CN104436317A - Method for preparing biodegradable high polymer material for preventing postoperative adhesion - Google Patents
Method for preparing biodegradable high polymer material for preventing postoperative adhesion Download PDFInfo
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- CN104436317A CN104436317A CN201410623782.4A CN201410623782A CN104436317A CN 104436317 A CN104436317 A CN 104436317A CN 201410623782 A CN201410623782 A CN 201410623782A CN 104436317 A CN104436317 A CN 104436317A
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Abstract
The invention discloses a method for preparing a biodegradable high polymer material for preventing postoperative adhesion. The biodegradable high polymer material is prepared by the following steps: adding a cross-linking agent to 0.5-3% of a sodium hyaluronate solution, carrying out a cross-linking reaction at 0-90 DEG C, dialyzing mixed liquid in water after the reaction, mixing the dialyzed solution with 0.2-3% of a water-soluble chitosan solution at the ratio of (2-8) to 1 by volume, reacting for 0.5-3h while stirring and drying reaction mixed liquid to obtain the biodegradable high polymer material. The biodegradable high polymer material disclosed by the invention has the following beneficial effects: besides excellent physical and chemical properties, the self-cross-linked biodegradable material disclosed by the invention is also reliable in biological safety and effectiveness. On the basis of GB13886-series standards, the cytotoxicity of the self-cross-linked biodegradable material produced by the method disclosed by the invention is 1-grade, and the biodegradable material is free from sensitization and intracutaneous irritation, free from genetic toxicity and compatible with blood. Preclinical animal experiments show that the self-cross-linked biodegradable material can be used for effectively preventing adhesion in a rat abdominal wall defect model.
Description
Technical field
The present invention relates to a kind of macromolecular material, particularly a kind of method of degraded macromolecular material.
Background technology
Adhesion is surgical operation, particularly the ubiquitous problem of abdominal postoperative, and tissue adhesion can cause serious complication, and such as, in abdominal operation, adhesion may cause the diseases such as intestinal obstruction, infertility and chronic pelvic pain.At present, conventional adherence preventing material comprises polylactic acid, hyaluronate sodium, chitosan, chitosan, collagen protein etc.Wherein, hyaluronate sodium is proved the generation that can reduce abdominal operation posterior synechiae, is therefore a kind of material of desirable prevention of postoperative adhesion.
Summary of the invention
For existing technical deficiency, the invention provides a kind of method of degraded macromolecular material.
To achieve these goals, the technical solution used in the present invention: for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, cross-linking agent is added in the sodium hyaluronate solution of 0.5%-3%, cross-linking reaction is there is in 0 DEG C-90 DEG C, in water, mixed liquor is dialysed after reaction terminates, solution after dialysis mixes by the volume ratio of 2-8:1 with the water-soluble chitosan solution of 0.2%-3%, react 0.5-3h under stirring condition, namely reaction mixture drying obtains Biodegradable polymer material; Wherein, the mol ratio of cross-linking agent and hyaluronate sodium is 1:2-13, and described cross-linking agent includes but not limited to the chloro-N-pyridiniujm of water-soluble carbodiimide, 2-.
Described water-soluble carbodiimide includes but not limited to dicyclohexylcarbodiimide, 1-(3-dimethylamino amyl group)-3-ethyl-carbodiimide hydrochloride; Described 2-chloro-N-pyridiniujm includes but not limited to 2-chloro-N-dococylpyridinium salt iodide, the chloro-1-methyl pyridinium iodide of 2-.
The molecular weight of described hyaluronate sodium is 15-220 ten thousand dalton, and the molecular weight of water-soluble chitosan is 1-120 ten thousand dalton.
The time of cross-linking reaction is 5-20h.
Dry method is lyophilization and/or vacuum drying.
Cryodesiccated condition is :-5 DEG C ~-40 DEG C freezing 1 ~ 5h, then in 5 DEG C ~ 40 DEG C drying 15 ~ 24h.
Vacuum drying condition is: 30 DEG C ~ 45 DEG C vacuum drying 15 ~ 24h.
Dialysis uses distilled water deionized water or pure water.
Rotating speed during stirring is 245rpm ~ 450rpm.
The Biodegradable polymer material for prevention of postoperative adhesion that according to any one of claim 1-9 prepared by method.
