CN113813395A - Sustained-release tablet and preparation method thereof - Google Patents
Sustained-release tablet and preparation method thereof Download PDFInfo
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- CN113813395A CN113813395A CN202111093627.2A CN202111093627A CN113813395A CN 113813395 A CN113813395 A CN 113813395A CN 202111093627 A CN202111093627 A CN 202111093627A CN 113813395 A CN113813395 A CN 113813395A
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- vinyl caprolactam
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- 239000007939 sustained release tablet Substances 0.000 title claims description 5
- JWYVGKFDLWWQJX-UHFFFAOYSA-N 1-ethenylazepan-2-one Chemical compound C=CN1CCCCCC1=O JWYVGKFDLWWQJX-UHFFFAOYSA-N 0.000 claims abstract description 49
- 229920001661 Chitosan Polymers 0.000 claims abstract description 40
- 229960001592 paclitaxel Drugs 0.000 claims abstract description 35
- 229930012538 Paclitaxel Natural products 0.000 claims abstract description 21
- 238000013268 sustained release Methods 0.000 claims abstract description 21
- 239000012730 sustained-release form Substances 0.000 claims abstract description 21
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims abstract description 21
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6953—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a fibre, a textile, a slab or a sheet
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
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Abstract
本发明公开一种缓释膜片及其制备方法，属于缓释膜片制备技术领域。本发明所述方法包括壳聚糖(CTS)的纯化，然后依次制备聚N‑乙烯基己内酰胺(PNVCL)、聚N‑乙烯基己内酰胺接枝壳聚糖(PNVCL‑g‑CS)、聚N‑乙烯基己内酰胺接枝壳聚糖羧基(PNVCL‑g‑CS‑COOH)，聚N‑乙烯基己内酰胺接枝壳聚糖‑紫杉醇(PNVCL‑g‑CS‑PTX)，聚N‑乙烯基己内酰胺接枝壳聚糖‑紫杉醇(PNVCL‑g‑CS‑PTX)缓释膜片；本发明所述方法制备步骤简单、产物可靠，所得到的产品紫杉醇载药量大，并可通过改变水溶液环境的温度进行可控的药物释放量同时，本发明产品合成的原料的蛋白质含量极低，将来可以安全应用于人体。The invention discloses a sustained-release film and a preparation method thereof, and belongs to the technical field of sustained-release film preparation. The method of the invention comprises the steps of purifying chitosan (CTS), and then preparing poly-N-vinyl caprolactam (PNVCL), poly-N-vinyl caprolactam-grafted chitosan (PNVCL-g-CS), poly-N-vinyl caprolactam in sequence Vinyl caprolactam grafted chitosan carboxyl group (PNVCL‑g‑CS‑COOH), polyN‑vinyl caprolactam grafted chitosan‑paclitaxel (PNVCL‑g‑CS‑PTX), polyN‑vinyl caprolactam grafted Chitosan-paclitaxel (PNVCL-g-CS-PTX) sustained-release film; the method of the invention has simple preparation steps, reliable products, and the obtained product has a large drug-loading capacity of paclitaxel, and can be carried out by changing the temperature of the aqueous solution environment. At the same time, the drug release amount is controllable, and the protein content of the raw material synthesized by the product of the present invention is extremely low, which can be safely applied to the human body in the future.
Description
Technical Field
The invention relates to a sustained-release membrane and a preparation method thereof, belonging to the technical field of sustained-release membrane preparation.
Background
Benign Biliary Stricture (BBS) refers to scarring narrowing of the biliary lumen caused by injury to the bile duct and recurrent cholangitis, which can be caused by a variety of injury conditions. The affected bile duct is stimulated by repeated chronic inflammation and bile salt, which causes fibrous tissue hyperplasia, thickening of the duct wall and narrowing of the duct cavity, and further causes the pathological and clinical manifestations of biliary obstruction and infection. In recent years, the incidence of BBS has been on the rise with the popularization of biliary surgery, the popularization of endoscopic techniques, and the development of liver transplantation. It has been reported that the restenosis rate after biliary repair is as high as 60%. The clinical treatment of BBS is always a great problem to the biliary tract surgeons, once it occurs, it not only causes great trauma and pain to the mind and body of the patient, but also brings high treatment cost, and increases the economic burden of the family of the patient. Therefore, the research on how to effectively prevent and treat BBS formation and reduce restenosis rate is always a research hotspot and difficulty of hepatobiliary pancreas surgery, and has great clinical significance.
