CN1293952A - Chitosan and fibroin mixed microsphere and its usage and preparing process - Google Patents
Chitosan and fibroin mixed microsphere and its usage and preparing process Download PDFInfo
- Publication number
- CN1293952A CN1293952A CN99120027A CN99120027A CN1293952A CN 1293952 A CN1293952 A CN 1293952A CN 99120027 A CN99120027 A CN 99120027A CN 99120027 A CN99120027 A CN 99120027A CN 1293952 A CN1293952 A CN 1293952A
- Authority
- CN
- China
- Prior art keywords
- chitosan
- fibroin
- microsphere
- solution
- medicine
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
A chitosan and fibroin mixed microsphere is prepared through dissolving fibroin in CaCl2-H2O-alcohol solution, dialyzing, mixing with solution of chitosan in acetic acid, mixing with atoleine and dewatered sorbitol laurate, adding ethyl acetate and glutaraldhyde and drying. Said microsphere can be used as slow-releasing carrier of medicine.
Description
The present invention relates to the fall bag medicine method for preparing microsphere of fragrant calcium medicine of the purposes of a kind of chitosan and fibroin mixed microsphere, this mixed microsphere and preparation method and chitosan and the non-promise of fibroin mixed back enclose, belong to chemical field.
Studies show that recently biodegradable polymer is significant to the application of medicine as pharmaceutical carrier, and pharmaceutical pack is wrapped in the polymer microsphere, through active and Passive Control, enter pre-determined target organ or tissue, slowly release, can reduce its toxic and side effects, improve its bioavailability.Chitosan (being called for short CS) is a kind of natural alkaline polysaccharide, and is nonpoisonous and tasteless, has good bioaffinity and biodegradability, and chitosan is unstable under acidic condition, is easy to dissolving.Fibroin (being called for short FB) has another name called fibroin albumen, is the main composition of silkworm silk (accounting for 70%～80%), contain 18 seed amino acids, and fibroin is more acidproof, and strong acid does not have obviously destruction to it.Chitosan and fibroin mixed the two performance of improving.Fenoprofen calcium (Fenoprofen) is the non-steroidal anti-inflammatory analgesic, is used for acute and chronic, rheumatic, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.Because its biological half-life is shorter, need frequently take medicine, and it is bigger to the intestines and stomach stimulation, therefore makes the untoward reaction that slow releasing preparation can reduce medicining times and medicine.
In recent years, the chitosan that studies show that in a large number both domestic and external can be used as the carrier of medicament slow release preparation, and people such as POLK (J.Pharm.Sci.83,178,1994) report uses chitosan and sodium alginate at CaCl
2Reaction is formed with the microcapsule of polyelectrolyte film in the solution, and with chitosan and the sodium alginate albuminous slow-release microcapsule that has been preparing carriers, shows that albumin has certain slow releasing function in microcapsule.People's such as HARI (J Appl PolymSci 59,1795,1996) studies show that chitosan and sodium alginate micro gel capsule can be used as the carrier of biomacromolecule albumin and insulin sustained-release oral preparation.People such as THOMAS (J Appl Polym Sci 70,2143,1998) report chitosan and sodium alginate reaction are used to prepare the Orally-taken hirudin microcapsule.People such as LIN (Chem Pharm Bull 40,2491,1992) report chitosan and sodium carboxymethyl cellulose form the micropowder grain, can be used as the carrier of the floating microcapsule of theophylline stomach.People such as Wang Yamin (Acta Pharmaceutica Sinica, 31,300,1996) have reported the preparation and the characteristic of cisplatin chitosan microball, the preparation method of people such as Liu Xiangjun (Acta Pharmaceutica Sinica, 26,782,1991) report rotundine/chitosan medicament slow release bead.But the preparation method of chitosan and fibroin mixed microsphere and be used for fall fragrant calcium medicine and make bag medicine microsphere and do not appear in the newspapers of the non-promise of enclose.
Up to the present, the relatively more responsive microsphere of PH still is not reported.Therefore known chitosan and fibroin make mixed microsphere with them all to the PH sensitivity, help being suitable for the sustained release under the different PH conditions, and this mixed microsphere may have the important application prospect in the sustained release medicine.
Based on above situation, the object of the present invention is to provide purposes of a kind of chitosan and fibroin mixed microsphere, this mixed microsphere and preparation method thereof, with this microsphere as enclose the fall preparation method of medicine micro computer ball carriers such as fragrant calcium of non-promise.
