CN113181141A

CN113181141A - Flurbiprofen gel plaster and preparation method thereof

Info

Publication number: CN113181141A
Application number: CN202110441973.9A
Authority: CN
Inventors: 俞帮和; 俞洋; 徐�明; 蒋志刚
Original assignee: Hangzhou Rende Pharmaceutical Co ltd
Current assignee: Hangzhou Rende Pharmaceutical Co ltd
Priority date: 2021-04-23
Filing date: 2021-04-23
Publication date: 2021-07-30
Anticipated expiration: 2041-04-23
Also published as: CN113181141B

Abstract

The invention relates to the technical field of medicinal preparations, and discloses a flurbiprofen gel plaster and a preparation method thereof. The flurbiprofen gel plaster comprises a back lining layer and a drug-containing ointment, wherein the drug-containing ointment comprises flurbiprofen emulsion, a gel matrix and a pH regulator; the gel matrix comprises the following raw materials in parts by weight: 50-60 parts of sodium polyacrylate, 15-20 parts of gelatin, 3-5 parts of slow-release gelatinase, 0.5-2.5 parts of cross-linking agent, 3-8 parts of transdermal enhancer, 30-60 parts of humectant and 200 parts of water 150-; the slow-release gelatinase is a microcapsule embedded with gelatinase and prepared by taking sodium alginate and chitosan as shell raw materials; the pH of the ointment containing the medicine is 5.0-6.0. The gel plaster can promote the release of flurbiprofen by slowly releasing the gelatinase, and prevent the drug effect of the plaster from lasting for a limited time due to slow release of the drug at the later stage of application.

Description

Flurbiprofen gel plaster and preparation method thereof

Technical Field

The invention relates to the technical field of medicinal preparations, in particular to a flurbiprofen gel plaster and a preparation method thereof.

Background

Flurbiprofen (FP) is named as (+/-) -2- (2-fluoro-4-biphenyl) -propionic acid in chemical name, is a propionic acid non-steroidal anti-inflammatory drug (NSAIDs), has the effects of easing pain, diminishing inflammation and relieving fever, is clinically used for treating diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and the like, and has the advantages of high efficiency, low toxicity, low side effect and good tolerance compared with the traditional non-steroidal anti-inflammatory analgesic, so that the flurbiprofen has wide market prospect.

However, oral flurbiprofen causes great stimulation to gastrointestinal tracts, and transdermal administration by using the plaster can improve the drug concentration of the flurbiprofen at pain parts, and does not reduce adverse reactions of oral administration. As one of the common plaster types, the gel plaster (also called cataplasm) is prepared by uniformly mixing a medicament and a proper hydrophilic matrix and then coating the mixture on the surface of a backing material, and compared with the traditional rubber plaster, the gel plaster has better affinity, permeability, sweat resistance and repeated adhesion, has no obvious sensitization and irritation to the skin, has good application comfort and is beneficial to promoting the penetration and absorption of the contained medicament, so the gel plaster is the main medicament form of the flurbiprofen transdermal administration at present.

For example, chinese patent publication No. CN100502852C discloses a flurbiprofen cataplasm and a method for preparing the same, wherein the flurbiprofen cataplasm comprises a backing layer, a drug reservoir and a protective film, and the drug reservoir comprises flurbiprofen powder or flurbiprofen emulsion, a hydrophilic cataplasm matrix, a permeation enhancer and an additive. The flurbiprofen cataplasm has the advantages of large drug loading, good moisture retention and air permeability, convenient use, obvious curative effect and no side effects such as sensitization, but also has the following problems: in the early stage of application, the content of flurbiprofen in the plaster is high, so that the medicine release speed is high, but in the later stage of application, along with the reduction of the content of flurbiprofen in the plaster, the medicine release speed is too low, so that the effective exertion of the pain and the inflammation diminishing effect is difficult, and the duration of the medicine effect of the plaster is limited.

Disclosure of Invention

In order to solve the technical problems, the invention provides a flurbiprofen gel plaster and a preparation method thereof. The gel plaster can promote the release of flurbiprofen by slowly releasing gelatinase, and prevent the drug effect of the plaster from lasting for a limited time due to slow release in the later stage of application.

