Efficient transdermal permeation preparation and preparation method thereof

Abstract

The invention provides a high-efficiency transdermal permeation preparation. The high-efficiency transdermal permeation preparation comprises the following components: isosorbide dimethyl ether, inositol, tetrahydropiperine, an Odorsi seaweed extract, a rhodiola rosea root extract, an aloe extract, deionized water and the like. More effective components are obtained by self-preparing the Odorsi seaweed extract, the Rhodiola rosea root extract and the aloe extract; all the components are combined to form a mixture with high fat solubility, the efficient transdermal permeation effect is achieved, and the prepared transdermal permeation preparation is free of irritation to skin and does not cause inflammation.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of permeation preparations, and specifically relates to a highly efficient transdermal permeation preparation and a preparation method thereof. Background Art

[0002] In the process of drug penetration through the skin, the hard lamellae structure of the stratum corneum lipids forms a barrier to drug penetration. The stratum corneum limits the rate at which drugs penetrate the skin, and the penetration rate is usually very slow. Therefore, transdermal applications are not suitable for delivering large amounts of drugs in a short period of time. Transdermal applications are more commonly used to deliver drugs continuously over an extended period of time.

[0003] Transdermal formulations often include permeation enhancers to improve the rate at which a drug penetrates the skin; permeation enhancers may act by disrupting the highly ordered structure of stratum corneum lipids, interacting with intercellular proteins, and / or improving the partitioning of the drug into the stratum corneum.

[0004] Patent CN105188686A proposes a transdermal preparation, comprising a hydroxyl-free solvent, a non-heterocyclic ester solvent and / or a tripropylene glycol alkyl ether, which can be used to deliver a variety of active ingredients and combinations thereof to mammals transdermally; Patent CN103179970A proposes a transdermal absorption preparation, containing 4-{3-[4-(3-{4-[amino(imino)methyl]phenoxy}propyl)-1-piperidinyl]propoxy}benzamidine or its salt and a transdermal absorption enhancer, which can effectively treat fungal infections. However, one problem with transdermal preparations is that these penetration enhancers can cause skin irritation and inflammation. Therefore, it is necessary to develop a transdermal preparation that is non-irritating to the skin and has a good penetration effect. Summary of the invention

[0005] The purpose of the present invention is to provide a high-efficiency transdermal permeation preparation and a preparation method thereof, wherein an extract of Algae ostreatus, a root extract of Rhodiola rosea and an aloe extract are used as improving agents, and under the action of dimethyl isosorbide, inositol, tetrahydropiperine and the like, a high-efficiency transdermal permeation effect is achieved, and the prepared transdermal permeation preparation has no irritation to the skin and does not cause inflammation.

[0006] In order to achieve the above object, the present invention provides the following technical solutions: A highly effective transdermal permeation preparation comprises the following components by weight: 75-95 parts of dimethyl isosorbide, 0.1-3 parts of inositol, 0.1-3 parts of tetrahydropiperine, 0.1-0.3 parts of kelp extract, 0.5-3 parts of rhodiola rosea root extract, 0.5-3 parts of aloe extract and 5-10 parts of deionized water.

[0007] Furthermore, in terms of weight, the preferred components are: 86 parts of dimethyl isosorbide, 2.5 parts of inositol, 1 part of tetrahydropiperine, 0.2 parts of Algae extract, 2 parts of Rhodiola rosea root extract, 3 parts of aloe extract, and 7.5 parts of deionized water.

[0008] The preparation method of the above-mentioned high-efficiency transdermal permeation preparation comprises the following steps: S1: preparing the extract of Algae ostreatus, the extract of Rhodiola rosea root and the extract of Aloe vera respectively; S2: In parts by weight, at a temperature of 35-45° C., 0.1-0.3 parts of the Algae extract, 0.5-3 parts of the Rhodiola rosea root extract and 0.5-3 parts of the Aloe vera extract in step S1 are added dropwise in sequence while stirring, and after the addition is completed, the mixture is stirred at a rate of 500-700 r / min for 20-50 min to obtain liquid A; S3: In parts by weight, 0.1-3 parts of inositol, 0.1-3 parts of tetrahydropiperine and 5-10 parts of deionized water are stirred at a rate of 400-600 r / min for 10-20 min to obtain liquid B; S4: Mix the liquid A obtained in step S2 and the liquid B obtained in step S3, and stir at a temperature of 70-90° C. and a speed of 800-1000 r / min for 1-3 h to obtain a highly efficient transdermal permeation preparation.

