Alcohol gel patch and production process thereof

Abstract

The invention discloses an alcogel patch and a production process thereof, which are characterized in that an alcohol solvent is used as a dispersion medium, medicines or cosmetics with functional components are directly extracted by the alcohol solvent or dissolved and dispersed in the alcohol solvent, and then dispersed in a gel skeleton to form alcogel; in the alcogel, the proportion of the dispersing solvent can reach up to 80%, the alcogel can be formed by using a very small amount of the alcohol dispersing solvent for volatile oil medicines with weak polarity, and the medicines mean that the drug loading capacity can reach close to 80%; the alcohol dispersing solvent is adopted to effectively dissolve and disperse the medicine, and the medicine has good dispersing performance in the alcohol dispersing solvent, so that the phenomenon of local condensation and aggregation in the later stage of the alcohol gel patch is avoided.

Description

Technical Field

[0001] The invention relates to the fields of medicine and cosmetics, and in particular to a gel patch. Background Art

[0002] Hydrogel is a kind of extremely hydrophilic three-dimensional network structure gel, which swells rapidly in water and can retain a large volume of water without dissolving in this swollen state. Due to the presence of a cross-linked network, hydrogel can swell and retain a large amount of water. As a highly water-absorbent and water-retaining material, hydrogel is widely used in many fields, such as: drought resistance in arid areas, facial masks, antipyretic patches, analgesic patches, agricultural films in cosmetics, condensation preventers and humidity regulators in construction, water plugging regulators in petrochemicals, dehydration of crude oil or refined oil, dust suppressants in mining, preservatives and thickeners in food, drug carriers in medical treatment, etc. It has been widely used in the field of medicine, especially in the field of medicine, and is called Babu ointment. In medicine and cosmetics, since hydrogel contains a large amount of water as a dispersion medium, hydrogel has a large drug loading capacity for components with good water solubility, which is one of its biggest advantages. However, for some components with poor water solubility or insoluble in water, other excipients such as surfactants need to be added, or inclusion technology and other methods are used to disperse such components, which greatly increases the production cost.

[0003] For some weakly polar components and non-polar components, such as volatile oil components, inclusion complexation may easily cause drug aggregation and crystallization, resulting in uneven drug distribution. At the same time, for components with poor stability in aqueous systems, they cannot be used as plasters, which greatly limits their application.

[0004] In addition, the photoinitiator generates two free radicals during the cleavage process, which combine with the skeleton material or other free radical species in different ways. The generated free radicals can also further break to produce other free radicals and photoproducts. Studies have shown that a single photoinitiator can produce 12 or more photoproducts. The most direct impact on the product is bad smell and color change. The potential impact is that it may react with drug components to produce toxic components, etc., so the gel needs to be decontaminated. Summary of the invention

[0005] The object of the present invention is to provide an alcohol gel patch with uniform drug distribution, good stability and less impurities.

[0006] Another object of the present invention is to provide a method for producing the above-mentioned alcohol gel patch.

[0007] To achieve the above-mentioned purpose, the present invention provides an alcohol gel patch, which consists of a gel layer and an anti-adhesive protective layer, wherein the gel layer includes a dispersion medium, a skeleton material, an initiator, and a cross-linking agent, wherein the dispersion medium is an alcohol solvent dispersed in a grid-like gel skeleton material, and the quantitative ratio of the initiator, the cross-linking agent, and the skeleton material is (1.5-6.0):(1.5-6.0):(90-110).

[0008] The gel layer contains a drug component.

[0009] The gel layer contains cosmetic ingredients.

[0010] The dispersion medium is one or a combination of plant-extracted ethanol, propylene glycol, glycerol, n-butanol, hexadecanol, octadecyl alcohol, cetostearyl alcohol, and benzyl alcohol.

[0011] The initiator is benzoin and its derivatives, benzil, alkyl phenone, acylphosphine oxide, benzophenone or thioxanthone.

[0012] The initiator is 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone.

[0013] The skeleton material is natural rubber and its hydrolyzate, and a high molecular polymer containing a cis-butadiene or trans-butadiene structure.

[0014] The skeleton material is terminal hydroxy butadiene.

[0015] The cross-linking agent is a compound containing 1 to 3 thiol groups, a compound containing a disulfide bond, or phorone and its derivatives.

[0016] A production process of alcohol gel patch:

[0017] 1) Weigh the skeleton material and stir at high speed;

[0018] 2) Initiator and cross-linker are added sequentially until a uniform emulsion is formed;

[0019] 3) slowly adding the functional components directly extracted by the alcohol solvent or the functional components dissolved by the alcohol solvent to the aforementioned emulsion and stirring at high speed until a uniform dispersion system is formed;

[0020] 4) coating and irradiating with ultraviolet light to obtain an alcohol gel patch.