The specific technical scheme of the invention is as follows:

a flurbiprofen gel patch comprises a back lining layer and a drug-containing paste, wherein the drug-containing paste comprises flurbiprofen emulsion, a gel matrix and a pH regulator; the gel matrix comprises the following raw materials in parts by weight: 50-60 parts of sodium polyacrylate, 15-20 parts of gelatin, 3-5 parts of slow-release gelatinase, 0.5-2.5 parts of cross-linking agent, 3-8 parts of transdermal enhancer, 30-60 parts of humectant and 200 parts of water 150-; the slow-release gelatinase is a microcapsule embedded with gelatinase and prepared by taking sodium alginate and chitosan as shell raw materials; the pH of the ointment containing the medicine is 5.0-6.0.

In the gel plaster, the sodium polyacrylate and the gelatin can form a cross-linking network, and play a role of a skeleton in the ointment-containing body, and the cross-linking agent can further improve the cross-linking degree and the stability of the cross-linking network; the pH of the ointment containing the medicine is adjusted to 5.0-6.0 by adopting the pH regulator, so that the ointment keeps better stability and is close to the normal pH range of human skin, and the application comfort level is higher.

In the slow-release gelatinase used by the invention, the polymer is adopted to embed the gelatinase, and in the process of applying the gel plaster, the gelatinase slowly permeates out of the polymer shell and contacts with gelatin to break molecular chains of the gelatinase and destroy a cross-linked network structure in a gel matrix, so that the release of the flurbiprofen loaded in the gelatin shell is promoted, the problem that the release speed of the medicine is slowed down in the later period of application is solved, the release speed of the medicine is more uniform in the period of application, and the duration time of the medicine effect of the plaster can be prolonged.

In the test process, the inventor finds that due to the poor flowability of a gel matrix and other reasons, when single sodium alginate is used for embedding the gelatinase, the release rate of the gelatinase is low, the optimum pH of the gelatinase is about 7.0, and the activity of the gelatinase is low at the pH of 5.0-6.0, so that the problem that the release speed of the medicine is slow in the later stage of plaster application cannot be effectively solved. Therefore, the invention adopts sodium alginate and chitosan to embed the gelatinase, in the embedding process, part of sodium ions in the sodium alginate are coated on the surface of the gelatinase after sodium-calcium ion exchange, wherein chitosan is inserted in the sodium alginate, and when the pH value is adjusted to 5.0-6.0 in the preparation process of the medicine-containing paste, the chitosan can be dissolved at the pH value, so that the finally obtained shell layer has higher porosity, thereby accelerating the release of the gelatinase.

Preferably, in the shell raw material for slowly releasing the gelatinase, the mass ratio of the sodium alginate to the chitosan is 7-10: 1.

The mass ratio of the sodium alginate to the chitosan in the shell raw material can influence the release speed of the gelatinase, namely, when the relative dosage of the sodium alginate is higher, the porosity of a shell layer in which the chitosan is dissolved is too low, the release speed of the gelatinase is too slow, the degradation speed of the gelatin is too slow, and the problem that the release speed of the medicine is slow at the later stage of plaster application is difficult to effectively solve; when the relative dosage of the chitosan is too high, the porosity of the shell layer after the chitosan is dissolved is too high, and the gelatin is rapidly degraded, so that the flurbiprofen is rapidly released during the storage period of the plaster and at the early stage of application, and the duration of the drug effect is too short. According to the invention, the mass ratio of sodium alginate to chitosan is controlled within the range of 7-10:1, so that the release of the medicine in the later application period can be accelerated, and the medicine can be prevented from being released too fast in the storage period and the early application period of the plaster, and the duration of the medicine effect can be effectively prolonged.

