Pharmaceutical preparation for treating alopecia, its preparation method and use

Abstract

The present invention provides a pharmaceutical formulation for treating alopecia, its preparation method, and use. Specifically, the present invention provides a formulation or composition for treating alopecia, which contains the active ingredients (a) 5% minoxidil and (b) 0.07-0.095% finasteride, calculated according to mass percentage (w / w) or mass volume percentage (w / v), and the formulation or composition is a foam or liniment. When the formulation is a foam, the total mass in the mass percentage does not include the mass of the propellant. The foam and liniment of the present invention have fast onset of effect, good efficacy, and few side effects.

Description

[Technical Field]

[0001] The present invention relates to the field of pharmaceutical preparations, and more particularly to a pharmaceutical preparation for treating alopecia, its preparation method and use. [Background technology]

[0002] Nowadays, alopecia has become an increasingly serious problem for people of all ages, which not only affects the appearance but also has a significant negative impact on the psychological and social life of patients.

[0003] Take androgenetic alopecia (AGA), one of the most common types of hair loss. It is a progressive hair loss disorder characterized by hair follicle shrinkage that occurs during or after puberty. Both men and women can develop the condition, but they show different patterns of hair loss and different prevalence rates. While AGA does not affect physical health, it does have a serious impact on patients' mental health and quality of life. For example, early diagnosis and treatment can slow the progression of hair loss and improve patients' quality of life.

[0004] Because AGA is progressive and ultimately leads to alopecia, the importance of early and long-term treatment should be emphasized. Generally, the earlier treatment is started, the better the treatment effect. Treatment methods include systemic drug therapy, topical drug therapy, hair transplantation, mesotherapy, and low-energy laser therapy. However, currently, the main drugs used to treat alopecia still have many drawbacks, such as slow onset of action, insufficient efficacy, or side effects.

[0005] Therefore, it is of great importance in the art to develop a drug or combination preparation for treating alopecia that has a fast onset of effect, good efficacy and few side effects. Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention provides a drug for treating alopecia that has a rapid onset of effect, good efficacy, and few side effects. [Means for solving the problem]

[0007] A first aspect of the present invention provides a preparation or composition having an effect of treating alopecia, the preparation or composition comprising: (a) minoxidil 5%, and (b) Contains 0.07 to 0.095% of the active ingredient finasteride; Calculate according to mass percentage (w / w) or mass volume percentage (w / v). In another preferred embodiment, the formulation or composition comprises: (a) minoxidil 5%, and (b) Contains 0.07 to 0.09% of the active ingredient finasteride, Calculate according to mass percentage or mass volume percentage.

[0008] In another preferred embodiment, the formulation or composition comprises: (a) minoxidil 5%, and (b) Contains 0.07 to 0.085% of the active ingredient finasteride; Calculate according to mass percentage or mass volume percentage. In another preferred embodiment, the formulation or composition comprises: (a) minoxidil 5%, and (b) Contains 0.07-0.08% of the active ingredient finasteride, Calculate according to mass percentage or mass volume percentage.

[0009] In another preferred embodiment, the formulation or composition comprises: (a) minoxidil 5%, and (b) Contains 0.07 to 0.075% of the active ingredient finasteride; Calculate according to mass percentage or mass volume percentage. In another preferred embodiment, the formulation or composition comprises: (a) minoxidil 5%, and (b) Contains the active ingredient finasteride 0.075% Calculate according to mass percentage or mass volume percentage.

[0010] In another preferred embodiment, the formulation or composition further comprises a pharmaceutically acceptable carrier. In another preferred embodiment, the dosage form of the preparation or composition is selected from the group consisting of foam, paint, tincture, spray, and gel. In another preferred embodiment, the formulation or composition is in the form of a foam or a liniment. In another preferred embodiment, the formulation or composition is a foam. In another preferred embodiment, the preparation or composition is a liniment.

[0011] In another preferred embodiment, the formulation or composition may or may not contain propylene glycol and isopropanol. In another preferred example, when the preparation or composition is a foam, the preparation or composition does not contain propylene glycol and isopropanol. In another preferred embodiment, when the formulation or composition is a foam, it is calculated according to the active ingredient mass percentage (w / w). In another preferred example, when the preparation or composition is a liniment, it is calculated according to the active ingredient mass volume percentage (w / v).

[0012] In another preferred embodiment, the formulation is a laboratory formulation. In another preferred embodiment, the formulation is a pharmaceutical formulation. In another preferred embodiment, the composition is a pharmaceutical composition. In another preferred embodiment, the formulation or composition further comprises an additional ingredient that promotes hair growth.

[0013] A second aspect of the present invention provides a foam for treating alopecia, the foam comprising: (a) minoxidil 5%, and (b) Contains 0.07 to 0.095% of the active ingredient finasteride; Calculate according to mass percentage (w / w). In another preferred embodiment, the foaming agent is (a) minoxidil 5%, and (b) Contains 0.07 to 0.09% of the active ingredient finasteride, Calculate according to mass percentage.

[0014] In another preferred embodiment, the foaming agent is (a) minoxidil 5%, and (b) Contains 0.07 to 0.085% of the active ingredient finasteride; Calculate according to mass percentage. In another preferred embodiment, the foaming agent is (a) minoxidil 5%, and (b) Contains 0.07-0.08% of the active ingredient finasteride, Calculate according to mass percentage.

[0015] In another preferred embodiment, the foaming agent is (a) minoxidil 5%, and (b) Contains 0.07 to 0.075% of the active ingredient finasteride; Calculate according to mass percentage. In another preferred embodiment, the foaming agent is (a) minoxidil 5%, and (b) Contains the active ingredient finasteride 0.075% Calculate according to mass percentage, Here, the total mass in the mass percentage does not include the mass of the propellant.

[0016] In another preferred example, the mass percentage is the mass percentage of the active ingredient relative to the total mass of the foam, and the total mass of the foam does not include the mass of the propellant. In another preferred embodiment, the foam further comprises a pharmaceutically acceptable carrier. In another preferred embodiment, the foaming agent further comprises an ingredient selected from the group consisting of a humectant, a solubilizer, a pH adjuster, an antioxidant, a proppant, a diluent, a complexing agent, a propellant, or a combination thereof. In another preferred embodiment, the humectant is selected from the group consisting of glycerin, polyethylene glycol 2000, polyethylene glycol 4000, polyethylene glycol 6000, or a combination thereof. In another preferred embodiment, the moisturizer is glycerin.

[0017] In another preferred example, the mass percentage of the moisturizing agent in the foaming agent is 1 to 10 wt %, preferably 1 to 5 wt %, more preferably 2 to 3 wt %, more preferably 2 to 2.5 wt %. In another preferred embodiment, the solubilizer is selected from the group consisting of Tween 40, Tween 60, Tween 80, sodium lauryl sulfate, docusate sodium, or a combination thereof. In another preferred embodiment, the solubilizer is Tween 60. In another preferred example, the mass percentage of the solubilizer in the foaming agent is 0.1 to 5.0 wt%, preferably 0.1 to 1.0 wt%, more preferably 0.1 to 0.5 wt%, more preferably 0.3 to 0.5 wt%.

[0018] In another preferred embodiment, the pH adjuster is selected from the group consisting of lactic acid, hydrochloric acid, sodium hydroxide, acetic acid, or a combination thereof. In another preferred embodiment, the pH adjuster is lactic acid. In another preferred example, the mass percentage of the pH adjuster in the foaming agent is 0.1 to 5.0 wt%, preferably 0.5 to 2.5 wt%, more preferably 1.0 to 2.0 wt%, more preferably 1.0 to 1.5 wt%.

