CN102935235A - Preparation method of modified casein drug-carrying controlled-release thin film - Google Patents
Preparation method of modified casein drug-carrying controlled-release thin film Download PDFInfo
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- CN102935235A CN102935235A CN2012104761182A CN201210476118A CN102935235A CN 102935235 A CN102935235 A CN 102935235A CN 2012104761182 A CN2012104761182 A CN 2012104761182A CN 201210476118 A CN201210476118 A CN 201210476118A CN 102935235 A CN102935235 A CN 102935235A
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Abstract
The invention relates to a preparation method of a modified casein drug-carrying controlled-release thin film. In the prior art that a drug-carrying material is made from the natural high molecular material, a drug-carrying medium is usually made from chitosan, starch and cellulose, while the research that the drug-carrying thin film is prepared by taking natural protein casein as the medium is hard to see in public reports. The preparation method takes casein as the drug-carrying medium, and comprises the following steps of: firstly, introducing nano-silica particles by the in-situ hydrolysis of ethyl orthosilicate, and introducing a silane coupling agent capable of stabilizing a system and improving the crosslinking degree of the thin film to prepare casein-base composite emulsion; and filming by drying the emulsion, and immersing the film into ibuprofen solution dissolved in organic solvent to form into the drug-carrying thin film by means of freeze drying after the adsorption reaches the balance. Therefore, a stronger acting force is formed between the active group of the composite emulsion and the active group of the drug to obtain the drug-carrying thin film of which the loading efficiency is greater than 60%, wherein the drug-carrying thin film is better in controlled-release performance, and has the potential application value.
Description
Technical field
The present invention relates to the composite drug-loaded thin film technology method of a kind of natural polymer subbase, particularly a kind of modified Casein carried medicine sustained-release thin film technology method.
Background technology
In recent years, biodegradable polymer is because its more excellent biocompatibility and the parent that day by day is subject to biological medicine and pharmaceutical field researcher looks at.Wherein, the natural product based high molecular is because wide material sources and avirulence, and be widely used in research (the Y. Lu of drug carrier material aspect, S.C. Chen, Micro and nano-fabrication of biodegradable polymers for drug delivery[J]. Advanced Drug Delivery Reviews. 2004,56: 1621 – 1633).
Casein is as a kind of protein of natural fully biodegradable, (the Y.D. Livney that in medicine-carried system, receives much concern owing to have stronger ionic adsorption, surface activity, emulsibility, self assembly and stability, Milk proteins as vehicles for bioactives[J] .Curr. Opin. Journal of Colloid and Interface Science. 2010,15: 73-83).According to bibliographical information, it can be prepared to (the Ahmed O. Elzoghby such as different shape such as hydrogel, micro-/ nano particle, composite as pharmaceutical carrier, Wael S. Abo El-Fotoh, Nazik A. Elgindy. Casein-based formulations as promising controlled release drug delivery systems[J]. Journal of Controlled Release. 2011,153: 206 – 216).Yet, openly report for the research of casein base load medicine thin film is also rarely seen.Find through the retrieval to the prior art document, it is matrix that the employing caseins such as Abu Diak et al are only arranged, prepared the material that can be used for medication coat by introducing the plasticizers such as oleic acid, yet the prepared medication coat drug loading rate of this method is not high, and slow-releasing (the O. Abu Diak that can not meet the demands, A. Bani-Jaber, B. Amro, D. Jones, G.P. Andrews, The manufacture and characterization of casein films as novel tablet coatings, Trans. IChemE, C, Food Bioproducts Process. 2007: 85:284 – 290.).
Nanoparticle such as silicon dioxide are because its special small-size effect, specific surface area effect and the parent who day by day is subject to researcher with the strong combination of polymeric matrix look at, be introduced into polymer and can give performance such as the thermostability of matrix uniqueness, mechanical strength, surface tension and drug adsorption (W. Sto ¨ ber, A. Fink, E. Bohn, Controlled growth of monodisperse silica spheres in the micron size range. Journal of Colloid and Interface Science. 1968,26:62-69.).Yet, so far, nano silicon is introduced the research that casein prepares drug carrier material yet there are no open report.