Clinical treatment methods for benign biliary stricture are numerous, surgical operation is still the gold standard of treatment, but secondary stricture can still occur after biliary repair, obstructive jaundice, cholestatic cirrhosis and complications difficult to correct are caused, and finally the life of a patient is threatened. At present, paclitaxel can be used for treating various tumors clinically, and has good quality effects in the aspects of treating coronary artery stenosis and scleroderma by using a stent, preventing postoperative scar formation of glaucoma and the like. But the clinical popularization and application of the paclitaxel are limited due to the defects of poor water solubility of the paclitaxel, toxic and side effects of the cosolvent and the like. Therefore, the development of a new drug delivery system and the improvement of a drug delivery mode to improve the efficiency and avoid adverse reactions become research hotspots in the field of drug sustained release. Therefore, the invention prepares a new sustained-release material, and avoids adverse reactions caused by using the paclitaxel.
Disclosure of Invention
The invention aims to provide a sustained-release membrane, which has the following structural formula:
the invention also aims to provide a preparation method of the sustained-release membrane, which comprises the following steps:
(1) purification of Chitosan (CTS):
adding chitosan into sodium hydroxide (NaOH) solution, stirring at 70 deg.C for 3 hr to decolorize and deproteinize, vacuum-filtering with vacuum pump after reaction, separating solid and liquid, repeatedly washing solid with distilled water, neutralizing, and freeze drying to obtain purified chitosan.
(2) Preparation of poly N-vinylcaprolactam (PNVCL):
and (3) putting the N-vinyl caprolactam (NVCL) reagent into a reactor, and distilling at 60-70 ℃ under reduced pressure to remove the stabilizer in the N-vinyl caprolactam (NVCL).
Adding 15g of stabilizer-removed N-vinyl caprolactam (NVCL) into a reactor, sequentially adding 0.06g of Azobisisobutyronitrile (AIBN) and 0.5g of a chain transfer agent, stirring and reacting for 12-14h in an oil bath kettle at 65-70 ℃ under the protection of nitrogen, stirring to obtain a yellow substance, adding tetrahydrofuran, stirring and dissolving, dripping a dropper into a beaker filled with sufficient petroleum ether for coprecipitation, generating a white flocculent precipitate after dripping, fully standing, sucking supernatant liquid of the standing solution to obtain a solid, dissolving with water after the solvent is volatilized, dialyzing for 72h in a dialysis bag, and freeze-drying to obtain the poly-N-vinyl caprolactam (PNVCL).
(3) Preparation of Poly N-vinyl caprolactam grafted Chitosan (PNVCL-g-CS):
dissolving 0.5g of chitosan in 100mL of 1% acetic acid solution, stirring uniformly, and adding 5mL of deionized water solution in which 0.2g of poly N-vinyl caprolactam grafted chitosan (PNVCL-g-CS) is dissolved; 0.4g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and 0.2g N-hydroxysuccinimide (NHS) were dissolved in 5mL of deionized water and added dropwise to the reaction mixture, and the reaction was stirred at room temperature for 24 hours; dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain the product.
(4) Preparation of Poly N-vinyl caprolactam grafted Chitosan carboxyl (PNVCL-g-CS-COOH):
fully dissolving poly N-vinyl caprolactam grafted chitosan (PNVCL-g-CS) powder in deionized water to obtain a poly N-vinyl caprolactam grafted chitosan (PNVCL-g-CS) solution with the concentration of 0.1g/mL, pouring the solution into a reactor, adding a dimethyl sulfoxide (DMSO) solution of 0.2g/mL succinic anhydride, and stirring at room temperature for reaction for 24 hours. Dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain the product.
(5) Preparation of poly-N-vinylcaprolactam-grafted chitosan-paclitaxel (PNVCL-g-CS-PTX):
fully dissolving poly N-vinyl caprolactam grafted chitosan carboxyl (PNVCL-g-CS-COOH) in deionized water, and then adding paclitaxel; after stirring uniformly, 4-Dimethylaminopyridine (DMAP) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) were added to the mixture and the mixture was stirred at room temperature for reaction for 48 hours. Dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain the product.
(6) Preparation of poly N-vinyl caprolactam grafted chitosan-paclitaxel (PNVCL-g-CS-PTX) sustained-release membrane:
fully dissolving the poly N-vinyl caprolactam grafted chitosan-paclitaxel (PNVCL-g-CS-PTX) prepared in the step (5) in distilled water, evenly dividing the solution into four parts, adding 1, 4-butanediol glycidyl ether serving as a crosslinking agent, and performing crosslinking according to the weight ratio of the poly N-vinyl caprolactam grafted chitosan-paclitaxel (PNVCL-g-CS-PTX): adding 1, 4-butanediol diglycidyl ether (BDDGE) as a crosslinking agent into the BDDGE at a molar ratio of 20: 1-80: 1, and stirring at room temperature for reaction for 3 hours; dialyzing the four groups of reaction liquid with distilled water for 48h after the reaction is finished, fixing the volume of the dialyzate to 20mL after the dialysis is finished, respectively adding 1 drop of glycerol, stirring for 30-60min, adding the liquid into a polytetrafluoroethylene mold, and drying the mold in a 50 ℃ drying oven to form a film; thus obtaining the drug sustained-release membrane.
In the step (1), the concentration of the NaOH solution is 0.03-0.04 g/mL, and the addition amount of the chitosan is 0.2 g/mL.
In the step (2), the mass percent of the dilute hydrochloric acid is 1 percent, and the concentration of the sodium hydroxide solution is 1 mol/L.
The invention has the beneficial effects that:
(1) the poly-N-vinyl caprolactam (PNVCL) is a polymer with temperature-sensitive characteristic, when the PNVCL is put into an aqueous solution with physiological temperature (32-38 ℃), the phase change can occur, and the PNVCL has the characteristics of non-ionicity, biodegradability, no toxicity and good biocompatibility; in addition, unlike most polyacrylamide polymers, PNVCL does not produce toxic small molecule amine compounds after hydrolysis, which makes PNVCL a class of polymers suitable for biomedical in vivo applications.
(2) The invention prepares a macromolecule carrier poly N-vinyl caprolactam grafting chitosan (PNVCL-g-CS), the PNVCL-g-CS is soluble in water, has satisfactory physicochemical properties and biological characteristics, such as good histocompatibility, no harm to human body by the metabolite after hydrolysis, complete biodegradation, no toxicity, capability of being absorbed by human body, hemostasis, promotion of tissue repair, inhibition of proliferation of connective tissue and reduction of the formation of narrow scar.
(3) The invention adopts hydrophobic Paclitaxel (PTX) as a drug, grafts chitosan carboxyl (PNVCL-g-CS-COOH) with modified polymer carrier poly N-vinyl caprolactam to generate esterification covalent bonding to form poly N-vinyl caprolactam grafted chitosan-paclitaxel (PNVCL-g-CS-PTX) polymer as a polymer of the polymer, and the polymer is dried in a polytetrafluoroethylene mould to form a film. The membrane can obviously improve the water solubility of hydrophobic drug Paclitaxel (PTX) in-vitro water solution, maintain the stability of the drug effect, and slowly, continuously and stably release the drug Paclitaxel (PTX) when the temperature of the water solution is 32-38 ℃.
(4) The Paclitaxel (PTX) local drug sustained-release technology related in the membrane can be applied to the treatment of benign biliary tract scar stenosis forming parts, lung, liver, pancreas, gastrointestinal tract and other malignant tumors of thoracic cavity and abdominal cavity, obviously reduces the systemic toxic reaction of Paclitaxel (PTX) and a dissolution assisting compound thereof, can reduce the risk of re-operation due to restenosis after Benign Biliary Stricture (BBS) operation, can reduce the frequency and single dose of late cancer chemotherapy, and obviously relieves the psychological and economic pressure of patients and families thereof.
(5) The invention focuses on the problem of Benign Biliary Stricture (BBS), an internal hotspot and troublesome biliary tract surgery, invents a practical novel polymer hydrophobic drug sustained-release membrane poly-N-vinyl caprolactam grafted chitosan-paclitaxel (PNVCL-g-CS-PTX) sustained-release membrane by adopting a method of organic chemical synthesis, and has good in-vitro release performance. At present, a high-molecular drug polymer formed after esterification reaction of hydrophobic drug Paclitaxel (PTX) and modified temperature-sensitive chitosan derivative poly N-vinyl caprolactam grafting chitosan carboxyl (PNVCL-g-CS-COOH) is dried into a membrane, and the local drug slow release system can prevent Benign Biliary Stricture (BBS) from forming, thereby providing a new treatment method and a certain theoretical basis for clinical prevention and treatment of Benign Biliary Stricture (BBS).
(6) The preparation method has simple steps and reliable product, the obtained product paclitaxel has large drug-loading rate, and the controllable drug release amount can be carried out by changing the temperature of the aqueous solution environment.
Drawings
FIG. 1 shows the synthesis scheme of PNVCL-CS-PTX.
Detailed Description
The present invention is further described in detail with reference to the following specific examples, but the scope of the present invention is not limited to the above description.
The experimental reagents used in the examples of the present invention were: (Chitosan (CS viscosity 100-. Except for special instructions, the reagents used in the invention are all commercially available analytical grade.
Example 1
The preparation method of the sustained-release membrane of the embodiment specifically comprises the following steps:
(1) purification of Chitosan (CTS):
adding chitosan into NaOH solution, stirring at 70 deg.C for 3 hr for decolorizing and deproteinizing, vacuum filtering with vacuum pump after reaction, separating solid and liquid, washing solid with distilled water repeatedly, neutralizing, and freeze drying to obtain purified chitosan;
(2) preparation of poly N-vinylcaprolactam (PNVCL):
NVCL (N-vinyl caprolactam) reagent was placed in a flask and distilled at 70 ℃ under reduced pressure to remove the stabilizer inside the NVCL.
Adding 15g of NVCL without a stabilizer into a flask, sequentially adding 0.06g of AIBN and 0.5g of a chain transfer agent, stirring and reacting for 12 hours in an oil bath kettle at 70 ℃ under the protection of nitrogen, stirring to obtain a yellow substance, adding tetrahydrofuran, stirring and dissolving, dripping a dropper into a beaker filled with sufficient petroleum ether for coprecipitation, generating a white flocculent precipitate after dripping, fully standing, sucking supernatant liquid of the standing solution to leave a solid, dissolving with water after the solvent is volatilized, putting into a dialysis bag, dialyzing for 372 hours, and freeze-drying to obtain PNVCL;
(3) preparation of Poly N-vinyl caprolactam grafted Chitosan (PNVCL-g-CS):
dissolving 0.5g of chitosan in 100mL of 1% acetic acid solution, stirring uniformly, and adding 5mL of deionized water solution in which 0.2g of PNVCL is dissolved; 0.4g EDC and 0.2g NHS were dissolved in 5mL deionized water and added dropwise to the reaction mixture, and the reaction was stirred at room temperature for 24 h. Dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain the product.
(4) Preparation of Poly N-vinyl caprolactam grafted Chitosan carboxyl (PNVCL-g-CS-COOH):
fully dissolving PNVCL-g-CS powder in deionized water to obtain a PNVCL-g-CS solution with the concentration of 0.1g/mL, pouring the PNVCL-g-CS solution into a flask, adding a DMSO solution of 0.2g/mL succinic anhydride, and stirring at room temperature for reacting for 24 hours. Dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain the product.
(5) Preparation of poly-N-vinylcaprolactam-grafted chitosan-paclitaxel (PNVCL-g-CS-PTX):
PNVCL-g-CS-COOH is fully dissolved in deionized water, and then paclitaxel is added. After stirring uniformly, DMAP and EDC are added into the mixed solution, and the mixture is stirred and reacted for 48 hours at room temperature. Dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain the product.
(6) Preparation of poly N-vinyl caprolactam grafted chitosan-paclitaxel (PNVCL-g-CS-PTX) sustained-release membrane:
fully dissolving the PNVCL-CS-PTX prepared in the step (5) in distilled water, averagely dividing the solution into four parts, adding 1, 4-butanediol glycidyl ether serving as a crosslinking agent, and mixing the components according to the weight ratio of PNVCL-CS-PTX: adding BDDGE with the molar ratio of 20:1, 40:1 and 80:1, and stirring and reacting at room temperature for 3 hours, wherein the rest group is a non-crosslinking group; dialyzing the four groups of reaction liquid for 48 hours by using distilled water after the reaction is finished, fixing the volume of the dialyzate to 20mL after the dialysis is finished, respectively adding 1 drop of glycerol, stirring for 30min, adding the four groups of liquid into a polytetrafluoroethylene die self-made by 16 small grids by 5mL of each part, and placing the die in a 50 ℃ drying oven to be dried into a film; 4 tablets of the four drug sustained-release tablets without crosslinking, 80:1, 40:1 and 20:1 are obtained.
Claims (4)
1. A sustained release film sheet, characterized in that: the structural formula of the sustained-release membrane is as follows:
2. the preparation method of the sustained-release film patch according to claim 1, which comprises the following steps:
(1) purifying chitosan:
adding chitosan into sodium hydroxide solution, stirring at 70 deg.C for 3 hr for decolorizing and deproteinizing, vacuum filtering with vacuum pump after reaction, separating solid and liquid, repeatedly washing solid with distilled water, neutralizing, and freeze drying to obtain purified chitosan;
(2) preparation of poly-N-vinylcaprolactam:
putting the N-vinyl caprolactam reagent into a reactor, and distilling at 60-70 ℃ under reduced pressure to remove the stabilizer in the N-vinyl caprolactam;
adding 15g of N-vinyl caprolactam without stabilizer into a reactor, sequentially adding 0.06g of azobisisobutyronitrile and 0.5g of chain transfer agent, stirring and reacting for 12-14h in an oil bath kettle at 65-70 ℃ under the protection of nitrogen, stirring to obtain a yellow substance, adding tetrahydrofuran, stirring and dissolving, dripping a dropper into a beaker filled with sufficient petroleum ether for coprecipitation, generating white flocculent precipitate after dripping, fully standing, sucking supernatant liquid of the standing solution to obtain solid, dissolving with water after the solvent is volatilized, dialyzing for 72h in a dialysis bag, and freeze-drying to obtain poly-N-vinyl caprolactam (PNVCL);
(3) preparing poly N-vinyl caprolactam grafted chitosan:
dissolving 0.5g of chitosan in 100mL of 1% acetic acid solution, uniformly stirring, and adding 5mL of deionized water solution in which 0.2g of poly N-vinyl caprolactam grafted chitosan is dissolved; 0.4g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 0.2g N-hydroxysuccinimide are dissolved in 5mL of deionized water and added dropwise to the reaction mixture, and the reaction is stirred at room temperature for 24 hours; dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain a product;
(4) preparation of poly N-vinyl caprolactam grafted chitosan carboxyl:
fully dissolving poly-N-vinyl caprolactam grafted chitosan powder in deionized water to obtain a poly-N-vinyl caprolactam grafted chitosan solution with the concentration of 0.1g/mL, pouring the poly-N-vinyl caprolactam grafted chitosan solution into a reactor, adding a dimethyl sulfoxide solution of 0.2g/mL succinic anhydride, stirring at room temperature for reaction for 24 hours, dialyzing for 72 hours after the reaction is finished, and finally freeze-drying to obtain a product;
(5) preparing poly N-vinyl caprolactam grafted chitosan-paclitaxel:
fully dissolving poly-N-vinyl caprolactam grafted chitosan carboxyl in deionized water, and then adding paclitaxel; after stirring uniformly, adding 4-dimethylaminopyridine and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride into the mixed solution, and stirring at room temperature for reaction for 48 hours; dialyzing for 72h after the reaction is finished, and finally freeze-drying to obtain a product;
(6) preparing a poly N-vinyl caprolactam grafted chitosan-paclitaxel sustained-release membrane:
fully dissolving the poly N-vinyl caprolactam grafted chitosan-paclitaxel prepared in the step (5) in distilled water, adding a cross-linking agent 1, 4-butanediol glycidyl ether, and according to the weight ratio of poly N-vinyl caprolactam grafted chitosan-paclitaxel: adding 1, 4-butanediol diglycidyl ether serving as a cross-linking agent into the 1, 4-butanediol diglycidyl ether at a molar ratio of 20: 1-80: 1, and stirring at room temperature for reaction for 3 hours; dialyzing the four groups of reaction liquid with distilled water for 48h after the reaction is finished, fixing the volume of the dialyzate to 20mL after the dialysis is finished, respectively adding 1 drop of glycerol, stirring for 30-60min, adding the liquid into a polytetrafluoroethylene mold, and drying the mold in a 50 ℃ drying oven to form a film; the non-crosslinked drug sustained-release membrane is obtained.
3. The process for preparing a sustained-release tablet according to claim 2, wherein: in the step (1), the concentration of the sodium hydroxide solution is 0.03-0.04 g/mL, and the addition amount of the chitosan is 0.2 g/mL.
4. The process for preparing a sustained-release tablet according to claim 2, wherein: in the step (2), the mass percent of the dilute hydrochloric acid is 1 percent, and the concentration of the sodium hydroxide solution is 1 mol/L.
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| CN116212753A (en) * | 2023-03-09 | 2023-06-06 | 西南大学 | A kind of preparation method of CS-g-PNVCL microgel and its stable Pickering emulsion |
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| CN116212753A (en) * | 2023-03-09 | 2023-06-06 | 西南大学 | A kind of preparation method of CS-g-PNVCL microgel and its stable Pickering emulsion |
| CN116212753B (en) * | 2023-03-09 | 2025-11-18 | 西南大学 | A method for preparing CS-g-PNVCL microgels and their stabilized Pickering emulsions |
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