CN103126973B - Sugar water gel liquid emboliaztion agent for hemangioma cure and preparation method thereof - Google Patents
Sugar water gel liquid emboliaztion agent for hemangioma cure and preparation method thereof Download PDFInfo
- Publication number
- CN103126973B CN103126973B CN201310044084.4A CN201310044084A CN103126973B CN 103126973 B CN103126973 B CN 103126973B CN 201310044084 A CN201310044084 A CN 201310044084A CN 103126973 B CN103126973 B CN 103126973B
- Authority
- CN
- China
- Prior art keywords
- gellan gum
- agent
- emboliaztion
- hemangioma
- water gel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 33
- 239000007788 liquid Substances 0.000 title claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 201000011066 hemangioma Diseases 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 208000005189 Embolism Diseases 0.000 claims abstract description 57
- 229920002148 Gellan gum Polymers 0.000 claims abstract description 52
- 239000000216 gellan gum Substances 0.000 claims abstract description 50
- 235000010492 gellan gum Nutrition 0.000 claims abstract description 50
- 150000004676 glycans Chemical class 0.000 claims abstract description 13
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 13
- 239000005017 polysaccharide Substances 0.000 claims abstract description 13
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 208000001435 Thromboembolism Diseases 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 22
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- -1 dimethyl sulfoxine Chemical compound 0.000 claims description 10
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 10
- 238000011161 development Methods 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 4
- 239000012279 sodium borohydride Substances 0.000 claims description 4
- 229920005654 Sephadex Polymers 0.000 claims description 3
- 239000012507 Sephadex™ Substances 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 3
- 239000012535 impurity Substances 0.000 claims description 3
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 claims description 3
- 229960001025 iohexol Drugs 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 abstract description 34
- 239000000463 material Substances 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 8
- 208000007536 Thrombosis Diseases 0.000 abstract description 5
- 238000007254 oxidation reaction Methods 0.000 abstract description 4
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 abstract 2
- 230000001939 inductive effect Effects 0.000 abstract 1
- 229910052751 metal Inorganic materials 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- 239000000829 suppository Substances 0.000 description 31
- 238000002474 experimental method Methods 0.000 description 29
- 238000000034 method Methods 0.000 description 19
- 206010002329 Aneurysm Diseases 0.000 description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000012530 fluid Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 239000001301 oxygen Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 230000017531 blood circulation Effects 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 238000010276 construction Methods 0.000 description 7
- 239000003292 glue Substances 0.000 description 7
- 230000010102 embolization Effects 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 210000001367 artery Anatomy 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229920000219 Ethylene vinyl alcohol Polymers 0.000 description 3
- 238000002583 angiography Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- JJJFUHOGVZWXNQ-UHFFFAOYSA-N enbucrilate Chemical compound CCCCOC(=O)C(=C)C#N JJJFUHOGVZWXNQ-UHFFFAOYSA-N 0.000 description 2
- UFRKOOWSQGXVKV-UHFFFAOYSA-N ethene;ethenol Chemical compound C=C.OC=C UFRKOOWSQGXVKV-UHFFFAOYSA-N 0.000 description 2
- 239000004715 ethylene vinyl alcohol Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920002239 polyacrylonitrile Polymers 0.000 description 2
- 238000002601 radiography Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000001732 thrombotic effect Effects 0.000 description 2
- 101100165177 Caenorhabditis elegans bath-15 gene Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 208000036828 Device occlusion Diseases 0.000 description 1
- 102100038285 Endogenous retroviral envelope protein HEMO Human genes 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101001033183 Homo sapiens Endogenous retroviral envelope protein HEMO Proteins 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 206010025219 Lymphangioma Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 208000034541 Rare lymphatic malformation Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 208000031320 Teratogenesis Diseases 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000010109 chemoembolization Effects 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000002697 interventional radiology Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229920006163 vinyl copolymer Polymers 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a sugar water gel liquid emboliaztion agent for hemangioma cure. The sugar water gel liquid emboliaztion agent for hemangioma cure comprises that an effective embolism component is natural polysaccharide gellan gum, a developing component is metal tantalum powder and a solvent component is organic solvent dimethyl sulfoxide. The natural polysaccharide gellan gum is processed by oxidation of sugar chain cutting technology. The invention further discloses a preparation method of the sugar water gel liquid emboliaztion agent. According to the sugar water gel liquid emboliaztion agent for hemangioma cure and the preparation method of the sugar water gel liquid emboliaztion agent, an embolism condition is groped, the technical problems that the effective embolism and inducing thrombosis are formed in a tumor cavity range and a far-end drifting is prevented under the condition that auxiliary materials of sacculus, a support frame and the like are not needed are solved. The natural polysaccharide gellan gum in the embolism component plays a role in good biology compatibility and promoting the forming of the thrombosis. Requirements that the ideal liquid emboliaztion agent should be provided are met, thus a good embolism effect and high safety are achieved.
