Minoxidil liniment and preparation method thereof

Abstract

The invention belongs to the technical field of pharmacy, and particularly relates to minoxidil liniment and a preparation method thereof. According to the minoxidil liniment disclosed by the invention, the nano-liposome prepared from the lichen extract-phospholipid complex is used for wrapping minoxidil, the common allergic dermatitis phenomenon in the using process of the minoxidil liniment is avoided by utilizing a synergistic drug loading mechanism of the lichen extract and the phospholipid complex and through anti-inflammatory and anti-oxidation effects, and meanwhile, the drug structure is protected; the action time of the minoxidil liniment is prolonged; the gel substance formed by the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid reduces the surface exposure of minoxidil, avoids the precipitation of minoxidil crystals, and ensures the delivery and absorption efficiency of minoxidil drugs.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceuticals, and particularly relates to a minoxidil liniment and a preparation method thereof. Background Art

[0002] The primary characteristics of androgenic alopecia are a shortened growth phase and miniaturized hair follicles (HF). Currently, only two drugs, minoxidil and finasteride, are approved for the treatment of androgenic alopecia worldwide. Minoxidil is the preferred topical medication, offering fewer adverse reactions, a higher safety profile, and a faster onset of action compared to finasteride, making it a good choice for the treatment of androgenic alopecia. As hair loss becomes increasingly recognized, minoxidil is gaining acceptance among those experiencing it.

[0003] Minoxidil is an aminopyridine potassium channel opener that can cause vasodilation, prematurely induce the growth phase of resting hair follicles, and increase follicle size. Its positive effect on hair growth is primarily due to its metabolite, minoxidil sulfate. Commercially available minoxidil lotions generally use solvents such as ethanol and propylene glycol. While minoxidil is safer and has fewer adverse reactions than finasteride, frequent use of the allergenic solvent propylene glycol can lead to itching and facial breakouts. The volatility of organic solvents like ethanol can cause minoxidil crystallization, impacting drug delivery and absorption. Furthermore, ethanol damages skin keratin, enhancing the drug's ability to penetrate the epidermis, further amplifying minoxidil's high permeability and potentially leading to the side effect of rapidly increasing hair loss. Summary of the Invention

[0004] The object of the present invention is to provide a minoxidil liniment and a preparation method thereof to solve the above-mentioned technical problems.

[0005] In order to achieve the above technical objectives, the technical solution of the present invention is: A minoxidil liniment comprises a component A and a component B, wherein the component A is nanoliposome-encapsulated minoxidil and the component B is a polyvinyl alcohol-sodium carboxymethylcellulose composite coating liquid.

[0006] 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, and then anhydrous ethanol is added to obtain an oil phase; Tween 80 is dissolved in pure water to obtain an aqueous phase, and the oil phase is added to the aqueous phase in an 80°C water bath, and stirred for 10 minutes to obtain colostrum; the colostrum is dispersed at high speed and then homogenized, and finally cooled in a cold water bath for 12 hours to obtain the nanoliposome-encapsulated minoxidil.

[0007] As a further improvement, the oil phase comprises, by weight: 8 to 12 parts of oleic acid, 2 to 6 parts of lichen extract-phospholipid complex, and 2 to 4 parts of minoxidil; the mass ratio of dichloromethane to minoxidil is 50:1, and the volume ratio of dichloromethane to anhydrous ethanol is 3:2; the mass ratio of Tween 80 to pure water is 1:50; and the mass ratio of the oil phase to the aqueous phase is 1:1.5.

[0008] As a further improvement, the preparation method of the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid is as follows: polyvinyl alcohol is dissolved in deionized water, and stirred and heated at an oil bath temperature of 120~130°C until the polyvinyl alcohol is completely dissolved to obtain a polyvinyl alcohol solution; the rotation speed is adjusted to 900 rpm, and sodium carboxymethyl cellulose is added to the polyvinyl alcohol solution at an oil bath of 70~80°C, glycerol and Tween 80 are added, and the oil bath is heated and stirred for 10 minutes to obtain the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid.

[0009] As a further improvement, the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution includes, by weight: 6 to 12 parts of polyvinyl alcohol, 10 to 15 parts of sodium carboxymethyl cellulose, 2 to 3 parts of glycerol, and 1 to 2 parts of Tween 80.