Beneficial effect of the present invention: except good physicochemical property, the self-crosslinking degradable biomaterial that the present invention relates to, also has reliable biological safety and effectiveness.According to GB13886 series standard, the cytotoxicity of the self-crosslinking degradable biomaterial that the inventive method is produced is 1 grade, stimulates, hereditary-less toxicity, and and blood compatibility without sensitization and Intradermal.Preclinical animal studies shows, self-crosslinking degradable biomaterial effectively can prevent the generation of adhesion in rat abdominal-wall defect model.
Detailed description of the invention:
Embodiment 1: for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, cross-linking agent is added in the sodium hyaluronate solution of 0.5%, cross-linking reaction is there is in 40 DEG C, in water, mixed liquor is dialysed after reaction terminates, solution after dialysis with 1% water-soluble chitosan solution mix by the volume ratio of 2:1, react 0.5h under stirring condition, namely reaction mixture drying obtains Biodegradable polymer material;
Wherein, the mol ratio of cross-linking agent and hyaluronate sodium is 1:2, and described cross-linking agent includes but not limited to the chloro-N-pyridiniujm of water-soluble carbodiimide, 2-.
Described water-soluble carbodiimide includes but not limited to dicyclohexylcarbodiimide, 1-(3-dimethylamino amyl group)-3-ethyl-carbodiimide hydrochloride; Described 2-chloro-N-pyridiniujm includes but not limited to 2-chloro-N-dococylpyridinium salt iodide, the chloro-1-methyl pyridinium iodide of 2-.
The molecular weight of described hyaluronate sodium is 220,000 dalton, and the molecular weight of water-soluble chitosan is 120,000 dalton.
The time of cross-linking reaction is 5h.
Dry method is lyophilization and/or vacuum drying.
Cryodesiccated condition is :-25 DEG C of freezing 1 ~ h, then in 20 DEG C of dry 15h.
Vacuum drying condition is: 35 DEG C of vacuum drying 15h.
Dialysis uses distilled water deionized water or pure water.
Rotating speed during stirring is 300rpm.
The Biodegradable polymer material for prevention of postoperative adhesion that according to any one of claim 1-9 prepared by method.
Embodiment 2: for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, cross-linking agent is added in the sodium hyaluronate solution of 3%, cross-linking reaction is there is in 90 DEG C, in water, mixed liquor is dialysed after reaction terminates, solution after dialysis with 3% water-soluble chitosan solution mix by the volume ratio of 8:1, react 3h under stirring condition, namely reaction mixture drying obtains Biodegradable polymer material; Wherein, the mol ratio of cross-linking agent and hyaluronate sodium is 1:13, and described cross-linking agent includes but not limited to the chloro-N-pyridiniujm of water-soluble carbodiimide, 2-.
Described water-soluble carbodiimide includes but not limited to dicyclohexylcarbodiimide, 1-(3-dimethylamino amyl group)-3-ethyl-carbodiimide hydrochloride; Described 2-chloro-N-pyridiniujm includes but not limited to 2-chloro-N-dococylpyridinium salt iodide, the chloro-1-methyl pyridinium iodide of 2-.
The molecular weight of described hyaluronate sodium is 2,200,000 dalton, and the molecular weight of water-soluble chitosan is 1,200,000 dalton.
The time of cross-linking reaction is 20h.
Dry method is lyophilization and/or vacuum drying.
Cryodesiccated condition is :-40 DEG C of freezing 5h, then in 40 DEG C of dry 24h.
Vacuum drying condition is: 45 DEG C of vacuum drying 24h.
Dialysis uses distilled water deionized water or pure water.
Rotating speed during stirring is 450rpm.
Claims (10)
1. for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, cross-linking agent is added in the sodium hyaluronate solution of 0.5%-3%, cross-linking reaction is there is in 0 DEG C-90 DEG C, in water, mixed liquor is dialysed after reaction terminates, solution after dialysis mixes by the volume ratio of 2-8:1 with the water-soluble chitosan solution of 0.2%-3%, reacts 0.5-3h under stirring condition, and namely reaction mixture drying obtains Biodegradable polymer material; Wherein, the mol ratio of cross-linking agent and hyaluronate sodium is 1:2-13, and described cross-linking agent includes but not limited to the chloro-N-pyridiniujm of water-soluble carbodiimide, 2-.