For achieving the above object, the technical solution adopted in the present invention is as follows:
A kind of chitosan and fibroin mixed microsphere, it is that fibroin is dissolved in CaCl
2-H
2In the O-alcoholic solution, with the chitosan-acetic acid solution blend, mix stirring after the dialysis, add ethyl acetate, glutaraldehyde blended cross linking products therefrom microsphere with liquid paraffin, anhydrous sorbitol laurate.
Because chitosan and fibroin are all to the PH sensitivity, therefore make the carrier of mixed microsphere useful as drug sustained release with them, behind carrying medicament, can be at the sustained release under the different PH conditions, therefore, this mixed microsphere has the important application prospect in the sustained release medicine.
The preparation method of chitosan and fibroin mixed microsphere:
The NaHCO with 0.5% is removed behind the pupa in the preparation of fibroin solution, Bombyx bombycis
3Solution boils at 100 ℃ that 30min comes unstuck, dry fibroin, and fibroin is dissolved in 1: 8: 2 CaCl of mol ratio
2-H
2In the O-ethanol water, 3 days after-filtration of dialysis get certain density fibroin solution in water then, and this solution is stored in the brown bottle, and is In Shade.
The preparation of chitosan and fibroin mixed microsphere, fibroin solution with 1% and 2% chitosan solution are at normal temperatures in 1: 4 to 4: 1 ratio blend, get above-mentioned blended liquid 10mL and liquid paraffin 10～50mL, Span-20 0.8～1.4g adds ethyl acetate 2mL after mixing stirring 30min, glutaraldehyde 1～2mL uses acetone thorough washing solid product after stirring 1～2h, and 60 ℃ of following vacuum dryings get the chitosan fibroin mixed microsphere.
This microsphere loads medicine can dual mode, and the one, prepare mixed microsphere earlier, adopt the passive load mode to load medicine again, also can in the preparation mixed microsphere, add pharmaceutical compositions, disposablely obtain wrapping the medicine microsphere, concrete grammar is as follows:
Get a certain amount of non-promise fragrant calcium that falls and be dissolved in the glacial acetic acid, chitosan solution and fibroin solution compare blend by 1: 4 to 4: 1 quality.Blended liquid adds liquid paraffin after stirring half an hour, Span-20, and ethyl acetate, fully stirring makes reaction system be emulsion, and keeps reaction 30min, adds glutaraldehyde 1～1.5ml then and stirs 1～2h.With acetone thorough washing solid product, product must wrap the medicine microsphere in 45 ℃ of following vacuum dryings.
Compared with prior art, adopt the obtained beneficial effect of technical measures of the present invention:
Technical scheme of the present invention has obvious improvement and innovation than existing technology: the present invention adds fibroin in chitosan, but and with the microsphere of formation rule behind the glutaraldehyde cross-linking bag medicine, and cavity arranged, and, fibroin also is the material to the PH sensitivity, can be under different PH conditions sustained release.These two kinds of compositions all are biodegradable materials in the body simultaneously, are the ideal materials as pharmaceutical carrier, and therefore, the present invention has important use at field of medicaments and is worth.
Below in conjunction with specific embodiment technical scheme of the present invention is further described:
Embodiment 1
The preparation of chitosan and fibroin mixed microsphere, chitosan are dissolved in the chitosan solution that gets 2% (w/w) in the acetic acid; The chitosan solution of (w/w) fibroin solution and 2% (w/w) with 1% is at normal temperatures in 1: 4 ratio blend of mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 20mL, anhydrous sorbitol laurate (Span-20) 0.8g adds ethyl acetate 2mL after mixing stirring 30min, glutaraldehyde 1.5mL uses acetone thorough washing solid product after stirring 2h, and product gets chitosan-heart protein mixed microsphere in 60 ℃ of following vacuum dryings.
Embodiment 2
The chitosan solution of (w/w) fibroin solution and 2% (w/w) with 1% is at normal temperatures in 4: 1 ratio blend of mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 30mL, Span-20 1.2g adds ethyl acetate 2mL after mixing stirring 30min, glutaraldehyde 1.5mL uses acetone thorough washing solid product after stirring 2h, and product gets chitosan-heart protein mixed microsphere in 60 ℃ of following vacuum dryings.
