CN1813687A - Method for preparing tinidazole biological composite membrane - Google Patents
Method for preparing tinidazole biological composite membrane Download PDFInfo
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- CN1813687A CN1813687A CN 200510061683 CN200510061683A CN1813687A CN 1813687 A CN1813687 A CN 1813687A CN 200510061683 CN200510061683 CN 200510061683 CN 200510061683 A CN200510061683 A CN 200510061683A CN 1813687 A CN1813687 A CN 1813687A
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Abstract
The present invention relates to a preparation method of tinidazole biological complex membrane. Said preparation method includes the following steps: slowly adding 0.05-2.0% of sodium alginate solution into mixed aqueous solution of 0.01-2.0% of chitosan solution and 0.05-0.5% of tinidazole solution, the pH value of the described chitosan solution is 4-6, under the condition of stirring according to 150-5000 rpm making reaction for 30-60 min to obtain sodium alginate-chitosan gel beads, making centrifugal treatment, adding calcium chloride aqueous solution, stirring with 5000-10000 rpm and making reaction for 30-120 min, pouring the obtained mixed suspension into culture dish, drying in drying oven so as to obtain the invented tinidazole biological complex membrane.
Description
Technical field
The present invention relates to the Biodegradable high-molecular composite membrane, particularly relate to tinidazole biological composite membrane and preparation method.
Background technology
Tinidazole (Tinidazole, TNZ), chemical name: 1-[2 (ethylsulfonyl)-ethyl]-2-methyl-5-nitro imidazoles.Be the nitroimidazoles medicine of a new generation, the clinical infection that is mainly used in treatment and prevention anaerobism mattress.Compare with metronidazole, its characters function is stronger, onset is faster, distribute in the long half time, body wide, high, the better tolerance of curative effect, and common formulations is mainly based on tablet and infusion solution.But behind the systemic administration, still have comparatively serious digestive system and neural untoward reaction such as nauseating, vomiting, anorexia, stomachache.The patent of Song Cangsang (CN 1279945A) has been set forth tinidazole and stomach floating preparation adjuvant (being made up of carboxymethyl cellulose, hard ester acid, sodium bicarbonate, polyvidon) and has been mixed in proportion and is mixed with capsule, be used for digestion such as gastric ulcer shape treatment of diseases, can reduce every day, each dosage.By changing the pharmaceutical dosage form of tinidazole, place the part that the position of pathological changes is arranged, the untoward reaction that can avoid systemic administration to cause reduces poisonous side effect of medicine and dosage.Continually developed novel form such as membrane, suppository and the stick of the various patient's of being used for topical therapeutics in recent years, obtained the curative effect identical with tablet.The patent of Song Cangsang (CN 1278429A) has disclosed tinidazole behind beta-cyclodextrin inclusion compound agent enclose, forms vagina slowly-releasing suppository with the auxiliary shape agent mixed-forming again, and it is fast that its characteristics blood drug level reaches the peak, and duration of efficacy is long.The patent of Yuan Hui (CN 1559406A) has been invented one group of pharmaceutical preparation, and this pharmaceutical preparation is tinidazole beta-schardinger dextrin-or derivatives thereof clathrate, and gel, medicine membrane of oral cavity, compound recipe gargarism and stick etc. are arranged.In order further to improve curative effect, keep the valid density of local patholoic change position long period, seen at present about the relevant report of oral cavity with slow-release medicine-membrane research.Zhou Yanni (Chinese Hospitals pharmaceutical journal, 1999,19 (6), 368～369) is a principal agent with the tinidazole, and high molecular slow-release material polyvinyl alcohol, sodium carboxymethyl cellulose are carrier, make the matrix type sustained release film formulation, are used for the treatment of periodontitis, gingivitis.Wang Zhichao (Chinese biochemical drug magazine, 2003,24 (3), 144～145) is that filmogen prepares tinidazole chitosan tooth slow-release medicine-membrane with chitosan, carbopol, carboxymethyl cellulose.But slow-releasing system in the past is confined to blend, and medicine is not to be embedded in macromolecular structure inside, can not reach the purpose of sustained release, causes the medicine unnecessary loss, has limited the performance of curative effect simultaneously.Therefore need further improvement and perfect.
Summary of the invention
The object of the invention is to provide a kind of preparation method of tinidazole biological composite membrane.Pharmaceutical pack is embedded in the macromolecule network, improves the embedding rate of medicine, reach the purpose of sustained release tinidazole by regulating preparation condition and sodium alginate and chitosan proportioning.The preparation method of tinidazole biological composite membrane provided by the invention is as follows:
Composition of raw materials is formed: weight percentage % (w/w)
Tinidazole 0.05～0.5
Sodium alginate 0.05～2.0
Chitosan 0.01～2.0
Calcium chloride 0～1.0
Yu Weishui.
