Local external composition containing 5 alpha-reductase inhibitor and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and discloses a local external composition containing a 5 alpha-reductase inhibitor and a preparation method thereof.The composition comprises 0.01%-0.1% of dutasteride or pharmaceutically acceptable salt thereof, 3%-14% of crystal inhibitor and 85.9%-96.99% of solvent based on the total weight of the compound.The preparation process is simple, the composition is prepared, and the preparation method is simple. The problem that the dutasteride is easy to crystallize and separate out in the using process due to extremely low solubility is solved, the stability of the dutasteride is improved, the curative effect of the dutasteride is ensured, the bioavailability of the dutasteride is improved, the systemic side effect caused by oral administration is reduced, the safety of the dutasteride is improved, and the medication compliance of a patient is improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, in particular to the technical field of hair loss treatment, and specifically to a topical external composition containing a 5α-reductase inhibitor and a preparation method thereof. Background Art

[0002] Androgenic alopecia is a chronic progressive hair loss disease accompanied by miniaturization of hair follicles. It is the most common type of hair loss in the world. It can affect both men and women, and the affected population is getting younger and younger. Although androgenic alopecia is not life-threatening, the progressive thinning of hair can seriously affect the patient's appearance and self-confidence, cause mental stress, reduce the patient's quality of life, and even become a high-risk factor for depression and anxiety.

[0003] There are two 5α-reductase isozymes related to androgenic alopecia in hair follicles, namely type I and type II 5α-reductase. Type I 5α-reductase is mainly distributed in sebaceous glands, epidermis, secretory sweat glands, apocrine sweat glands and hair follicles, while type II 5α-reductase is mainly found in the dermal papilla, inner layer of the outer root sheath, sebaceous ducts and near inner root sheath of scalp hair follicles. Increased expression of androgen receptor genes or type II 5α-reductase genes in hair follicles in the alopecia area leads to an increase in the effect of androgens on susceptible hair follicles. Susceptible hair follicles contain specific type II 5α-reductase, which can convert testosterone into dihydrotestosterone (DHT), which then binds to androgen receptors, causing a series of reactions, leading to miniaturization of hair follicles and hair loss.

[0004] Dutasteride is a synthetic 4-azasteroid compound that is a selective inhibitor of the class I and class II isomers of steroid 5α-reductase (an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone DHT). The original 0.5 mg specification dutasteride soft capsule was launched under the trade name It is used to treat moderate to severe symptoms of benign prostatic hyperplasia with prostate enlargement and reduce the risk of acute urinary retention and benign prostatic hyperplasia-related surgery. The Japanese Food and Drug Administration has approved 0.1mg and 0.5mg dutasteride tablets and soft capsules for the treatment of androgenic alopecia.

[0005] The main mechanism of action of dutasteride in the treatment of androgenic alopecia is to inhibit the activity of 5α-reductase, reduce the production of dihydrotestosterone, thereby improving the microenvironment of hair follicles, thereby reducing hair follicle atrophy and promoting hair growth. However, in my country, the marketed dosage form of dutasteride is soft capsules, and oral administration has serious adverse reactions, such as loss of libido, erectile dysfunction, and breast enlargement. Therefore, how to reduce the adverse reactions of dutasteride through other administration methods, such as local skin application, while ensuring its efficacy, is a hot topic of current research.

[0006] The existing solutions are mainly to change the administration mode of dutasteride, such as making it into topical preparations, such as gels, topical solutions (including tinctures, liniments, sprays, aerosols, foams), etc., and administering it through local skin topical administration. The drug is absorbed through the skin in molecular form, and local use is effective locally to reduce the adverse reactions of its oral administration. However, dutasteride is a highly lipophilic molecule that is insoluble in water and soluble in organic solvents such as ethanol. After the solvents (such as ethanol and water) evaporate during use of these topical preparations, the problem of drug crystallization on the skin surface often occurs, which not only affects the patient's experience of use, but also affects the continuous penetration and absorption of the drug and the efficacy. There are also some technical solutions that prepare it into nano, liposomes and other forms to increase the dissolution of the drug and promote the absorption of the drug, and administer it through local skin topical administration. However, the advantages of percutaneous absorption of these special drug carrier delivery methods are not yet clear, and the preparation process is difficult and the industrial feasibility is low.

