CN102070791B - Polyvinyl alcohol crosslinked thiolated hyaluronic acid/polyvinyl alcohol film and preparation method and application thereof - Google Patents
Polyvinyl alcohol crosslinked thiolated hyaluronic acid/polyvinyl alcohol film and preparation method and application thereof Download PDFInfo
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- CN102070791B CN102070791B CN2010105999536A CN201010599953A CN102070791B CN 102070791 B CN102070791 B CN 102070791B CN 2010105999536 A CN2010105999536 A CN 2010105999536A CN 201010599953 A CN201010599953 A CN 201010599953A CN 102070791 B CN102070791 B CN 102070791B
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- polyvinyl alcohol
- mucinase
- sulfhydrylation
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Abstract
The invention belongs to the technical field of the macromolecular material and particularly discloses a polyvinyl alcohol crosslinked thiolated hyaluronic acid/polyvinyl alcohol film and a preparation method and application thereof. The preparation method comprises the following steps: using biodegradable thiolated hyaluronic acid and polyvinyl alcohol (PVA) as raw material to crosslink with PVA by using glutaraldehyde (GA), and performing vacuum drying at the room temperature to prepare the polyvinyl alcohol crosslinked thiolated hyaluronic acid/polyvinyl alcohol film. The film is used as the back lining layer of the drug carrier to control the one-way release of the drug. The invention expands the application range of the polymer film and provides a new back lining layer material for the drug carrier.
Description
Technical field
The invention belongs to technical field of polymer materials, be specifically related to a kind of polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film and preparation method thereof and application.
Background technology
For improving the effective absorption of medicine at absorption site, reduce drug loss, can design the multilayered structure drug administration carrier that contains the impermeability back sheet, reach the purpose of unidirectional release, raising drug bioavailability.In carriers such as film, sheet, hydrogel, introduce back sheet, form bilayer or multilayer carrier structure, be widely used in oral, cheek mucous membrane, nasal mucosa,, effectively improve the absorption of medicine through route of administration such as skins.The common used material of back sheet is mainly TKK 021 etc. at present, and this type material can effectively avoid medicine to discharge from back sheet, the unidirectional release of control medicine; But because TKK 021 is insoluble in the water; Swelling property is lower, with swelling property preferably when material prepn bilayer or multilayered structure carrier, because of the material swelling property differs bigger; Breaking, coming off can appear in back sheet in the aqueous solution, causes drug loss.
Z 150PH (PVA) is a kind of widely used water-soluble high-molecular material, has good film-forming properties, emulsifying property, agglutinating value(of coal), safety non-toxic, and nonirritant can slowly be degraded in vivo.As a kind of bio-medical material commonly used, PVA can be used for preparing variety carrier such as hydrogel, film, and physical strength is better, has in fields such as drug delivery system and biomedical engineerings more widely to use.
The sulfhydrylation mucinase is the mucinase carboxyl is modified gained through sulfhydryl compound a high molecular polymer; Not only has good mucosa adhesion of sulfhydrylation polymkeric substance and situ-gel character; Also keep characteristics such as mucinase physiologically acceptable, biodegradable, high water conservation, can be used for preparing drug administration carriers such as gel, matrix tablet and tissue engineering bracket etc.
Summary of the invention
The purpose of this invention is to provide a kind of polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film.
Another object of the present invention provides the application of a kind of polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film as the drug administration carrier back sheet, to overcome the deficiency of prior art.
The present invention is a material with biodegradable sulfhydrylation mucinase and Z 150PH (PVA); Through LUTARALDEHYDE (GA) cross-linking polyvinyl alcohol; Room temperature vacuum-drying; Make polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film, as the back sheet of pharmaceutical carrier, the unidirectional release of control medicine.
Polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film of the present invention can obtain with following method: the mixing solutions of preparation sulfhydrylation mucinase and Z 150PH, add the glutaraldehyde cross-linking Z 150PH, and room temperature vacuum-drying promptly gets.
In described polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film, the mass ratio of sulfhydrylation mucinase and Z 150PH is 1:10-1:1.
In described polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film, the LUTARALDEHYDE consumption is the 0.1%-1% of Z 150PH quality.