2. according to claim 1 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, described water-soluble carbodiimide includes but not limited to dicyclohexylcarbodiimide, 1-(3-dimethylamino amyl group)-3-ethyl-carbodiimide hydrochloride; Described 2-chloro-N-pyridiniujm includes but not limited to 2-chloro-N-dococylpyridinium salt iodide, the chloro-1-methyl pyridinium iodide of 2-.
3. according to claim 1 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, the molecular weight of described hyaluronate sodium is 15-220 ten thousand dalton, and the molecular weight of water-soluble chitosan is 1-120 ten thousand dalton.
4. according to claim 1 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, the time of cross-linking reaction is 5-20h.
5. according to claim 1 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, dry method is lyophilization and/or vacuum drying.
6. according to claim 5 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, cryodesiccated condition is :-5 DEG C ~-40 DEG C freezing 1 ~ 5h, then in 5 DEG C ~ 40 DEG C drying 15 ~ 24h.
7. according to claim 5 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, vacuum drying condition is: 30 DEG C ~ 45 DEG C vacuum drying 15 ~ 24h.
8. according to claim 1 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, dialysis uses distilled water deionized water or pure water.
9. according to claim 1 for the preparation of the method for the Biodegradable polymer material of prevention of postoperative adhesion, it is characterized in that, rotating speed during stirring is 245rpm ~ 450rpm.
10. according to any one of claim 1-9 for the preparation of the Biodegradable polymer material for prevention of postoperative adhesion prepared by the Biodegradable polymer material method of prevention of postoperative adhesion.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410623782.4A CN104436317A (en) | 2014-11-06 | 2014-11-06 | Method for preparing biodegradable high polymer material for preventing postoperative adhesion |
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| CN201410623782.4A CN104436317A (en) | 2014-11-06 | 2014-11-06 | Method for preparing biodegradable high polymer material for preventing postoperative adhesion |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265127A (en) * | 2016-08-24 | 2017-01-04 | 杭州美库生物技术有限公司 | A kind of micro-self-crosslinking hyaluronic acid lyophilized powder and preparation method thereof |
| CN108264581A (en) * | 2017-02-20 | 2018-07-10 | 上海昊海生物科技股份有限公司 | A kind of self-crosslinking Sodium Hyaluronate and preparation method thereof |
| JP2019019201A (en) * | 2017-07-14 | 2019-02-07 | キユーピー株式会社 | Crosslinked hyaluronic acid and manufacturing method therefor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007083870A1 (en) * | 2006-01-19 | 2007-07-26 | Seoul National University Of Technology Center For Industry Collaboration | Chitosan or hyaluronic acid-poly(ethylene oxide)- and chitosan-hyaluronic acid-poly(ethylene oxide)-based hydrogel and manufacturing method therefor |
| CN101537205A (en) * | 2009-04-10 | 2009-09-23 | 暨南大学 | Degradable medical hemostatic non-viscous material and preparation method thereof |
| CN103800947A (en) * | 2014-01-16 | 2014-05-21 | 北京大清生物技术有限公司 | Biodegradable macromolecular material for preventing postoperative adhesion and preparation method thereof |
-
2014
- 2014-11-06 CN CN201410623782.4A patent/CN104436317A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007083870A1 (en) * | 2006-01-19 | 2007-07-26 | Seoul National University Of Technology Center For Industry Collaboration | Chitosan or hyaluronic acid-poly(ethylene oxide)- and chitosan-hyaluronic acid-poly(ethylene oxide)-based hydrogel and manufacturing method therefor |
| CN101537205A (en) * | 2009-04-10 | 2009-09-23 | 暨南大学 | Degradable medical hemostatic non-viscous material and preparation method thereof |
| CN103800947A (en) * | 2014-01-16 | 2014-05-21 | 北京大清生物技术有限公司 | Biodegradable macromolecular material for preventing postoperative adhesion and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265127A (en) * | 2016-08-24 | 2017-01-04 | 杭州美库生物技术有限公司 | A kind of micro-self-crosslinking hyaluronic acid lyophilized powder and preparation method thereof |
| CN108264581A (en) * | 2017-02-20 | 2018-07-10 | 上海昊海生物科技股份有限公司 | A kind of self-crosslinking Sodium Hyaluronate and preparation method thereof |
| JP2019019201A (en) * | 2017-07-14 | 2019-02-07 | キユーピー株式会社 | Crosslinked hyaluronic acid and manufacturing method therefor |
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