Sodium alginate soln with 0.05～2.0% slowly joins in the mixed aqueous solution of 0.01～2.0% chitosan solution and 0.05～0.5% tinidazole solution, the pH value of described chitosan solution is 4～6, after 1500-5000rpm stirs and reacts 30～60min down, obtain the sodium alginate-chitosan gel beads, in the mixture impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens, and skinning gets faint yellow tinidazole biological composite membrane.
The present invention above-mentioned obtain the sodium alginate-chitosan gel beads after, carry out centrifugal treating, add 0＜～1.0% calcium chloride water, after 5000～10000rpm stirs and reacts 30～120min down, in the mixing suspension impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens, obtains tinidazole biological composite membrane of the present invention.
Chitosan solution of the present invention contains 2% acetic acid.
Chitosan solution of the present invention is formulated by 2% acetic acid and acetone 1: 1 by volume.
Tinidazole solution of the present invention is formulated by acetone.
Technique effect of the present invention:
Because sodium alginate that is adopted and chitosan are the macromolecular materials of two kinds of difference bear electricity and positive electricity, carrier material self is charged, if in the tinidazole adding system with positively charged, can with the sodium alginate generation electrostatic interaction of bear electricity, along with sodium alginate and chitosan form polyelectrolyte, the tinidazole pharmaceutical pack is embedded in the macromolecule network, show good medicine carrying character, avoid the medicine unnecessary loss, reach the purpose of sustained release tinidazole medicine simultaneously.Add calcium chloride and can make carrier polymer further crosslinked, the tinidazole embedding rate further improves.
The tinidazole biological composite membrane that the present invention prepares is in pH=4～8 scopes, and it is lower to demonstrate water sucting degree, is suitable for the use of oral cavity partial diseased region and keeps composite membrane intensity constant; The tinidazole embedding rate reaches 30%～96%.The pH value by regulating chitosan aqueous solution or the ratio of sodium alginate and chitosan can be controlled the release of tinidazole.
The specific embodiment
Embodiment 1
Under high speed machine stirs, 1% (w/w) chitosan solution (containing 2% acetic acid) is slowly joined in the mixed solution of 1% (w/w) sodium alginate and 0.5% (w/w) tinidazole (formulated) by acetone, 1500-5000rpm stirs reaction 30～60min down, in the mixture impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens, skinning gets faint yellow tinidazole biological composite membrane.
Embodiment 2
Under high speed machine stirs, in 0.25% (w/w) sodium alginate aqueous solution, slowly add pH and be 4.0 0.25% (w/w) chitosan solution (solvent is formed by the configuration in 1: 1 by volume of 2% acetic acid and acetone) and the mixed solution of 0.5% (w/w) tinidazole acetone soln, stir reaction 30～60min down through 1500-5000rpm, obtain the sodium alginate-chitosan gel beads, centrifugal (rotating speed 3000rpm, 10min), the volumetric soiutions volume adds 0.07%CaCl again
2After 5000～10000rpm stirred and reacts 30～120min down, in the mixing suspension impouring culture dish with gained, it was dry to put into 20～50 ℃ of baking ovens, and skinning gets faint yellow tinidazole biological composite membrane.
Embodiment 3
Under high speed machine stirs, in 0.25% (w/w) sodium alginate aqueous solution, slowly add pH and be 5.0 0.25% (w/w) chitosan solution (solvent is formed by the configuration in 1: 1 by volume of 2% acetic acid and acetone) and the mixed solution of 0.5% (w/w) tinidazole acetone soln, stir reaction 30～60min down through 1500-5000rpm, obtain the sodium alginate-chitosan gel beads, centrifugal (rotating speed 3000rpm, 10min), the volumetric soiutions volume adds 0.07%CaCl again
2Behind vigorous stirring 30～120min, in the mixing suspension impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens again, and skinning gets faint yellow tinidazole biological composite membrane.
Embodiment 4
Under high speed machine stirs, in 0.25% (w/w) sodium alginate aqueous solution, slowly add pH and be 6.0 0.25% (w/w) chitosan solution (solvent is formed by the configuration in 1: 1 by volume of 2% acetic acid and acetone) and the mixed solution of 0.5% (w/w) tinidazole acetone soln, stir reaction 30～60min down through 1500-5000rpm, obtain the sodium alginate-chitosan gel beads, centrifugal (rotating speed 3000rpm, 10min), the volumetric soiutions volume adds 0.07%CaCl again
2Behind vigorous stirring 30～120min, in the mixing suspension impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens again, and skinning gets faint yellow tinidazole biological composite membrane.