[0010] As a further improvement, the preparation method of the lichen extract-phospholipid complex is as follows: take lichen extract, use distilled water to make up the volume in a volumetric flask to obtain a lichen extract solution; take phospholipid and dissolve it in anhydrous ethanol, add the lichen extract solution, stir and react in an oil bath at 30~40℃ for 2h, evaporate the solvent at 50℃ and 0.1MPa, add 50wt% ethanol as a re-dissolution solvent, centrifuge at 4500rpm for 15min, take the supernatant and evaporate the solvent, and freeze-dry at -35℃ and 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.

[0011] As a further improvement, the preparation method of the lichen extract is as follows: dissolve the lichen powder in 60wt% ethanol at a mass ratio of 1:60, keep it in a water bath at 70°C for 8h, centrifuge it at 4000rpm for 10min, separate the supernatant and the precipitate, extract the precipitate repeatedly with 60wt% ethanol for 5 times, combine the supernatants, filter and concentrate under reduced pressure, and freeze-dry it in vacuum for 24h to obtain a crude extract; mix the crude extract with anhydrous ethanol at a liquid-to-solid ratio of 5:1, let it stand for 24h, separate the upper extract, repeat the extraction 5 times, and concentrate under reduced pressure at 60°C and 0.10MPa to obtain a secondary extract. Finally, extract the secondary extract repeatedly with chloroform at a material-to-liquid ratio of 3:1 for 6 times, concentrate under reduced pressure, wash with acetone, and dry to obtain a lichen extract.

[0012] The present invention also provides a method for preparing minoxidil liniment, comprising the following steps: vacuum-filling nanoliposome-encapsulated minoxidil and polyvinyl alcohol-sodium carboxymethylcellulose composite coating liquid into different sub-bottles to obtain the minoxidil liniment.

[0013] Due to the adoption of the above technical solution, the present invention has the following beneficial effects: (1) The nanoliposomes prepared by lichen extract-phospholipid complex were used to encapsulate minoxidil, thus avoiding the allergic dermatitis problem caused by the frequent use of propylene glycol and ethanol in traditional minoxidil lotion. The lichen extract was embedded in the pores of the phospholipid layer through a synergistic drug delivery mechanism. Its anti-inflammatory and antioxidant effects can effectively avoid the allergic dermatitis phenomenon that occurs when minoxidil lotion is used, while protecting the drug structure, preventing minoxidil from being oxidized, and prolonging the duration of action of minoxidil lotion.

[0014] (2) Polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid is used as component B and coated on the surface of the nanoliposome containing minoxidil in component A. After coating, polyvinyl alcohol-sodium carboxymethyl cellulose can absorb the aqueous phase in the nanoliposome containing minoxidil to form a gel-like substance, preventing the solvent from evaporating and causing the formation of minoxidil crystals, thereby avoiding affecting the absorption of minoxidil and the drug delivery efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 Figure 2 is a diagram of the hair condition on the back of mice, where A is a diagram of the hair condition on the back of mice 9 weeks after modeling; B is a picture of the hair condition on the back of mice after 9 weeks of modeling and 20 weeks of using the minoxidil liniment obtained in Example 3; C is a diagram showing the hair condition on the back of mice after 9 weeks of modeling and 20 weeks of using the minoxidil liniment obtained in Comparative Example 1; D is a diagram showing the hair condition on the back of mice after 9 weeks of modeling and 20 weeks of using the minoxidil liniment obtained in Comparative Example 2; E is a diagram showing the hair condition on the back of mice after 9 weeks of modeling and 20 weeks of using the minoxidil ointment obtained in Comparative Example 3.

