CN101676000A - Preparation method of hyaluronic acid-chitosan biomembrane - Google Patents
Preparation method of hyaluronic acid-chitosan biomembrane Download PDFInfo
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- CN101676000A CN101676000A CN200810200147A CN200810200147A CN101676000A CN 101676000 A CN101676000 A CN 101676000A CN 200810200147 A CN200810200147 A CN 200810200147A CN 200810200147 A CN200810200147 A CN 200810200147A CN 101676000 A CN101676000 A CN 101676000A
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Abstract
The invention provides a preparation method of a hyaluronic acid-chitosan biomembrane, wherein the biomembrane, which contains hyaluronic acid and carboxymethyl shitosan, is prepared by the crosslinking reaction of hyaluronic acid, carboxymethyl shitosan and polyvinyl alcohol in the presence of a crosslinking agent. The hyaluronic acid-chitosan biomembrane of the invention has good biological compatibility and longer half-life, and is favorable to improve the success rate of the glaucoma filtration operation and widely popularize the non - penetrating trabecular operation.
Description
Technical field
The present invention relates to a kind of preparation method of hyaluronic acid-chitosan biomembrane.
Background technology
Hyaluronic acid (Hyaluronic Acid is called for short HA) gel is widely used in fields such as ophthalmology, orthopaedics, gynecological surgery, plastic surgery, and it is in the history of clinical existing more than ten years, and its safety and effectiveness have obtained the generally approval of medical science all circles.Natural ectogenic hyaluronan molecule amount is greatly about 100,000～5,000,000 Dalton, and retention time in vivo about about 3～15 days, has limited its application in some field greatly to a great extent.
Chitosan is that biosphere is only second to cellulosic second largest class polysaccharide, research has both at home and abroad confirmed that chitosan has bioadhesive and multiple biological activity, comprise that chitosan can promote epithelial growth, suppress fibroblasts proliferation, the propagation that suppresses tumor cell, suppress microbial growths such as antibacterial, promote to organize the multiple effects such as reparation of wound surface.
Glaucoma is the irreversibility diseases causing blindness of China first place, and operation is still the first-selected strategy of China's glaucoma quality.But because the wound healing mechanism that biological event has, the scarring that filters passage behind the glaucoma operation is the successful biggest obstacle of operation for glaucoma treatment.In recent years at the designed new operation of primary open angle glaucoma---the non-trabeculectomy associating SK glue that penetrates is implanted in and has obtained clinically using widely, wherein the effect of mechanical support filtration passage has been played in the implantation of SK glue, SK glue composition is a cross-linking hyaluronic acid sodium, early stage behind filtration surgery, kept the filtration passage, because continue flowing of aqueous humor, also delay to a certain extent and suppressed growth of fibroblasts, improved success rate of operation.
Cross-linked hyaluronic acid gel is the cross-linking products of hyaluronic acid and cross-linking agent, have excellent biological compatibility and good biodegradability, according to the above-mentioned character of cross-linked hyaluronic acid gel, be applied to that anti, osteoarthrosis are lubricated, fields such as medicament slow release preparation and tissue filling agent.
Summary of the invention
The preparation method that the purpose of this invention is to provide a kind of hyaluronic acid one chitosan biomembrane is to overcome the above-mentioned defective that prior art exists.
Method of the present invention comprises the steps:
(1) get purification good aseptic pyrogen-free hyaluronic acid, carboxymethyl chitosan, polyvinyl alcohol, three's mass ratio is 7-8: 1-2: 1-2, and is soluble in water;
(2) add cross-linking agent butanediol diglycidyl ether solution by calculating good amount, stir.
(3) salivation method film.
(4) dry in the vacuum desiccator.
(5) after film was done, sterile razor blade was cut into small pieces.
(6) aseptic packaging, the time spent is placed in the PBS buffer of pH7.4 soaks.
Said hyaluronic molecular weight is 1,000,000～3,000,000 dalton;
In the hyaluronic acid solution, the concentration of cross-linking agent is 0.0002～0.02g/mL;
Said cross-linking agent is selected from having the chemical compound of 2 above functional groups, carboxyl, hydroxyl, acetylamino isoreactivity functional group reactions that its functional group can be had with hyaluronan molecule and the functional group that forms covalent bond;
Preferably, said cross-linking agent is more than one in epoxide, aldehyde, diglycidyl ether or the divinyl sulfone etc., consider cross-linking agent to the side effect of human body and in conjunction with the LD50 index, most preferably toxicity less 1,4-butanediol diglycidyl ether (BDDE).
Among the present invention, the use amount of cross-linking agent is not particularly limited, but consider the organism adaptability of cross-linked hyaluronic acid gel, preferentially select for use a small amount of as far as possible cross-linking agent to carry out cross-linking reaction, the concentration of cross-linking agent in mixture is preferably 0.0002～0.02g/mL;
The hyaluronic acid of being washed is the straight chain polymer polysaccharide that disaccharidase unit forms by N-n acetylglucosamine n-D-glucuronic acid, comprises hyaluronate sodium, hyaluronic acid magnesium or calcium hyauronate etc.;
Among the present invention, the hyaluronic acid raw material select for use the bacterial fermentation method produce or tissue extraction all can, for reducing antigenicity, preferentially select bacterial fermentation method raw material for use, adopt as hyaluronic acid and fermenting and producing thereof are summarized the method for (Guo Xue equality);
The present invention utilizes the biological nature of hyaluronic acid and chitosan, synthetic hyaluronic acid-chitosan biomembrane, this biomembrane had both had the mechanical support effect of external product SK glue at the filtration surgery passage, has simultaneously the effect that suppresses fibroblast proliferation again, and the prices of raw and semifnished materials are cheap, product cost is significantly less than external imported product, will help the raising of glaucoma filtration surgery success rate and the extensive popularization of Non Penetrating Trabecular Surgery (NPTS) and carry out, and can reduce patient's medical expense.