Description
Technical field
The invention belongs to biological pharmacy technical field, relate to a kind of sugar water gel liquid emboliaztion agent for hemangioma cure and preparation method thereof.
Background technology
Hemangioma comprises aneurysm, phlebangioma and lymphangioma, can betide multiple body parts such as intracranial, liver, lower limb, and its incidence rate increases with the age and increases, and has larger harm.For the common disease of this neurosurgery of entocranial artery hemangioma, after aneurysm rupture, subarachnoid hemorrhage can be caused.The first Rupture haemorrhag mortality rate of aneurysm is about 30-40%, and the mortality rate that again breaks can reach 60%.The unique method of traditional treatment adopts surgery operation of opening cranium folder to close aneurysm.But the shortcoming of surgery operation of opening cranium is fairly obvious: 1, the Proportion of patients that can undergo surgery is limited: or because of age, the health person of being not suitable for, or the repeatedly higher person of SAH, HH classification, or has vasospasm person, and operation risk is all very big; 2, surgical clamp is closed has very large blind area: be difficult to close to or cannot carry out folder completely close for Posterior circle or giant aneurysm etc.; 3, surgical rehabilitation is slow, and relapse rate is high, brings painful large to patient.And recent two decades comes, along with reaching its maturity of intravascular Interventional Treatment, increasing doctor starts to select this low-risk, Micro trauma, and effectively makes up the new method of operative treatment blind area.At present, all do not needed to adopt operation of opening cranium in the aneurysm of European countries 80% and only used intervention embolization.
The basic skills being used as interventional therapy mainly contains three kinds: can shirk sacculus, Detachable coil (GDC), and liquid embolizing agent.Can be difficult to some the aneurysm that surgical clips closes by the sacculus reinstated the earliest and carry out thromboembolism, but its defect also clearly: 1, thromboembolism can not be carried out for tumor shape, easily cause aneurysm rupture; 2, sacculus easily bounces back, necessary filling silicone fluid or firming agent (HEMO) in it; 3, sacculus and delivery conduit pliability poor, be difficult to operation.The current GDC having obtained domestic and international clinical practice then has two larger technical restrictions: 1, GDC compression is recurred with aneurysm, and can cause the pressure symptom of brain essence or cranial nerve, and this is at wide neck and more often occur greatly or in giant aneurysm; 2, GDC metal material has any biological inert, and in tumor, thrombosis is not easily formed.The treatment principle of liquid embolizing agent is the contacting blood by entering tumor chamber and tumor chamber, and the rapid disperse of solvent, embolization material is condensed into solid thromboembolism aneurysm within very short time.Compared with above two kinds of methods, liquid embolizing agent has easy flowing, easy to control, many irreplaceable advantages such as good biocompatibility, the advanced subject be developed in order to interventional radiology of a suitable liquid embolic material.
A kind of desirable liquid embolizing agent should possess following condition: 1, good biocompatibility; 2, can effective blood vessel embolism be produced and bring out thrombosis; 3, nontoxic, without teratogenesis, carcinogenesis; 4, low concentration, low viscosity, easy to control, easily by the conduit of different size; 5, can develop under x-ray; 6, distally do not drift about after entering tumor chamber.The intravascular fluid embolism materials of experiment and Clinical practice is various in style in recent years, report that more is BCA (NBCA), cellulose acetate polymer (cellulose acetate polymer, CAP), polypropylene cyanogen (polyacrylonitrile, PAN), ethylene and vinyl alcohol polymer EVAL(ethylene vinyl copolymer) and EVOH(ethylene vinyl alcohol copolymer) several.The shortcomings such as the application shortcoming of these materials is also clearly: as NBCA has adhesiveness, easily make microtubular and blood vessel adhesion, and each thromboembolism focus amount is few; Traditional CAP solution does not well solve the technical barrier controlling the drift of tumor intracavity far-end.Liquid embolizing agent ONYX the most ripe at present, be then the following vinyl alcohol copolymer (EVOH) be main, also there is the problem of uncontrollable tumor intracavity far-end drift, in the imported product of clinical practice, then have employed to solve at the parent artery placement shutoff sacculus of aneurysm eck, both increase cost like this, introduce new foreign body in vivo again.In addition, all these materials all adopt the polymer of synthetic, part is conventional industrial chemicals, and its biocompatibility and biological absorbable degree are very unclear, and this all greatly limit such for human body, the range of application especially contacting blood vessel and the liquid embolizing agent in intracranial use.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of sugar water gel liquid emboliaztion agent for hemangioma treated by transcatheter arterial chemoembolization, the application of this sugar water gel liquid emboliaztion agent can stop far-end drift also can form effective thromboembolism preferably within the scope of tumor chamber, bring out thrombosis in without the need to the auxiliary material such as sacculus, support situation, and has fabulous biocompatibility with body.