[0016] Figure 2 Figure 1 is a picture of the skin condition on the back of a mouse 9 weeks after modeling after using minoxidil liniment for 20 weeks, wherein A is a picture of the skin condition on the back of a mouse 9 weeks after modeling after using the minoxidil liniment obtained in Example 3 for 20 weeks; B is a picture of the skin condition on the back of mice after 9 weeks of modeling and 20 weeks of using the minoxidil liniment obtained in Comparative Example 1; C is a picture of the skin condition on the back of mice after 9 weeks of modeling and 20 weeks of using the minoxidil liniment obtained in Comparative Example 2; D is a picture of the skin condition on the back of mice 9 weeks after modeling after using the minoxidil ointment obtained in Comparative Example 3 for 20 weeks. DETAILED DESCRIPTION

[0017] The technical solution of the present invention will be clearly and completely described below in conjunction with specific embodiments, but those skilled in the art will understand that the embodiments described below are some embodiments of the present invention, not all embodiments, and are only used to illustrate the present invention, and should not be regarded as limiting the scope of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. For those whose specific conditions are not specified in the examples, the conventional conditions or the conditions recommended by the manufacturer are followed. The lichen powder used is from Shaanxi Yongyuan Biotechnology Co., Ltd., and the reagents or instruments used without indicating the manufacturer are all conventional products that can be purchased commercially.

[0018] Example 1 A method for preparing minoxidil liniment comprises the following steps: 1. Dissolve the lichen powder in 60wt% ethanol at a mass ratio of 1:60, keep warm in a water bath at 70℃ for 8h, centrifuge at 4000rpm for 10min, separate the supernatant and precipitate, extract the precipitate with 60wt% ethanol repeatedly 5 times, combine the supernatants, filter with filter paper, and concentrate under reduced pressure at 60℃ and 0.10MPa to evaporate the solvent. After vacuum freeze-drying at -50℃ and 10Pa for 24h, a crude extract was obtained.

[0019] 2. The crude extract was mixed with anhydrous ethanol at a material-liquid ratio of 5:1. After standing for 24 hours, the upper extract was separated and the extraction was repeated 5 times. The secondary extract was concentrated under reduced pressure at 60°C and 0.10 MPa to obtain a secondary extract. Finally, the secondary extract was extracted with chloroform at a material-liquid ratio of 3:1. After repeated extraction 6 times, the secondary extract was concentrated under reduced pressure at 55°C and 0.10 MPa, washed with acetone, and dried at 70°C for 6 hours to obtain the lichen extract.

[0020] 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 at 30°C oil bath and 600 rpm for 2 hours, evaporate the solvent at 50°C and 0.1 MPa, then add 50 wt% ethanol as a re-dissolution solvent, centrifuge at 4500 rpm for 15 minutes, take the supernatant and evaporate the solvent, then freeze-dry at -35°C and 10 Pa for 4 hours to obtain a 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.

[0021] 4. Dissolve 8 parts of oleic acid, 2 parts of lichen extract-phospholipid complex, and 2 parts of minoxidil in dichloromethane, and add anhydrous ethanol to obtain an 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; Dissolve 1 part of Tween 80 in 50 parts of pure water to obtain the aqueous phase; In a water bath at 80°C, the oil phase was added to the water phase at a mass ratio of 1:1.5, and the mixture was stirred at 1500 rpm for 10 min to obtain colostrum.

[0022] 5. The colostrum was dispersed at a high speed of 1000 rpm for 1 minute, and a high-pressure homogenizer was used for two cycles at a pressure of 20,000 psi. Finally, the colostrum was cooled in a cold water bath for 12 hours to obtain nanoliposome-encapsulated minoxidil.

[0023] 6. Take 6 parts of polyvinyl alcohol, 10 parts of sodium carboxymethyl cellulose, 2 parts of glycerol, and 1 part of Tween 80 by weight; dissolve the polyvinyl alcohol in 100 parts of deionized water, and heat at a stirring speed of 1200 rpm at a temperature of 120°C in an oil bath 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 at a temperature of 70°C in an oil bath, add glycerol and Tween 80, and stir at 800 rpm for 10 minutes to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution.

[0024] 7. The nanoliposome-encapsulated minoxidil and the polyvinyl alcohol-sodium carboxymethylcellulose composite coating liquid are vacuum-filled in different sub-bottles to obtain the minoxidil ointment.