Embodiment 5
Under high speed machine stirs, in 0.1% (w/w) sodium alginate aqueous solution, slowly add certain pH and be 6.0 0.25% (w/w) chitosan solution (solvent is formed by the configuration in 1: 1 by volume of 2% acetic acid and acetone) and the mixed solution of 0.5% (w/w) tinidazole acetone soln, stir reaction 30～60min down through 1500-5000rpm, obtain the sodium alginate-chitosan gel beads, centrifugal (rotating speed 3000rpm, 10min), the volumetric soiutions volume adds 0.07%CaCl again
2Behind vigorous stirring 30～120min, in the mixing suspension impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens again, and skinning gets faint yellow tinidazole biological composite membrane.
Embodiment 6
Under high speed machine stirs, in 0.4% (w/w) sodium alginate aqueous solution, slowly add pH and be 6.0 0.25% (w/w) chitosan solution (solvent is formed by the configuration in 1: 1 by volume of 2% acetic acid and acetone) and the mixed solution of 1mL 0.5% (w/v) tinidazole acetone soln, stir reaction 30～60min down through 1500-5000rpm, obtain the sodium alginate-chitosan gel beads, centrifugal (rotating speed 3000rpm, 10min), the volumetric soiutions volume adds 0.07%CaCl again
2Behind vigorous stirring 30～120min, in the mixing suspension impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens again, and skinning gets faint yellow tinidazole biological composite membrane.
Embodiment 7
Under high speed machine stirs, in 0.4% (w/w) sodium alginate aqueous solution, slowly add certain pH and be 6.0 0.1% (w/w) chitosan solution (solvent is formed by the configuration in 1: 1 by volume of 2% acetic acid and acetone) and the mixed solution of 0.5% (w/w) tinidazole acetone soln, stir reaction 30～60min down through 1500-5000rpm, obtain the sodium alginate-chitosan gel beads, centrifugal (rotating speed 3000rpm, 10min), the volumetric soiutions volume adds 0.07%CaCl again
2Behind vigorous stirring 30～120min, in the mixing suspension impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens again, and skinning gets faint yellow tinidazole biological composite membrane.
Embodiment 8
Under high speed machine stirs, in 0.4% (w/w) sodium alginate aqueous solution, slowly add certain pH and be 6.0 0.4% (w/v) chitosan solution (solvent is formed by the configuration in 1: 1 by volume of 2% acetic acid and acetone) and the mixed solution of 0.5% (w/w) tinidazole acetone soln, stir reaction 30～60min down through 1500-5000rpm, obtain the sodium alginate-chitosan gel beads, centrifugal (rotating speed 3000rpm, 10min), the volumetric soiutions volume adds 0.07%CaCl again
2Behind vigorous stirring 30～120min, in the mixing suspension impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens again, and skinning gets faint yellow tinidazole biological composite membrane.
Claims (5)
1, a kind of preparation method of tinidazole biological composite membrane is characterized in that: adopt tinidazole, and sodium alginate, chitosan, calcium chloride, water are raw material, and composition of raw materials is a weight percentage, and wherein the calcium chloride weight percentage is 0～1.0%, the steps include:
Sodium alginate soln with 0.05～2.0% slowly joins in the mixed aqueous solution of 0.01～2.0% chitosan solution and 0.05～0.5% tinidazole solution, the pH value of described chitosan solution is 4～6, after 1500-5000rpm stirs and reacts 30～60min down, obtain the sodium alginate-chitosan gel beads, in the mixture impouring culture dish with gained, it is dry to put into 20～50 ℃ of baking ovens, and skinning gets faint yellow tinidazole biological composite membrane.
2, according to the preparation method of the described tinidazole biological composite membrane of claim 1, it is characterized in that obtaining the sodium alginate-chitosan gel beads, centrifugal back, adding weight percentage are 0＜～1.0% calcium chloride water, after 5000～10000rpm stirs and reacts 30～120min down, the mixing suspension of gained is poured in the culture dish, it is dry to put into 20～50 ℃ of baking ovens of baking oven, obtains tinidazole biological composite membrane of the present invention.
3,, it is characterized in that described chitosan solution contains 2% acetic acid according to the preparation method of the described tinidazole biological composite membrane of claim 1.
4, according to the preparation method of the described tinidazole biological composite membrane of claim 1, it is characterized in that described chitosan solution, solvent is formulated by 2% acetic acid and acetone 1: 1 by volume.
5,, it is characterized in that described tinidazole solution is formulated by acetone according to the preparation method of the described tinidazole biological composite membrane of claim 1.
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| CN 200510061683 CN1813687A (en) | 2005-11-25 | 2005-11-25 | Method for preparing tinidazole biological composite membrane |
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| CN 200510061683 CN1813687A (en) | 2005-11-25 | 2005-11-25 | Method for preparing tinidazole biological composite membrane |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102511481A (en) * | 2011-12-14 | 2012-06-27 | 贵州省烟草科学研究所 | Method for embedding metalaxyl |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102511481A (en) * | 2011-12-14 | 2012-06-27 | 贵州省烟草科学研究所 | Method for embedding metalaxyl |
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