Sugar water gel liquid emboliaztion agent for hemangioma cure of the present invention, comprises effective thromboembolism composition gellan gum and solvent composition dimethyl sulfoxine; The molecular weight 10-60 ten thousand of described effective thromboembolism composition gellan gum, preferred 25-35 ten thousand.
Of the present invention in the sugar water gel liquid emboliaztion agent of hemangioma cure, in every 10 milliliters of dimethyl sulfoxines, containing effective thromboembolism composition gellan gum 0.18-0.28 gram.
Preferably, in every 10 milliliters of dimethyl sulfoxines, also contain development composition as any X-ray contrast agent, preferable alloy tantalum powder or iohexol 8-12 milligram.
A kind of preparation method of the sugar water gel liquid emboliaztion agent for hemangioma cure of the present invention, comprises the steps:
(1) be oxidized sugar chain cutting natural polysaccharide gellan gum: get natural polysaccharide gellan gum, heating obtained aqueous solution, add oxidizing agent sodium periodate cutting sugar chain, and the effective thromboembolism composition gellan gum after must cutting after adopting sodium borohydride reduction;
(2) liquid embolizing agent preparation: under non-aqueous sterile operating condition, take the gellan gum after cutting, uniform dissolution is in organic solvent dimethyl sulfoxine, and after cooling, cold preservation is for subsequent use.
The another kind of preparation method of the sugar water gel liquid emboliaztion agent for hemangioma cure of the present invention, comprises the steps:
(1) sugar chain cutting natural polysaccharide gellan gum is oxidized: get natural polysaccharide gellan gum, be heated to 40-80
oc prepares transparent homogeneous aqueous solution, add oxidizing agent sodium periodate reactant aqueous solution after 10-80 hour, add glycol reaction 10-60 minute again, after sodium borohydride reduction, obtain effective thromboembolism composition gellan gum sample, sample is crossed the remove impurity of Sephadex G25 SEC chromatographic column, obtain the effective thromboembolism composition gellan gum after cutting;
(2) liquid embolizing agent preparation: under non-aqueous sterile operating condition, take the gellan gum after cutting, uniform dissolution is in organic solvent dimethyl sulfoxine, and add development composition tantalum powder after cooling, after dissolving, cold preservation is for subsequent use.
Preferably, in described step (1), it is for subsequent use that the effective thromboembolism composition gellan gum after gained cutting is lyophilized into powder; In described step (1), add oxidizing agent sodium periodate reactant aqueous solution 12-48 hour.
Preferably, in described step (2), the gellan gum after cutting is heated to 30 ° of C-40 ° of C and is dissolved in organic solvent dimethyl sulfoxine.
The method of described step (1) oxidation sugar chain cutting natural polysaccharide gellan gum can refer to 1. Gong et al., Journal of Materials Chemistry 2009; 19:1925; And 2. Ameer et al., Journal of Orthopaedic Research 2002; 20:16.
In the present invention, the natural polysaccharide gellan gum (gellan gum) of one of effective thromboembolism composition, is antibacterial
pseudomonas elodeaproduce, through the natural polysaccharide that FDA (Food and Drug Adminstration) (FDA) approval uses.Commercial product comprises the Phytagel of Sigma Aldrich Company.The monosaccharide component of gellan gum is bimolecular D-Glucose, the L-rhamnose of a part, and the D-glucuronic acid of a part.Large quantity research shows, gellan gum has fabulous gelling performance and biocompatibility, is developed as the host material for becoming Bone Defect Repari, medicine transmission and organizational project by domestic and international multiple seminar.