Preferably, the preparation method of the slow-release gelatinase is as follows:

(I) adding gelatinase into sodium alginate solution, wherein the mass ratio of gelatinase to sodium alginate is 2-3:1, mixing well, adding dropwise into liquid paraffin containing emulsifier under stirring, and stirring and emulsifying for 10-20min to obtain emulsion;

(II) adding calcium chloride into acetic acid solution of chitosan, and uniformly mixing to obtain mixed solution;

(III) dropwise adding the mixed solution into the emulsion under stirring, continuously stirring for 35-45min after dropwise adding, demulsifying, layering, vacuum filtering, and washing to obtain the slow-release gelatinase.

Further, the mass ratio of the calcium chloride in the step (II) to the sodium alginate in the step (I) is 1: 4-7.

Further, in the step (I), the mass fraction of the sodium alginate in the sodium alginate solution is 2-3 wt%.

Further, in the step (II), the mass fraction of the chitosan in the acetic acid solution of the chitosan is 0.4-0.6 wt%.

Further, in the step (I), the volume ratio of the sodium alginate solution to the liquid paraffin is 1: 5-8.

Further, in the step (II), the mass fraction of acetic acid in the acetic acid solution is 1-2 wt%.

Further, in the step (I), the emulsifier is Span-80, and the volume ratio of the Span-80 to the liquid paraffin is 1: 40-50.

Preferably, the flurbiprofen emulsion comprises the following components in parts by weight: 1-2 parts of flurbiprofen, 6-8 parts of water, 3-8 parts of organic solvent and 1-2 parts of emulsifier.

Further, the preparation method of the flurbiprofen emulsion comprises the following steps: dissolving flurbiprofen in an organic solvent, adding water containing an emulsifier under stirring, and uniformly mixing to obtain the flurbiprofen emulsion.

Further, the organic solvent comprises one or more of liquid paraffin, caprylic capric glyceride and diethyl adipate.

Further, the emulsifier comprises one or more of Tween-20, Span-80 and emulsifier OP.

Preferably, the mass ratio of the flurbiprofen emulsion to the gel matrix is 1: 6-8.

Preferably, the cross-linking agent comprises one or more of aluminum hydroxide, aluminum chloride, aluminum citrate, aluminum potassium sulfate and aluminum glycollate.

Preferably, the pH adjusting agent comprises citric acid and/or tartaric acid.

Preferably, the transdermal enhancer comprises one or more of N, N-dimethylformamide, N-methylpyrrolidone and urea.

Preferably, the humectant comprises one or more of glycerin, propylene glycol, sorbitol, polyethylene glycol.

The preparation method of the flurbiprofen gel plaster comprises the following steps:

(1) preparing flurbiprofen emulsion;

(2) uniformly mixing all the raw materials in the gel matrix to prepare the gel matrix;

(3) adding flurbiprofen emulsion into gel matrix, mixing, adding pH regulator to adjust pH to 5.0-6.0 to obtain ointment containing medicine;

(4) and uniformly coating the ointment containing the medicine on a back lining layer to obtain the flurbiprofen gel plaster.

Compared with the prior art, the invention has the following advantages:

(1) according to the invention, the slow-release gelatinase is added in the paste preparation process, so that the gelatinase can be slowly released, and the release of flurbiprofen at the later stage of application is accelerated, thereby prolonging the duration time of the drug effect of the plaster;

(2) in the sustained-release gelatinase, the gelatinase is embedded by compounding sodium alginate and chitosan in a proper proportion, and after the chitosan is dissolved, the shell layer has higher porosity, the release of the gelatinase is accelerated, and the problem of slow release speed of the medicine in the later period of plaster application is effectively solved.

Drawings

FIG. 1 is an in vitro transdermal release profile of the gel patch of example 1 and comparative examples 1-4;

fig. 2 is an in vitro transdermal release profile of the gel patch of example 3 and comparative example 5.

Detailed Description

The present invention will be further described with reference to the following examples.

General examples

A flurbiprofen gel patch comprises a backing layer and a paste containing drug.

The ointment containing the medicine comprises flurbiprofen emulsion, a gel matrix and a pH regulator. The mass ratio of the flurbiprofen emulsion to the gel matrix is 1: 6-8. The pH of the ointment containing the medicine is 5.0-6.0.