[0025] Example 2 A method for preparing minoxidil liniment comprises the following steps: 1. Dissolve the lichen powder in 60wt% ethanol at a mass ratio of 1:60, keep warm in a water bath at 70℃ for 8h, centrifuge at 4000rpm for 10min, separate the supernatant and precipitate, extract the precipitate with 60wt% ethanol repeatedly 5 times, combine the supernatants, filter with filter paper, and concentrate under reduced pressure at 60℃ and 0.10MPa to evaporate the solvent. After vacuum freeze-drying at -50℃ and 10Pa for 24h, a crude extract was obtained.

[0026] 2. The crude extract was mixed with anhydrous ethanol at a material-liquid ratio of 5:1. After standing for 24 hours, the upper extract was separated and the extraction was repeated 5 times. The secondary extract was concentrated under reduced pressure at 60°C and 0.10 MPa to obtain a secondary extract. Finally, the secondary extract was extracted with chloroform at a material-liquid ratio of 3:1. After repeated extraction 6 times, the secondary extract was concentrated under reduced pressure at 55°C and 0.10 MPa, washed with acetone, and dried at 70°C for 6 hours to obtain the lichen extract.

[0027] 3. Take lichen extract and dilute it to volume in a volumetric flask with distilled water to obtain a 2 mg / mL lichen extract solution; dissolve phospholipid in anhydrous ethanol, add lichen extract solution, stir and react at 35°C oil bath and 600 rpm for 2 hours, evaporate the solvent at 50°C and 0.1 MPa, then add 50 wt% ethanol as a re-dissolution solvent, centrifuge at 4500 rpm for 15 minutes, take the supernatant and evaporate the solvent, then freeze-dry at -35°C and 10 Pa for 4 hours to obtain 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 0.9:10.

[0028] 4. Dissolve 10 parts of oleic acid, 4 parts of lichen extract-phospholipid complex, and 3 parts of minoxidil in dichloromethane, and add anhydrous ethanol to obtain an 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; Dissolve 1 part of Tween 80 in 50 parts of pure water to obtain the aqueous phase; In a water bath at 80°C, the oil phase was added to the water phase at a mass ratio of 1:1.5, and the mixture was stirred at 1500 rpm for 10 min to obtain colostrum.

[0029] 5. The colostrum was dispersed at a high speed of 1000 rpm for 1 minute, and a high-pressure homogenizer was used for two cycles at a pressure of 20,000 psi. Finally, the colostrum was cooled in a cold water bath for 12 hours to obtain nanoliposome-encapsulated minoxidil.

[0030] 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; dissolve the polyvinyl alcohol in 100 parts of deionized water, and heat at a stirring speed of 1200 rpm at a temperature of 125°C in an oil bath 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 at a temperature of 75°C in an oil bath, add glycerol and Tween 80, and stir at 800 rpm for 10 minutes to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution.

[0031] 7. The nanoliposome-encapsulated minoxidil and the polyvinyl alcohol-sodium carboxymethylcellulose composite coating liquid are vacuum-filled in different sub-bottles to obtain the minoxidil ointment.

[0032] Example 3 A method for preparing minoxidil liniment comprises the following steps: 1. According to the mass ratio of 1:60, lichen powder is dissolved in 60wt% ethanol, and the water bath is kept at 70°C for 8h, and centrifuged at 4000rpm for 10min, and the supernatant and precipitate are separated, and the precipitate is repeatedly extracted with 60wt% ethanol for 5 times, and the supernatant is 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.

[0033] 2. According to the solid-liquid ratio of 5:1, the crude extract is mixed with anhydrous ethanol, and after standing for 24h, the upper extract is separated, and after repeated extraction for 5 times, it is concentrated under reduced pressure at 60°C and 0.10MPa to obtain the secondary extract, and finally according to the solid-liquid ratio of 3:1, the secondary extract is extracted with chloroform, and after repeated extraction for 6 times, it is concentrated under reduced pressure at 55°C and 0.10MPa, washed with acetone, and dried at 70°C for 6h to obtain the lichen extract.

[0034] 3. Take the lichen extract, and use distilled water to make up the volume in a volumetric flask to obtain a 3mg / mL lichen extract solution; take phospholipid and dissolve it in anhydrous ethanol, add the lichen extract solution, stir at 600rpm for 2h under 40°C oil bath, rotary evaporate to evaporate the solvent at 50°C and 0.1MPa, then add 50wt% ethanol as the redissolving solvent, centrifuge at 4500rpm for 15min, take the supernatant, rotary evaporate to evaporate the solvent, freeze-dry at-35°C and 10Pa for 4h 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 1:10.

[0035] 4. According to the weight fraction, 12 parts of oleic acid, 6 parts of lichen extract-phospholipid complex, and 4 parts of minoxidil are dissolved in dichloromethane, and anhydrous ethanol is added to obtain an 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; Take 1 part of Tween 80 and dissolve it in 50 parts of pure water to obtain an aqueous phase; Under 80°C water bath, add the oil phase to the aqueous phase according to the mass ratio of 1:1.5, stir at 150rpm for 10min to obtain the initial emulsion.

[0036] 5. Disperse the initial emulsion at 1000rpm for 1min, use a high-pressure homogenizer at a pressure of 20000psi for two cycles, and finally cool in a cold water bath for 12h to obtain nanoliposome-encapsulated minoxidil.

[0037] 6. Take 12 parts of polyvinyl alcohol, 15 parts of sodium carboxymethyl cellulose, 3 parts of glycerol, and 2 parts of Tween 80 by weight; dissolve the polyvinyl alcohol in 100 parts of deionized water, and heat at a stirring speed of 1200 rpm at an oil bath temperature of 130°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 at an oil bath of 80°C, add glycerol and Tween 80, and stir at 800 rpm for 10 minutes to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution.

[0038] 7. The nanoliposome-encapsulated minoxidil and the polyvinyl alcohol-sodium carboxymethylcellulose composite coating liquid are vacuum-filled in different sub-bottles to obtain the minoxidil ointment.

[0039] Comparative Example 1 A method for preparing a minoxidil liniment, which differs from Example 1 in that component B, i.e., polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution, is not included, specifically comprising the following steps: 1. Dissolve the lichen powder in 60wt% ethanol at a mass ratio of 1:60, keep warm in a water bath at 70℃ for 8h, centrifuge at 4000rpm for 10min, separate the supernatant and precipitate, extract the precipitate with 60wt% ethanol repeatedly 5 times, combine the supernatants, filter with filter paper, and concentrate under reduced pressure at 60℃ and 0.10MPa to evaporate the solvent. After vacuum freeze-drying at -50℃ and 10Pa for 24h, a crude extract was obtained.

[0040] 2. The crude extract was mixed with anhydrous ethanol at a material-liquid ratio of 5:1. After standing for 24 hours, the upper extract was separated and the extraction was repeated 5 times. The secondary extract was concentrated under reduced pressure at 60°C and 0.10 MPa to obtain a secondary extract. Finally, the secondary extract was extracted with chloroform at a material-liquid ratio of 3:1. After repeated extraction 6 times, the secondary extract was concentrated under reduced pressure at 55°C and 0.10 MPa, washed with acetone, and dried at 70°C for 6 hours to obtain the lichen extract.

[0041] 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 at 30°C oil bath and 600 rpm for 2 hours, evaporate the solvent at 50°C and 0.1 MPa, then add 50 wt% ethanol as a re-dissolution solvent, centrifuge at 4500 rpm for 15 minutes, take the supernatant and evaporate the solvent, then freeze-dry at -35°C and 10 Pa for 4 hours to obtain a 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.

[0042] 4. Dissolve 8 parts of oleic acid, 2 parts of lichen extract-phospholipid complex, and 2 parts of minoxidil in dichloromethane, and add anhydrous ethanol to obtain an 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; Dissolve 1 part of Tween 80 in 50 parts of pure water to obtain the aqueous phase; In a water bath at 80°C, the oil phase was added to the water phase at a mass ratio of 1:1.5, and the mixture was stirred at 1500 rpm for 10 min to obtain colostrum.

[0043] 5. The colostrum was dispersed at a high speed of 1000 rpm for 1 minute, and a high-pressure homogenizer was used for two cycles at a pressure of 20,000 psi. Finally, the colostrum was cooled in a cold water bath for 12 hours to obtain nanoliposome-encapsulated minoxidil.

[0044] 6. The nanoliposomes encapsulate minoxidil and vacuum-fill the nanoliposomes into sub-bottles to obtain minoxidil liniment.

[0045] Comparative Example 2 A method for preparing a minoxidil liniment, which differs from Example 1 in that the minoxidil in component A is not subjected to nanoliposome inclusion, specifically comprising the following steps: 1. Mix 90 wt% ethanol, propylene glycol, and pure water in a mass ratio of 1:3:5, stir at 600 rpm for 5 min, add minoxidil raw material, stir and emulsify at 1500 rpm for 15 min, and then perform high-pressure homogenization at 20,000 psi. After the homogenization cycle for 60 min, filter the obtained emulsion to obtain a minoxidil emulsion.

[0046] 2. Take 6 parts of polyvinyl alcohol, 10 parts of sodium carboxymethyl cellulose, 2 parts of glycerol, and 1 part of Tween 80 by weight; dissolve the polyvinyl alcohol in 100 parts of deionized water, and heat at a stirring speed of 1200 rpm at a temperature of 120°C in an oil bath 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 at a temperature of 70°C in an oil bath, add glycerol and Tween 80, and stir at 800 rpm for 10 minutes to obtain a polyvinyl alcohol-sodium carboxymethyl cellulose composite coating solution.

[0047] 3. Vacuum-fill the minoxidil emulsion and the polyvinyl alcohol-sodium carboxymethylcellulose composite coating solution into different sub-bottles to obtain the minoxidil ointment.

[0048] Comparative Example 3 This comparative example provides a minoxidil liniment purchased randomly from the market.

[0049] 100 ICR male mice were selected, weighing 20-23 g. After being raised alone for one week, the mice were injected with testosterone propionate for modeling at 5 mg / kg d daily. The modeling was successful when the hair on the back of the mice was sparse, fell off or partially fell off. After 9 weeks of injection, 40 mice were randomly selected from the mice with successful modeling and randomly divided into 4 groups, 10 mice in each group. The minoxidil liniment of Example 3 and Comparative Example 1-3 was applied to the 4 groups of mice respectively. The amount of application was 0.2 g per day. During the treatment period, the testosterone propionate was injected daily to maintain the hormone level in the body. The skin of the smearing area was observed to have abnormal reactions such as erythema, edema, erosion, and rough skin, and the hair growth situation was observed. During the 21st week of medication, the hair growth situation of the mice was observed, and the back of the mice was depilated to observe the skin state.

[0050] 1. Figure 1 The figures are as follows: hair growth of mice in each group, wherein A shows the hair condition of mice after modeling. Nine weeks after modeling, the hair on the back of mice fell off more, with varying degrees of sparseness and shedding. Figures B, C, D, and E show the growth of hair on the back of mice in each group after using the minoxidil liniment obtained in Example 3, Comparative Example 1, Comparative Example 2, and Comparative Example 3 for 20 weeks, respectively.

[0051] Depend on Figure 1 As can be seen, compared to Example 3, the back hair of mice in Comparative Examples 1-3 was relatively sparse and of varying lengths. In Example 3, the hair in the original hair loss area on the back of the mice had grown well, with no visible skin. Comparative Example 1 lacked the polyvinyl alcohol-sodium carboxymethylcellulose composite coating, exposing the minoxidil to the skin surface. The active ingredients therein evaporated, resulting in a poor hair growth effect. Comparative Example 2 lacked the nanoliposome coating and the antioxidant effect of the lichen extract-phospholipid complex, shortening the duration of minoxidil's action and affecting its hair growth effect. Comparative Example 3, a minoxidil liniment purchased randomly from the market, showed some hair growth on the back of the mice compared to before treatment, but the hair was sparse, with visible hair loss areas.

[0052] 2. Figure 2 The skin conditions of mice in each group after hair removal. Figure 2As can be seen, after using the minoxidil liniments obtained from different examples and comparative examples, the back skin of the mice in Example 3 became rosy and elastic, with no obvious abnormal changes; while the skin surfaces of the mice in Comparative Examples 1 to 3 showed varying degrees of dryness, erythema, roughness, and damage. The polyvinyl alcohol-sodium carboxymethylcellulose nanoliposomes in Example 3 can absorb and encapsulate the aqueous phase of the minoxidil, forming a gel-like substance. This reduces surface exposure of the minoxidil, prevents the precipitation of minoxidil crystals, and reduces the risk of skin allergies after using the minoxidil liniment. The inclusion of minoxidil using a lichen extract-phospholipid complex avoids the allergic dermatitis that may be caused by frequent use of propylene glycol and ethanol. The anti-inflammatory and antioxidant effects of the lichen extract can effectively prevent the allergic dermatitis that occurs when using the minoxidil liniment.