Summary of the invention
The object of the invention is to overcome the shortcoming of above-mentioned prior art, a kind of modified Casein carried medicine sustained-release thin film technology method is provided, according to said method the medicine-carried system of preparation has improved medicine carrying efficient, and has controlled the prominent phenomenon of releasing of medicine.
For achieving the above object, the technical solution used in the present invention is:
Getting mass fraction is that 2.1～8.4 parts casein, 0.525～2.1 part of triethanolamine and 33～83 parts of deionized waters add in the there-necked flask, the control temperature is 65～70 ℃, keep stirring 120～150 minutes, get mass fraction and be 0.9～3.6 part caprolactam, add in 3.6～12.4 parts the deionized water, it is 25% caprolactam water solution that uniform stirring obtains mass percent; Regulate temperature and reach 75 ℃～80 ℃, drip simultaneously the silane coupler of caprolactam water solution and 0.6 part～1.8 parts, wait to dropwise, continued insulation reaction 30～60 minutes, get mass fraction and be 0.4 part～1.6 parts ethyl orthosilicate, with mass percent be that the water soluble starter aqueous solution of 10%～20% concentration is added dropwise to system simultaneously, after dropwising, insulation reaction 120～180 minutes; Be down to room temperature, add an amount of mass percent and be 30% ammonia regulation system pH value and be 7.5 ±, namely get casein base silicon dioxide composite emulsion; Be casting film-forming in the plastic culture dish of 90mm with emulsion at diameter, behind the drying at room temperature 12h, put dry 4h to 50 ℃ of vacuum drying ovens.Namely obtain casein base silicon dioxide laminated film.Get 0.05 part～0.10 part ibuprofen, it is dissolved in 100 parts～200 parts the oxolane, after medicine dissolves fully, get 5.0 parts～6.0 parts casein base silicon dioxide laminated films in the bag filter of packing into, and in the immersion medicine dispersion liquid medicine is adsorbed, monitor during this time the concentration of solution Chinese medicine every 2h, when treating that concentration no longer changes, be considered as medicine and reach adsorption equilibrium, boil off organic solvent, lyophilization obtains the composite drug-loaded thin film of casein base silicon dioxide.
Product among the present invention is native protein casein based nano composite material, therefore, it has the excellent specific property of protein-based filmogen and the nano effect of inorganic silicon dioxide particle concurrently, has the characteristics such as high temperature resistant, that resistance to water is strong, mechanical property is excellent, drug adsorption is strong.Measure by experiment, the drug loading efficient of such material reaches more than 60%, and sustained release rate is slower, and 15h medicine accumulative total rate of release is 100%.Therefore, adopting the modified Casein of the method preparation is the good drug carrier material of a class.
Description of drawings:
Fig. 1 is the surface (a, c) and section (b, d) SEM figure of (c, d) behind casein based coextruded film carrying medicament (a, b) and the drug release;
Fig. 2 is that different dioxide-containing silicas are to the influence curve of medicine carrying laminated film medicament slow release performance.
The specific embodiment:
The present invention take at casein as base material, introduce the nano silicon that medicine is had absorption property by the mode of in-situ hydrolysis, on the one hand, the discontinuity of the film forming of casein own cause become thin film to have micropore, on the other hand, silicon dioxide has huge specific surface area and can produce stronger interface interaction with polymeric matrix, therefore, the active group of complex emulsions can and the pharmaceutically active group between form stronger active force, thereby can obtain the higher medicine carrying casein based coextruded film of load efficiency.Be intended to develop bio-compatible, medicine carrying is efficient, rate of release is slow drug delivery system.