[0007] Patent CN110869020B discloses a topical composition of dutasteride, which contains medium-chain triglycerides, castor oil and ethanol. When the drug specifications are much smaller than conventional oral preparations, the topically applied preparation can take effect quickly, significantly improve treatment compliance, and have mild side effects. Patent CN103596550A discloses a topical composition for preventing hair loss and promoting hair growth, which effectively prevents hair loss from the beginning of treatment and can provide an effect of improving patient treatment compliance. Patent CN111163759A discloses a nanoliposome-microbubble assembly encapsulating a hair loss treatment drug and a composition comprising the nanoliposome-microbubble assembly for alleviating or treating hair loss. The composition improves the drug delivery efficiency of finasteride by means of a delivery support.

[0008] Although existing technologies have proposed some solutions to enable dutasteride to exert an effect equivalent to or higher than that of conventional therapeutic agents (oral dutasteride & finasteride), existing technologies have not been fully studied in terms of improving the drug permeation rate and cumulative drug permeation amount of dutasteride, which limits its prescription development and clinical application. Summary of the invention

[0009] The present invention aims at the technical problems existing in the above-mentioned prior art and provides a dissolving pharmaceutical composition for local application to the scalp hair loss area, which plays a role in preventing hair loss and promoting hair growth. The crystal inhibitor can inhibit the crystallization during the use of the topical preparation, solves the problem of drug precipitation during the use of the dutasteride topical preparation, and shows excellent sustained release characteristics.

[0010] The objective of the present invention is achieved through the following technical solutions:

[0011] In a first aspect, the present invention provides a topical composition containing a 5α-reductase inhibitor, comprising 0.01% to 0.1% of dutasteride or a pharmaceutically acceptable salt thereof, 3% to 14% of a crystal inhibitor, and 85.9% to 96.99% of a solvent, based on the total weight of the composition, for local application to inhibit the precipitation of drug crystals, form a high-concentration drug reservoir, and promote sustained release and absorption of the drug.

[0012] The crystal inhibitor is selected from one or more of Tween, HPMC (hydroxypropyl methylcellulose), glycerol, SDS (sodium dodecyl sulfate), polyvinyl pyrrolidone (PVP), PEG (polyethylene glycol), poloxamer, caprylic acid capric acid macrogol glyceride,

[0013] The solvent is a mixture of one or more selected from lower monohydric alcohols having 1 to 4 carbon atoms, polyhydric alcohols, oleic acid, DMSO and water.

[0014] Preferably, the crystal inhibitor is polyvinyl pyrrolidone, and its content is 3% to 9% of the total weight of the composition.

[0015] Preferably, the crystal inhibitor is a mixture of Tween and polyvinyl pyrrolidone, wherein the amount of Tween is 1% to 5% of the total weight of the composition, and the amount of polyvinyl pyrrolidone is 2% to 9% of the total weight of the composition.

[0016] Preferably, the lower monohydric alcohol having 1 to 4 carbon atoms includes methanol, ethanol, isopropanol and butanol, and the polyhydric alcohol includes ethylene glycol, propylene glycol, glycerol and diethylene glycol monoethyl ether.

[0017] Preferably, the solvent is a mixture of one or more selected from diethylene glycol monoethyl ether, glycerol, ethanol, propylene glycol and water.

[0018] The topical composition containing the 5α-reductase inhibitor can be filled into a suitable container and presented in the form of tincture, liniment, spray, aerosol, foam, external gel, etc. The composition of the present invention can be used directly or mixed with other excipients. For example, it can be used directly as a tincture or liniment; or filled in a special device, and when used, the contents are released in the form of mist or foam by the pressure of a manual pump, high-pressure gas, ultrasonic vibration or other methods, and used as a spray or foam; or it can be sealed together with a suitable propellant in a pressure-resistant container with a special valve system, and when used, the contents are sprayed onto the skin in the form of mist or foam by the pressure of the propellant, and used as an aerosol or foam; or it can be mixed with a gel material, such as 0.2% to 2% carbomer, and presented in the form of a gel. The composition of the present invention can be packaged into unit dose or multi-dose containers.

[0019] In a second aspect, the present invention provides a method for preparing a topical composition containing a 5α-reductase inhibitor, the method comprising the following steps: adding the 5α-reductase inhibitor to a solvent at room temperature and stirring until dissolved; then mixing with a crystal inhibitor and stirring evenly until completely dissolved to obtain a composition.

[0020] Preferably, when the solvent is propylene glycol, glycerol, ethanol and water, the preparation method is as follows:

[0021] The 5α-reductase inhibitor is added to ethanol at room temperature, stirred until dissolved, and then mixed with a crystal inhibitor, propylene glycol, glycerin and water, and stirred evenly until all dissolved to obtain a composition.

[0022] Preferably, when the solvent is propylene glycol, diethylene glycol monoethyl ether, glycerol, ethanol and water, the preparation method is as follows:

[0023] The 5α-reductase inhibitor is added to ethanol and diethylene glycol monoethyl ether at room temperature, and then mixed with a crystal inhibitor, propylene glycol, glycerin and water, and stirred evenly until all dissolved to obtain a composition.

[0024] The composition contains a crystal inhibitor, which can be adsorbed on the surface of nano droplets to hinder the formation of dutasteride crystal nuclei, and on the other hand, can be adsorbed on the solid-liquid interface to hinder the combination of dutasteride molecules with the crystal surface, while increasing the equilibrium solubility of dutasteride, reducing the supersaturation of the solution, that is, reducing the driving force of crystallization, and preventing the precipitation of drug crystals after losing all or part of the solvent, thereby improving the solubility of the poorly soluble drug dutasteride; the solvent increases the diffusion capacity of the drug in the skin and promotes the continuous penetration of the drug through the stratum corneum, has high permeability, and is conducive to exerting the drug effect in the skin. The composition has a suitable skin feel, suitable viscosity and good spreadability, and is easy to apply.

[0025] The term "pharmaceutically acceptable" as used herein refers to any substance that does not interfere with the effectiveness of the biological activity of the active ingredient and is non-toxic to the host to which it is administered.

[0026] The present invention has the following beneficial effects: The present invention provides a composition of dutasteride or a pharmaceutically acceptable salt thereof for topical application for preventing hair loss and promoting hair growth,

[0027] (1) It solves the problem of drug precipitation during the use of dutasteride topical preparations, solves the problem that the drug is easy to crystallize during use due to the extremely low solubility of dutasteride, improves the stability of the drug, and ensures its efficacy. The composition of the present invention shows that 12 hours after simulated use, the drug still has no crystal precipitation under a polarizing microscope.

[0028] (2) The present invention exhibits excellent sustained release characteristics. It provides a higher cumulative drug penetration amount and drug penetration rate, reduces the adverse reactions of dutasteride while ensuring its efficacy, and improves the bioavailability of the drug.

[0029] (3) The method of applying the composition of the present invention in the form of an external preparation has a good skin feel, is easy to use, improves patient compliance, and is expected to reduce the risk of systemic side effects and reduce hair loss. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 : Microscopic state diagram of the composition prepared in Examples 1-4 under 32°C 30% RH conditions (a, b, c, d are respectively microscopic state diagrams of Examples 1-4 under 12h, e, f, g, h are respectively microscopic state diagrams of Examples 1-4 under 24h);

[0031] Figure 2 : Microscopic state diagram of the composition prepared in Example 5-7 under 32°C 30% RH conditions (a, b, c are respectively microscopic state diagrams of Example 5-7 under 12h, d, e, f are respectively microscopic state diagrams of Example 5-7 under 24h);

[0032] Figure 3 : Microscopic state diagram of the composition prepared in Comparative Example 1-2 under 32°C 30% RH conditions (a and b are respectively microscopic state diagrams of Comparative Example 1-2 under 12h, c and d are respectively microscopic state diagrams of Comparative Example 1-2 under 24h);

[0033] Figure 4 : Comparison of flux curves of the compositions prepared in Example 1, Example 2, Comparative Example 1 and Comparative Example 2. DETAILED DESCRIPTION

[0034] The following examples also describe certain specific aspects and embodiments, which are provided for illustrative purposes only and should not be construed as limiting the scope of the invention in any way.