Embodiment 3
The chitosan solution of (w/w) fibroin solution and 2% (w/w) with 1% is at normal temperatures in 1: 1 ratio blend of mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 50mL, Span-20 1.0g adds ethyl acetate 2mL after mixing stirring 30min, glutaraldehyde 1.5mL uses acetone thorough washing solid product after stirring 2h, and product gets chitosan-heart protein mixed microsphere in 60 ℃ of following vacuum dryings.
The preparation of embodiment 4 bag medicine microspheres
Get 0.1g Fei Nuofen calcium and be dissolved in the glacial acetic acid of 5mL, get the fibroin solution blend of 20g 5% (w/w) chitosan solution and 20g 10% (w/w).Blended liquid adds liquid paraffin 40mL, Span-20 1g after stirring 30min, ethyl acetate 2mL, and fully stirring makes reaction system be emulsion, and keeps reaction 30min, adds glutaraldehyde 1.2mL then and stirs 2h.With acetone thorough washing solid product, product must wrap the medicine microsphere in 45 ℃ of following vacuum dryings.
Claims (4)
1. chitosan and fibroin mixed microsphere, it is characterized in that, this blend is little globally to be prepared by following method: fibroin solution and chitosan-acetic acid solution are 1: 4 to 4: 1 ratio blend at normal temperatures in mass ratio, get above-mentioned blended liquid 10mL and liquid paraffin 20～50mL, anhydrous sorbitol laurate 0.8～1.4g adds ethyl acetate 2mL after mixing stirring 20～40min, glutaraldehyde 1～2mL uses acetone thorough washing solid product after stirring 2h, and product gets chitosan-fibroin mixed microsphere in 60 ℃ of following vacuum dryings.
2. described chitosan of claim 1 and fibroin mixed microsphere are as the sustained-release micro-spheres carrier of medicine.
3. method for preparing described chitosan of claim 1 and fibroin mixed microsphere, it is characterized in that: fibroin solution with 1% and 2% chitosan-acetic acid solution are 1: 4 to 4: 1 ratio blend at normal temperatures in mass ratio, and get 10mL blended liquid and liquid paraffin 20～50mL, anhydrous sorbitol laurate 0.8～1.5g adds ethyl acetate 2mL after mixing stirring 20～40min, glutaraldehyde 1～2mL stirs 2h, gets the chitosan fibroin mixed microsphere with washing with acetone solid product, vacuum drying then.
4. one kind prepares the fall method of fragrant calcium medicine microspheres of chitosan and the non-promise of fibroin mixed enclose medicine, it is characterized in that: get the quantitative non-promise fragrant calcium that falls and be dissolved in the glacial acetic acid, 5% chitosan solution and 10% fibroin solution compare blend by 1: 4 to 4: 1 quality, blended liquid adds liquid paraffin 20～50mL after stirring 30min, anhydrous sorbitol laurate 0.8～1.5g adds ethyl acetate 2mL after stirring 20～40, fully stirring makes reaction system be emulsion, and keep and react 30min, add glutaraldehyde 1～2ml then and stir 1～2h, with acetone thorough washing solid product, must wrap the medicine microsphere in 45 ℃ of following vacuum dryings.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB991200276A CN1235571C (en) | 1999-11-02 | 1999-11-02 | Chitosan and fibroin mixed microsphere and its usage and preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB991200276A CN1235571C (en) | 1999-11-02 | 1999-11-02 | Chitosan and fibroin mixed microsphere and its usage and preparing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1293952A true CN1293952A (en) | 2001-05-09 |
| CN1235571C CN1235571C (en) | 2006-01-11 |
Family
ID=5281308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB991200276A Expired - Fee Related CN1235571C (en) | 1999-11-02 | 1999-11-02 | Chitosan and fibroin mixed microsphere and its usage and preparing process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1235571C (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003035124A3 (en) * | 2001-10-25 | 2003-09-12 | Univ Connecticut | Fibroin compositions and methods of making the same |
| WO2011017930A1 (en) * | 2009-08-11 | 2011-02-17 | 南方医科大学珠江医院 | Macroporous microcarrier specific to liver cell, preparation mathod and use thereof |
| CN101565515B (en) * | 2008-04-25 | 2011-05-11 | 西北师范大学 | Karaya gum complex polysaccharide microsphere used as bioactive molecular vector and preparation method thereof |
| CN101624473B (en) * | 2009-08-11 | 2012-10-10 | 南方医科大学珠江医院 | Method for culturing hepatic cells on a large scale |