Embodiment 1:
Getting mass fraction is that 2.1 parts casein, 0.525 part of triethanolamine and 33 parts of deionized waters add in the there-necked flask, 65 ℃ of control temperature, keep stirring 120 minutes, get mass fraction and be 0.9 part caprolactam, add in 3.6 parts the deionized water, it is 25% caprolactam water solution that uniform stirring obtains mass percent; Regulate temperature and reach 75 ℃, drip simultaneously the silane coupler of caprolactam water solution and 0.6 part, wait to dropwise, continued insulation reaction 30 minutes, get mass fraction and be 0.4 part ethyl orthosilicate, with mass percent be that the water soluble starter aqueous solution of 10% concentration is added dropwise to system simultaneously, after dropwising, insulation reaction 120 minutes; Be down to room temperature, add an amount of mass percent and be 30% ammonia regulation system pH value and be 7.5 ±, namely get casein base silicon dioxide composite emulsion.Be casting film-forming in the plastic culture dish of 90mm with emulsion at diameter, behind the drying at room temperature 12h, put dry 4h to 50 ℃ of vacuum drying ovens, namely obtain casein base silicon dioxide laminated film; Get 0.05 part ibuprofen, it is dissolved in 100 parts the oxolane, after medicine dissolves fully, get 5.0 parts of casein base silicon dioxide laminated films in the bag filter of packing into, and in the immersion medicine dispersion liquid medicine is adsorbed, every the concentration of 2h monitoring solution Chinese medicine, when treating that concentration no longer changes, be considered as medicine and reach adsorption equilibrium during this time; Boil off organic solvent, lyophilization obtains the composite drug-loaded thin film of casein base silicon dioxide.
Embodiment 2:
Getting mass fraction is that 4.2 parts casein, 1.05 parts of triethanolamine and 50 parts of deionized waters add in the there-necked flask, 67 ℃ of control temperature, keep stirring 130 minutes, get mass fraction and be 1.8 parts caprolactam, add in 6.6 parts the deionized water, it is 25% caprolactam water solution that uniform stirring obtains mass percent; Regulate temperature and reach 77 ℃, drip simultaneously the silane coupler of caprolactam water solution and 1.0 parts, wait to dropwise, continued insulation reaction 40 minutes, get mass fraction and be 0.8 part ethyl orthosilicate, with mass percent be that the water soluble starter aqueous solution of 13% concentration is added dropwise to system simultaneously, after dropwising, insulation reaction 140 minutes; Be down to room temperature, add an amount of mass percent and be 30% ammonia regulation system pH value and be 7.5 ±, namely get casein base silicon dioxide composite emulsion; Be casting film-forming in the plastic culture dish of 90mm with emulsion at diameter, behind the drying at room temperature 12h, put dry 4h to 50 ℃ of vacuum drying ovens, namely obtain casein base silicon dioxide laminated film.Get 0.075 part ibuprofen, it is dissolved in 130 parts the oxolane, after medicine dissolves fully, get 5.3 parts of casein base silicon dioxide laminated films in the bag filter of packing into, and in the immersion medicine dispersion liquid medicine is adsorbed, every the concentration of 2h monitoring solution Chinese medicine, when treating that concentration no longer changes, be considered as medicine and reach adsorption equilibrium during this time.Boil off organic solvent, lyophilization obtains the composite drug-loaded thin film of casein base silicon dioxide.
Embodiment 3:
Getting mass fraction is that 6.3 parts casein, 1.575 parts of triethanolamine and 66 parts of deionized waters add in the there-necked flask, 69 ℃ of control temperature, keep stirring 140 minutes, get mass fraction and be 2.7 parts caprolactam, add in 9.4 parts the deionized water, it is 25% caprolactam water solution that uniform stirring obtains mass percent; Regulate temperature and reach 78 ℃, drip simultaneously the silane coupler of caprolactam water solution and 1.4 parts, wait to dropwise, continued insulation reaction 50 minutes, get mass fraction and be 1.2 parts ethyl orthosilicate, with mass percent be that the water soluble starter aqueous solution of 15% concentration is added dropwise to system simultaneously, after dropwising, insulation reaction 160 minutes.Be down to room temperature, add an amount of mass percent and be 30% ammonia regulation system pH value and be 7.5 ±, namely get casein base silicon dioxide composite emulsion; Be casting film-forming in the plastic culture dish of 90mm with emulsion at diameter, behind the drying at room temperature 12h, put dry 4h to 50 ℃ of vacuum drying ovens, namely obtain casein base silicon dioxide laminated film.Get 0.087 part ibuprofen, it is dissolved in 170 parts the oxolane, after medicine dissolves fully, get 5.7 parts of casein base silicon dioxide laminated films in the bag filter of packing into, and in the immersion medicine dispersion liquid medicine is adsorbed, every the concentration of 2h monitoring solution Chinese medicine, when treating that concentration no longer changes, be considered as medicine and reach adsorption equilibrium during this time; Boil off organic solvent, lyophilization obtains the composite drug-loaded thin film of casein base silicon dioxide.