[0035] Example 1

[0036] Weighed by weight / weight %: 0.05% dutasteride, 7.00% polyvinylpyrrolidone K30, 3.00% Tween 80, 50.00% ethanol, 7.00% glycerol, 6.00% propylene glycol, 26.95% purified water;

[0037] Preparation process:

[0038] Mix dutasteride and ethanol at room temperature and stir until the drug is dissolved. Add propylene glycol, polyvinyl pyrrolidone K30, Tween 80, and glycerol into purified water and stir until all are dissolved evenly. Then add the drug-containing ethanol solution and stir evenly.

[0039] The obtained preparation is a clear and transparent solution with a light skin feel and is easy to apply. The appearance is uniform and stable even after long-term storage. In addition, the composition enables the active substance to be continuously delivered to the scalp and / or hair.

[0040] Example 2

[0041] Weighed by weight / weight %: 0.05% dutasteride, 7.00% polyvinylpyrrolidone K30, 3.00% Tween 80, 20.00% ethanol, 30.00% diethylene glycol monoethyl ether, 7.00% glycerol, 6.00% propylene glycol, 26.95% purified water;

[0042] Preparation process:

[0043] Dutasteride was mixed with ethanol and diethylene glycol monoethyl ether at room temperature and stirred until dissolved. Propylene glycol, polyvinyl pyrrolidone K30, Tween 80 and glycerol were added to purified water and stirred until all dissolved evenly, and then the drug-containing solution was added and stirred evenly.

[0044] The obtained preparation is a clear and transparent solution with a light skin feel and is easy to apply. The appearance is uniform and stable even after long-term storage. In addition, the composition enables the active substance to be continuously delivered to the scalp and / or hair.

[0045] Example 3

[0046] Weighed by weight / weight %: 0.05% dutasteride, 7.00% polyvinylpyrrolidone K30, 3.00% Tween 80, 26.00% ethanol, 7.00% glycerol, 30.00% diethylene glycol monoethyl ether, 26.95% purified water;

[0047] Preparation process:

[0048] Mix dutasteride with ethanol and diethylene glycol monoethyl ether at room temperature and stir until dissolved. Add polyvinyl pyrrolidone K30, Tween 80 and glycerol into purified water and stir until completely dissolved. Then add the drug-containing solution and stir evenly.

[0049] The obtained preparation is a clear and transparent solution with a light skin feel and is easy to apply. The appearance is uniform and stable even after long-term storage. In addition, the composition enables the active substance to be continuously delivered to the scalp and / or hair.

[0050] Example 4

[0051] Weighed by weight / weight %: 0.03% dutasteride, 9.00% polyvinylpyrrolidone K30, 50.00%, ethanol, 4.00% propylene glycol, 3.00% glycerol, 33.97% purified water;

[0052] Preparation process:

[0053] Dutasteride was mixed with ethanol at room temperature and stirred until dissolved. Propylene glycol, polyvinyl pyrrolidone K30 and glycerol were added to purified water and stirred until completely dissolved. Then, the drug-containing solution was added and stirred evenly.

[0054] The obtained preparation is a clear and transparent solution with a light skin feel and is easy to apply. The appearance is uniform and stable even after long-term storage. In addition, the composition enables the active substance to be continuously delivered to the scalp and / or hair.

[0055] Example 5

[0056] Weighed by weight / weight %: 0.08% Dutasteride, 7.00% Polyvinylpyrrolidone K30, 5.00% Tween 80, 50.00% Ethanol, 4.00% Propylene Glycol, 3.00% Glycerol, 30.92% Purified Water

[0057] Preparation process:

[0058] Mix dutasteride and ethanol at room temperature and stir until dissolved. Add propylene glycol, polyvinyl pyrrolidone K30, Tween 80 and glycerol into purified water and stir until all are dissolved evenly. Then add the drug-containing solution and stir evenly.

[0059] The obtained preparation is a clear and transparent solution with a light skin feel and is easy to apply. The appearance is uniform and stable even after long-term storage. In addition, the composition enables the active substance to be continuously delivered to the scalp and / or hair.

