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 abstract description 5
- 102000004169 proteins and genes Human genes 0.000 abstract description 5
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 abstract description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 4
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 3
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 3
- 201000006966 adult T-cell leukemia Diseases 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 208000001848 dysentery Diseases 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229960002766 tetanus vaccines Drugs 0.000 description 3
- 206010006500 Brucellosis Diseases 0.000 description 2
- 241001647374 Chlamydia felis Species 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 101710091977 Hydrophobin Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000710799 Rubella virus Species 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
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- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 241000186227 Corynebacterium diphtheriae Species 0.000 description 1
- 241000606678 Coxiella burnetii Species 0.000 description 1
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- 241001466953 Echovirus Species 0.000 description 1
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- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
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- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000000464 Henipavirus Infections Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 241000701027 Human herpesvirus 6 Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 241000710842 Japanese encephalitis virus Species 0.000 description 1
- 206010023927 Lassa fever Diseases 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 208000000932 Marburg Virus Disease Diseases 0.000 description 1
- 201000011013 Marburg hemorrhagic fever Diseases 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
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- 241000150452 Orthohantavirus Species 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000531795 Salmonella enterica subsp. enterica serovar Paratyphi A Species 0.000 description 1
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000710886 West Nile virus Species 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
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- 229940065181 bacillus anthracis Drugs 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
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- 239000003610 charcoal Substances 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 208000028104 epidemic louse-borne typhus Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229940124644 immune regulator Drugs 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000037797 influenza A Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
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- 244000000010 microbial pathogen Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 210000003681 parotid gland Anatomy 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 108010052441 tetanolysin Proteins 0.000 description 1
- 206010061393 typhus Diseases 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6087—Polysaccharides; Lipopolysaccharides [LPS]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to technical field of organic synthesis, more particularly to a kind of hydrophobic polysaccharide and its preparation method and application, the hydrophobic polysaccharide is that the hydroxyl of glucan is reacted with succinic anhydride, first prepare the glucan butyrate with butyric acid group, reacted again with dicyclohexylcarbodiimide (DCC), carboxyl is set to be modified by dicyclohexylurea (DCU) (DCU), end group is modified and be connected using butyric acid as linking arm with glucan with ester bond by DCU.Preparation method is using glucan or other polysaccharide as raw material, prepared with butyric anhydride and dicyclohexylcarbodiimide (DCC) reaction, its molecular weight ranges is between 20K 500K, the hydrophobic polysaccharide has self-emulsifying, suitably as protein medicaments, the especially carrier of amino acid, vaccine type medication.
Description
Technical field
The present invention relates to technical field of organic synthesis, more particularly to a kind of hydrophobic polysaccharide and its preparation method and application.
Background technology
Protein in biological cell keeps its biological activity under glycoprotein, water and certain temperature, when it leaves the environment of human body, is easy for inactivation, occurs cohesion rotten.And as many protein medicaments such as vaccine of medicinal application, though through inactivation treatment, storage request condition is harsh, made troubles for transport, preservation.The present invention is that hydrophobic polysaccharide is substituted to traditional vaccine protectant, proteic drugs is packaged in the center of polysaccharide shell, albumen is with hydrophobic polysaccharide under hydrogen bond and hydrophobicity effect; carry out bridge joint conjunction; when pH conditions change, this bridge joint closes disintegration, discharges protein exhibits drug action.As the hydrophobic polysaccharide for containing thing, into organism after can also be degraded in the presence of acid condition or enzyme and discharge protein and play pharmacological activity.Hydrophobic polysaccharide synthesized by the present invention, yet there are no information.
The content of the invention
First purpose of the present invention is to provide a kind of hydrophobic polysaccharide, and it is that, using succinic acid as linking arm, the succinic acid that end group is modified with dicyclohexylurea (DCU) is connected with ester bond with the hydroxyl of glucan to polysaccharide that the hydrophobic polysaccharide, which is,.The molecular weight of the hydrophobic polysaccharide is between 2K-50K.
The hydrophobic polysaccharide, with self-emulsifying, can individually carry medicine as emulsifying agent.
The step of second object of the present invention is to provide the preparation method of above-mentioned hydrophobic polysaccharide, the preparation method and the reaction mechanism mechanism of reaction are：
(1) glucan succinate is prepared：Glucan and succinic anhydride reaction are obtained into butyric acid glucan by catalyst of pyridine in the solution；
(2) hydrophobic polysaccharide is prepared：In a solvent, the butyric acid glucan is 20 according to weight ratio with dicyclohexylcarbodiimide: (1-10) reacts, and obtains the hydrophobic polysaccharide.
Preferably, the concrete operations of step (2) are：Weight ratio according to polysaccharide and dicyclohexylcarbodiimide is 20: (1-10) meter, the polysaccharide is dissolved in solvent, dicyclohexylcarbodiimide is added into the solvent, reacted under the conditions of 10-80 DEG C, water is added in the completely backward reaction solution of reaction, filtering removes dicyclohexylurea (DCU) solid and impurity, obtains filtrate, alcohols solvent is added into the filtrate and separates out solid, the solid is hydrophobization heparin.