Composition advantage of the present invention is very significant: gellan gum is as the main component of suppository, and plastic character and the viscosity of utilization itself on the one hand serve thromboembolism effect; On the other hand due to the mechanism of its absorption calcium ion, facilitate the process of blood coagulation.In addition gellan gum also possesses the function supporting Various Tissues Growth of Cells, achieves many things at one stroke.Whole suppository containing the polymer of any synthetic, biocompatibility and biological degradability high.
The present invention by groping thromboembolism condition, on the one hand, solves well and stops far-end to drift about in without the need to the auxiliary material such as sacculus, support situation and within the scope of tumor chamber, form effective thromboembolism and bring out thrombotic technical barrier; On the other hand, the natural polysaccharide glue in thromboembolism composition, has fabulous biocompatibility and short thrombotic effect.The present invention meets the condition that a desirable liquid embolizing agent should possess, and reaches the safety of better effect of embolization and Geng Gao.
Accompanying drawing explanation
Fig. 1 is the video surveillance figure of the thromboembolism of thromboembolism model experiment when starting;
Fig. 2 is the ongoing video surveillance figure of thromboembolism of thromboembolism model experiment;
Fig. 3 is the video surveillance figure of the thromboembolism of thromboembolism model experiment when completing;
Detailed description of the invention
Provide embodiment below to be specifically described the present invention; what be necessary to herein means out is that following examples are only used to further illustrate the present invention; simply should not be interpreted as limiting the scope of the invention, the those of ordinary skill in this field must belong to protection scope of the present invention based on flesh and blood of the present invention to the replacement of the unsubstantiality that the present invention makes and adjustment.
embodiment 1(the sugar chain oxygen cutting of gellan gum)
Take 8 grams of commercial gellan gum Phytagel, be scattered in 1L deionized water solution, maintain 75 ± 0.5
oc heats 2 hours to obtain transparent and homogeneous solution.Cool and maintain 45
oc.Add 0.4M sodium metaperiodate aqueous solution 5 ml, after reacting 1,6,12,24,48,72,96 hour respectively under uniform stirring, then within 30 minutes, stop oxidation reaction with glycol reaction and spend the night with the sodium borohydride reduction of 0.1M, obtaining the sample of different degree of oxidation.Sephadex G25 chromatographic column crossed by sample, removes the micromolecule of impurity or fracture.By the gellan gum lyophilizing of gained oxygen cutting, compare with unreacted gellan gum original, the intrinsic viscosity of employing automatic viscometer mensuration [
], and adopt Kuhn-Mark-Houwink Equation for Calculating molecular weight of product.The results are shown in Table 1.
Product viscosity after table 1. sugar chain oxygen cutting and molecular weight
embodiment 2(preparation of liquid embolizing agent)
Under aseptic technique, take the gellan gum sterling after oxygen cutting, heat and remain on 50
oc-60
oc, magnetic agitation makes it to be dissolved in organic solvent dimethyl sulfoxine completely.Be cooled to room temperature, add development composition tantalum powder, again stir, be fully formed to transparent uniform solution.After the thromboembolism principle of liquid embolizing agent is contact aqueous phase, the rapid disperse of dimethyl sulfoxine, effective embolization material is condensed into solid within very short time, and the whole process therefore operated avoids suppository to contact with water or aqueous phase solution.After liquid embolizing agent preparation, cold preservation is in 4
oc refrigerator, uses front 37
oc heating in water bath 15 minutes.
contrast model experiment 1
Model is made up of three parts: parent artery, aneurysm and heart.The silica gel tube that parent artery is 3mm by internal diameter is simulated, and aneurysm is simulated by the made ball-type cavity of the silica gel tube of 4mm, and the blood-pumping function of heart is simulated by water pump, and " blood vessel " inner blood is simulated by normal saline.Parent artery and aneurysm are embedded in curved groove that veneer carves.
The building method of model is: the internal diameter that first clip 1.6 cm is long is the silica gel tube of 4mm, puts into and makes it to expand, by the taking-up of steel ball from segment silica gel tube after cooling, then sealed other end, become tumor chamber with the steel ball of internal diameter 5mm after burning heat; At internal diameter be 3mm silica gel tube on cut an osculum, coincide tumor chamber opening with it adhesion, but will reserve duct entry.Water flowing leak detection in pipe after several minutes.Water pump provides normal saline in pipe to keep the pressure of flowing, requires that flow velocity is at 280ml/more than min.