Embodiment 4:
Getting mass fraction is that 8.4 parts casein, 2.1 parts of triethanolamine and 83 parts of deionized waters add in the there-necked flask, the control temperature 70 C, keep stirring 150 minutes, get mass fraction and be 3.6 parts caprolactam, add in 12.4 parts the deionized water, it is 25% caprolactam water solution that uniform stirring obtains mass percent; Regulate temperature and reach 80 ℃, drip simultaneously the silane coupler of caprolactam water solution and 1.8 parts, wait to dropwise, continued insulation reaction 60 minutes, get mass fraction and be 1.6 parts ethyl orthosilicate, with mass percent be that the water soluble starter aqueous solution of 20% concentration is added dropwise to system simultaneously, after dropwising, insulation reaction 180 minutes; Be down to room temperature, add an amount of mass percent and be 30% ammonia regulation system pH value and be 7.5 ±, namely get casein base silicon dioxide composite emulsion; Be casting film-forming in the plastic culture dish of 90mm with emulsion at diameter, behind the drying at room temperature 12h, put dry 4h to 50 ℃ of vacuum drying ovens, namely obtain casein base silicon dioxide laminated film.Get 0.10 part ibuprofen, it is dissolved in 200 parts the oxolane, after medicine dissolves fully, get 6.0 parts of casein base silicon dioxide laminated films in the bag filter of packing into, and in the immersion medicine dispersion liquid medicine is adsorbed, every the concentration of 2h monitoring solution Chinese medicine, when treating that concentration no longer changes, be considered as medicine and reach adsorption equilibrium during this time.Boil off organic solvent, lyophilization obtains the composite drug-loaded thin film of casein base silicon dioxide.
Be the surface (a, c) and section (b, d) SEM figure of (c, d) behind casein based coextruded film carrying medicament (a, b) and the drug release from Fig. 1; Fig. 2 is that different dioxide-containing silicas are to the influence curve of medicine carrying laminated film medicament slow release performance.Can find out with reference to Fig. 1: crystallization does not all appear in surface and section at the medicine carrying thin film, and equably load and being distributed in the thin film of medicine is described.Can get with reference to Fig. 2: thin film reaches 100% to medicine accumulative total release rate at the 15h rear, illustrates that it has stronger slow releasing function.
Claims (6)
1. a modified Casein carried medicine sustained-release thin film technology method is characterized in that, comprises the steps:
(1) preparation of modified Casein emulsion
Getting mass fraction is that 2.1～8.4 parts casein, 0.525～2.1 part of triethanolamine and 33～83 parts of deionized waters add in the there-necked flask, 65～70 ℃ of control temperature, keep stirring 120～150 minutes, get mass fraction and be 0.9～3.6 part caprolactam, add in 3.6～12.4 parts the deionized water, it is 25% caprolactam water solution that uniform stirring obtains mass percent; Regulate temperature and reach 75 ℃～80 ℃, drip simultaneously the silane coupler of caprolactam water solution and 0.6 part～1.8 parts, wait to dropwise, continued insulation reaction 30～60 minutes, get mass fraction and be 0.4 part～1.6 parts ethyl orthosilicate, with mass percent be that the water soluble starter aqueous solution of 10%～20% concentration is added dropwise to system simultaneously, after dropwising, insulation reaction 120～180 minutes; Be down to room temperature, add an amount of mass percent and be 30% ammonia regulation system pH value and be 7.5 ±, namely get casein base silicon dioxide composite emulsion; Be casting film-forming in the plastic culture dish of 90mm with emulsion at diameter, behind the drying at room temperature 12h, put dry 4h to 50 ℃ of vacuum drying ovens, namely obtain casein base silicon dioxide laminated film; (2) modified Casein medicine carrying thin film technology
Get mass fraction and be 0.05 part～0.10 part ibuprofen, it is dissolved in 100 parts～200 parts the oxolane, after medicine dissolves fully, get 5.0 parts～6.0 parts casein base silicon dioxide laminated films in the bag filter of packing into, and in the immersion medicine dispersion liquid medicine is adsorbed, every the concentration of 2h monitoring solution Chinese medicine, when treating that concentration no longer changes, be considered as medicine and reach adsorption equilibrium during this time; Boil off organic solvent, lyophilization obtains the composite drug-loaded thin film of casein base silicon dioxide.