The flurbiprofen emulsion comprises the following components in parts by weight: 1-2 parts of flurbiprofen, 6-8 parts of water, 3-8 parts of organic solvent and 1-2 parts of emulsifier. The organic solvent comprises one or more of liquid paraffin, caprylic capric glyceride and diethyl adipate. The emulsifier comprises one or more of Tween-20, Span-80 and emulsifier OP.

The gel matrix comprises the following raw materials in parts by weight: 50-60 parts of sodium polyacrylate, 15-20 parts of gelatin, 3-5 parts of slow-release gelatinase, 0.5-2.5 parts of cross-linking agent, 3-8 parts of transdermal enhancer, 30-60 parts of humectant and 200 parts of water 150-. The cross-linking agent comprises one or more of aluminum hydroxide, aluminum chloride, aluminum citrate, aluminum potassium sulfate and aluminum glyceroxide. The pH regulator comprises citric acid and/or tartaric acid. The transdermal enhancer comprises one or more of N, N-dimethylformamide, N-methylpyrrolidone and urea. The humectant comprises one or more of glycerol, propylene glycol, sorbitol and polyethylene glycol.

The slow-release gelatinase is a microcapsule which is prepared by taking sodium alginate and chitosan as shell raw materials and is embedded with gelatinase, and the preparation method comprises the following steps:

(I) adding gelatinase into 2-3wt% of sodium alginate solution, wherein the mass ratio of the gelatinase to the sodium alginate is 2-3: 1; after uniformly mixing, dropwise adding the mixture into liquid paraffin containing Span-80 under stirring, wherein the volume ratio of the sodium alginate solution to the liquid paraffin is 1:5-8, and the volume ratio of the Span-80 to the liquid paraffin is 1: 40-50; after the dropwise addition is finished, continuously stirring and emulsifying for 10-20min to obtain an emulsion;

(II) dissolving chitosan in 1-2 wt% acetic acid solution, wherein the mass ratio of sodium alginate in the step (I) to chitosan in the step (II) is 7-10:1, and preparing the acetic acid solution of chitosan, wherein the mass fraction of chitosan in the solution is 0.4-0.6 wt%; adding calcium chloride into acetic acid solution of chitosan, wherein the mass ratio of the calcium chloride in the step (II) to the sodium alginate in the step (I) is 1:4-7, and uniformly mixing to obtain mixed solution;

(1) dissolving flurbiprofen in an organic solvent, adding water containing an emulsifier under stirring, and uniformly mixing to obtain a flurbiprofen emulsion;

Example 1

A flurbiprofen gel patch comprises a backing layer, a medicated paste and a protective film. The ointment containing the medicine comprises flurbiprofen emulsion, a gel matrix and a pH regulator, and the specific formula is shown in table 1.

TABLE 1

(1) preparing the slow-release gelatinase:

(1.1) adding gelatinase into a 2 wt% sodium alginate solution, wherein the mass ratio of the gelatinase to the sodium alginate is 2: 1; after uniformly mixing, dropwise adding the mixture into liquid paraffin containing Span-80 under stirring, wherein the volume ratio of the sodium alginate solution to the liquid paraffin is 1:5, and the volume ratio of the Span80 to the liquid paraffin is 1: 40; after the dropwise addition is finished, continuously stirring and emulsifying for 10min to obtain an emulsion;

(1.2) dissolving chitosan in a 1 wt% acetic acid solution, wherein the mass ratio of sodium alginate in the step (1.1) to chitosan in the step (1.2) is 10:1, and preparing the acetic acid solution of chitosan, wherein the mass fraction of chitosan in the solution is 0.4 wt%; adding calcium chloride into acetic acid solution of chitosan, wherein the mass ratio of the calcium chloride in the step (1.2) to the sodium alginate in the step (1.1) is 1:7, and uniformly mixing to obtain mixed solution;

and (1.3) dropwise adding the mixed solution into the emulsion under stirring, continuously stirring for 35min after dropwise adding is finished, and performing demulsification, layering, vacuum filtration and washing to obtain the slow-release gelatinase.