[0009] Furthermore, the preparation process of the Osmanthus algae extract obtained in step S1 is as follows: by weight, take 0.1-0.5 parts of Osmanthus algae powder, add 30-60 parts of deionized water, heat to 65-85°C and soak for 1-2h; under nitrogen protection, heat to 100-110°C and extract for 1.5-3h; after cooling, add 0.1-0.2 parts of Kalibik Mayer yeast, keep the temperature at 30-35°C, and ferment for 5-9 days; after filtering, the filtrate is concentrated at a pressure of 0.01-0.03Mpa and a temperature of 50-60°C for 20-40min to obtain the Osmanthus algae extract.

[0010] Furthermore, the optimized process of the Oswald Seaweed extract is as follows: by weight, take 0.3 parts of Oswald Seaweed powder, add 45 parts of deionized water, heat to 70°C and soak for 1.5 hours; under nitrogen protection, heat to 105°C and extract for 2 hours; after cooling, add 0.015 parts of Kalibik Meyer yeast, keep the temperature at 32°C, and ferment for 7 days; after filtering, the filtrate is concentrated at a pressure of 0.02Mpa and a temperature of 55°C for 30 minutes to obtain the Oswald Seaweed extract; the Kalibik Meyer yeast was purchased from Ningbo Mingzhou Biotechnology Co., Ltd.

[0011] Furthermore, the preparation process of the Rhodiola rosea root extract obtained in step S1 is as follows: by weight, 0.5-3 parts of Rhodiola rosea powder and 80-120 parts of anhydrous ethanol are mixed, and the mixture is immersed and extracted at a temperature of 85-95°C for 30-60 minutes; in a supercritical extraction device, carbon dioxide supercritical fluid is used, and the temperature is 40-60°C, the pressure is 30-40MPa, and the flow rate is 300-500L / h. Extraction is performed for 2-4 hours to obtain the Rhodiola rosea root extract.

[0012] Furthermore, the preparation process of Rhodiola rosea root extract was optimized as follows: 0.5 parts of Rhodiola rosea powder and 100 parts of anhydrous ethanol were mixed, and the mixture was immersed and extracted at a temperature of 90°C for 45 minutes; carbon dioxide supercritical fluid was used, and the temperature was 55°C, the pressure was 36 MPa, and the flow rate was 400 L / h. The extraction was performed for 2.5 hours to obtain the Rhodiola rosea root extract.

[0013] Furthermore, the preparation process of the aloe extract in step S1 is as follows: by weight, 0.5-3 parts of aloe are added to 55-65 parts of deionized water, and then 0.1-0.3 parts of cellulase and 0.2-0.8 parts of pectinase are added, and enzymolysis is performed at a temperature of 40-50°C for 2-4 hours; then the temperature is increased to 100-120°C, and reflux extraction is performed for 1-2 hours; and the aloe extract is obtained after filtration.

[0014] Furthermore, the preparation process of aloe extract is optimized as follows: by weight, 7 parts of aloe are added to 60 parts of deionized water, and then 0.2 parts of cellulase and 0.6 parts of pectinase are added, and enzymolysis is performed at a temperature of 45°C for 3.5 hours; then the temperature is increased to 116°C, and reflux extraction is performed for 1.5 hours; and the aloe extract is obtained after filtration.

[0015] Furthermore, step S2 is specifically as follows: in parts by weight, at a temperature of 42° C., 0.2 parts of the Algae extract, 3 parts of the Rhodiola rosea root extract and 3 parts of the Aloe extract in step S1 are added dropwise in sequence while stirring; after the addition is completed, the mixture is stirred at a rate of 650 r / min for 35 minutes to obtain liquid A.