[0019] In another preferred embodiment, the antioxidant is selected from the group consisting of butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), vitamin E, or a combination thereof. In another preferred embodiment, the antioxidant is butylated hydroxytoluene. In another preferred example, the mass percentage of the antioxidant in the foaming agent is 0.01 to 1 wt %, preferably 0.05 to 0.5 wt %, and more preferably 0.1 to 0.2 wt %. In another preferred example, the proppant is selected from the group consisting of hexadecanol, octadecanol, or a combination thereof. In another preferred embodiment, the proppant is hexadecanol and octadecanol. In another preferred example, the mass percentage of the proppant in the foaming agent is 0.5 to 10 wt%, preferably 0.5 to 5 wt%, more preferably 1.5 to 2.5 wt%, more preferably 1.5 to 2.0 wt%.

[0020] In another preferred embodiment, the diluent is selected from the group consisting of purified water, absolute ethanol, n-propanol, or a combination thereof. In another preferred embodiment, the diluent is selected from the group consisting of purified water, absolute ethanol, or a combination thereof. In another preferred embodiment, the diluent is selected from a mixture of purified water and absolute ethanol.

[0021] In another preferred embodiment, the complexing agent is selected from the group consisting of lactic acid, anhydrous citric acid, acetic acid, malic acid, maleic acid, or a combination thereof. In another preferred embodiment, the complexing agent is anhydrous citric acid. In another preferred example, the mass percentage of the complexing agent in the foaming agent is 0.1 to 5.0 wt%, preferably 0.1 to 1.0 wt%, more preferably 0.1 to 0.5 wt%, more preferably 0.1 to 0.3 wt%, more preferably 0.1 to 0.2 wt%.

[0022] In another preferred embodiment, the propellant is selected from the group consisting of propane, butane, isobutane, or combinations thereof. In another preferred embodiment, the propellant comprises a mixture of 48% propane, 30% butane and 22% isobutane, calculated according to mass percentage (w / w). In another preferred example, the mass percentage of the propellant in the foam is 1.5 to 8.5 wt%, preferably 2.5 to 7.5 wt%, more preferably 3.5 to 6.5 wt%, more preferably 4.5 to 5.5 wt%. In another preferred embodiment, the foaming agent does not contain propylene glycol or isopropanol. In another preferred embodiment, the foaming agent comprises glycerin, Tween 60, lactic acid, butylated hydroxytoluene, hexadecanol, octadecanol, anhydrous citric acid, absolute ethanol, purified water and a propellant.

[0023] In another preferred example, without the propellant, the foaming agent further comprises 2.11% glycerin, 0.42% Tween 60, 1.05% lactic acid, 0.1% butylated hydroxytoluene, 1.16% hexadecanol, 0.53% octadecanol, 0.11% anhydrous citric acid, 56.46% absolute ethanol, 32.985% purified water, calculated according to mass percentage (w / w). In another preferred embodiment, the foam further comprises 5.00% propellant, calculated according to mass percentage (w / w). In another preferred embodiment, the foam further comprises an additional ingredient that promotes hair growth.

[0024] A third aspect of the present invention provides an application for treating alopecia, the application comprising: (a) minoxidil 5%, and (b) Contains 0.07 to 0.095% of the active ingredient finasteride; Calculate according to mass volume percentage (w / v). In another preferred embodiment, the coating agent is (a) minoxidil 5%, and (b) Contains 0.07 to 0.09% of the active ingredient finasteride, Calculate according to mass volume percentage.

[0025] In another preferred embodiment, the coating agent is (a) minoxidil 5%, and (b) Contains 0.07 to 0.085% of the active ingredient finasteride; Calculate according to mass volume percentage. In another preferred embodiment, the coating agent is (a) minoxidil 5%, and (b) Contains 0.07-0.08% of the active ingredient finasteride, Calculate according to mass volume percentage.

[0026] In another preferred embodiment, the coating agent is (a) minoxidil 5%, and (b) Contains 0.07 to 0.075% of the active ingredient finasteride; Calculate according to mass volume percentage. In another preferred embodiment, the coating agent is (a) minoxidil 5%, and (b) Contains the active ingredient finasteride 0.075% Calculate according to mass volume percentage. In another preferred example, the mass volume percentage is a mass (g) percentage of the active ingredient relative to the total volume (ml) of the application agent.

[0027] In another preferred example, the liniment further comprises a pharmaceutically acceptable carrier. In another preferred embodiment, the application agent further comprises a penetration enhancer, a cosolvent, a solvent, or a combination thereof. In another preferred embodiment, the penetration enhancer is selected from the group consisting of propylene glycol, laurocapram, cyclohexanehexol, decylmethyl sulfoxide, or a combination thereof. In another preferred embodiment, the penetration enhancer is propylene glycol. In another preferred example, the volume percentage (v / v) of the penetration enhancer in the application agent is 35% to 60% (v / v), preferably 45% to 55% (v / v), and more preferably 50% to 55% (v / v).

[0028] In another preferred embodiment, the co-solvent is selected from the group consisting of absolute ethanol, glycerin, isopropanol, polyethylene glycol, liquid paraffin, or a combination thereof. In another preferred embodiment, the co-solvent is absolute ethanol. In another preferred example, the volume percentage (v / v) of the co-solvent in the coating agent is 15% to 45% (v / v), preferably 20% to 40% (v / v), and more preferably 25% to 35% (v / v). In another preferred example, the solvent is purified water.

[0029] In another preferred example, the application agent further contains propylene glycol, absolute ethanol, and purified water. In another preferred example, the liniment further contains 50% (v / v) propylene glycol and 30% (v / v) absolute ethanol. In another preferred example, the application agent further contains purified water adjusted to a predetermined volume. In another preferred embodiment, the application agent further comprises an additional ingredient for promoting hair growth.

[0030] A fourth aspect of the present invention provides the use of a formulation or composition according to the first aspect of the present invention, a foam according to the second aspect of the present invention, or an application agent according to the third aspect of the present invention for use in the preparation of a medicament for treating alopecia. In another preferred embodiment, the treatment includes promoting hair growth and preventing further alopecia. In another preferred embodiment, the alopecia is male pattern baldness, drug (e.g., chemotherapy)-induced alopecia, radiation therapy-induced alopecia, age-induced alopecia, autoimmune disease-induced alopecia, hormone-induced alopecia, infection-induced alopecia, or a combination thereof. In another preferred embodiment, the alopecia is male pattern baldness. In another preferred embodiment, the alopecia is male pattern baldness or female postmenopausal alopecia.

[0031] A fifth aspect of the present invention provides a method for preparing a foam according to the second aspect of the present invention, comprising the steps of: (s1) Calculate according to mass percentage, (a) minoxidil 5%, and (b) Stockpiling active ingredient raw materials such as finasteride 0.07-0.095% (s2) mixing and dissolving the active ingredient and the pharmaceutically acceptable carrier, and then filling and sealing the mixture; and (s3) A propellant is filled into the sealed solution to prepare the foam.

[0032] In another preferred embodiment, when preparing a foaming agent, the calculation is made according to mass percentage, and step (s2) further comprises the following steps: (s2a) Aqueous phase: A complexing agent is dissolved in purified water. (s2b) Alcohol phase: The finasteride is dissolved in a small amount of absolute ethanol, and then a moisturizer, a solubilizer, a pH adjuster, a finasteride solution, an antioxidant, and a proppant are added to the absolute ethanol and dissolved, and then the minoxidil is added, stirred, and dispersed; and (s2c) The aqueous solution of the complexing agent and (s2b) are mixed and stirred until the minoxidil is completely dissolved, and then the mixture is filled and sealed.

[0033] In another preferred embodiment, when preparing a foaming agent, the calculation is made according to mass percentage, and step (s2) further comprises the following steps: (s2a) Aqueous phase: Anhydrous citric acid is dissolved in purified water, (s2b) Alcohol phase: The finasteride is dissolved in a small amount of absolute ethanol, and then glycerin, Tween 60, lactic acid, a finasteride ethanol solution, butylated hydroxytoluene, hexadecanol, and octadecanol are added to the absolute ethanol and dissolved, and then the minoxidil is added, stirred, and dispersed; and (s2c) (s2a) The aqueous phase and (s2b) the alcohol phase solution are mixed and stirred until the minoxidil is completely dissolved, then filled and sealed.