(2) Adding flurbiprofen into liquid paraffin, heating to dissolve, adding water containing Span-80 under stirring, and mixing to obtain flurbiprofen emulsion.

(3) And uniformly mixing all the raw materials in the gel matrix to obtain the gel matrix.

(4) Adding the flurbiprofen emulsion into the gel matrix, fully mixing, adding citric acid to adjust the pH to 5.2, and obtaining the ointment containing the medicine.

(5) And uniformly coating the ointment-containing paste on a back lining layer, covering a protective film on the ointment-containing paste, slicing and packaging to obtain the flurbiprofen gel plaster.

Example 2

A flurbiprofen gel patch comprises a backing layer, a medicated paste and a protective film. The ointment containing the medicine comprises flurbiprofen emulsion, a gel matrix and a pH regulator, and the specific formula is shown in table 2.

TABLE 2

(1) preparing the slow-release gelatinase:

(1.1) adding gelatinase into a 2.5 wt% sodium alginate solution, wherein the mass ratio of the gelatinase to the sodium alginate is 2.5: 1; after uniformly mixing, dropwise adding the mixture into liquid paraffin containing Span-80 under stirring, wherein the volume ratio of the sodium alginate solution to the liquid paraffin is 1:6, and the volume ratio of the Span80 to the liquid paraffin is 1: 45; after the dropwise addition is finished, continuously stirring and emulsifying for 15min to obtain an emulsion;

(1.2) dissolving chitosan in 1.5 wt% acetic acid solution, wherein the mass ratio of sodium alginate in the step (1.1) to chitosan in the step (1.2) is 10:1, and preparing the acetic acid solution of chitosan, wherein the mass fraction of chitosan in the solution is 0.5 wt%; adding calcium chloride into acetic acid solution of chitosan, wherein the mass ratio of the calcium chloride in the step (1.2) to the sodium alginate in the step (1.1) is 1:6, and uniformly mixing to obtain mixed solution;

and (1.3) dropwise adding the mixed solution into the emulsion under stirring, continuously stirring for 40min after dropwise adding, demulsifying and layering, vacuum-filtering, and washing to obtain the slow-release gelatinase.

(2) Adding flurbiprofen into a mixed solvent of liquid paraffin and caprylic/capric glyceride, heating to dissolve, adding water containing Tween-20 while stirring, and mixing to obtain flurbiprofen emulsion.

(4) Adding flurbiprofen emulsion into gel matrix, mixing, adding tartaric acid to adjust pH to 5.6 to obtain ointment containing medicine.

Example 3

A flurbiprofen gel patch comprises a backing layer, a medicated paste and a protective film. The ointment containing the medicine comprises flurbiprofen emulsion, a gel matrix and a pH regulator, and the specific formula is shown in table 3.

TABLE 3

(1) preparing the slow-release gelatinase:

(1.1) adding gelatinase into a 3wt% sodium alginate solution, wherein the mass ratio of the gelatinase to the sodium alginate is 3: 1; after uniformly mixing, dropwise adding the mixture into liquid paraffin containing Span-80 under stirring, wherein the volume ratio of the sodium alginate solution to the liquid paraffin is 1:8, and the volume ratio of the Span80 to the liquid paraffin is 1: 50; after the dropwise addition is finished, continuously stirring and emulsifying for 20min to obtain an emulsion;

(1.2) dissolving chitosan in 2 wt% acetic acid solution, wherein the mass ratio of sodium alginate in the step (1.1) to chitosan in the step (1.2) is 7:1, and preparing the acetic acid solution of chitosan, wherein the mass fraction of chitosan in the solution is 0.6 wt%; adding calcium chloride into acetic acid solution of chitosan, wherein the mass ratio of the calcium chloride in the step (1.2) to the sodium alginate in the step (1.1) is 1:4, and uniformly mixing to obtain mixed solution;

and (1.3) dropwise adding the mixed solution into the emulsion under stirring, continuously stirring for 45min after dropwise adding, demulsifying and layering, vacuum-filtering, and washing to obtain the slow-release gelatinase.

(2) Dissolving flurbiprofen in an organic solvent, adding water containing an emulsifier under stirring, and uniformly mixing to obtain the flurbiprofen emulsion.

(4) Adding flurbiprofen emulsion into gel matrix, mixing, adding citric acid to adjust pH to 6.0 to obtain ointment containing medicine.

Comparative example 1

The comparative example is different from example 1 in that the sustained-release gelatinase is not added, and the rest of the raw materials and the preparation process are the same as those of example 1.

Comparative example 2

This comparative example is different from example 1 in that gelatinase was used directly for the preparation of the gel matrix in step (3) without being subjected to the embedding treatment in step (1), and the remaining raw materials and preparation process were the same as those in example 1.

Comparative example 3

The difference between this comparative example and example 1 is that no chitosan was added in step (1.2), i.e., the shell layer of the sustained-release gelatinase did not contain chitosan, and the rest of the raw materials and the preparation process were the same as those in example 1.

Comparative example 4

The difference between the comparative example and the example 1 is that the mass ratio of the sodium alginate in the step (1.1) to the chitosan in the step (1.2) is 13:1, and the rest of the raw materials and the preparation process are the same as those in the example 1.

Comparative example 5

The difference between the comparative example and the example 3 is that the mass ratio of the sodium alginate in the step (1.1) to the chitosan in the step (1.2) is 5:1, and the rest of the raw materials and the preparation process are the same as those in the example 3.

Test example

The gel patches obtained in examples 1-3 and comparative examples 1-5 were subjected to in vitro transdermal release tests by methods described in reference "selection of ibuprofen ointment penetration enhancer and determination of in vitro transdermal release rate" (zi\29783; "crystal, kingdom, anyone, J. Pharma., 1992, 6 th, 346-347), in which the transdermal release rates were measured and recorded at 1h, 2h, 4h, 6h, 8h, and 12h, respectively, and the results are shown in Table 4 and FIG. 1 and FIG. 2 (unit of transdermal release rate%).

TABLE 4

	0h	1h	2h	4h	6h	8h	12h
								Example 1	0	9.3	16.7	28.3	37.9	44.8	52.0
Example 2	0	8.9	16.6	27.5	37.6	43.6	49.6
								Example 3	0	8.7	16.5	28.0	37.2	43.3	48.5
Comparative example 1	0	8.9	15.4	24.0	29.2	32.9	35.7
								Comparative example 2	0	8.6	16.1	26.2	30.8	34.4	37.1
Comparative example 3	0	8.8	14.9	25.2	31.9	36.0	39.7
								Comparative example 4	0	9.0	16.0	27.5	34.3	39.2	43.9
Comparative example 5	0	8.7	16.3	25.7	31.8	35.7	39.0

As can be seen from Table 4 and FIG. 1, the transdermal release rate in the later stage of the test of example 1 was significantly higher as compared with those of comparative examples 1 and 2, indicating that the absorption of the drug in the later stage of application could be improved by adding the sustained-release gelatinase of the present invention to the gel base. The reason is that: the slow-release gelatinase can release gelatinase in the application process, so that gelatin molecular chains are broken to destroy a cross-linked network structure in a gel matrix, and the release of flurbiprofen loaded in the gel matrix is promoted; compared with the method for directly using the gelatinase, the invention has the advantages that the gelatinase is embedded in the polymer and can be slowly released, so that the gelatinase is prevented from causing a large amount of cross-linked networks to be damaged in the early stage, a large amount of flurbiprofen released in the early stage cannot be absorbed by the skin, and the release is too slow in the later stage due to the fact that the medicine content in the paste is too low.

As can be seen from Table 4 and FIG. 1, the transdermal delivery rate in the latter stage of the test is significantly higher in example 1 as compared with comparative example 3 and comparative example 4, indicating that the use of sodium alginate alone or the use of chitosan in an amount of too small as compared with the use of sodium alginate and chitosan as the chitosan material in the present invention results in less absorption of the drug in the latter stage of application. The reason is that: when single sodium alginate is used for embedding the gelatinase, the problem that the release speed of the medicine is slow at the later stage of plaster application cannot be effectively solved due to the fact that the release rate of the gelatinase is too low and the activity of the gelatinase is low in a weak acid environment; sodium alginate and chitosan are used for embedding gelatinase, when the pH is adjusted to 5.0-6.0 in the preparation process of the ointment containing medicine, chitosan can be dissolved at the pH, so that the finally obtained shell layer has higher porosity, and the release of the gelatinase is accelerated; if the amount of chitosan is too small, the porosity of the shell layer is low, and the effect of accelerating the release of gelatinase is limited.