[0016] Compared with the prior art, the advantages and beneficial effects of the present invention are: 1. The present invention uses isosorbide dimethyl ether as a solvent, and under the action of Osmanthus algae extract, Rhodiola rosea root extract, aloe extract, inositol and tetrahydropiperine, it is adjusted to a highly fat-soluble mixture (octanol / water partition coefficient is 100-1000), thereby improving the transdermal property of the preparation and achieving high penetration efficiency.

[0017] 2. In the preparation of the extract of Algae ostreatus, the extract is subjected to nitrogen protection extraction, fermentation with Kalibikerella meyerii yeast, filtration and concentration, etc., and the extraction effect of the active ingredients is better; the content of irritating substances in the extract is small, it is not easy to irritate the skin, and the safety is higher; at the same time, the skin antioxidant effect is enhanced.

[0018] 3. In the preparation of the Rhodiola rosea root extract of the present invention, supercritical carbon dioxide extraction is adopted, which has a short extraction time, high efficiency, high content of active ingredients, less irritating substances, is not easy to cause skin allergies, and enhances immune function.

[0019] 4. In the preparation of aloe extract of the present invention, cellulase and pectinase are used for enzymatic hydrolysis and reflux, which greatly improves the extraction rate of aloe extract and plays an anti-inflammatory, analgesic and immunomodulatory role. DETAILED DESCRIPTION

[0020] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0021] The sources of the substances in the present invention are as follows: Kalibik Mayer yeast was produced by Shanghai Xuanke Biotechnology Co., Ltd., XK-SH-7895, pectinase was produced by Shanghai Yuanye Biotechnology Co., Ltd., item number S10007, and cellulase was produced by Shanghai Yuanye Biotechnology Co., Ltd., item number S10041.

[0022] Example 1 This embodiment provides a method for preparing a highly effective transdermal permeation preparation, comprising the following steps: S1: Take 0.3g of Algae powder, add 10g of deionized water, heat to 65℃ and soak for 1h; under nitrogen protection, heat to 100℃ and extract for 1.5h; after cooling, add 0.1g of Kalibik Mayer yeast, keep the temperature at 30℃, and ferment for 5 days; after filtering, the filtrate is concentrated at a pressure of 0.01Mpa and a temperature of 50℃ for 20min to obtain Algae extract.

[0023] Take 3g of Rhodiola rosea powder and mix it with 80g of anhydrous ethanol, soak and extract at a temperature of 85°C for 30 minutes; in a supercritical extraction equipment, use carbon dioxide supercritical fluid, extract for 2 hours at a temperature of 40°C, a pressure of 30MPa, and a flow rate of 300L / h to obtain the Rhodiola rosea root extract.

[0024] Take 5g of aloe vera and add it to 55g of deionized water, then add 0.1g of cellulase and 0.2 parts of pectinase, and perform enzymolysis at 40°C for 2h; then increase the temperature to 100°C and reflux extraction for 1h; after filtering, the aloe vera extract is obtained.

[0025] S2: At a temperature of 35° C., 0.1 g of the Algae extract, 0.5 g of the Rhodiola rosea root extract and 1 g of the Aloe extract in step S1 were added dropwise at a rate of 30 drops / min to 75 g of isosorbide anhydride dimethyl ether while stirring at a rate of 250 r / min. After the addition was completed, the mixture was stirred at a rate of 500 r / min for 20 min to obtain liquid A; S3: 0.1 g of inositol, 0.1 g of tetrahydropiperine and 10 g of deionized water were stirred at a rate of 400 r / min for 10 min to obtain liquid B; S4: Mix the liquid A obtained in step S2 and the liquid B obtained in step S3, and stir them at a temperature of 70° C. and a speed of 800 r / min for 1 hour to obtain a highly efficient transdermal permeation preparation.

[0026] Example 2 This embodiment provides a method for preparing a highly effective transdermal permeation preparation, comprising the following steps: S1: Take 0.5g of Algae powder, add 10g of deionized water, heat to 85℃ and soak for 2h; under nitrogen protection, heat to 110℃ and extract for 3h; after cooling, add 0.2g of Kalibik Mayer yeast, keep the temperature at 35℃, and ferment for 9 days; after filtering, the filtrate is concentrated at a pressure of 0.03Mpa and a temperature of 60℃ for 40min to obtain Algae extract.

[0027] Take 5g of Rhodiola rosea powder and 120g of anhydrous ethanol, mix them, and soak and extract them at a temperature of 95°C for 60 minutes; in a supercritical extraction equipment, use carbon dioxide supercritical fluid, at a temperature of 60°C, a pressure of 40MPa, and a flow rate of 500L / h, and extract for 4 hours to obtain the Rhodiola rosea root extract.

[0028] Take 10g of aloe vera and add it to 65g of deionized water, then add 0.3g of cellulase and 0.8 parts of pectinase, and perform enzymolysis at 50°C for 4h; then increase the temperature to 120°C and reflux extraction for 2h; after filtering, the aloe vera extract is obtained.

[0029] S2: At a temperature of 45° C., 0.3 g of the Algae extract, 3 g of the Rhodiola rosea root extract and 3 g of the Aloe extract in step S1 were added dropwise at a rate of 60 drops / min to 95 g of isosorbide anhydride dimethyl ether while stirring at a rate of 350 r / min. After the addition was completed, the mixture was stirred at a rate of 700 r / min for 50 min to obtain liquid A; S3: 3 g of inositol, 3 g of tetrahydropiperine and 30 g of deionized water were stirred at a rate of 600 r / min for 20 min to obtain liquid B; S4: Mix the liquid A obtained in step S2 and the liquid B obtained in step S3, and stir at a temperature of 90° C. and a speed of 1000 r / min for 3 h to obtain a highly efficient transdermal permeation preparation.

[0030] Example 3 This embodiment provides a method for preparing a highly effective transdermal permeation preparation, comprising the following steps: S1: Take 0.4g of Algae powder, add 7.5g of deionized water, heat to 70℃ and soak for 1.5h; under nitrogen protection, heat to 105℃ and extract for 2h; after cooling, add 0.015g of Kalibik Mayer yeast, keep the temperature at 32℃, and ferment for 7 days; after filtering, the filtrate is concentrated at a pressure of 0.02Mpa and a temperature of 55℃ for 30min to obtain Algae extract.

[0031] Take 4g of Rhodiola rosea powder and 100g of anhydrous ethanol, mix them, and soak and extract them at a temperature of 90°C for 45 minutes; in a supercritical extraction equipment, use carbon dioxide supercritical fluid, at a temperature of 55°C, a pressure of 36MPa, and a flow rate of 400L / h, extract for 2.5h to obtain the Rhodiola rosea root extract.

[0032] Take 7g of aloe vera and add it to 60g of deionized water, then add 0.2g of cellulase and 0.6 parts of pectinase, and perform enzymolysis at 45°C for 3.5h; then increase the temperature to 116°C and perform reflux extraction for 1.5h; after filtering, the aloe vera extract is obtained.

[0033] S2: At a temperature of 42° C., 0.2 g of the Algae extract, 2 g of the Rhodiola rosea root extract and 3 g of the Aloe extract in step S1 were added dropwise at a rate of 50 drops / min to 80 g of isosorbide anhydride dimethyl ether while stirring at a rate of 300 r / min. After the addition was completed, the mixture was stirred at a rate of 650 r / min for 35 min to obtain liquid A; S3: 2.5 g of inositol, 1.5 g of tetrahydropiperine and 16 g of deionized water were stirred at a rate of 500 r / min for 16 min to obtain liquid B; S4: Mix the liquid A obtained in step S2 and the liquid B obtained in step S3, and stir at a temperature of 85° C. and a speed of 900 r / min for 2.5 h to obtain a highly efficient transdermal permeation preparation.

[0034] Comparative Example 1 The difference between this comparative example and Example 1 is that the commercially available Algae extract from Shanghai Xinkai Pharmaceutical Technology Co., Ltd. is directly added into step S1, and the other steps are the same.

[0035] Comparative Example 2 The difference between this comparative example and Example 1 is that the commercially available Rhodiola rosea root extract produced by Xi'an Tianyi Biotechnology Co., Ltd. is directly added in step S1, and the other steps are the same.

[0036] Comparative Example 3 The difference between this comparative example and Example 1 is that the commercially available aloe extract produced by Shaanxi New Horizon Biotechnology Co., Ltd. is directly added into step S1.

[0037] Comparative Example 4 The difference between this comparative example and Example 1 is that in step S2, the dropping method is not adopted, but direct mixing is adopted, and the other steps are the same.

[0038] Comparative Example 5 The difference between this comparative example and Example 1 is that inositol is missing in step S3, and the other steps are the same.

[0039] Comparative Example 6 The difference between this comparative example and Example 1 is that tetrahydropiperine is missing in step S3, and the other steps are the same.

[0040] Performance Test: Permeability test: refer to GB / T27818-2011 standard for in vitro test methods for skin absorption of chemicals. This test selects suckling pig skin as the test model, and selects suckling pig skin-Franzcell diffusion cell system as the test system; the transdermal permeation preparations prepared in each embodiment and comparative example are subjected to permeability test. Allergy test: 6 rabbits are selected, and the hair on both sides of their backs are removed 24 hours before administration, and the hair removal area is about 5cm×5cm on each side; the transdermal permeation preparation is applied to the hair removal area on the back of the rabbit, and removed after 6 hours, and the skin allergic reaction is observed immediately, and the situation is observed again after 12 hours. The test results are shown in the following table.

[0041] Table 1 Performance test results

[0042] From the above performance test results, it can be seen that Examples 1-3 have good permeability and non-sensitivity; in particular, the comprehensive performance of Example 3 is the most outstanding. However, since Comparative Examples 1-6 do not adopt the necessary technical solutions, their corresponding performance tests are significantly worse than those of the Examples. The above experimental results further prove the importance of the technical solutions defined in the present invention for its technical effects.

[0043] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A highly effective transdermal permeation preparation, characterized in that: The invention comprises the following components in parts by weight: 75-95 parts of isosorbide dimethyl ether, 0.1-3 parts of inositol, 0.1-3 parts of tetrahydropiperine, 0.1-0.3 parts of kelp extract, 0.5-3 parts of rhodiola rosea root extract, 0.5-3 parts of aloe extract and 5-10 parts of deionized water.

2. A highly effective transdermal permeation preparation according to claim 1, characterized in that: In terms of weight, the preferred components are as follows: 86 parts of dimethyl isosorbide, 2.5 parts of inositol, 1 part of tetrahydropiperine, 0.2 parts of Algae extract, 2 parts of Rhodiola rosea root extract, 3 parts of aloe extract, and 7.5 parts of deionized water.

3. A method for preparing a highly effective transdermal permeation preparation, characterized in that: The steps include: S1: preparing the extract of Algae ostreatus, the extract of Rhodiola rosea root and the extract of Aloe vera respectively; S2: In parts by weight, at a temperature of 35-45° C., 0.1-0.3 parts of the Algae extract, 0.5-3 parts of the Rhodiola rosea root extract and 0.5-3 parts of the Aloe vera extract in step S1 are added dropwise in sequence while stirring, and after the addition is completed, the mixture is stirred at a rate of 500-700 r / min for 20-50 min to obtain liquid A; S3: In parts by weight, 0.1-3 parts of inositol, 0.1-3 parts of tetrahydropiperine and 7.5 parts of deionized water are stirred at a rate of 400-600 r / min for 10-20 min to obtain liquid B; S4: Mix the liquid A obtained in step S2 and the liquid B obtained in step S3, and stir at a temperature of 70-90° C. and a speed of 800-1000 r / min for 1-3 h to obtain a highly efficient transdermal permeation preparation.