Wherein, the solvent is dimethylformamide, dimethyl sulfoxide (DMSO) or dichloromethane.
The alcohols solvent is ethanol.
Third object of the present invention is to provide application of the above-mentioned hydrophobic polysaccharide as pharmaceutical carrier in medicine preparation.
Preferably, the hydrophobic polysaccharide is applied to the carrier separately as albumen, polypeptide and amino acids drug.
It is further preferred that the hydrophobic polysaccharide is particularly suitable for the carrier separately as vaccine type medication.Infection of the antigenic source of the vaccine in bacterium, virus, fungi and protozoon to animal, such as microorganism Influenza A types, Influenza Type Bs, hepatitis C virus, hepatitis A virus, hepatitis B virus, Rotavirus viruses, Cytomegalovirus：CMV viruses, RS viruses, pharynx conjunctiva heat, HIV, varicellazoster virus, the simple viral types of 1 type 2 of herpes, ATL (adult T cell leukemia) viruses, Coxsackie viruses, entero viruses, sudden dermexanthesis is viral (HHV-6), measles virus, rubella virus, the scorching virus of popular parotid gland, the acute scorching virus of grey white pulp, japanese encephalitis virus, hydrophobin, hepatitis C virus, Norwalk viruses, hydrophobin, RS viruses, Cytomegalovirus viruses, foot and mouth disease virus, infectious gastroenteritis virus, rubella virus, ATL viruses, adeno viruses, Echovirus, Herpes viruses, natural poxvirus, dengue fever fever viruses, yellow fever virus, West Nile virus, SARS (virus), Ebola hemorrhagic fever virus, Marburg hemorrhagic fever, Lassa fever viruses, Hantavirus, pathogenic virus such as Nipah virus infection etc.；The bacterium is the pathogenicity coliforms such as intestinal tube hemorrhagic coliform, staphylococcus aureus, meningitis bacterium, Pseudomonas aeruginosa, the chain coccus of worm tooth, Cholera bacterium, Typhus bacterium, Chlamydophila felis dysentery characterized by blood in the stool bacterium, pneumococcus, bacillus pertussis, Corynebacterium diphtheriae bacterium, tetanolysin, Influenza bacterium, pestis bacterium, botulinum bacterium, Bacillus anthracis charcoal ancient sacrificial utensil bacterium, hare germ, Salmonella bacterium, VRE (enterococcus), tulase, dysentery characterized by blood in the stool bacterium, Salmonella Typhi intestines bacterium, Salmonella Paratyphi A bacterium, Chlamydophila felis bacterium, Ameba dysentery characterized by blood in the stool, Legionella bacterium, Lyme borreliosis bacterium, the pathogenic bacterias such as brucellosis disease (undulant fever) bacterium；The Rickettsia such as Coxiella burnetii Q heat, Chlamydia；The protozoon classes such as malaria protozoon, Cryptosporidium Tyzzer；The proteantigen of the microorganisms such as the fungies such as cryptococcosisaspergillosis.Pathogenic microorganism proteantigen also includes amino acid, enzyme, hormone and immune regulator, and the molecular weight of these materials is not limited, can be between 100-100 ten thousand.
Fourth object of the present invention is to provide more than one and states the method that any hydrophobic polysaccharide prepares load powder for carrier：Camptothecine or camptothecin derivative are subjected to emulsification treatment with the hydrophobic polysaccharide in alkaline aqueous solution and produce load powder.
Preferably, the weight ratio of the vaccine and the hydrophobic polysaccharide is 1: 1-1: 20, preferably 1: 3-1: 10.
The present invention provides a kind of method for being prepared preferably by carrier of any of the above-described hydrophobic polysaccharide and carrying powder：It is 1: 3-1: 10 meters according to the weight ratio of camptothecine or camptothecin derivative and hydrophobic polysaccharide, first vaccine is dissolved in the alkali lye that pH value is 7.2-10, then hydrophobic polysaccharide is added, using mulser emulsification treatment until forming nano-particle under the conditions of 1-10 DEG C, obtain mixed solution, load powder is produced, particle is rounded, between 10-1000 nanometers of particle diameter.
Brief description of the drawings
The electron microscope image for the tetanus vaccine nano-particle particle in aqueous that Fig. 1 loads for hydrophobic polysaccharide described in embodiment 3.
Embodiment
Following examples are used to illustrate the present invention, but are not limited to the scope of the present invention.
The preparation method of the polysaccharide of embodiment 1
A kind of preparation method of polysaccharide, the preparation method is specially：Glucan 20g (dalton of molecular weight 2-50 ten thousand) is dissolved in 200ml dimethyl sulfoxide (DMSO)s, plus butanoic anhydride 10g, pyridine 2ml in room temperature reaction 4h, plus deionized water stopped reaction.Plus 2.54L ethanol.Static 3h, separates out precipitation, is refined again with ethanol, be dried under reduced pressure to obtain butyric acid polysaccharide.
The method that embodiment 2 prepares hydrophobic polysaccharide by raw material of polysaccharide
The butyric acid polysaccharide 200mg that embodiment 1 is prepared is dissolved in dimethyl sulfoxide (DMSO), plus dicyclohexylcarbodiimide 50mg, 1h is reacted under the conditions of 10 DEG C, after reaction completely, the 20ml aqueous solution is added into reaction solution, filtering removes DCU solids, dialysis, which is carried out, using 1000ml deionized waters goes the removal of impurity, dialyzate is obtained, 500ml ethanol is then added into the dialyzate, the material of precipitation is the hydrophobic polysaccharide.
Embodiment 3 carries the preparation of powder
The present embodiment provides the hydrophobic polysaccharide prepared using embodiment 2 as carrier, prepares the method for carrying powder, and methods described is：
40mg tetanus vaccines are dissolved in the 18mLpH9 NaOH aqueous solution, 80mg hydrophobic polysaccharides are added, in room temperature, emulsification 10min obtains mixed solution, produces the nano-particle for loading vaccine.This hydrophobic polysaccharide medicine-carried nano particles are rounded in alkaline aqueous solution, in polydispersion state.Fig. 1 loads the photo that tetanus vaccine nano-particle is taken under inverted microscope by hydrophobic polysaccharide.
Although above having used general explanation, embodiment and experiment, the present invention is described in detail, on the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to the scope of protection of present invention.
Claims (10)
1. a kind of hydrophobic polysaccharide, the hydrophobic polysaccharide is using succinic acid as linking arm and terminal carboxyl group is modified with dicyclohexylurea (DCU).
2. hydrophobic polysaccharide according to claim 1, it is characterised in that：The molecular weight of the hydrophobic polysaccharide is between 20K-500K.
3. prepare the method for the hydrophobic polysaccharide described in claim 1 or 2, it is characterised in that methods described comprises the following steps：
(1) butyric acid esterificated polysaccharide is prepared：Glucan is first reacted with succinic anhydride in a solvent, butyric acid esterificated polysaccharide or the reaction carried out with other dicarboxylic anhydrides is obtained；
(2) hydrophobic polysaccharide is prepared：In a solvent, the polysaccharide is 20 according to weight ratio with dicyclohexylcarbodiimide: (1-10) reacts, and obtains the hydrophobic polysaccharide.
4. preparation method according to claim 3, it is characterised in that：Before hydrophobic polysaccharide is prepared, first the polysaccharide is pre-processed, the pretreatment is：Polysaccharide is soluble in water, ion exchange column is crossed, using deionized water as eluent, eluent is collected, and alkali is added into salt into the eluent, it is dried under reduced pressure and produces after freezing；Preferably, the alkali is tri-n-butylamine.
5. the method according to claim 3 or 4, it is characterised in that：The concrete operations of step (2) are：The polysaccharide is dissolved in solvent, dicyclohexylcarbodiimide is added into the solvent, reacted under the conditions of 10-80 DEG C, water is added in the completely backward reaction solution of reaction, filtering removes dicyclohexylurea (DCU) solid and impurity, filtrate is obtained, alcohols solvent is added into the filtrate and separates out solid, the solid is hydrophobic polysaccharide；Preferably, the solvent is dimethylformamide, dimethyl sulfoxide (DMSO) or dichloromethane；Preferably, the alcohols solvent is ethanol.
6. application of the hydrophobic polysaccharide that any described preparation method of hydrophobic polysaccharide or claim 3-5 described in claim 1 or 2 is obtained as pharmaceutical carrier in medicine preparation, it is characterised in that：The medicine is amino acids, peptides, vaccine or protide.
7. a kind of hydrophobic polysaccharide with described in claim 1 or 2, or any described hydrophobic polysaccharides of claim 3-5 prepare the method for carrying powder for carrier, it is characterised in that：Methods described is：Vaccine is emulsified in the basic conditions with the hydrophobic polysaccharide, medicament-carried nano emulsion is obtained, the infection of the antigenic source of the vaccine in bacterium, virus, fungi and protozoon to animal.
8. method according to claim 7, it is characterised in that：The weight ratio of the vaccine type medication and the hydrophobic polysaccharide is 1: 1-1: 20, preferably 1: 4-1: 10.
9. the method according to claim 7 or 8, it is characterised in that：Methods described is：It is 1: 1-1: 10 meters according to the weight ratio of vaccine and hydrophobic polysaccharide, first vaccine is dissolved in the alkaline aqueous solution that pH value is 8-10, then add hydrophobic polysaccharide, use the processing of probe emulsifier until forming nano-particle under the conditions of 2-10 DEG C, mixed solution is obtained, corresponding antioxidant, preservative, antifreezing agent and amino acid etc. can also be added.
10. according to any described methods of claim 7-9, it is characterised in that：Described hydrophobic polysaccharide can also be prepared by raw material with low anticoagulant property heparin, starch, amylopectin, amylose, pulullan polysaccharide, ethoxy dextran, mannosan, levulan, synanthrin, chitin, chitosan, xyloglucan and water-soluble cellulose etc..
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