2. a kind of modified Casein carried medicine sustained-release thin film technology method according to claim 1, it is characterized in that: this medicine carrying thin film is as carrier take casein, take nano silicon as adsorbent, utilize the discontinuity of the film forming of casein own and the adsorptivity of silicon dioxide, the medicine carrying thin film that the absorption ibuprofen forms; The raising of its sustained release performance also mainly relies on shell silicon dioxide to the drug release rate inhibition.
3. a kind of modified Casein carried medicine sustained-release thin film technology method according to claim 1 is characterized in that: initiator is the water solublity persulfate in the described step (1), comprises potassium peroxydisulfate or Ammonium persulfate..
4. a kind of modified Casein carried medicine sustained-release thin film technology method according to claim 3, it is characterized in that: described water solublity persulfate is potassium peroxydisulfate or Ammonium persulfate..
5. a kind of modified Casein carried medicine sustained-release thin film technology method according to claim 1, it is characterized in that: silane coupler is the alkoxy silane that contains two keys in the described step (1), comprises vinyltrimethoxy silane, VTES, γ-methacryloxypropyl trimethoxy silane or γ-methacryloxypropyl trimethoxy silane.
6. a kind of modified Casein carried medicine sustained-release thin film technology method according to claim 1, it is characterized in that: the method to monitor drug concentration adopts ultraviolet-visible spectrophotometer at the absorbance of 264nm wavelength place detection of drugs solution, treat that absorbance remains unchanged, think that then the thin film adsorbs medicine reaches capacity.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105601949A (en) * | 2016-01-13 | 2016-05-25 | 陕西科技大学 | TiO2-SiO2 co-modified casein composite emulsion and method for preparing same |
| WO2018086248A1 (en) * | 2016-11-11 | 2018-05-17 | 陕西科技大学 | Casein-based silica dual drug-loading composite microcapsule and preparation method therefor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681517A (en) * | 1993-03-24 | 1997-10-28 | Doxa Gmbh | Method of producing casein film |
| CN102167786A (en) * | 2011-03-10 | 2011-08-31 | 陕西科技大学 | Method for preparing modified casein/nanometer silica composite film-forming agent through in-situ soap-free seed emulsion polymerization |
| CN102504131A (en) * | 2011-12-02 | 2012-06-20 | 陕西科技大学 | Double in-situ method for preparing casein-based nano silicon dioxide composite leather finishing agent |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681517A (en) * | 1993-03-24 | 1997-10-28 | Doxa Gmbh | Method of producing casein film |
| CN102167786A (en) * | 2011-03-10 | 2011-08-31 | 陕西科技大学 | Method for preparing modified casein/nanometer silica composite film-forming agent through in-situ soap-free seed emulsion polymerization |
| CN102504131A (en) * | 2011-12-02 | 2012-06-20 | 陕西科技大学 | Double in-situ method for preparing casein-based nano silicon dioxide composite leather finishing agent |
Non-Patent Citations (3)
| Title |
|---|
| AHMED O. ELZOGHBY ET AL.: "Casein-based formulations as promising controlled release drug delivery systems", 《JOURNAL OF CONTROLLED RELEASE》 * |
| O. ABU DIAK ET AL.: "The manufacture and characterization of casein films as novel tablet coatings", 《TRANS ICHEME, PART C》 * |
| 申晓庆 等: "酪素改性的技术手段与改性产品的性能特点", 《西部皮革》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105601949A (en) * | 2016-01-13 | 2016-05-25 | 陕西科技大学 | TiO2-SiO2 co-modified casein composite emulsion and method for preparing same |
| CN105601949B (en) * | 2016-01-13 | 2017-11-17 | 陕西科技大学 | A kind of TiO2‑SiO2Modified Casein complex emulsions and preparation method thereof altogether |
| WO2018086248A1 (en) * | 2016-11-11 | 2018-05-17 | 陕西科技大学 | Casein-based silica dual drug-loading composite microcapsule and preparation method therefor |
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