The specific embodiment
Below provide embodiments of the invention, further the present invention is described in detail, but the present invention is not limited to this.
Embodiment 1
Get purification good aseptic pyrogen-free hyaluronic acid 2g, carboxymethyl chitosan 0.25g, polyvinyl alcohol 0.25g, soluble in water;
Add cross-linking agent butanediol diglycidyl ether 1% solution 6.5ml, add water to 100ml, stir.
The salivation method film.
Dry in the vacuum desiccator.
After film was done, sterile razor blade was cut into small pieces.
Aseptic packaging, the time spent is placed in the PBS buffer of pH7.4 soaks.
Embodiment 2
Get purification good aseptic pyrogen-free hyaluronic acid 1.5g, carboxymethyl chitosan 0.15g, polyvinyl alcohol 0.15g, soluble in water;
Add cross-linking agent butanediol diglycidyl ether 1% solution 5ml, add water to 100ml, stir.
The salivation method film.
Dry in the vacuum desiccator.
After film was done, sterile razor blade was cut into small pieces.
Aseptic packaging, the time spent is placed in the PBS buffer of pH7.4 soaks.
Embodiment 3
Embodiment 2
Get purification good aseptic pyrogen-free hyaluronic acid 2g, carboxymethyl chitosan 0.15g, polyvinyl alcohol 0.15g, soluble in water;
Add cross-linking agent butanediol diglycidyl ether 1% solution 5ml, add water to 100ml, stir.
The salivation method film.
Dry in the vacuum desiccator.
After film was done, sterile razor blade was cut into small pieces.
Aseptic packaging, the time spent is placed in the PBS buffer of pH7.4 soaks.
Claims (8)
1. the preparation method of a hyaluronic acid-chitosan biomembrane is characterized in that, comprises the steps:
(1) get purification good aseptic pyrogen-free hyaluronic acid, carboxymethyl chitosan, polyvinyl alcohol, three's mass ratio is 8: 1: 1, and is soluble in water;
(2) add cross-linking agent butanediol diglycidyl ether solution by calculating good amount, stir.
(3) salivation method film.
(4) dry in the vacuum desiccator.
(5) after film was done, sterile razor blade was cut into small pieces.
(6) aseptic packaging, the time spent is placed in the PBS buffer of pH7.4 soaks.
2. method according to claim 1 is characterized in that, said hyaluronic molecular weight is 1,500,000～3,000,000 dalton.
3. method according to claim 1 is characterized in that, in the hyaluronic acid solution, the concentration of cross-linking agent is 0.0002～0.02g/mL.
4. method according to claim 1 is characterized in that, said cross-linking agent is 1, the 4-butanediol diglycidyl ether.
5. method according to claim 1 is characterized in that, the concentration of cross-linking agent in mixture is 0.0002～0.02g/mL.
6. according to each described method of claim 1～6, it is characterized in that, select the hyaluronic acid of bacterial fermentation method production or the hyaluronic acid of tissue extraction for use.
7. according to each described method of claim 1～6, it is characterized in that hyaluronic acid is hyaluronate sodium, hyaluronic acid magnesium or calcium hyauronate.
8. according to the cross-linked hyaluronic acid gel of each described method preparation of claim 1～8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810200147A CN101676000A (en) | 2008-09-19 | 2008-09-19 | Preparation method of hyaluronic acid-chitosan biomembrane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810200147A CN101676000A (en) | 2008-09-19 | 2008-09-19 | Preparation method of hyaluronic acid-chitosan biomembrane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101676000A true CN101676000A (en) | 2010-03-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810200147A Withdrawn CN101676000A (en) | 2008-09-19 | 2008-09-19 | Preparation method of hyaluronic acid-chitosan biomembrane |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014032780A1 (en) | 2012-08-28 | 2014-03-06 | University Of Geneva | Hybrid hydrogels |
| CN110314252A (en) * | 2019-05-22 | 2019-10-11 | 嘉兴市爵拓科技有限公司 | Collagen Implant is preparing the purposes in operation for glaucoma auxiliary reconstruction |
| WO2022246922A1 (en) * | 2021-05-27 | 2022-12-01 | 江南大学 | Microgel, preparation method therefor, and application thereof |
-
2008
- 2008-09-19 CN CN200810200147A patent/CN101676000A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014032780A1 (en) | 2012-08-28 | 2014-03-06 | University Of Geneva | Hybrid hydrogels |
| CN110314252A (en) * | 2019-05-22 | 2019-10-11 | 嘉兴市爵拓科技有限公司 | Collagen Implant is preparing the purposes in operation for glaucoma auxiliary reconstruction |
| WO2022246922A1 (en) * | 2021-05-27 | 2022-12-01 | 江南大学 | Microgel, preparation method therefor, and application thereof |
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| PB01 | Publication | ||
| C04 | Withdrawal of patent application after publication (patent law 2001) | ||
| WW01 | Invention patent application withdrawn after publication |
Open date: 20100324 |