| CN102010601B (en) * | 2009-08-11 | 2012-11-21 | 南方医科大学珠江医院 | Macroporous micro-carrier with liver cell specificity as well as preparation method and applications thereof |
| CN104928741A (en) * | 2015-05-21 | 2015-09-23 | 武汉大学 | Multi-sensitive chitosan gel with brick-mud structure and preparation method and application thereof |
-
1999
- 1999-11-02 CN CNB991200276A patent/CN1235571C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003035124A3 (en) * | 2001-10-25 | 2003-09-12 | Univ Connecticut | Fibroin compositions and methods of making the same |
| US7727542B2 (en) | 2001-10-25 | 2010-06-01 | University Of Connecticut | Bioactive materials, methods of making bioactive materials and method of use thereof |
| US8071118B2 (en) | 2001-10-25 | 2011-12-06 | University Of Connecticut | Method of inducing cell proliferation using fibroin |
| CN101565515B (en) * | 2008-04-25 | 2011-05-11 | 西北师范大学 | Karaya gum complex polysaccharide microsphere used as bioactive molecular vector and preparation method thereof |
| WO2011017930A1 (en) * | 2009-08-11 | 2011-02-17 | 南方医科大学珠江医院 | Macroporous microcarrier specific to liver cell, preparation mathod and use thereof |
| CN101624473B (en) * | 2009-08-11 | 2012-10-10 | 南方医科大学珠江医院 | Method for culturing hepatic cells on a large scale |
| CN102010601B (en) * | 2009-08-11 | 2012-11-21 | 南方医科大学珠江医院 | Macroporous micro-carrier with liver cell specificity as well as preparation method and applications thereof |
| CN104928741A (en) * | 2015-05-21 | 2015-09-23 | 武汉大学 | Multi-sensitive chitosan gel with brick-mud structure and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1235571C (en) | 2006-01-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW577758B (en) | Intra-articular preparation for the treatment of arthropathy | |
| JP2571874B2 (en) | Protein microsphere composition | |
| EP1328258B1 (en) | A controlled-release, parenterally administrable microparticle preparation | |
| KR100535319B1 (en) | Drug composition with controlled drug release rate | |
| WO1994014420A1 (en) | Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof | |
| CA2160692A1 (en) | Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof | |
| CN101716161B (en) | New thymosin chitosan microsphere type oral medicinal preparation and preparation method thereof | |
| JP2006510731A (en) | Targeted delivery | |
| CN102058562A (en) | Method for preparing gamma-polyglutamic acid/chitosan nano capsules | |
| EP0616802B1 (en) | Oral preparation for release in lower digestive tracts | |
| CN112353765B (en) | Preparation method of ceftiofur microspheres | |
| CN1235571C (en) | Chitosan and fibroin mixed microsphere and its usage and preparing process | |
| CN107432936A (en) | A kind of purposes of modification of chitosan and the nano-complex comprising the modification of chitosan | |
| AU618748B2 (en) | Pellets with enzymatically controlled drug release | |
| CN104244927B (en) | Include the method for the enteric alginate microcapsules of diclofenac or a kind of its salt and many particle medicinal compositions comprising the microcapsule by ionic gelation production | |
| CN103965287A (en) | Deuterohemin-beta-Ala-His-Lys(DhHP-3), and preparation method and application thereof | |
| CN101653609A (en) | Octenyl succinate starch with colon targeting controlled release function and preparation method thereof | |
| CN107281159A (en) | Preparation method of sustained-release drug-loaded microcapsule with multilayer core-shell structure | |
| EP1973570B1 (en) | Pharmaceutical formulations comprising dextran with molecular weight of 1.0-100kda and processes for their preparation | |
| CN1771912B (en) | Orally taken nanometer protein polypetide composite nano-particle and its preparation | |
| CN101062408B (en) | Oral insulin compound medicine preparation and its preparing method | |
| CN1771913A (en) | Emulifying solvent diffusing process for preparing taste masked micro ball | |
| CN100484573C (en) | Method for preparing floating-biological adhesion synergistic microparticle | |
| CN1476825A (en) | Grain prolamin microsphere and preparation method | |
| CN1315530C (en) | Method of preparing system for controlled release of medication in protein category |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB1A | Publication of application | ||
| 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 | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |