A minoxidil liniment and a preparation method thereof

Abstract

The application belongs to the technical field of pharmacy, and particularly relates to a minoxidil liniment and a preparation method thereof. The application wraps minoxidil by using a lichen extract-phospholipid complex to prepare nano-liposomes, utilizes the synergistic drug loading mechanism of the lichen extract and the phospholipid complex, avoids the common allergic dermatitis phenomenon in the use process of the minoxidil liniment through anti-inflammatory and antioxidant effects, protects the drug structure, and prolongs the action time of the minoxidil liniment; the gel-like substance formed by using a polyvinyl alcohol-carboxymethylcellulose sodium complex coating solution reduces the surface exposure of minoxidil, avoids the precipitation of minoxidil crystals, and guarantees the delivery and absorption efficiency of minoxidil drugs.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pharmacy, and particularly relates to a minoxidil liniment and a preparation method thereof. BACKGROUND

[0002] The main characteristics of androgenetic alopecia are shortening of the growth phase and miniaturization of hair follicles (HF). At present, only minoxidil and finasteride are approved for treating androgenetic alopecia worldwide. The external use of drugs is preferred for minoxidil. The adverse reactions of minoxidil are relatively lower than those of finasteride, and the safety is higher. Minoxidil has a faster effect and is a good choice for treating androgenetic alopecia. In the environment where alopecia is paid more and more attention, minoxidil products are gradually recognized by people with alopecia.

[0003] Minoxidil is a potassium channel opener of aminopyridine, which can cause vasodilation and premature entry of resting hair follicles into the growth phase, and increase the size of hair follicles. The positive effect on hair growth is mainly due to the metabolic product of minoxidil, minoxidil sulfate. Commercially available minoxidil liniment generally uses ethanol and propylene glycol as solvents. Although minoxidil has higher safety and relatively lower adverse reactions than finasteride, the use of the sensitizing solvent propylene glycol may cause a phenomenon of itching all over the body and full-face acne after frequent use of minoxidil. The volatile organic solvents such as ethanol can cause minoxidil to crystallize and out, affecting drug delivery and absorption. In addition, ethanol can also damage the cuticle of the skin, enhance the ability of the drug to penetrate the epidermis, further magnify the disadvantages of high permeability of minoxidil, and may cause the side effect of rapid increase of alopecia. SUMMARY

[0004] The purpose of the present application is to provide a minoxidil liniment and a preparation method thereof to solve the above technical problems.

[0005] To achieve the above technical purposes, the technical scheme of the present application is as follows:

[0006] A minoxidil liniment comprises A component and B component, wherein the A component is nanoliposome-encapsulated minoxidil, and the B component is polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution.

[0007] As a further improvement, the preparation method of the nanoliposome-encapsulated minoxidil is as follows: oleic acid, lichen extract-phospholipid complex and minoxidil are dissolved in dichloromethane to obtain an oil phase; Tween 80 is dissolved in pure water to obtain an aqueous phase; the oil phase is added to the aqueous phase under 80℃ water bath, and stirred for 10 min to obtain a preliminary emulsion; the preliminary emulsion is homogenized after high-speed dispersion, and finally cooled in a cold water bath for 12 h to obtain nanoliposome-encapsulated minoxidil.

[0008] As a further improvement, the oil phase comprises, by weight parts: 8-12 oleic acid, 2-6 lichen extract-phospholipid complex, 2-4 minoxidil; the mass ratio of dichloromethane to minoxidil is 50:1, the volume ratio of dichloromethane to anhydrous ethanol is 3:2; the mass ratio of Tween 80 to pure water is 1:50; the mass ratio of the oil phase to the aqueous phase is 1:1.5.

[0009] As a further improvement, the preparation method of the polyvinyl alcohol-carboxymethyl cellulose sodium composite coating solution is: polyvinyl alcohol is dissolved in deionized water, heated to complete dissolution of polyvinyl alcohol under oil bath at 120-130℃, and the stirring speed is adjusted to 900rpm, and carboxymethyl cellulose sodium is added to the polyvinyl alcohol solution under oil bath at 70-80℃, glycerol and Tween 80 are added, and the mixture is heated and stirred for 10min to obtain the polyvinyl alcohol-carboxymethyl cellulose sodium composite coating solution.

[0010] As a further improvement, the polyvinyl alcohol-carboxymethyl cellulose sodium composite coating solution comprises, by weight parts: 6-12 polyvinyl alcohol, 10-15 carboxymethyl cellulose sodium, 2-3 glycerol, and 1-2 Tween 80.

[0011] As a further improvement, the preparation method of the lichen extract-phospholipid complex is: lichen extract is taken, distilled water is used to adjust the volume in a volumetric flask to obtain a lichen extract solution; phospholipid is dissolved in anhydrous ethanol, the lichen extract solution is added, and the mixture is stirred for 2h under oil bath at 30-40℃, then the solvent is evaporated under 0.1MPa at 50℃, 50wt% ethanol is added as a redissolving solvent, centrifuged at 4500rpm for 15min, the supernatant is evaporated to dryness, and then freeze-dried at -35℃ under 10Pa for 4h to obtain the lichen extract-phospholipid complex; wherein the concentration of the lichen extract solution is 1-3mg / mL; the mass ratio of lichen extract to phospholipid is 1:3; and the volume ratio of anhydrous ethanol to distilled water is 0.8-1:10.

[0012] As a further improvement, the preparation method of the lichen extract is: lichen powder is dissolved in 60wt% ethanol at a mass ratio of 1:60, and then the mixture is placed in a water bath at 70℃ for 8h, centrifuged at 4000rpm for 10min, and the supernatant and precipitate are separated; the precipitate is repeatedly extracted with 60wt% ethanol for 5 times, the supernatants are combined, filtered, and then concentrated under reduced pressure; vacuum freeze-drying is performed for 24h to obtain a crude extract; the crude extract is mixed with anhydrous ethanol at a liquid-to-material ratio of 5:1, and then the mixture is allowed to stand for 24h; the upper extract is separated, repeatedly extracted for 5 times, concentrated under reduced pressure at 60℃ and 0.10MPa, and then extracted with chloroform at a material-to-liquid ratio of 3:1 for 6 times; finally, the extract is concentrated under reduced pressure, washed with acetone, and dried to obtain the lichen extract.

[0013] The application further provides a preparation method of the minoxidil liniment, comprising the following steps: vacuum filling nanoliposome-encapsulated minoxidil and polyvinyl alcohol-sodium carboxymethyl cellulose complex coating solution in different sub-packaging bottles respectively, and combining to obtain the minoxidil liniment.

[0014] By adopting the technical scheme, the application has the following beneficial effects:

[0015] (1) The lichen extract-phospholipid complex is used to prepare nanoliposomes to encapsulate minoxidil, so that the problem of allergic dermatitis caused by frequent use of propylene glycol and ethanol in traditional minoxidil liniment is avoided; the lichen extract is embedded in the pores of the phospholipid layer through a synergistic drug loading mechanism, and the anti-inflammatory and antioxidant effects of the lichen extract can effectively avoid the allergic dermatitis phenomenon during use of the minoxidil liniment, and protect the structure of the drug, prevent the minoxidil from being oxidized, and prolong the action time of the minoxidil liniment.

[0016] (2) The polyvinyl alcohol-sodium carboxymethyl cellulose complex coating solution is used as the B component and coated on the surface of the nanoliposome-encapsulated minoxidil in the A component, after coating, the polyvinyl alcohol-sodium carboxymethyl cellulose can adsorb the water phase in the nanoliposome-encapsulated minoxidil to form a gel-like substance, which prevents the formation of minoxidil crystals caused by solvent evaporation, and avoids affecting the absorption and drug delivery efficiency of minoxidil. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 A is a hair condition diagram of the back of the mouse after 9 weeks of modeling;

[0018] B is a hair condition diagram of the back of the mouse after 20 weeks of using the minoxidil liniment obtained in Example 3 after 9 weeks of modeling;

[0019] C is a hair condition diagram of the back of the mouse after 20 weeks of using the minoxidil liniment obtained in Comparative Example 1 after 9 weeks of modeling;

[0020] D is a hair condition diagram of the back of the mouse after 20 weeks of using the minoxidil liniment obtained in Comparative Example 2 after 9 weeks of modeling;

[0021] E is a hair condition diagram of the back of the mouse after 20 weeks of using the minoxidil liniment obtained in Comparative Example 3 after 9 weeks of modeling.

[0022] Figure 2 A is a skin condition diagram of the back of the mouse after 20 weeks of using the minoxidil liniment obtained in Example 3 after 9 weeks of modeling;

[0023] B is a skin condition diagram of the back of the mouse after 20 weeks of using the minoxidil liniment obtained in Comparative Example 1 after 9 weeks of modeling;

[0024] C is a skin state chart of the back of the mouse after 20 weeks of using the minoxidil liniment obtained from Comparative Example 2 after 9 weeks of modeling;

[0025] D is a skin state chart of the back of the mouse after 20 weeks of using the minoxidil liniment obtained from Comparative Example 3 after 9 weeks of modeling. DETAILED DESCRIPTION

[0026] The technical solutions of the present application will be described clearly and completely in combination with the specific embodiments below, but those skilled in the art will understand that the following described embodiments are part of the embodiments of the present application, not all the embodiments, and are only used to illustrate the present application, and should not be regarded as limiting the scope of the present application. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without making creative efforts are within the scope of protection of the present application. The specific conditions not mentioned in the embodiments are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The lichen powder used is from Shaanxi Yongyuan Biotechnology Co., Ltd., and the reagents or instruments not mentioned by the manufacturer are all conventional products that can be purchased on the market.

[0027] Example 1 A preparation method of a minoxidil liniment, specifically comprising the following steps:

[0028] 1. Dissolve the lichen powder in 60 wt% ethanol according to the mass ratio of 1:60, and keep it in water bath at 70°C for 8h, centrifuge at 4000rpm for 10min, separate the supernatant and the precipitate, repeat the extraction of the precipitate with 60 wt% ethanol for 5 times, then combine the supernatant, filter it with filter paper, and concentrate and dry the solvent under reduced pressure at 60°C and 0.10MPa, then freeze dry it under vacuum at-50°C and 10Pa for 24h to obtain the crude extract.

[0029] 2. Mix the crude extract with anhydrous ethanol according to the solid-liquid ratio of 5:1, separate the upper extract after standing for 24h, repeat the extraction for 5 times, then concentrate it under reduced pressure at 60°C and 0.10MPa to obtain the secondary extract, finally extract the secondary extract with chloroform according to the solid-liquid ratio of 3:1, repeat the extraction for 6 times, concentrate it under reduced pressure at 55°C and 0.10MPa, wash it with acetone, and dry it at 70°C for 6h to obtain the lichen extract.

[0030] 3. Take the lichen extract and dilute it to volume in a volumetric flask with distilled water to obtain a 1 mg / mL lichen extract solution; dissolve the phospholipid in anhydrous ethanol, add the lichen extract solution, stir and react for 2 h at 600 rpm in an oil bath at 30 °C, evaporate the solvent by rotary evaporation at 0.1 MPa at 50 °C, then add 50 wt% ethanol as a redissolution solvent, centrifuge at 4500 rpm for 15 min, take the supernatant and evaporate the solvent by rotary evaporation, then freeze-dry at -35 °C and 10 Pa for 4 h to obtain the lichen extract-phospholipid complex; wherein the mass ratio of lichen extract to phospholipid is 1:3; the volume ratio of anhydrous ethanol to distilled water is 0.8:10.

[0031] 4. By weight, dissolve 8 parts oleic acid, 2 parts lichen extract-phospholipid complex, and 2 parts minoxidil in dichloromethane, add anhydrous ethanol to obtain the oil phase, wherein the mass ratio of dichloromethane to minoxidil is 50:1 and the volume ratio of dichloromethane to anhydrous ethanol is 3:2.

[0032] Dissolve 1 part of Tween 80 in 50 parts of pure water to obtain the aqueous phase;

[0033] Under an 80°C water bath, the oil phase was added to the aqueous phase at a mass ratio of 1:1.5, and the mixture was stirred at 1500 rpm for 10 minutes to obtain the colostrum.

[0034] 5. Disperse the colostrum at 1000 rpm for 1 min, homogenize it for two cycles at 20000 psi using a high-pressure homogenizer, and finally cool it in a cold water bath for 12 h to obtain nanoliposome-encapsulated minoxidil.

[0035] 6. By weight, take 6 parts polyvinyl alcohol, 10 parts sodium carboxymethyl cellulose, 2 parts glycerin, and 1 part Tween 80; dissolve the polyvinyl alcohol in 100 parts deionized water, and heat at 1200 rpm in an oil bath at 120°C until the polyvinyl alcohol is completely dissolved to obtain a polyvinyl alcohol solution; adjust the speed to 900 rpm, add sodium carboxymethyl cellulose to the polyvinyl alcohol solution in an oil bath at 70°C, add glycerin and Tween 80, and stir at 800 rpm for 10 min to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid.

[0036] 7. The nanoliposome-encapsulated minoxidil and polyvinyl alcohol-carboxymethyl cellulose sodium composite coating solution were vacuum-filled into different dispensing bottles to obtain minoxidil liniment.

[0037] Example 2: A method for preparing a minoxidil liniment, specifically including the following steps:

[0038] 1. According to the mass ratio of 1:60, lichen powder was dissolved in 60wt% ethanol, and the water bath was kept at 70°C for 8h, and centrifuged at 4000rpm for 10min, and the supernatant and precipitate were separated, and the precipitate was repeatedly extracted with 60wt% ethanol for 5 times, and the supernatant was combined, and filtered with filter paper, and concentrated under reduced pressure at 60°C and 0.10MPa to evaporate the solvent, and vacuum freeze-dried at-50°C and 10Pa for 24h to obtain the crude extract.

[0039] 2. According to the solid-liquid ratio of 5:1, the crude extract was mixed with anhydrous ethanol, and the supernatant was separated after standing for 24h, and the extraction was repeated for 5 times, and the secondary extract was obtained by vacuum concentration at 60°C and 0.10MPa, and finally the secondary extract was extracted with chloroform according to the solid-liquid ratio of 3:1, and the extraction was repeated for 6 times, and vacuum concentration was carried out at 55°C and 0.10MPa, and washed with acetone, and dried at 70°C for 6h to obtain the lichen extract.

[0040] 3. The lichen extract was taken and dissolved in a volumetric flask with distilled water to obtain a lichen extract solution of 2mg / mL; the phospholipid was dissolved in anhydrous ethanol, and the lichen extract solution was added, and stirred at 600rpm for 2h under 35°C oil bath, and the solvent was evaporated by rotary evaporation at 50°C and 0.1MPa, and then 50wt% ethanol was added as a redissolving solvent, and centrifuged at 4500rpm for 15min, and the supernatant was evaporated by rotary evaporation, and freeze-dried at-35°C and 10Pa for 4h to obtain the lichen extract-phospholipid complex; wherein the mass ratio of lichen extract to phospholipid was 1:3; the volume ratio of anhydrous ethanol to distilled water was 0.9:10.

[0041] 4. According to the weight fraction, 10 parts of oleic acid, 4 parts of lichen extract-phospholipid complex and 3 parts of minoxidil were dissolved in dichloromethane, and anhydrous ethanol was added to obtain an oil phase, wherein the mass ratio of dichloromethane to minoxidil was 50:1, and the volume ratio of dichloromethane to anhydrous ethanol was 3:2.

[0042] 1 part of Tween 80 was dissolved in 50 parts of pure water to obtain an aqueous phase.

[0043] Under the water bath at 80°C, the oil phase was added to the aqueous phase according to the mass ratio of 1:1.5, and stirred at 1500rpm for 10min to obtain the initial emulsion.

[0044] 5. The initial emulsion was dispersed at 1000rpm for 1min, and the high-pressure homogenizer was used at 20000psi pressure for two cycles, and finally cooled in a cold water bath for 12h to obtain the nanoliposome-encapsulated minoxidil.

[0045] 6. Take 9 parts of polyvinyl alcohol, 13 parts of sodium carboxymethyl cellulose, 3 parts of glycerol, and 2 parts of Tween 80 by weight fraction; dissolve the polyvinyl alcohol in 100 parts of deionized water, heat and stir at 1200 rpm under an oil bath at 125°C until the polyvinyl alcohol is completely dissolved to obtain a polyvinyl alcohol solution; adjust the stirring speed to 900 rpm, and add the sodium carboxymethyl cellulose to the polyvinyl alcohol solution under an oil bath at 75°C, then add the glycerol and Tween 80, and stir at 800 rpm for 10 min to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution.

[0046] 7. The nano-liposome-encapsulated minoxidil is vacuum-filled in a different sub-packaging bottle, and the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution is also vacuum-filled in a different sub-packaging bottle to obtain a minoxidil liniment by combination.

[0047] Example 3 A preparation method of a minoxidil liniment, specifically comprising the following steps:

[0048] 1. Dissolve the lichen powder in 60 wt% ethanol at a mass ratio of 1:60 under a water bath at 70°C for 8 h, and centrifuge at 4000 rpm for 10 min to separate the supernatant and the precipitate. Repeat the extraction of the precipitate with 60 wt% ethanol for 5 times, then combine the supernatants, filter with filter paper, and perform vacuum concentration at 60°C and 0.10 MPa to evaporate the solvent. Freeze-dry the combined supernatant at -50°C and 10 Pa for 24 h to obtain a crude extract.

[0049] 2. Mix the crude extract with anhydrous ethanol at a solid-liquid ratio of 5:1, and separate the upper extract after standing for 24 h. Repeat the extraction for 5 times, then perform vacuum concentration at 60°C and 0.10 MPa to obtain a secondary extract. Finally, extract the secondary extract with chloroform at a solid-liquid ratio of 3:1, repeat the extraction for 6 times, perform vacuum concentration at 55°C and 0.10 MPa, wash with acetone, and dry at 70°C for 6 h to obtain a lichen extract.

[0050] 3. Take the lichen extract, and use distilled water to make up the volume in a volumetric flask to obtain a lichen extract solution of 3 mg / mL. Take phospholipid, dissolve it in anhydrous ethanol, and add the lichen extract solution. Stir at 600 rpm under an oil bath at 40°C for 2 h, evaporate the solvent by rotary evaporation at 50°C and 0.1 MPa, then add 50 wt% ethanol as a redissolving solvent, centrifuge at 4500 rpm for 15 min, evaporate the solvent by rotary evaporation from the supernatant, freeze-dry at -35°C and 10 Pa for 4 h, and obtain a lichen extract-phospholipid complex. The mass ratio of the lichen extract to the phospholipid is 1:3, and the volume ratio of the anhydrous ethanol to the distilled water is 1:10.

[0051] 4. 12 parts of oleic acid, 6 parts of lichen extract-phospholipid complex, and 4 parts of minoxidil were dissolved in dichloromethane to obtain an oil phase, wherein the mass ratio of dichloromethane to minoxidil was 50:1, and the volume ratio of dichloromethane to anhydrous ethanol was 3:2;

[0052] 1 part of Tween 80 was dissolved in 50 parts of pure water to obtain an aqueous phase;

[0053] The oil phase was added to the aqueous phase at a mass ratio of 1:1.5 under a water bath at 80°C, and stirred at 150 rpm for 10 min to obtain a preliminary emulsion.

[0054] 5. The preliminary emulsion was dispersed at a high speed of 1000 rpm for 1 min, and subjected to two cycles of action at a pressure of 20000 psi using a high-pressure homogenizer, and finally cooled in a cold water bath for 12 h to obtain nanoliposome-encapsulated minoxidil.

[0055] 6. 12 parts of polyvinyl alcohol, 15 parts of sodium carboxymethyl cellulose, 3 parts of glycerol, and 2 parts of Tween 80 were taken according to the weight fraction, polyvinyl alcohol was dissolved in 100 parts of deionized water, and the stirring speed was 1200 rpm under an oil bath at 130°C to heat until the polyvinyl alcohol was completely dissolved to obtain a polyvinyl alcohol solution; the stirring speed was adjusted to 900 rpm, and sodium carboxymethyl cellulose was added to the polyvinyl alcohol solution under an oil bath at 80°C, and glycerol and Tween 80 were added, and stirred at 800 rpm for 10 min to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution.

[0056] 7. The nanoliposome-encapsulated minoxidil and the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution were respectively vacuum-filled in different sub-packing bottles to obtain a minoxidil liniment by combination.

[0057] Comparative Example 1 is a preparation method of a minoxidil liniment, which is different from Example 1 in that the B component, i.e., the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution, is not included, and specifically includes the following steps:

[0058] 1. Lichen powder was dissolved in 60 wt% ethanol at a mass ratio of 1:60 under a water bath at 70°C for 8 h, centrifuged at 4000 rpm for 10 min, and the supernatant and precipitate were separated, the precipitate was repeatedly extracted with 60 wt% ethanol for 5 times, the supernatant was combined, filtered using filter paper, and then concentrated and dried under reduced pressure at 60°C and 0.10 MPa to remove the solvent, and then vacuum freeze-dried at -50°C and 10 Pa for 24 h to obtain a crude extract.

[0059] 2. Mix the crude extract with anhydrous ethanol at a material-to-liquid ratio of 5:1. After standing for 24 hours, separate the upper extract. Repeat the extraction 5 times. After concentration under reduced pressure at 60℃ and 0.10MPa, a secondary extract is obtained. Finally, extract the secondary extract with chloroform at a material-to-liquid ratio of 3:1. Repeat the extraction 6 times. After concentration under reduced pressure at 55℃ and 0.10MPa, wash with acetone, and dry at 70℃ for 6 hours to obtain the lichen extract.

[0060] 3. Take the lichen extract and dilute it to volume in a volumetric flask with distilled water to obtain a 1 mg / mL lichen extract solution; dissolve the phospholipid in anhydrous ethanol, add the lichen extract solution, stir and react for 2 h at 600 rpm in an oil bath at 30 °C, evaporate the solvent by rotary evaporation at 0.1 MPa at 50 °C, then add 50 wt% ethanol as a redissolution solvent, centrifuge at 4500 rpm for 15 min, take the supernatant and evaporate the solvent by rotary evaporation, then freeze-dry at -35 °C and 10 Pa for 4 h to obtain the lichen extract-phospholipid complex; wherein the mass ratio of lichen extract to phospholipid is 1:3; the volume ratio of anhydrous ethanol to distilled water is 0.8:10.

[0061] 4. By weight, dissolve 8 parts oleic acid, 2 parts lichen extract-phospholipid complex, and 2 parts minoxidil in dichloromethane, add anhydrous ethanol to obtain the oil phase, wherein the mass ratio of dichloromethane to minoxidil is 50:1 and the volume ratio of dichloromethane to anhydrous ethanol is 3:2.

[0062] Dissolve 1 part of Tween 80 in 50 parts of pure water to obtain the aqueous phase;

[0063] Under an 80°C water bath, the oil phase was added to the aqueous phase at a mass ratio of 1:1.5, and the mixture was stirred at 1500 rpm for 10 minutes to obtain the colostrum.

[0064] 5. Disperse the colostrum at 1000 rpm for 1 min, homogenize it for two cycles at 20000 psi using a high-pressure homogenizer, and finally cool it in a cold water bath for 12 h to obtain nanoliposome-encapsulated minoxidil.

[0065] 6. The nanoliposomes were encapsulated with minoxidil and vacuum-filled into dispensing bottles to obtain minoxidil topical solution.

[0066] Comparative Example 2: A method for preparing a minoxidil topical solution, differing from Example 1 in that the minoxidil in component A is not encapsulated in nanoliposomes. The method specifically includes the following steps:

[0067] 1. Mix 90wt% ethanol, propylene glycol and pure water at a mass ratio of 1:3:5, stir at 600rpm for 5min, add minoxidil raw material, stir and emulsify at 1500rpm for 15min, then perform high pressure homogenization at 20000psi, homogenize for 60min, filter the resulting emulsion to obtain minoxidil emulsion.

[0068] 2. By weight, take 6 parts polyvinyl alcohol, 10 parts sodium carboxymethyl cellulose, 2 parts glycerin, and 1 part Tween 80; dissolve the polyvinyl alcohol in 100 parts deionized water, and heat at 1200 rpm in an oil bath at 120°C until the polyvinyl alcohol is completely dissolved to obtain a polyvinyl alcohol solution; adjust the speed to 900 rpm, add sodium carboxymethyl cellulose to the polyvinyl alcohol solution in an oil bath at 70°C, add glycerin and Tween 80, and stir at 800 rpm for 10 min to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid.

[0069] 3. Minoxidil emulsion and polyvinyl alcohol-carboxymethyl cellulose sodium composite coating liquid were vacuum-filled into different dispensing bottles to obtain minoxidil liniment.

[0070] Comparative Example 3: This comparative example provides a commercially available minoxidil topical solution.

[0071] One hundred male ICR mice, weighing 20-23g, were selected and housed separately for one week. Testosterone propionate was injected daily at a dose of 5mg / kg / day to establish the model. Successful modeling was indicated by sparse, absent, or partial hair loss on the backs of the mice. After nine weeks of injection, 40 mice were randomly selected from the successfully modeled mice and randomly divided into four groups of ten each. The four groups were treated with minoxidil topical solution (Example 3 and Comparative Examples 1-3), at a dosage of 0.2g per mouse daily. During the treatment period, daily injections of testosterone propionate continued to maintain hormone levels. The skin at the application site was observed daily for any abnormal reactions such as erythema, edema, erosion, or roughness, and hair growth was also monitored. At week 21 of treatment, hair growth was observed, and the backs of the mice were shaved to assess skin condition.

[0072] 1. Figure 1 The images show the hair growth of mice in each group. A represents the hair condition of mice after modeling. Nine weeks after modeling, mice experienced significant hair loss on their backs, with varying degrees of thinning and shedding. B, C, D, and E represent the hair growth on the backs of mice in each group after 20 weeks of using the minoxidil topical solution obtained in Example 3, Comparative Example 1, Comparative Example 2, and Comparative Example 3, respectively.

[0073] Depend on Figure 1It can be seen that the back hair of the mice in the comparative examples 1-3 is sparse and uneven in length. The hair in the alopecia area of the mice in the example 3 has grown well, and the skin is not visible to the naked eye. Comparative example 1 lacks a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating, and minoxidil is exposed on the skin surface. After the effective components volatilize, the hair growth effect is poor. Comparative example 2 lacks nanoliposome coating and the antioxidant effect of the lichen extract-phospholipid complex, and the action time of minoxidil is shortened, which affects its hair growth effect. Comparative example 3 is a minoxidil liniment randomly purchased on the market. The hair of the mice on the back has grown to a certain extent, but the hair is sparse, and the alopecia area is visible to the naked eye.

[0074] 2、 Figure 2 The skin conditions of the mice in each group after hair removal are shown in Table 2. Figure 2 It can be seen that after using the minoxidil liniments obtained by different examples and comparative examples, the skin of the mice in the example 3 is red and elastic, and has no obvious abnormal changes. The skin surfaces of the mice in the comparative examples 1-3 are dry, red, rough and damaged to different degrees. The polyvinyl alcohol-sodium carboxymethyl cellulose in the example 3 can adsorb the water phase in the nanoliposome-encapsulated minoxidil to form a gel-like substance, reduce the surface exposure of minoxidil, avoid the precipitation of minoxidil crystals, and reduce the risk of skin allergy after using the minoxidil liniment. The lichen extract-phospholipid complex is used to encapsulate minoxidil, which can avoid the problem of allergic dermatitis caused by frequent use of propylene glycol and ethanol. The anti-inflammatory and antioxidant effects of the lichen extract can effectively avoid the allergic dermatitis phenomenon that occurs when the minoxidil liniment is used.

[0075] The specific embodiments of the application described above do not constitute a limitation on the scope of protection of the application. Any various other corresponding changes and modifications made according to the technical concept of the application shall be included in the scope of protection of the claims of the application.

Claims

1. A minoxidil liniment, characterized by, The application relates to a minoxidil nano-liposome preparation method and a minoxidil nano-liposome preparation. The preparation method of the minoxidil nano-liposome comprises the following steps: dissolving oleic acid, lichen extract-phospholipid complex and minoxidil in dichloromethane, adding anhydrous ethanol to obtain an oil phase; dissolving Tween 80 in pure water to obtain an aqueous phase; under the condition of 80 DEG C water bath, the oil phase is added into the aqueous phase and stirred for 10 min to obtain a preliminary emulsion; the preliminary emulsion is subjected to high-speed dispersion and homogenization, and finally cooled in a cold water bath for 12 h to obtain the minoxidil nano-liposome. The preparation method of the lichen extract-phospholipid complex comprises the following steps: taking lichen extract, using distilled water to make up the volume in a volumetric flask to obtain a lichen extract solution; taking phospholipid, dissolving the phospholipid in anhydrous ethanol, adding the lichen extract solution, stirring under the condition of 30-40 DEG C oil bath for 2 h, evaporating the solvent under the condition of 50 DEG C and 0.1 MPa, adding 50wt% ethanol as a redissolving solvent, centrifuging at 4500 rpm for 15 min, evaporating the solvent of the supernatant, and freeze-drying under the condition of-35 DEG C and 10 Pa for 4 h to obtain the lichen extract-phospholipid complex; wherein the concentration of the lichen extract solution is 1-3 mg / mL; the mass ratio of the lichen extract to the phospholipid is 1:3; and the volume ratio of the anhydrous ethanol to the distilled water is 0.8-1:

10. The preparation method of the lichen extract comprises the following steps: according to the mass ratio of 1:60, the lichen powder is dissolved in 60wt% ethanol, and the mixture is subjected to water bath preservation at 70 DEG C for 8 h, centrifuged at 4000 rpm for 10 min, and then the supernatant and the precipitate are separated; the precipitate is repeatedly extracted with 60wt% ethanol for 5 times, the supernatants are combined, filtered, and subjected to vacuum concentration, and then vacuum freeze-drying is carried out for 24 h to obtain a crude extract; according to the liquid-material ratio of 5:1, the crude extract and anhydrous ethanol are mixed, and then the mixture is statically placed for 24 h, the upper extraction solution is separated, and the extraction is repeated for 5 times; the secondary extract is obtained by vacuum concentration under the condition of 60 DEG C and 0.10 MPa; finally, the secondary extract is repeatedly extracted with chloroform for 6 times according to the material-liquid ratio of 3:1, and then the chloroform is removed by vacuum concentration, the extract is washed with acetone, and then dried to obtain the lichen extract.

2. The minoxidil liniment according to claim 1, characterized in that, According to the weight fraction, the oil phase comprises 8-12 parts of oleic acid, 2-6 parts of lichen extract-phospholipid complex and 2-4 parts of minoxidil; the mass ratio of the dichloromethane to the minoxidil is 50:1, the volume ratio of the dichloromethane to the anhydrous ethanol is 3:2; the mass ratio of the Tween 80 to the pure water is 1:50; and the mass ratio of the oil phase to the aqueous phase is 1:1.

5.

3. The minoxidil liniment according to claim 1, characterized in that, The preparation method of the polyvinyl alcohol-carboxymethyl cellulose sodium composite coating solution comprises the following steps: polyvinyl alcohol is dissolved in deionized water, the polyvinyl alcohol is completely dissolved by stirring and heating under the condition of 120-130 DEG C oil bath temperature to obtain a polyvinyl alcohol solution; the stirring speed is adjusted to 900 rpm, carboxymethyl cellulose sodium is added into the polyvinyl alcohol solution under the condition of 70-80 DEG C oil bath, glycerol and Tween 80 are added, and then the mixture is heated and stirred for 10 min to obtain the polyvinyl alcohol-carboxymethyl cellulose sodium composite coating solution.

4. The minoxidil liniment according to claim 3, wherein the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution comprises, by weight fraction: 6~12 parts of polyvinyl alcohol, 10~15 parts of sodium carboxymethyl cellulose, 2~3 parts of glycerol, 1~2 parts of Tween 80.

5. The method for preparing the minoxidil liniment of claim 1, characterized in that, The nano-liposome-encapsulated minoxidil and the polyvinyl alcohol-sodium carboxymethyl cellulose complex coating solution are respectively vacuum filled in different sub-packing bottles, and a minoxidil liniment is obtained by combination.

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