[0021] After adopting the above scheme, the present invention uses alcohol solvents as dispersion medium, and the functional component drugs or cosmetics are directly extracted or dissolved and dispersed in alcohol solvents by alcohol solvents, and then dispersed in the gel skeleton to form alcohol gel. In the alcohol gel, the proportion of the dispersion solvent can be as high as 80% (dispersion solvent: skeleton material and alcohol solvent). For volatile oil drugs and weak polar drugs, alcohol gel can be formed by using a very small amount of alcohol dispersion solvent, which means that the drug loading for such drugs can reach nearly 80%; the use of alcohol dispersion solvents can effectively dissolve and disperse drugs, and the drugs have good dispersion properties therein, so the alcohol gel patch will not have the phenomenon of local condensation and aggregation in the later stage.

[0022] The degree of dissociation of the alcohol dispersion medium in the alcohol gel patch is extremely low, so the stability of the drug is much better than that of the aqueous system.

[0023] Dispersing solvents are divided into bound solvents and free solvents (such as bound water and free water). The drug is dispersed in the solvent, so the drug molecules have better freedom. Compared with pressure-sensitive adhesives, the drug is released more quickly and has a higher utilization rate under the gel system. The surface of skin cells is a lipid bilayer structure, with lipophilic groups in the outer layer and hydrophilic groups in the middle. Alcohol gel is mainly composed of lipophilic components, which has a certain protective effect on the stability of skin cell membranes. Therefore, it has lower skin irritation when applied to the skin surface.

[0024] By adjusting the ratio of initiator to skeleton material and cross-linking agent, the content of all by-products was reduced by more than 90%, and the content was all below 0.1 ppm (how was it achieved).

[0025] The invention is produced at low temperature and room temperature, and has the advantages of simple production process, low raw material cost, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The structure of the alcohol gel patch of the present invention is schematically shown;

[0027] Figure 2 Gel chromatogram of leucopenia;

[0028] Figure 3 In vitro drug release chromatogram of alcohol gel patch. DETAILED DESCRIPTION

[0029] In order to explain the technical content, structural features, achieved objectives and effects of the present invention in detail, the following is a detailed description in conjunction with the implementation methods and the accompanying drawings.

[0030] like Figure 1The alcohol gel patch of the present invention is shown, which is composed of a backing 1, a gel layer 2, and an anti-adhesive protective layer 3. The gel layer includes a dispersion medium, a skeleton material, an initiator, and a cross-linking agent. The dispersion medium is an alcohol solvent including plant-extracted ethanol, propylene glycol, glycerol, n-butanol, hexadecanol, octadecyl alcohol, cetostearyl alcohol, benzyl alcohol, or a combination thereof, which is dispersed in a grid-shaped gel skeleton material. The production process of the present invention is as follows:

[0031] 1) Weigh the skeleton material and stir at high speed;

[0032] 2) Initiator and cross-linker are added sequentially until a uniform emulsion is formed;

[0033] 3) slowly adding the functional components directly extracted by the alcohol solvent or the functional components dissolved by the alcohol solvent to the aforementioned emulsion and stirring at high speed until a uniform dispersion system is formed;

[0034] 4) coating and irradiating with ultraviolet light to obtain an alcohol gel patch.

[0035] The embodiment of the present invention is shown in Appendix 1:

[0036]

[0037]

[0038]

[0039] 1. Stability inspection

[0040] Take the white vein alcohol gel obtained in application example 4, put it into a stable incubator together with the commercial white vein ointment, and place it under the conditions of 40°C and 75% relative humidity for one month, and then use HPLC to detect it with curcumin as the evaluation index. The results show that the degradation rate of the white vein alcohol gel in the one-month accelerated experiment is about 0.1, while the degradation rate of the white vein ointment is 6%, indicating that the water-based unstable component has good stability in the alcohol gel, and such components can be considered to replace the ointment and hydrogel with alcohol gel. In the hydrogel, water molecules can be divided into bound water and free water according to their distribution. Free water will "escape" from the hydrogel as the environment changes, and the phenomenon of local condensation will occur, just as we have observed that water droplets appear in the patch bag after heating. The drug in the alcohol gel is dispersed in an alcohol solvent and combined with the skeleton material is relatively stable, so it is not easy to have the phenomenon of local condensation as the environment changes.