[0053] The specific embodiments of the present invention described above do not limit the scope of protection of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the scope of protection of the claims of the present invention.

Claims

1. A minoxidil liniment, characterized in that: The invention comprises component A and component B, wherein component A is nanoliposome-encapsulated minoxidil, and component B is polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid.

2. A minoxidil liniment according to claim 1, characterized in that The preparation method of the nanoliposome-encapsulated minoxidil comprises the following steps: dissolving oleic acid, a 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; adding the oil phase to the aqueous phase in an 80°C water bath, and stirring for 10 minutes to obtain colostrum; and homogenizing the colostrum through high-speed dispersion, and finally cooling in a cold water bath for 12 hours to obtain the nanoliposome-encapsulated minoxidil.

3. A minoxidil liniment according to claim 2, characterized in that In parts by weight, the oil phase comprises: 8 to 12 parts of oleic acid, 2 to 6 parts of lichen extract-phospholipid complex, and 2 to 4 parts of 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; and the mass ratio of the oil phase to the aqueous phase is 1:1.

5.

4. The minoxidil liniment according to claim 1, wherein The preparation method of the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid comprises the following steps: dissolving polyvinyl alcohol in deionized water, stirring and heating at an oil bath temperature of 120-130° C. until the polyvinyl alcohol is completely dissolved, thereby obtaining a polyvinyl alcohol solution; adjusting the rotation speed to 900 rpm, adding sodium carboxymethyl cellulose to the polyvinyl alcohol solution at an oil bath temperature of 70-80° C., adding glycerol and Tween 80, and heating and stirring in the oil bath for 10 minutes, thereby obtaining the polyvinyl alcohol-sodium carboxymethyl cellulose composite coating liquid.

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

6. A minoxidil liniment according to claim 2, characterized in that: The preparation method of the lichen extract-phospholipid complex comprises the following steps: taking a lichen extract, diluting the volume with distilled water in a volumetric flask to obtain a lichen extract solution; dissolving a phospholipid in anhydrous ethanol, adding the lichen extract solution, stirring and reacting in an oil bath at 30-40° C. for 2 hours, evaporating the solvent by rotary evaporation at 50° C. and 0.1 MPa, adding 50 wt% ethanol as a re-dissolution solvent, centrifuging at 4500 rpm for 15 minutes, evaporating the solvent from the supernatant, and freeze-drying the supernatant at -35° C. and 10 Pa for 4 hours 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.

7. A minoxidil liniment according to claim 6, characterized in that: The preparation method of the lichen extract comprises the following steps: dissolving lichen powder in 60wt% ethanol at a mass ratio of 1:60, keeping the mixture in a water bath at 70°C for 8h, centrifuging at 4000rpm for 10min, separating the supernatant and the precipitate, repeatedly extracting the precipitate with 60wt% ethanol for 5 times, combining the supernatants, filtering, concentrating under reduced pressure, and freeze-drying the mixture for 24h to obtain a crude extract; mixing the crude extract with anhydrous ethanol at a liquid-to-solid ratio of 5:1, standing the mixture for 24h, separating the upper extract, repeating the extraction for 5 times, and concentrating the mixture under reduced pressure at 60°C and 0.10MPa to obtain a secondary extract; and finally, repeatedly extracting the secondary extract with chloroform for 6 times at a liquid-to-solid ratio of 3:1, concentrating the mixture under reduced pressure, washing with acetone, and drying the mixture to obtain the lichen extract.

8. The method for preparing the minoxidil liniment according to claim 1, wherein: The nanoliposome-encapsulated minoxidil and the polyvinyl alcohol-sodium carboxymethylcellulose composite coating liquid are vacuum-filled in different sub-bottles to obtain the minoxidil liniment.

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