Described hyaluronan molecule amount is 1.98 * 10
4-5 * 10
6Da, preferred molecular weight is 1 * 10
5-1.5 * 10
6Da.Molecular weight is too high, and solution is too sticky in the preparation process, is unfavorable for material and linking agent homodisperse; Molecular weight is low excessively, and solution viscosity and viscoelasticity are lower, and the gained material fragility is bigger.
Described sulfhydrylation mucinase is one or more of mucinase-halfcystine, mucinase-thioethanolamine, mucinase-homocysteine, mucinase-acthiol-J, mucinase-ethycysteine.
Described sulfhydrylation mucinase, every relatively gram sulfhydrylation mucinase, covalently bound free sulfhydryl groups content are 10-500 μ mol/g, disulfide bond content is 0-1000 μ mol/g.
Described polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film, the thickness of film are 25-500 μ m.
Polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film of the present invention can be used as the back sheet of pharmaceutical carrier, and carrier comprises sheet, film, gel etc., is applied to oral, mucous membrane, through multiple route of administration such as skins.
The invention has the advantages that:
(1) used sulfhydrylation mucinase and the Z 150PH of the present invention is Biodegradable material, and biocompatibility is good;
(2) polyvinyl alcohol crosslinked sulfhydrylation mucinase of the present invention/polyvinyl alcohol film compact structure can prevent effectively that medicine from discharging from back sheet;
(3) polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film of the present invention is compared with traditional ethyl cellulose, has swelling behavior preferably, is used for swelling property carrier preferably, is difficult for breaking or separating.
Description of drawings
Fig. 1 is the SEM figure of the crosslinked mucinase-thioethanolamine of embodiment 2PVA/PVA film as back sheet.
Fig. 2 is the crosslinked mucinase-thioethanolamine of the embodiment 2PVA/PVA film drug release curve when making to carry the back sheet of Regular Insulin multilayer film.
Embodiment
Further describe the present invention through specific embodiment below.But they are not to qualification of the present invention.
Embodiment 1
(the hyaluronan molecule amount is 1 * 10 to take by weighing 0.02 g mucinase-halfcystine
5), put in the weighing bottle (25 mm * 25 mm), add 1 mL water dissolution, concentration is mucinase-halfcystine solution of 2%; Add 0.1 g PVA, dissolve the back and add 10 μ L, 5% GA, 12 h are placed in the room temperature sealing, put the vacuum-drying of vacuum drying oven room temperature, get the crosslinked mucinase-halfcystine/PVA film of PVA.
Embodiment 2
(the hyaluronan molecule amount is 5 * 10 to take by weighing 0.01 g mucinase-thioethanolamine
5), put in the weighing bottle (25 mm * 25 mm), add 1 mL water dissolution, concentration is mucinase-halfcystine solution of 1%; Add 0.05 g PVA, dissolve the back and add 10 μ L, 5% GA, 12 h are placed in the room temperature sealing, put the vacuum-drying of vacuum drying oven room temperature, get the crosslinked mucinase-thioethanolamine/PVA film of PVA.
Embodiment 3
(the hyaluronan molecule amount is 1.5 * 10 to take by weighing 0.01 g mucinase-homocysteine
6), put in the weighing bottle (25 mm * 25 mm), add 1 mL water dissolution, concentration is mucinase-homocysteine solution of 1%; Add 0.02 g PVA, dissolve the back and add 4 μ L, 5% GA, 12 h are placed in the room temperature sealing, put the vacuum-drying of vacuum drying oven room temperature, get the crosslinked mucinase-homocysteine/PVA film of PVA.
(the hyaluronan molecule amount is 1.98 * 10 to take by weighing 0.05 g mucinase-acthiol-J
4), put weighing bottle (among the 25mm * 25mm), add 1 mL water dissolution, concentration is mucinase-acthiol-J solution of 5%; Add 0.05 g PVA, dissolve the back and add 1 μ L, 5% GA, 12 h are placed in the room temperature sealing, put the vacuum-drying of vacuum drying oven room temperature, get the crosslinked mucinase-acthiol-J/PVA film of PVA.
Embodiment 5
(the hyaluronan molecule amount is 2 * 10 to take by weighing 0.01 g mucinase-ethycysteine
5), put weighing bottle (among the 25mm * 25mm), add 1 mL water dissolution, concentration is mucinase-ethycysteine solution of 2%; Add 0.1 g PVA, dissolve the back and add 4 μ L, 5% GA, 12 h are placed in the room temperature sealing, put the vacuum-drying of vacuum drying oven room temperature, get the crosslinked mucinase-ethycysteine/PVA film of PVA.
Crosslinked mucinase-thioethanolamine/PVA the film of the PVA of embodiment 2 gained is used as the back sheet that carries the Regular Insulin multilayer film, and profile carries out sem (SEM) to be observed.Shown in accompanying drawing 1, the back sheet compact structure, it is easy to differentiate with drug-loaded layer, does not have division, and backing layer thickness is about 50 μ m.
Embodiment 7
Crosslinked mucinase-thioethanolamine/PVA the film of the PVA of embodiment 2 gained is used as the back sheet that carries the Regular Insulin multilayer film, investigates the release of Regular Insulin from the film both sides with the Valia-Chien diffusion cell.To carry the Regular Insulin multilayer film and put between two diffusion cells, the phosphate buffered saline buffer that adds 5 mL pH 7.4 in both sides respectively is as release medium, and 37 ° of C are hatched timing sampling.The release of Regular Insulin can be known that by accompanying drawing 2 insulin release of back sheet side is less, shows that the crosslinked mucinase-thioethanolamine of PVA/PVA film can effectively stop the diffusion of Regular Insulin, the unidirectional release of control medicine.
Claims (8)
1. the preparation method of a polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film; It is characterized in that concrete steps are following: the mixing solutions of preparation sulfhydrylation mucinase and Z 150PH; Add the glutaraldehyde cross-linking Z 150PH, room temperature vacuum-drying promptly gets; Wherein:
The used sulfhydrylation mucinase and the mass ratio of Z 150PH are 1:10-1:1;
The LUTARALDEHYDE consumption is the 0.1%-1% of Z 150PH quality;
The hyaluronic molecular weight of described sulfhydrylation is 1.98 * 10
4-5 * 10
6Da;
Described sulfhydrylation mucinase is one or more of mucinase-halfcystine, mucinase-thioethanolamine, mucinase-homocysteine, mucinase-acthiol-J, mucinase-ethycysteine.
2. the preparation method of polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film according to claim 1; It is characterized in that every relatively gram sulfhydrylation mucinase; Covalently bound free sulfhydryl groups content is 10-500 μ mol/g, and disulfide bond content is 0-1000 μ mol/g.
3. the preparation method of polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film according to claim 1 and 2, the thickness that it is characterized in that film is 25-500 μ m.
4. the polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film for preparing like the said method of one of claim 1-3.
5. polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film as claimed in claim 4 is as the application of pharmaceutical carrier back sheet.
6. application according to claim 5 is characterized in that described pharmaceutical carrier is sheet, film or gel.
7. polyvinyl alcohol crosslinked sulfhydrylation mucinase/polyvinyl alcohol film as claimed in claim 4 is as the application of pharmaceutical carrier back sheet in drug delivery system.
8. application according to claim 7, the route of administration that it is characterized in that described drug delivery system are oral, mucous membrane or through skin.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105999536A CN102070791B (en) | 2010-12-22 | 2010-12-22 | Polyvinyl alcohol crosslinked thiolated hyaluronic acid/polyvinyl alcohol film and preparation method and application thereof |
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|---|---|---|---|
| CN2010105999536A CN102070791B (en) | 2010-12-22 | 2010-12-22 | Polyvinyl alcohol crosslinked thiolated hyaluronic acid/polyvinyl alcohol film and preparation method and application thereof |
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|---|---|
| CN102070791A CN102070791A (en) | 2011-05-25 |
| CN102070791B true CN102070791B (en) | 2012-08-01 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1515232A (en) * | 2003-01-09 | 2004-07-28 | 成都博联医疗信息产业有限责任公司 | Preparation method of medical film for dentistry |
| CN1961974A (en) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | Nano copolymer fibrous membrane material capable of being biodegraded and absorbed and preparation process and use thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9902652D0 (en) * | 1999-02-05 | 1999-03-31 | Fermentech Med Ltd | Process |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1515232A (en) * | 2003-01-09 | 2004-07-28 | 成都博联医疗信息产业有限责任公司 | Preparation method of medical film for dentistry |
| CN1961974A (en) * | 2005-11-09 | 2007-05-16 | 中国科学院化学研究所 | Nano copolymer fibrous membrane material capable of being biodegraded and absorbed and preparation process and use thereof |
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| CN102070791A (en) | 2011-05-25 |
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