[0041] 3. Alcohol gel release test

[0042] Using pig skin as raw material, white vein alcohol gel, and blank alcohol gel, after 1 hour, take a small piece of pig skin, rinse the surface of the pig skin with ethanol, then cut it into pieces and add physiological saline, make a homogenate, then extract with n-hexane, and filter the extract as the sample to be tested. Using asarone as an evaluation index, GC-MS is used for sample detection, such as Figure 3 The results show that a higher content of asarone can be detected in the pig skin sample of the alcohol gel, while no asarone can be detected in the blank alcohol gel, indicating that the drug in the alcohol gel has a good release rate.

[0043] Transdermal drug release includes two aspects: one is that the drug can penetrate the matrix barrier, and the other is that the drug can penetrate the skin barrier and enter the body through osmotic pressure to exert local or systemic effects. In the gel system, the dispersion solvent is divided into a bound solvent and a free solvent (such as bound water and free water). The drug is dispersed in the solvent, so the drug molecules have better freedom. Compared with pressure-sensitive adhesives, the drug is released more rapidly and has a higher utilization rate under the gel system. The surface of skin cells is a lipid bilayer structure, with lipophilic groups in the outer layer and hydrophilic groups in the middle. Alcohol gel is mainly composed of lipophilic components, which have a certain protective effect on the stability of the skin cell membrane. Therefore, it has lower skin irritation when applied to the skin surface.

[0044] In order to increase the air permeability of the alcohol gel patch, the present invention introduces air in the fourth step of the process. During the stirring process, a certain amount of air is continuously introduced to make the glue liquid become cavitational, and then it is quickly coated with ultraviolet light for curing to obtain a foamy alcohol gel, which can solve the problem of poor air permeability of the gel.

[0045] The research of transdermal patches has become one of the hot spots of new drug research in the pharmaceutical industry at home and abroad. Some progress has been made, but there are still many problems. The development of pharmaceutical polymer materials cannot meet the needs of research and production. Improving drug utilization, reducing skin irritation, improving stability, reducing production costs, and green production are all factors that need to be considered. Alcohol gel has largely made up for some of the problems of existing patches.

[0046] Since the drug loading capacity of the present invention is relatively large, the patch can be made into a smaller area, and can also be made into small patches of different shapes according to body characteristics or have corresponding patterns designed thereon.

[0047] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. An alcohol gel patch, consisting of a gel layer and an anti-adhesive protective layer, wherein the gel layer includes a dispersion medium, a skeleton material, an initiator, and a cross-linking agent, characterized in that: The dispersion medium is an alcohol solvent, which is dispersed in a grid-shaped gel skeleton material. The quantitative ratio of the initiator, the cross-linking agent and the skeleton material is (1.5-6.0):(1.5-6.0):(90-110).

2. An alcohol gel patch as claimed in claim 1, characterized in that: The gel layer contains a drug component.

3. An alcohol gel patch as claimed in claim 1, characterized in that: The gel layer contains cosmetic ingredients.

4. An alcohol gel patch as claimed in claim 1, characterized in that: The dispersion medium is one or a combination of plant-extracted ethanol, propylene glycol, glycerol, n-butanol, hexadecanol, octadecyl alcohol, cetostearyl alcohol, and benzyl alcohol.

5. An alcohol gel patch as claimed in claim 1, characterized in that: The initiator is benzoin and its derivatives, benzil, alkyl phenone, acylphosphine oxide, benzophenone or thioxanthone.

6. An alcohol gel patch as claimed in claim 5, characterized in that: The initiator is 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone.

7. An alcohol gel patch as claimed in claim 1, characterized in that: The skeleton material is natural rubber and its hydrolyzate with a molecular weight greater than 42,000, and a high molecular polymer containing a cis-butadiene or trans-butadiene structure.

8. An alcohol gel patch as claimed in claim 7, characterized in that: The skeleton material is terminal hydroxy butadiene.

9. An alcohol gel patch as claimed in claim 1, characterized in that: The cross-linking agent is a compound containing 1 to 3 thiol groups, a compound containing a disulfide bond, or phorone and its derivatives.

10. A process for producing an alcohol gel patch, characterized in that: 1) Weigh the skeleton material and stir at high speed; 2) Initiator and cross-linker are added sequentially until a uniform emulsion is formed; 3) slowly adding the functional components directly extracted by alcohol solvent or the functional components dissolved by alcohol solvent to the aforementioned emulsion and stirring at high speed until a uniform dispersion system is formed; 4) coating and irradiating with ultraviolet light to obtain an alcohol gel patch.

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