According to method obtaining liq suppository described in embodiment 2, but do not use the gellan gum of oxygen cutting, and use gellan gum original.Containing gellan gum 0.10 gram in the every 10 milliliters of dimethyl sulfoxines of consumption test, 0.01 gram, tantalum powder.Adopt 1.7F interposing catheter to test, gellan gum is rapid plastic in conduit, and 37
oc cannot inject.
contrast model experiment 2
Model construction is with model experiment 1.
According to method obtaining liq suppository described in embodiment 2, consumption is containing the oxygen cutting gellan gum of 12 hours 0.10 gram in every 10 milliliters of dimethyl sulfoxines, 0.01 gram, tantalum powder.
Carry out thromboembolism experiment in a model.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, and injecting fluid suppository can promote, and mobility is not good, and its contact " blood " after fixing is good.The blocking of solidification rear tube.
contrast model experiment 3
Model construction is with model experiment 1.
According to method obtaining liq suppository described in embodiment 2, consumption is containing the oxygen cutting gellan gum of 24 hours 0.10 gram in every 10 milliliters of dimethyl sulfoxines, 0.01 gram, tantalum powder.
Carry out thromboembolism experiment in a model.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, injecting fluid suppository, can promotion and mobility good, solidify immediately after its contact " blood ", quilt " blood flow " washes away and far-end drift phenomenon occurs.
contrast model experiment 4
Model construction is with model experiment 1.
According to method obtaining liq suppository described in embodiment 2, consumption is containing the oxygen cutting gellan gum of 24 hours 0.15 gram in every 10 milliliters of dimethyl sulfoxines, 0.01 gram, tantalum powder.
Carry out external thromboembolism experiment in a model.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, injecting fluid suppository, can promotion and mobility good, solidify immediately after its contact " blood ", quilt " blood flow " washes away and far-end drift phenomenon occurs.
contrast model experiment 5
Model construction is with model experiment 1.
According to method obtaining liq suppository described in embodiment 2, consumption is containing the oxygen cutting gellan gum of 24 hours 0.30 gram in every 10 milliliters of dimethyl sulfoxines, 0.01 gram, tantalum powder.
Carry out external thromboembolism experiment in a model.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, injecting fluid suppository, and initial 0.3-0.4 ml suppository can pass through conduit smoothly, and promote slowly afterwards, suppository glue mobility is not good, has the phenomenon of adhesion conduit.Continue to promote suppository, after its contact " blood " 10-15 second, catheter blockage occurs.
model experiment 6
Model construction is with model experiment 1.
According to method obtaining liq suppository described in embodiment 2, consumption is containing the oxygen cutting gellan gum of 24 hours 0.25 gram in every 10 milliliters of dimethyl sulfoxines, 0.005 gram, tantalum powder.
Carry out external thromboembolism experiment in a model.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, and " blood flow " fills in " tumor chamber ".Injecting fluid suppository, suppository glue can promotion and mobility good, contact " blood " after solidify within the 30-40 s time.
Open DSA digital subtraction angiography to monitor, carry out thromboembolism experiment.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, and " blood flow " fills in " tumor chamber ".Start injecting fluid suppository, development effect is clear not.Initial injection stage definition still can.Judge that injection fillers degree is comparatively difficult.
model experiment 7
Model construction is with model experiment 1.
According to method obtaining liq suppository described in embodiment 2, consumption is containing the oxygen cutting gellan gum of 24 hours 0.25 gram in every 10 milliliters of dimethyl sulfoxines, 0.01 gram, tantalum powder.
Carry out thromboembolism experiment in a model.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, and " blood flow " fills in " tumor chamber ".Injecting fluid suppository, suppository glue can promotion and mobility good, contact " blood " after solidify within the 30-40s time.