As can be seen from Table 4 and FIG. 2, the transdermal release rate in the latter stage of the test is significantly higher in example 3 compared to comparative example 5, indicating that when the amount of chitosan in the shell layer of the sustained-release gelatinase is too large, the absorption of the drug in the latter stage of application is also caused to be small. The reason is that: when the relative dosage of the chitosan is too high, the porosity of the shell layer after the chitosan is dissolved is too high, and the gelatin is rapidly degraded, so that the flurbiprofen can be rapidly released in the early stage of plaster application, and the drug release in the later stage of plaster application is too slow.

The raw materials and equipment used in the invention are common raw materials and equipment in the field if not specified; the methods used in the present invention are conventional in the art unless otherwise specified.

The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and all simple modifications, alterations and equivalents of the above embodiments according to the technical spirit of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. A flurbiprofen gel plaster comprises a back lining layer and a drug-containing ointment, and is characterized in that the drug-containing ointment comprises a flurbiprofen emulsion, a gel matrix and a pH regulator; the gel matrix comprises the following raw materials in parts by weight: 50-60 parts of sodium polyacrylate, 15-20 parts of gelatin, 3-5 parts of slow-release gelatinase, 0.5-2.5 parts of cross-linking agent, 3-8 parts of transdermal enhancer, 30-60 parts of humectant and 200 parts of water 150-; the slow-release gelatinase is a microcapsule embedded with gelatinase and prepared by taking sodium alginate and chitosan as shell raw materials; the pH of the ointment containing the medicine is 5.0-6.0.

2. The flurbiprofen gel patch as claimed in claim 1, wherein the mass ratio of sodium alginate to chitosan in the shell material of the sustained release gelatinase is 7-10: 1.

3. The flurbiprofen gel patch according to claim 1 or 2, wherein the sustained release gelatinase is prepared by the following method:

4. A flurbiprofen gel patch as claimed in claim 3, wherein the mass ratio of calcium chloride in step (II) to sodium alginate in step (I) is from 1:4 to 7.

5. A flurbiprofen gel patch as claimed in claim 3, wherein:

in the step (I), the mass fraction of sodium alginate in the sodium alginate solution is 2-3 wt%; and/or

In the step (II), the mass fraction of the chitosan in the acetic acid solution of the chitosan is 0.4-0.6 wt%.

6. A flurbiprofen gel patch as claimed in claim 3, wherein in step (I), the volume ratio of the sodium alginate solution to the liquid paraffin is 1: 5-8.

7. The flurbiprofen gel patch according to claim 1, wherein the flurbiprofen emulsion comprises the following ingredients in parts by weight: 1-2 parts of flurbiprofen, 6-8 parts of water, 3-8 parts of organic solvent and 1-2 parts of emulsifier.

8. A flurbiprofen gel patch according to claim 1 or claim 7, wherein the mass ratio of the flurbiprofen emulsion to the gel matrix is from 1:6 to 8.

9. A flurbiprofen gel patch as claimed in claim 1, wherein:

the cross-linking agent comprises one or more of aluminum hydroxide, aluminum chloride, aluminum citrate, aluminum potassium sulfate and aluminum glyceroxide; and/or

The pH regulator comprises citric acid and/or tartaric acid; and/or

The transdermal enhancer comprises one or more of N, N-dimethylformamide, N-methylpyrrolidone and urea; and/or

The humectant comprises one or more of glycerol, propylene glycol, sorbitol and polyethylene glycol.

10. A method of preparing a flurbiprofen gel patch as claimed in any one of claims 1 to 9, comprising the steps of:

(1) preparing flurbiprofen emulsion;