4. The method for preparing a highly effective transdermal permeation preparation according to claim 3, characterized in that: The preparation process of the Osmanthus algae extract obtained in step S1 is as follows: by weight, take 0.1-0.5 parts of Osmanthus algae powder, add 30-60 parts of deionized water, heat to 65-85°C and soak for 1-2h; under nitrogen protection, heat to 100-110°C and extract for 1.5-3h; after cooling, add 0.1-0.2 parts of Kalibik Mayer yeast, keep the temperature at 30-35°C, and ferment for 5-9 days; after filtering, the filtrate is concentrated at a pressure of 0.01-0.03Mpa and a temperature of 50-60°C for 20-40min to obtain the Osmanthus algae extract.

5. The method for preparing a highly effective transdermal permeation preparation according to claim 3, characterized in that: The optimized process of the extract of Algae ostreae is as follows: by weight, take 0.3 parts of Algae ostreae powder, add 45 parts of deionized water, heat to 70°C and soak for 1.5 hours; under nitrogen protection, heat to 105°C and extract for 2 hours; after cooling, add 0.015 parts of Kalibik Mayer yeast, keep the temperature at 32°C, and ferment for 7 days; after filtering, the filtrate is concentrated at a pressure of 0.02Mpa and a temperature of 55°C for 30 minutes to obtain the Algae ostreae extract.

6. The method for preparing a highly effective transdermal permeation preparation according to claim 3, characterized in that: The preparation process of the Rhodiola rosea root extract obtained in step S1 is as follows: by weight, 3-5 parts of Rhodiola rosea powder and 80-120 parts of anhydrous ethanol are mixed, and the mixture is immersed and extracted at a temperature of 85-95° C. for 30-60 minutes; in a supercritical extraction device, carbon dioxide supercritical fluid is used, and the temperature is 40-60° C., the pressure is 30-40MPa, and the flow rate is 300-500L / h. The extraction is performed for 2-4 hours to obtain the Rhodiola rosea root extract.

7. The method for preparing a highly effective transdermal permeation preparation according to claim 3, characterized in that: The preparation process of Rhodiola rosea root extract was optimized as follows: 4 parts of Rhodiola rosea powder were mixed with 100 parts of anhydrous ethanol, and the mixture was immersed and extracted at 90°C for 45 minutes; carbon dioxide supercritical fluid was used, and the temperature was 55°C, the pressure was 36 MPa, and the flow rate was 400 L / h. The extraction was performed for 2.5 hours to obtain the Rhodiola rosea root extract.

8. The method for preparing a highly effective transdermal permeation preparation according to claim 3, characterized in that: The preparation process of the aloe extract in step S1 is as follows: by weight, 5-10 parts of aloe are added to 55-65 parts of deionized water, and then 0.1-0.3 parts of cellulase and 0.2-0.8 parts of pectinase are added, and enzymolysis is performed at a temperature of 40-50° C. for 2-4 hours; Then the temperature is raised to 100-120°C and refluxed for extraction for 1-2 hours; after filtration, the aloe extract is obtained.

9. The method for preparing a highly effective transdermal permeation preparation according to claim 8, characterized in that: The preparation process of aloe extract is optimized as follows: by weight, 7 parts of aloe are added to 60 parts of deionized water, and then 0.2 parts of cellulase and 0.6 parts of pectinase are added, and enzymolysis is carried out at a temperature of 45°C for 3.5 hours; then the temperature is increased to 116°C, and reflux extraction is carried out for 1.5 hours; and the aloe extract is obtained after filtration.

10. The method for preparing a highly effective transdermal permeation preparation according to claim 3, characterized in that: Step S2 is specifically as follows: in parts by weight, at a temperature of 42° C., 0.2 parts of the Algae extract, 3 parts of the Rhodiola rosea root extract and 3 parts of the Aloe extract in step S1 are added dropwise in sequence while stirring; after the addition is completed, the mixture is stirred at a rate of 650 r / min for 35 min to obtain liquid A.

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