Open DSA digital subtraction angiography to monitor, carry out thromboembolism experiment.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, and " blood flow " fills in " tumor chamber ".Start injecting fluid suppository, development effect is clear, suppository glue can promotion good with mobility, bleach completely within the 20-45s time after contacting " blood ".The routine hemangioma model of thromboembolism 20 altogether, each example is all selected to exit microtubular after thromboembolism 80% cavity, exits process rapid, the adhesion of duct free mouth, and the drift of no-load tumor arterial distal or suppository ooze out into endovascular event and occur.Close radiography after thromboembolism to monitor, observe " tumor chamber " full colloid, touch hardness moderate, " tumor chamber " mouth is without thread residual.This result shows, in external model, the effect of embolization of experimental example of the present invention is desirable.Video surveillance process as shown in Figure 1, Figure 2 and Figure 3.Fig. 1 conduit puts in place, and thromboembolism starts; Fig. 2 thromboembolism carries out, clearness of catheter, and solidification is good, without bad phenomenon such as drifts; Fig. 3 thromboembolism completes, and thromboembolism result is good, exit noresidue.
model experiment 8
Model construction is with model experiment 1.
According to method obtaining liq suppository described in embodiment 2, consumption is containing the oxygen cutting gellan gum of 24 hours 0.20 gram in every 10 milliliters of dimethyl sulfoxines, iohexol 0.01 gram.
Carry out thromboembolism experiment in a model.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, and " blood flow " fills in " tumor chamber ".Injecting fluid suppository, suppository glue can promotion and mobility good, contact " blood " after solidify within the 30-40s time.
Open DSA digital subtraction angiography to monitor, carry out thromboembolism experiment.1.7F conduit is inserted tumor chamber, and open current, test speed is 300ml/min, and " blood flow " fills in " tumor chamber ".Start injecting fluid suppository, development effect is clear, suppository glue can promotion good with mobility, bleach completely within the 20-45s time after contacting " blood ".The routine hemangioma model of thromboembolism 20 altogether, each example is all selected to exit microtubular after thromboembolism 80% cavity, exits process rapid, the adhesion of duct free mouth, and the drift of no-load tumor arterial distal or suppository ooze out into endovascular event and occur.Close radiography after thromboembolism to monitor, observe " tumor chamber " full colloid, touch hardness moderate, " tumor chamber " mouth is without thread residual.This result shows, in external model, the effect of embolization of experimental example of the present invention is desirable.
Claims (4)
1., for a sugar water gel liquid emboliaztion agent for hemangioma cure, comprise effective thromboembolism composition gellan gum and solvent composition dimethyl sulfoxine; The molecular weight 25-35 ten thousand of described effective thromboembolism composition gellan gum; In every 10 milliliters of dimethyl sulfoxines, containing effective thromboembolism composition gellan gum 0.18-0.28 gram, containing development multicomponent metallic tantalum powder or iohexol 8-12 milligram.
2. described in claim 1 for the preparation method of the sugar water gel liquid emboliaztion agent of hemangioma cure, it is characterized in that, comprise the steps:
(1) sugar chain cutting natural polysaccharide gellan gum is oxidized: get natural polysaccharide gellan gum, be heated to 40-80
oc prepares transparent homogeneous aqueous solution, add oxidizing agent sodium periodate reactant aqueous solution after 20-30 hour, add glycol reaction 10-60 minute again, after sodium borohydride reduction, obtain effective thromboembolism composition gellan gum sample, sample is crossed the remove impurity of Sephadex G25 chromatographic column, obtain the effective thromboembolism composition gellan gum after cutting;
(2) liquid embolizing agent preparation: under non-aqueous sterile operating condition, take the gellan gum after cutting, uniform dissolution, in organic solvent dimethyl sulfoxine, adds development composition after cooling, after dissolving, cold preservation is for subsequent use.
3. as claimed in claim 2 for the preparation method of the sugar water gel liquid emboliaztion agent of hemangioma cure, it is characterized in that, in described step (1), it is for subsequent use that the effective thromboembolism composition gellan gum after gained cutting is lyophilized into powder.