[0034] A sixth aspect of the present invention provides a method for preparing a coating agent according to the third aspect of the present invention, comprising the steps of: (s1) Calculate according to mass volume percentage, (a) minoxidil 5%, and (b) Stockpiling finasteride 0.07-0.095% active ingredient raw material, (s2) uniformly mixing the active ingredient and a pharmaceutically acceptable carrier, adjusting the volume, filtering, and (s3) The filtered solution is filled to obtain the coating agent.

[0035] In another preferred embodiment, when preparing the coating agent, the calculation is made according to a mass volume percentage, and the step (s2) further comprises the following steps: (s2a) dissolving the finasteride in a small amount of a co-solvent; (s2b) After the penetration enhancer, co-solvent and some of the solvent are uniformly mixed, the minoxidil and finasteride solution is added and stirred to dissolve, and (s2c) The solution obtained after dissolution is made up to volume with the remaining solvent and filtered.

[0036] In another preferred embodiment, when preparing the coating agent, the calculation is made according to a mass volume percentage, and the step (s2) further comprises the following steps: (s2a) dissolving the finasteride in a small amount of absolute ethanol; (s2b) After uniformly mixing the propylene glycol, absolute ethanol, and a portion of purified water, the minoxidil and finasteride ethanol solution is added and stirred to dissolve; and (s2c) The solution obtained after dissolution is made up to volume with the remaining purified water and filtered.

[0037] A seventh aspect of the present invention provides a method of treating alopecia, comprising administering to a subject in need thereof a therapeutically effective amount of a formulation or composition according to the first aspect of the invention, or a foam according to the second aspect of the invention, or a topical application according to the third aspect of the invention. In another preferred embodiment, the method is non-diagnostic and non-therapeutic. [Effects of the Invention]

[0038] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (e.g., in the Examples) can be combined with each other to form new or preferred technical solutions, which will not be repeated here due to space limitations. [Brief explanation of the drawings]

[0039] [Figure 1] 1 shows the hair growth score results for each group of experimental mice after administration of the foam according to the present invention. [Figure 2] 1 shows the hair growth score results for each group of experimental mice after administration of the foam according to the present invention. [Figure 3] 1 shows the hair growth score results for each group of experimental mice after administration of the foam according to the present invention. [Figure 4] 1 shows the hair growth score results for each group of experimental mice after administration of the liniment according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0040] After extensive and thorough research and extensive screening, the inventors have unexpectedly discovered that a combination of minoxidil and finasteride as active ingredients in a specific ratio (e.g., minoxidil 5%, finasteride 0.075%, calculated according to mass percentage or mass-volume percentage) has a much better effect on treating alopecia than other ratios, with a shorter time to onset of effect and better efficacy. Based on this, the present invention has been completed.

[0041] Specifically, the present invention has carried out a number of comparative experiments, and has established minoxidil and finasteride single preparations and their specific content ratio combined preparations, and has carried out experiments on the constructed alopecia model mice.The experimental results show that when the minoxidil content is 5% and the finasteride content is 0.075%, the foam and topical agent of the present invention have unexpectedly excellent effects, and their alopecia treatment effect is better than that of 0.1% finasteride content.And when the finasteride content is 0.15%, their alopecia treatment effect is better than that of 0.1% finasteride content, that is, two peak effects appear when the finasteride content is about 0.075% and 0.15%, respectively.

[0042] term To facilitate understanding of this disclosure, certain terms are first defined. As used herein, unless otherwise specified herein, each of the following terms shall have the meaning indicated below. Other definitions are set forth throughout the invention.

[0043] The term "about" can refer to a particular value or configuration within an acceptable error range as determined by one of ordinary skill in the art, which depends in part on how the value or configuration is measured or determined. For example, as used herein, the phrase "about 100" includes all values ​​between 99 and 101 (e.g., 99.1, 99.2, 99.3, 99.4, etc.). As used herein, the terms "containing" or "comprising" can refer to open, semi-closed, and closed systems. In other words, the terms also include "consisting essentially of" or "consisting of."

[0044] As used herein, unless otherwise specified, any concentration range, percentage range, ratio range, or integer range is understood to include any integer value within said range, and fractional values ​​thereof (e.g., tenths and hundredths of integers), where appropriate. As used herein, the term "and / or" refers to and covers one or more of the associated listed items in any and all possible combinations.

[0045] As used herein, the terms "specification 5% to 0.075%" and "5% to 0.075%" have the same meaning, and refer to a foam formulation in which the mass percentage of minoxidil is 5% and the mass percentage of finasteride is 0.075%, and a topical formulation in which the mass percentage of minoxidil is 5% and the mass percentage of finasteride is 0.075%. Other identical expressions in this specification have the same meaning, i.e., in a foam formulation, the first (left) percentage value is the mass percentage of minoxidil and the second (right) percentage value is the mass percentage of finasteride, and in a topical formulation, the first percentage value is the mass percentage of minoxidil and the second percentage value is the mass percentage of finasteride.

[0046] The main advantages of the present invention are: (a) Compared with single preparations of minoxidil or finasteride, and minoxidil-finasteride combination preparations with other combination ratios and dosage forms, the pharmaceutical preparations or compositions provided by the present invention have the characteristics of rapid onset of effect, good efficacy, and fewer side effects, and have better prospects for clinical application. (b) When the pharmaceutical preparation provided by the present invention is in the form of a foam, it has the following additional advantages over other dosage forms: it is free of propylene glycol and isopropanol, which reduces irritation and hypersensitivity, the foam is uniformly dispersed and easily spreads, has a wide application area, has a clear local therapeutic effect, has a low foam density and a soft structure, and penetrates the stratum corneum through the hair follicle after bursting and is easily absorbed, the foam is easy to use, tasteless, non-viscous, and leaves little residue, and is generally well accepted by patients, resulting in high compliance.

[0047] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and do not limit the scope of the present invention. In the following examples, experimental methods without specific conditions are generally in accordance with conventional conditions or conditions suggested by manufacturers. Unless otherwise specified, percentages and parts are mass percentages and mass parts or volume parts.

[0048] Example 1. Pharmacodynamic Study 1 1.1. Experimental Reagents and Materials The experimental materials used in this example are as shown in Table 1.

[0049] [Table 1]

[0050] Preparation of testosterone propionate solution: 80 mg of testosterone propionate was accurately weighed and dissolved in 26.133 ml of corn oil for injection, vortexed, and ultrasonically mixed to obtain a homogeneous solution with a concentration of 3 mg / ml.

[0051] Preparation of finasteride suspension: Accurately weigh out 0.542 mg of finasteride, add 5.420 ml of 0.5% CMC-Na, vortex and mix ultrasonically to obtain a uniform suspension with a concentration of 0.1 mg / ml. Preparation of 5% minoxidil foam: 1) The formulation is as shown in Table 2.

[0052] [Table 2]

[0053] The propellant formulation and fill formulation are as shown in Tables 3 and 4. [Table 3] [Table 4]

[0054] 2) The preparation process is as follows: <1> Preparation of the solution Aqueous phase: Weigh out purified water according to the prescribed amount, add anhydrous citric acid, and stir until completely dissolved to obtain an aqueous phase. Alcohol phase: Add glycerin, Tween 60, lactic acid, butylated hydroxytoluene, hexadecanol, and octadecanol to absolute ethanol according to the prescribed amounts, and stir at 35°C to 60°C. Then add minoxidil, stir, and disperse to obtain an alcohol phase. Mixing: Add the aqueous phase to the alcoholic phase and stir until the minoxidil is completely dissolved, mixing the two phases evenly. <2> Filtration The mixed solution is filtered through a filter element. <3> filling The filtrate was filled into spray aluminum cans (57 g / can), <4> sealing Install and seal the valve <5> Gas filling Filled with mixed alkanes, the amount filled per can is 3g, <6> The mousse nozzle cover and outer lid are then closed and packaged to obtain the product.

[0055] Preparation of blank foam: The process is the same as for minoxidil foam (5% specification), except for the addition of an operation to remove minoxidil from the alcohol phase. The minoxidil is removed from the formula, the absolute ethanol dosage is 34.34g / bottle, and the formula volume is adjusted to 60.24% (propellant-free), and the purified water dosage is 19.54g / bottle, and the formula volume is adjusted to 34.28% (propellant-free), while the contents of other ingredients remain unchanged.

[0056] Preparation of minoxidil finasteride foam (specification 5% to 0.075%): 1) The formulation is as shown in Table 5. [Table 5]

[0057] The propellant formulation and fill formulation are as shown in Tables 6 and 7. [Table 6] [Table 7]

[0058] 2) The preparation process is as follows: <1> Preparation of the solution Aqueous phase: Weigh out purified water according to the prescribed amount, add anhydrous citric acid, and stir until completely dissolved to obtain an aqueous phase. Alcohol phase: Weigh out the absolute ethanol according to the prescribed amount. Dissolve finasteride in a small amount of absolute ethanol. According to the prescribed amounts, glycerin, Tween 60, lactic acid, finasteride ethanol solution, butylated hydroxytoluene, hexadecanol, and octadecanol are added to the remaining absolute ethanol, and the mixture is stirred at 35°C to 60°C. Then, minoxidil is added, stirred, and dispersed to obtain an alcohol phase. Mixing: Add the aqueous phase to the alcoholic phase and stir until the minoxidil is completely dissolved, mixing the two phases evenly. <2> Filtration The mixed solution is filtered through a filter element. <3> filling The filtrate was filled into spray aluminum cans (57 g / can), <4> sealing Install and seal the valve <5> Gas filling Filled with mixed alkanes, the amount filled per can is 3g, <6> The mousse nozzle cover and outer lid are then closed and packaged to obtain the product.

[0059] Preparation of minoxidil finasteride foam (specification 5% to 0.008%): The process is the same as that of minoxidil finasteride foam (specification 5%~0.075%), where the finasteride dosage is 0.005g / bottle, and the weight content without propellant is 0.008%, adjusted accordingly for the amount of purified water, and the contents of other ingredients remain unchanged.

[0060] Preparation of minoxidil finasteride foam (specification 5% to 0.025%): The process is the same as that of minoxidil finasteride foam (specification 5%~0.075%), where the finasteride dosage is 0.014g / bottle, and the weight content without propellant is 0.025%, adjusted accordingly for the amount of purified water, and the contents of other ingredients remain unchanged.

[0061] 1.2. Experimental procedures and results C57BL / 6J male mice were housed in single cages in an SPF grade, constant temperature and humidity laminar flow clean room. After acclimatization for one week, approximately 3 × 4 cm of hair was removed from the back using hair removal cream. 2 The hair was removed, the skin was pink and intact, and the hair follicles of the mice were confirmed to be in the telogen phase. The mice were randomly divided into seven groups, as shown in Table 8 below.

[0062] [Table 8]

[0063] In addition to the blank control group, which received multiple daily injections of corn oil, each group of mice received subcutaneous injections of testosterone propionate solution (to create an androgenetic alopecia model) at 30 mg / kg / day at multiple sites on the bald areas of their backs. 0.5 hours after the testosterone propionate injection, 200 mg of foam was applied to the bald areas on the backs of each group of mice once daily for 30 consecutive days. The blank control group and model group received blank foam once daily for 30 consecutive days. The finasteride group was administered orally, with an initial dose of 0.1 ml per mouse. The dose was adjusted weekly according to changes in body weight, with the initial body weight / 0.1 = weekly body weight / finasteride dose administered once daily for 30 consecutive days.

[0064] The combination of active ingredients in the specific amounts of the present invention has a fast onset of effect and a good effect. Hair growth score The skin and hair growth status of the hair loss sites of mice in each group were observed daily, and scored once a week for the first two weeks, and twice a week from the third week onwards. During scoring, photographs of each group were taken and the scores for hair growth status were recorded.

[0065] The scoring criteria are as shown in Table 9. [Table 9]

[0066] The score results are shown in Table 10 and FIG. [Table 10]

[0067] The results show that the score results of the finasteride group are not significantly different from those of the model group, and the score results of the experimental group III are not only significantly higher than those of the minoxidil group, but also significantly higher than those of the experimental groups I and II. Unexpectedly, experimental group III has a very good effect. On the other hand, after the 18th day of administration, the score results increased rapidly, and on the 21st day, a significant difference was observed between the experimental group I and the experimental group II. Taking the data on the 21st day as an example, the difference between the experimental group III and the model group was 1.7, while the differences between the minoxidil group, the finasteride group, the experimental group I, and the experimental group II and the model group were 0.7, 0.2, 0.5, and 1, respectively. Therefore, the difference (or effect) between the experimental group III and the model group was 2.4 times, 8.5 times, 3.4 times, and 1.7 times that of the minoxidil group, the finasteride group, the experimental group I, and the experimental group II, respectively. On the other hand, the significant difference persisted until the end of the experiment (30 days after administration). As can be seen, the onset time of minoxidil finasteride foam in Experimental Group III is obviously superior to that of Experimental Group I, Experimental Group II, and minoxidil-only foam formulation group.

[0068] Hair weight evaluation After the experiment, the experimental mice were euthanized, and the hair on the surface of the skin at the depilation site was removed and weighed. The experimental results are shown in Table 11. [Table 11]

[0069] The results show that the hair weight of finasteride group is not significantly different from that of model group.Unexpectedly, the hair weight of experiment III group is not only significantly higher than that of minoxidil group, but also significantly higher than that of experiment I and experiment II group. As can be seen from the difference with the model group, compared with the model group, the minoxidil group can significantly increase hair weight, while the hair weight of the finasteride group not only does not increase, but also slightly decreases. The effect of the experiment I group is worse than that of the minoxidil group. Unexpectedly, the effect of Experiment II is significantly improved compared to the minoxidil group.More unexpectedly, the hair growth effect of Experiment III (Δ=32.4) is about 2.3 times that of the minoxidil group.And the increase effect on hair weight is significantly better than that of the finasteride alone group, the minoxidil alone group, and the combined effect of the minoxidil alone group and the finasteride alone group (i.e., Δ=14.3+(-0.8)). Certain ratios of minoxidil and finasteride (e.g., 5% to 0.075%) have been shown to exert a synergistic effect.

[0070] Assessment of hair follicle count Skin was collected from the bald area parallel to the spine, cut into 1 cm strips, fixed in 10% neutral formalin solution for 24-36 hours, dehydrated in gradient alcohols, embedded in paraffin, cut, sectioned, stained with H&E, and observed under a light microscope to count the number of hair follicles. The experimental results are shown in Table 12. [Table 12]

[0071] The results showed that the number of hair follicles in the finasteride group was not significantly different from that in the model group, and was slightly reduced; there was no significant difference between experimental group I, experimental group II, and the minoxidil group, and the number of hair follicles in experimental group I and experimental group II was lower than that in the minoxidil group. Unexpectedly, the number of hair follicles in Experimental Group III (Δ=10) was greater than that of the minoxidil group and significantly greater than that of Experimental Groups I and II. The increasing effect on hair follicle number was significantly greater than that of the finasteride alone group, the minoxidil alone group, and the combined effect of the minoxidil alone group and the finasteride alone group (Δ=7+(-3)). Certain ratios of minoxidil and finasteride (e.g., 5% to 0.075%) have been shown to exert a synergistic effect.

[0072] Example 2. Pharmacodynamics Study 2 2.1. Experimental Reagents and Materials The experimental materials used in this example are as shown in Table 13. [Table 13]

[0073] Preparation of testosterone propionate solution: 80.65 mg of testosterone propionate was accurately weighed and dissolved in 26.346 ml of corn oil for injection, vortexed, and ultrasonically mixed to obtain a homogeneous solution with a concentration of 3 mg / ml.

[0074] Preparation of 5% minoxidil foam: The preparation method was the same as that of the 5% minoxidil foam preparation in Example 1.

[0075] Preparation of blank foam: The preparation method was the same as that of the blank foam in Example 1.

[0076] Preparation of minoxidil finasteride foam (specification 5% to 0.05%): The process is the same as that of Example 1, minoxidil finasteride foam (specification 5%-0.075%), where the dosage of finasteride is 0.029g / bottle, the mass content without propellant is 0.05%, adjusted accordingly with the dosage of purified water, and the contents of other ingredients remain unchanged.

[0077] Preparation of minoxidil finasteride foam (specification 5% to 0.06%): The process is the same as that of Example 1, minoxidil finasteride foam (specification 5%-0.075%), where the dosage of finasteride is 0.034g / bottle, and the mass content without propellant is 0.06%, adjusted accordingly with the dosage of purified water, and the contents of other ingredients remain unchanged.

[0078] Preparation of minoxidil finasteride foam (specification 5% to 0.07%): The process is the same as that of Example 1, where the minoxidil finasteride foam (specification 5%-0.075%), the dosage of finasteride is 0.04g / bottle, the mass content without propellant is 0.07%, adjusted accordingly with the dosage of purified water, and the contents of other ingredients remain unchanged.

[0079] 2.2. Experimental procedures and results C57BL / 6J male mice were housed in single cages in an SPF grade, constant temperature and humidity laminar flow clean room. After acclimatization for one week, approximately 3 × 4 cm of hair was removed from the back using hair removal cream. 2 The hair was removed, and the skin was pink and intact, confirming that the hair follicles of the mice were in the telogen phase. The mice were randomly divided into six groups, as shown in Table 14. [Table 14]

[0080] In addition to the blank control group, which received multiple daily injections of corn oil, each group of mice received subcutaneous injections of testosterone propionate solution (to construct an androgenetic alopecia model) at a dose of 30 mg / kg / day at multiple sites on the bald areas of their backs. 0.5 hours after the testosterone propionate injection, 200 mg of foam was applied to the bald areas on the backs of mice in each foam group once daily for 30 consecutive days. The blank control group and model group received blank foam once daily for 30 consecutive days.

[0081] The combination of active ingredients in the specific amounts of the present invention has a fast onset of effect and a good effect. Hair growth score The skin and hair growth status of the hair loss site of each group of mice were observed daily, and the mice were scored once a week for the first two weeks and twice a week from the third week onwards. During the scoring period, the mice were photographed and the scores for hair growth status were recorded. The scoring criteria are shown in Table 8.

[0082] The score results are shown in Table 15 and FIG. [Table 15]

[0083] The results show that the scores of all groups are significantly higher than those of the model group, and the scores of the experimental group III are significantly higher than those of the minoxidil group as well as those of the experimental groups I and II. Unexpectedly, experimental group III has a very good effect. On the other hand, after the 14th day of administration, the score results increased rapidly, and by the 18th day, a significant difference was already observed between Experimental Group I and Experimental Group II. Taking the data on the 18th day as an example, the difference between Experimental Group III and the model group was 1.2, the difference between the minoxidil group and Experimental Group I and the model group was 0.6, and the difference between Experimental Group II and the model group was 0.7. Therefore, the difference (or effect) between Experimental Group III and the model group was twice the difference between the minoxidil group alone and Experimental Group I, and more than 1.7 times the difference from Experimental Group II. On the other hand, this significant trend persisted until the end of the study (30 days after administration). As can be seen, the onset time of minoxidil finasteride foam in Experimental Group III is obviously superior to that of Experimental Group I, Experimental Group II, and minoxidil-only foam formulation group.

[0084] Hair weight evaluation After the experiment, the experimental mice were euthanized, and the hair on the surface of the skin at the depilation site was removed and weighed. The experimental results are shown in Table 16. [Table 16]

[0085] The results showed that the hair weight of the minoxidil group, experimental groups I, II, and III increased significantly compared with the model group, and the hair weight of experimental group III was not only significantly higher than that of the minoxidil group, but also significantly higher than that of experimental groups I and II. As can be seen from the difference with the model group, compared with the model group, the minoxidil group can significantly increase hair weight. The experimental effects of Experiment I and Experiment II are equivalent to the minoxidil group effect. Unexpectedly, Experimental Group III showed significant improvement compared with the minoxidil group, Experimental Group I and Experimental Group II, and the hair growth effect of Experimental Group III was about 1.5 times that of the minoxidil group. It has been found that a specific ratio of minoxidil and finasteride (e.g., 5% to 0.07%) achieves a very good effect and exerts a synergistic effect.

[0086] Hair follicle count evaluation Skin was collected from the bald area parallel to the spine, cut into 1 cm strips, fixed in 10% neutral formalin solution for 24-36 hours, dehydrated in gradient alcohols, embedded in paraffin, cut, sectioned, stained with H&E, and observed under a light microscope to count the number of hair follicles. The experimental results are shown in Table 17. [Table 17]

[0087] The results show that the hair follicle counts in the minoxidil group, experimental groups I, II, and III are higher than those in the model group, where the hair follicle count in experimental group III is higher than not only the minoxidil group but also both experimental groups I and II. As can be seen from the difference with the model group, compared with the model group, the minoxidil group can significantly increase hair weight, the experimental group I also has an increasing effect, but its effect is slightly weaker than that of the minoxidil group, and the experimental group II has an effect equivalent to that of the minoxidil group. Unexpectedly, the experimental group III showed further improvement compared to the minoxidil group, and its hair growth effect was about 1.3 times that of the minoxidil group. It has been found that a certain ratio of minoxidil and finasteride (e.g., 5% to 0.07%) can achieve a very significant increase in efficacy.

[0088] Example 3. Pharmacodynamics Experiment 3 3.1. Experimental Reagents and Materials The experimental materials for this example are as shown in Table 18. [Table 18]

[0089] Preparation of testosterone propionate solution: 92.29 mg of testosterone propionate was accurately weighed and dissolved in 30.148 ml of corn oil for injection, vortexed, and ultrasonically mixed to obtain a homogeneous solution with a concentration of 3 mg / ml.

[0090] Preparation of minoxidil finasteride foam (specification 5% to 0.075%): The preparation method was the same as that of the minoxidil finasteride foam (specification 5% to 0.075%) in Example 1.

[0091] Preparation of blank foam: The preparation method was the same as that of the blank foam in Example 1.

[0092] Preparation of minoxidil finasteride foam (specification 5% to 0.1%): The process is the same as that of Example 1, minoxidil finasteride foam (specification 5%-0.075%), where the dosage of finasteride is 0.057g / bottle, the mass content without propellant is 0.1%, adjusted accordingly with the dosage of purified water, and the contents of other ingredients remain unchanged.

[0093] Preparation of minoxidil finasteride foam (specification 5% to 0.15%): The process is the same as that of Example 1, minoxidil finasteride foam (specification 5%-0.075%), where the dosage of finasteride is 0.086g / bottle, the mass content without propellant is 0.15%, adjusted accordingly with the dosage of purified water, and the contents of other ingredients remain unchanged.

[0094] 3.2. Test Procedures and Results C57BL / 6J male mice were housed in single cages in an SPF grade, constant temperature and humidity laminar flow clean room. After acclimatization for one week, approximately 3 × 4 cm of hair was removed from the back using hair removal cream. 2 The hair was removed, and the skin was pink and intact, confirming that the hair follicles of the mice were in the telogen phase. The mice were randomly divided into five groups, as shown in Table 19. [Table 19]

[0095] In addition to the blank control group, which received multiple daily injections of corn oil, each group of mice received subcutaneous injections of testosterone propionate solution (to create an androgenetic alopecia model) at 30 mg / kg / day at multiple sites on the bald areas of their backs. 0.5 hours after the testosterone propionate injection, each group of mice received 200 mg of foam once daily for 30 consecutive days on the bald areas of their backs. The blank control group and model group received blank foam once daily for 30 consecutive days.

[0096] The combination of active ingredients in the specific amounts of the present invention has a fast onset of effect and a good effect. Hair growth score The skin and hair growth status of the hair loss site of each group of mice were observed daily, and the mice were scored once a week for the first two weeks and twice a week from the third week onwards. During the scoring period, the mice were photographed and the scores for hair growth status were recorded. The scoring criteria are shown in Table 8. The score results are shown in Table 20 and FIG. [Table 20]

[0097] The results show that the scores of all groups are significantly higher than those of the model group, and the scores of Experiment I are higher than those of Experiment II and Experiment III. Unexpectedly, experimental group I has a very good effect. On the other hand, under the condition that the finasteride dosage is reduced, the score results increase rapidly after the 14th day of administration, and by the 18th day, there is already a significant difference between experimental group II and experimental group III. Taking the data on the 14th day as an example, the difference between experimental group I and the model group is 0.8, and the difference between experimental group II and experimental group III and the model group is 0.5. Therefore, the difference (or effect) between experimental group I and the model group is 1.6 times that of experimental group II and experimental group III. On the other hand, this significant trend persisted until day 21 of administration. From day 25 to day 30, the symptom trends of Experimental Group I and Experimental Group III were similar, and higher than that of Experimental Group II. As can be seen from this, the onset time of minoxidil finasteride foam in Experimental Group I is significantly better than that of Experimental Group II and Experimental Group III.

[0098] Hair weight evaluation After the experiment, the experimental mice were euthanized, and the hair on the surface of the skin at the depilation site was removed and weighed. The experimental results are shown in Table 21. [Table 21]

[0099] The results show that the hair weight of Experimental Groups I, II, and III increased significantly compared with that of the model group, and the hair weight of Experimental Group I was greater than that of Experimental Groups II and III. As can be seen from the difference with the model group, the hair weight of experimental groups I-III is significantly increased compared to the model group. Unexpectedly, under the condition of decreasing finasteride dose, the experimental group I showed a significant increase compared with the experimental group II and the experimental group III, and the increasing effect was more than 1.2 times that of the experimental group II and the experimental group III. Certain ratios of minoxidil and finasteride (e.g., 5% to 0.075%) have been shown to exert a synergistic effect.

[0100] Hair follicle count evaluation Skin was collected from the bald area parallel to the spine, cut into 1 cm strips, fixed in 10% neutral formalin solution for 24-36 hours, dehydrated in graded alcohols, embedded in paraffin, cut, sectioned, stained with H&E, and observed under a light microscope to count the number of hair follicles. The experimental results are shown in Table 22. [Table 22]

[0101] The results show that the number of hair follicles in experimental groups I, II, and III is significantly increased compared with the model group. Unexpectedly, under the condition of decreasing finasteride dose, the number of hair follicles in Experimental Group I significantly increased compared with Experimental Groups II and III, and also significantly increased compared with the blank control group. It has been found that a specific ratio of minoxidil and finasteride (e.g., 5% to 0.075%) provides excellent results.

[0102] Example 4. Pharmacodynamics Study 4 4.1. Experimental Preparations and Materials The experimental materials for this example are as shown in Table 23. [Table 23]

[0103] Preparation of testosterone propionate solution: 66.42 mg of testosterone propionate was accurately weighed and dissolved in 21.697 ml of corn oil for injection, vortexed, and ultrasonically mixed to obtain a homogeneous solution with a concentration of 3 mg / ml.

[0104] Preparation of minoxidil finasteride topical solution (specification 5% to 0.075%): 1) The formulation is as shown in Table 24. [Table 24]

[0105] 2) The preparation process is as follows: <1> Minoxidil, finasteride, propylene glycol, and absolute ethanol were weighed according to the above formula. <2> Dissolve finasteride in a small amount of absolute ethanol. <3> The prescribed amount of propylene glycol, the remaining anhydrous ethanol, and a portion of the purified water were stirred and mixed uniformly. <4> <3> Add minoxidil and finasteride ethanol solutions to the mixed solutions obtained in step 1, and stir at room temperature until the drug solutions become transparent. <5> Add purified water and adjust to the prescribed volume to obtain a drug solution. <6> The obtained drug solution was filtered through a 0.45 μm microporous filter membrane, <7> The drug solution is filled into a bottle at 60 ml per bottle and then packaged.

[0106] Preparation of blank liniment: The process is the same as that for preparing minoxidil-finasteride ointment (specification 5%-0.075%), except that minoxidil and finasteride are removed from the formulation, and the contents of other ingredients remain unchanged.

[0107] Preparation of minoxidil finasteride topical solution (specification 5% to 0.05%): The process is the same as that for preparing minoxidil finasteride ointment (specification 5%-0.075%), where the finasteride ratio is 0.05% (w / v) and the dosage is 0.03 g / bottle, adjusted accordingly to the dosage of purified water, and the contents of other ingredients remain unchanged.

[0108] Preparation of minoxidil finasteride topical solution (specification 5% to 0.1%): The process is the same as that for preparing minoxidil finasteride topical solution (specification 5%-0.075%), where the finasteride content is 0.1% (w / v) and the dosage is 0.06 g / bottle, adjusted accordingly to the amount of purified water, and the contents of other ingredients remain unchanged.

[0109] 4.2. Experimental procedures and results C57BL / 6J male mice were housed in single cages in an SPF grade, constant temperature and humidity laminar flow clean room. After acclimatization for one week, approximately 3 × 4 cm of hair was removed from the back using hair removal cream. 2 The hair was removed, and the skin was pink and intact, confirming that the hair follicles of the mice were in the telogen phase. The mice were randomly divided into five groups, as shown in Table 25. [Table 25]

[0110] In addition to the blank control group receiving multiple daily corn oil injections, each group of mice received subcutaneous injections of testosterone propionate solution at 30 mg / kg / day at multiple sites on the bald back skin. 0.5 hours after the testosterone propionate injection, each group of mice received 0.2 ml of the liniment once daily for 30 consecutive days. The blank control group and model group received the blank liniment once daily for 30 consecutive days.

[0111] The combination of active ingredients in the specific amounts of the present invention has a fast onset of effect and a good effect. Hair growth score The skin and hair growth status of the hair loss site of each group of mice were observed daily to evaluate the effect of the drug on the mouse hair growth cycle. Scoring was performed once a week for the first two weeks and twice a week for the last two weeks. During scoring, photographs of each group were taken and the results of the hair growth status score were recorded. The scoring criteria are shown in Table 8.

[0112] The score results are shown in Table 26 and Figure 4. [Table 26]

[0113] The results show that the scores of all groups are significantly higher than those of the model group, and the scores of the experiment II group are significantly higher than those of the experiment I and experiment III groups. Unexpectedly, experimental group II has a very good effect. On the other hand, under the condition that the finasteride dosage is reduced, the score result increases rapidly after the 14th day of administration, and already shows a significant difference between experimental group I and experimental group III on the 18th day. Taking the data on the 18th day as an example, the difference between experimental group II and the model group is 1.1, the difference between experimental group I and the model group is 0.3, and the difference between experimental group III and the model group is 0.5, therefore, the difference (or effect) between experimental group II and the model group is more than 3.6 times that of experimental group I, and 2.2 times that of experimental group III. On the other hand, this trend persists until day 21 of administration, after which the three groups show a similar upward trend. As can be seen, the onset time of the minoxidil finasteride topical agent in Experimental Group II is significantly better than that of Experimental Group I and Experimental Group III.

[0114] Hair weight evaluation After the experiment, the experimental mice were euthanized, and the hair on the surface of the skin at the depilation site was removed and weighed. The experimental results are shown in Table 27. [Table 27]

[0115] The results show that the hair weight of experimental groups I, II, and III is significantly increased compared with that of the model group, and the hair weight of experimental group II is greater than that of experimental groups I and III. As can be seen from the difference with the model group, compared with the model group, the experiment I-III group can significantly increase hair weight.Unexpectedly, although the finasteride dose of experiment II group is less than that of experiment III group, its effect is 1.3 times that of experiment III group. Certain ratios of minoxidil and finasteride (e.g., 5% to 0.075%) have been shown to exert a synergistic effect.

[0116] Hair follicle count evaluation After the experiment, the skin of the animals was collected, fixed with formalin, and then stained with H&E. The number of hair follicles was counted in four selected fields. The experimental results are shown in Table 28. [Table 28]

[0117] The results show that the number of hair follicles in Experimental Groups I, II, and III is significantly increased compared to the model group, with the number of hair follicles in Experimental Group II being higher than that in Experimental Groups I and III. According to the difference with the model group, the number of hair follicles in experimental groups I-III is significantly increased compared with that of the model group. The effect of experimental group II is better than that of experimental group I. Unexpectedly, the dose of finasteride in Experimental Group II was lower than that in Experimental Group III, and its effect was more than 1.1 times that of Experimental Group III. Certain ratios of minoxidil and finasteride (e.g., 5% to 0.075%) have been shown to exert a synergistic effect.

[0118] Discussion Minoxidil is a potassium channel agonist that dilates local capillaries, increasing local blood flow and stimulating hair growth in affected areas. Commercially available products include minoxidil solution (2%, 5%) and minoxidil foam (5%). If recurrent local allergic symptoms, such as itching and redness, occur when using minoxidil solution, switching to propylene glycol-free minoxidil, an internationally recommended foam, may be considered to reduce or eliminate allergic side effects. Topical minoxidil suffers from a "shedding" phenomenon, resulting in low patient compliance. The so-called shedding phenomenon refers to the temporary hair loss experienced by approximately 20% of alopecia patients after approximately 2–4 weeks of minoxidil use, with excessive hair loss lasting approximately 1.5 months. Clinical studies have shown that the occurrence of "shedding" causes anxiety in many patients, leading some to discontinue use and worsening their alopecia symptoms.

[0119] Finasteride is a specific 5α-reductase inhibitor. 5α-reductase catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT), and high concentrations of DHT in the skin can lead to androgenetic alopecia (AGA). Finasteride inhibits the conversion of testosterone to DHT and treats male pattern baldness (MAB). Available products include finasteride tablets (1 mg) and finasteride spray (2.275 mg / mL). Finasteride's side effects significantly impact patient compliance. Finasteride is generally well tolerated, and side effects are usually mild, so discontinuing treatment is generally not necessary. The main side effects include decreased libido (1.9%), impotence (1.3%), and decreased ejaculation (1%), with incidence rates of less than 2%. Most side effects gradually resolve with continued treatment. Although finasteride has few side effects, its potential for sexual dysfunction significantly limits its use for many men. Finasteride spray replaces oral administration with topical administration, providing efficacy similar to oral finasteride but with significantly reduced systemic exposure, a smaller effect on serum dihydrotestosterone levels, and better tolerance. In a pivotal Phase III study, after topical finasteride administration at the planned dose (i.e., 200 μL, up to four sprays daily), mean peak plasma finasteride concentrations were >100-fold lower than those observed with daily oral finasteride at all sampling time points during the 6-month treatment period.

[0120] Existing clinical trials have proven that topical minoxidil solution, topical minoxidil foam, oral finasteride tablets, and topical finasteride spray are effective for treating male pattern baldness. However, drug treatments still have many drawbacks, primarily slow onset of effect and low efficacy. Currently, the average onset time for minoxidil is 6-9 months, with an efficacy rate of only 60%. The overall efficacy rate of finasteride tablets in treating mild and moderate AGA can reach 68%-77%, with the efficacy rates for mild improvement, moderate improvement, and significant improvement being 38.04%, 23.37%, and 13.59%, respectively. The overall therapeutic effect lasts for 6-9 months, and the therapeutic effect shows a positive correlation with the duration of treatment.

[0121] Minoxidil promotes hair growth, while finasteride prevents hair loss, complementing each other in terms of pharmacological mechanisms. Based on the 2023 China Clinical Practice Guidelines for the Diagnosis and Treatment of Male Pattern Baldness, the combined finasteride and minoxidil treatment scheme scores 0.80 points higher than the score after minoxidil treatment alone. Combined minoxidil-finasteride topical lipid solutions (3% minoxidil + 0.1% finasteride, 5% minoxidil + 0.1% finasteride, and 10% minoxidil + 0.1% finasteride) are commercially available in India, while minoxidil-finasteride foam is not available globally.

[0122] Finasteride is not recommended for women, and the standard for minoxidil for men is 5%. The present invention fixes minoxidil at 5%, thereby reducing the amount of finasteride and reducing side effects, while at the same time achieving a specific ratio with fast onset and good efficacy. The experimental results of the present invention fully demonstrate that when the minoxidil content is 5% and the finasteride content is 0.075%, it has an extremely excellent hair growth promoting effect, effectively treats alopecia, and has a synergistic effect at this specific ratio.

[0123] All documents mentioned in this application are incorporated by reference in this application as if each document were incorporated by reference individually. Furthermore, after reading the above teachings of the present invention, those skilled in the art will be able to make various changes or modifications to the present invention, and these equivalents will also fall within the scope defined by the appended claims of this application.

Claims

1. A formulation or composition for treating alopecia, comprising: The formulation or composition comprises: (a) minoxidil 5%, and (b) containing 0.07 to 0.095% of the active ingredient finasteride; The preparation or composition for treating alopecia, characterized in that it is calculated according to mass percentage (w / w) or mass volume percentage (w / v).

2. The formulation or composition comprises: (a) minoxidil 5%, and (b) containing 0.07 to 0.09% of the active ingredient finasteride; Calculate according to mass percentage or mass volume percentage, Preferably, the formulation or composition comprises: (a) minoxidil 5%, and (b) containing 0.07 to 0.085% of the active ingredient finasteride; Calculate according to mass percentage or mass volume percentage, Preferably, the formulation or composition comprises: (a) minoxidil 5%, and (b) containing 0.07-0.08% of the active ingredient finasteride; Calculate according to mass percentage or mass volume percentage, More preferably, the formulation or composition comprises: (a) minoxidil 5%, and (b) containing 0.07 to 0.075% of the active ingredient finasteride; Calculation is carried out according to mass percentage or mass volume percentage.

2. The formulation or composition of claim 1.

3. The formulation or composition comprises: (a) minoxidil 5%, and (b) containing 0.075% of the active ingredient finasteride; Calculate according to mass percentage or mass volume percentage.

2. The formulation or composition of claim 1.

4. The dosage form of the preparation or composition is a foam or a liniment. A formulation or composition according to any one of claims 1 to 3.

5. A foam for treating alopecia, comprising: The foaming agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.095% of the active ingredient finasteride; Calculated according to mass percentage (w / w), Preferably, the foaming agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.09% of the active ingredient finasteride; Calculate according to mass percentage, Preferably, the foaming agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.085% of the active ingredient finasteride; Calculate according to mass percentage, Preferably, the foaming agent is (a) minoxidil 5%, and (b) containing 0.07-0.08% of the active ingredient finasteride; Calculate according to mass percentage, Preferably, the foaming agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.075% of the active ingredient finasteride; Calculate according to mass percentage, More preferably, the foaming agent is (a) minoxidil 5%, and (b) containing 0.075% of the active ingredient finasteride; Calculate according to mass percentage, Here, the foam for treating alopecia is characterized in that the total mass in the mass percentage does not include the mass of the propellant.

6. the foaming agent further comprises a component selected from the group consisting of a humectant, a solubilizer, a pH adjuster, an antioxidant, a proppant, a diluent, a complexing agent, a propellant, or a combination thereof; The moisturizer is selected from the group consisting of glycerin, polyethylene glycol 2000, polyethylene glycol 4000, polyethylene glycol 6000, or a combination thereof; the solubilizing agent is selected from the group consisting of Tween 40, Tween 60, Tween 80, sodium lauryl sulfate, docusate sodium, or a combination thereof; the pH adjuster is selected from the group consisting of lactic acid, hydrochloric acid, sodium hydroxide, acetic acid, or a combination thereof; the antioxidant is selected from the group consisting of butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), vitamin E, or a combination thereof; the proppant is selected from the group consisting of hexadecanol, octadecanol, or a combination thereof; the diluent is selected from the group consisting of purified water, absolute ethanol, n-propanol, or a combination thereof; the complexing agent is selected from the group consisting of lactic acid, anhydrous citric acid, acetic acid, malic acid, maleic acid, or a combination thereof; The propellant is selected from the group consisting of propane, butane, isobutane, or a combination thereof. The foam according to claim 5.

7. When the foam does not contain a propellant, the mass percentage of the humectant in the foam is 1 to 10 wt %, preferably 1 to 5 wt %, more preferably 2 to 3 wt %, more preferably 2 to 2.5 wt %; When the foam does not contain a propellant, the mass percentage of the solubilizer in the foam is 0.1 to 5.0 wt %, preferably 0.1 to 1.0 wt %, more preferably 0.1 to 0.5 wt %, more preferably 0.3 to 0.5 wt %; When no propellant is included, the mass percentage of the pH adjuster in the foam is 0.1 to 5.0 wt %, preferably 0.5 to 2.5 wt %, more preferably 1.0 to 2.0 wt %, more preferably 1.0 to 1.5 wt %; When the foam does not contain a propellant, the mass percentage of the antioxidant in the foam is 0.01 to 1 wt %, preferably 0.05 to 0.5 wt %, more preferably 0.1 to 0.2 wt %; When no propellant is included, the mass percentage of the proppant in the foam is 0.5 to 10 wt %, preferably 0.5 to 5 wt %, more preferably 1.5 to 2.5 wt %, more preferably 1.5 to 2.0 wt %; the mass percentage of the complexing agent in the foam, without the propellant, is 0.1 to 5.0 wt %, preferably 0.1 to 1.0 wt %, more preferably 0.1 to 0.5 wt %, more preferably 0.1 to 0.3 wt %, more preferably 0.1 to 0.2 wt %; The mass percentage of the propellant in the foam is 1.5 to 8.5 wt%, preferably 2.5 to 7.5 wt%, more preferably 3.5 to 6.5 wt%, more preferably 4.5 to 5.5 wt%. The foam according to claim 6.

8. The foaming agent is characterized in that it contains glycerin, Tween 60, lactic acid, butylated hydroxytoluene, hexadecanol, octadecanol, anhydrous citric acid, anhydrous ethanol, purified water and a propellant. The foam according to claim 6.

9. The coating agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.095% of the active ingredient finasteride; Calculated according to mass volume percentage (w / v), Preferably, the coating agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.09% of the active ingredient finasteride; Calculate according to mass volume percentage, Preferably, the coating agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.085% of the active ingredient finasteride; Calculate according to mass volume percentage, Preferably, the coating agent is (a) minoxidil 5%, and (b) containing 0.07-0.08% of the active ingredient finasteride; Calculate according to mass volume percentage, Preferably, the coating agent is (a) minoxidil 5%, and (b) containing 0.07 to 0.075% of the active ingredient finasteride; Calculate according to mass volume percentage, More preferably, the coating agent is (a) minoxidil 5%, and (b) containing 0.075% of the active ingredient finasteride; The liniment for treating alopecia, wherein the amount is calculated according to a mass volume percentage.

10. the coating agent further comprises a penetration enhancer, a cosolvent, a solvent, or a combination thereof; and wherein the penetration enhancer is selected from the group consisting of propylene glycol, laurocapram, cyclohexanehexol, decyl methyl sulfoxide, or a combination thereof; The co-solvent is selected from the group consisting of absolute ethanol, glycerin, isopropanol, polyethylene glycol, liquid paraffin, or a combination thereof. The coating material according to claim 9.

11. the volume percentage (v / v) of the penetration enhancer in the application agent is 35% to 60% (v / v), preferably 45% to 55% (v / v), and more preferably 50% to 55% (v / v); The volume percentage (v / v) of the co-solvent in the coating agent is 15% to 45% (v / v), preferably 20% to 40% (v / v), and more preferably 25% to 35% (v / v). The coating material according to claim 10.

12. The coating agent is characterized in that it contains propylene glycol, absolute ethanol, and purified water. The coating material according to claim 10.

13. Use of the formulation or composition according to claim 1, the foam according to claim 5, or the application agent according to claim 9, Used in the preparation of drugs to treat alopecia, wherein the treatment includes promoting hair growth and preventing further alopecia.

14. The alopecia is male pattern baldness or female postmenopausal alopecia. The use according to claim 13.

15. 6. A method for preparing the foam of claim 5, comprising: It includes the following steps: (s1) calculated according to mass percentage, (a) minoxidil 5%, and (b) Stockpiling finasteride 0.07-0.095% active ingredient raw material; (s2) mixing and dissolving the active ingredient and the pharmaceutically acceptable carrier, and then filtering, filling and sealing the mixture; and (s3) filling the sealed solution with a propellant to prepare the foam.

16. Step (s2) further comprises the steps of: (s2a) Aqueous phase: A complexing agent is dissolved in purified water; (s2b) Alcohol phase: The finasteride is dissolved in a small amount of absolute ethanol, and then a moisturizer, a solubilizer, a pH adjuster, a finasteride solution, an antioxidant, and a proppant are added to the absolute ethanol and dissolved, and then the minoxidil is added, stirred, and dispersed; and (s2c) (s2a) the aqueous phase and (s2b) the alcohol phase are mixed, stirred until the active ingredient is completely dissolved, and then filtered, filled, and sealed.

16. The method of claim 15.

17. Step (s2) further comprises the steps of: (s2a) Aqueous phase: Anhydrous citric acid is dissolved in purified water, (s2b) Alcohol phase: The finasteride is dissolved in a small amount of absolute ethanol, and then glycerin, Tween 60, lactic acid, a finasteride ethanol solution, butylated hydroxytoluene, hexadecanol, and octadecanol are added to the absolute ethanol and dissolved, and then the minoxidil is added, stirred, and dispersed; and (s2c) (s2a) The aqueous phase and (s2b) the alcohol phase are mixed and stirred until the minoxidil is completely dissolved, and then the mixture is filtered, filled, and sealed.

16. The method of claim 15.

18. A method for preparing the coating agent according to claim 9, comprising: It includes the following steps: (s1) calculated according to mass volume percentage; (a) minoxidil 5%, and (b) Stockpiling finasteride 0.07-0.095% active ingredient raw material; (s2) uniformly mixing the active ingredient and a pharmaceutically acceptable carrier, adjusting the volume, and filtering; and (s3) filling the filtered solution to obtain the coating agent.

19. Step (s2) further comprises the steps of: (s2a) dissolving the finasteride in a small amount of a co-solvent; (s2b) After uniformly mixing the penetration enhancer, co-solvent, and a portion of the solvent, the minoxidil and finasteride solution is added and stirred to dissolve; and (s2c) The solution obtained after dissolution is adjusted to a constant volume with the remaining solvent and filtered.

20. The method of claim 18.

20. Step (s2) further comprises the steps of: (s2a) dissolving the finasteride in a small amount of absolute ethanol; (s2b) After uniformly mixing the propylene glycol, absolute ethanol, and a portion of purified water, the minoxidil and finasteride ethanol solution is added and stirred to dissolve; and (s2c) The solution obtained after dissolution is adjusted to a constant volume with the remaining purified water and filtered.

20. The method of claim 18.

Images