4., as claimed in claim 2 for the preparation method of the sugar water gel liquid emboliaztion agent of hemangioma cure, it is characterized in that, in described step (2), the gellan gum after cutting is heated to 30 ° of C-60 ° of C and is dissolved in organic solvent dimethyl sulfoxine.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310044084.4A CN103126973B (en) | 2013-02-01 | 2013-02-01 | Sugar water gel liquid emboliaztion agent for hemangioma cure and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310044084.4A CN103126973B (en) | 2013-02-01 | 2013-02-01 | Sugar water gel liquid emboliaztion agent for hemangioma cure and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103126973A CN103126973A (en) | 2013-06-05 |
CN103126973B true CN103126973B (en) | 2015-02-18 |
Family
ID=48487855
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310044084.4A Expired - Fee Related CN103126973B (en) | 2013-02-01 | 2013-02-01 | Sugar water gel liquid emboliaztion agent for hemangioma cure and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103126973B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP4061438A4 (en) * | 2019-11-20 | 2024-01-10 | The Regents of the University of California | LIQUID EMBOLIC MATERIAL COMPOSITION |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2909236T3 (en) * | 2016-11-16 | 2022-05-05 | Persica Pharmaceuticals Ltd | Antibiotic formulations for low back pain |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1192654A (en) * | 1995-07-27 | 1998-09-09 | 微治疗公司 | Novel embolizing compositions |
-
2013
- 2013-02-01 CN CN201310044084.4A patent/CN103126973B/en not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1192654A (en) * | 1995-07-27 | 1998-09-09 | 微治疗公司 | Novel embolizing compositions |
Non-Patent Citations (1)
Title |
---|
Yihong Gong,et al.An improved injectable polysaccharide hydrogel:modified gellan gum for long-term cartilage regeneration in vitro.《Journal of Materials Chemistry》.2009,第19卷(第14期),第1968页左栏第2段-第1969页左栏第3段,Table 1. * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP4061438A4 (en) * | 2019-11-20 | 2024-01-10 | The Regents of the University of California | LIQUID EMBOLIC MATERIAL COMPOSITION |
Also Published As
Publication number | Publication date |
---|---|
CN103126973A (en) | 2013-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5580568A (en) | Cellulose diacetate compositions for use in embolizing blood vessels | |
JP3356447B2 (en) | Vascular lesion embolic material composed of dried polymer gel | |
US9844597B2 (en) | Biocompatible in situ hydrogel | |
US20130211249A1 (en) | Drug eluting hydrogels for catheter delivery | |
JPS63281660A (en) | Closure forming composition and its use | |
CN102266591A (en) | Novel liquid embolic material based on collagen and preparation method thereof | |
CN106176292A (en) | A kind of biodegradable injection molding process decorative material and preparation method thereof | |
US7374568B2 (en) | Methods for embolizing aneurysmal sites with a high viscosity embolizing composition | |
CN111840265B (en) | Ethanol hardener and application thereof | |
CN103126973B (en) | Sugar water gel liquid emboliaztion agent for hemangioma cure and preparation method thereof | |
JP4817088B2 (en) | Embolization material | |
CN109044555A (en) | Intervention method establishes after dog autologous blood clots embolic cerebral infarction thrombolysis intracranial hemorrhage transformation model and its application | |
CN102100933B (en) | Embolic material composition and preparation method thereof | |
CN107550879A (en) | A kind of preparation method of gelfoam drug bearing microsphere | |
CN101999952A (en) | Polycaprolactone (PCL) and polylactic acid (PLA) human body absorbable vascular stent and preparation method thereof | |
CN102618954B (en) | Human serum albumin nano biomaterial and preparation method thereof | |
CN1634119A (en) | Liquid embolic agent for intracranial aneurysm and preparation method thereof | |
Chen et al. | Preparation of a modified silk-based gel/microsphere composite as a potential hepatic arterial embolization agent | |
CN109998621B (en) | Micro-plugging device for cerebral aneurysm | |
US20010022962A1 (en) | Cellulose diacetate compositions for use in embolizing blood vessels | |
JP2021164568A (en) | Preparation method of embolization substance, embolization substance and embolization substance preparation kit | |
Geutjes et al. | Preparation and characterization of injectable fibrillar type I collagen and evaluation for pseudoaneurysm treatment in a pig model | |
CN109431554A (en) | A kind of interventional medicine I-shaped closer of vascular puncture mouth and preparation method thereof | |
JPH0617312B2 (en) | Vascular blocker | |
Lin et al. | Clinical outcome observation of the embolization of orbital vascular malformation with medical glue under direct intra-operative view |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20170511 Address after: 230088, Hefei province high tech Zone Innovation Avenue 2800, innovation industry park two, E District 1, B, building 2, Anhui Patentee after: HEFEI SHUOJIAN PHARMACEUTICAL TECHNOLOGY CO.,LTD. Address before: 230088 No. 26, phreatic East Road, hi tech Zone, Anhui, Hefei Patentee before: ANHUI SIZHENG MEDICAL TECHNOLOGY Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150218 Termination date: 20220201 |
|
CF01 | Termination of patent right due to non-payment of annual fee |