[0060] Example 6

[0061] Weighed by weight / weight %: 0.05% dutasteride, 2.00% polyvinylpyrrolidone K90, 5.00% Tween 80, 50.00% ethanol, 6.00% propylene glycol, 7.00% glycerol, 29.95% purified water;

[0062] Preparation process:

[0063] Dutasteride and ethanol were mixed and stirred at room temperature until dissolved, propylene glycol, polyvinyl pyrrolidone K90, Tween 80, and glycerol were added to purified water and stirred until all dissolved evenly. Then, the drug-containing solution was added and stirred evenly.

[0064] The obtained preparation is a clear and transparent solution with a light skin feel and is easy to apply. The appearance is uniform and stable even after long-term storage. In addition, the composition enables the active substance to be continuously delivered to the scalp and / or hair.

[0065] Example 7

[0066] Weighed by weight / weight %: 0.05% dutasteride, 7.00% polyvinylpyrrolidone K30, 1.00% Tween 80, 41.00% ethanol, 7.00% glycerol, 15.00% diethylene glycol monoethyl ether, 28.95% purified water;

[0067] Preparation process:

[0068] Mix dutasteride with ethanol and diethylene glycol monoethyl ether at room temperature and stir until dissolved. Add polyvinyl pyrrolidone K30, Tween 80 and glycerol into purified water and stir until completely dissolved. Then add the drug-containing solution and stir evenly.

[0069] The obtained preparation is a clear and transparent solution with a light skin feel and is easy to apply. The appearance is uniform and stable even after long-term storage. In addition, the composition enables the active substance to be continuously delivered to the scalp and / or hair.

[0070] The proportions of the components required for preparing the compositions of Examples 1-7 are shown in Table 1.

[0071] Table 1 Proportion of each component in the composition of Examples 1-7

[0072]

[0073]

[0074] Note: The % concentration in the present invention represents the mass ratio (w / w %) concentration.

[0075] Comparative Example 1

[0076] Weighed by weight / weight %: 0.05% dutasteride, 50.00% ethanol, 6.00% propylene glycol, 43.95% purified water;

[0077] Preparation process:

[0078] Dutasteride and ethanol were mixed and stirred at room temperature until dissolved, propylene glycol was added to purified water and stirred until completely dissolved, and then the drug-containing solution was added and stirred evenly.

[0079] The obtained preparation is a clear and transparent solution with a refreshing skin feel and strong fluidity.

[0080] Comparative Example 2

[0081] Weighed by weight / weight %: 0.05% dutasteride, 50.00% ethanol, 6.00% propylene glycol, 30.00% diethylene glycol monoethyl ether, 13.95% purified water;

[0082] Preparation process:

[0083] Dutasteride was mixed with ethanol and diethylene glycol monoethyl ether at room temperature and stirred until dissolved. Propylene glycol was added to purified water and stirred until all dissolved. The drug-containing solution was then added and stirred evenly.

[0084] The obtained preparation is a clear and transparent solution with a refreshing skin feel and strong fluidity.

[0085] Experimental Example 1: Evaluation of the appearance and skin feel of the preparation

[0086] The appearance and skin feel of Examples 1-7 were evaluated, and all were clear and transparent liquids with an ethanol odor. The preparations of the above examples all met the requirements, had a suitable skin feel, were easy to apply, had suitable fluidity, had good skin compatibility and use feel, and improved the patient's medication compliance.

[0087] Comparative Examples 1-2 are also clear and transparent liquids with an ethanol odor, which are easy to flow down the skin and are not easy to stay on the skin surface.

[0088] Experimental Example 2 Study on crystallization during simulated use

[0089] Because dutasteride drug crystals have birefringence characteristics, when the drug is precipitated, green rod-shaped crystals appear in the dark field of view. When no drug is precipitated, the field of view is a dark field with a black background.

[0090] like Figure 1-3 As shown, the composition solutions of each embodiment and comparative example were horizontally spread on a glass slide with a thickness of about 1 mm, placed in a simulated use environment with a temperature of 32° C. and a humidity of 30% RH, and the microscopic morphology of the composition was observed under polarized light (dark field) using a BK6000 biological microscope (Ott Optics) at 12 h and 24 h.

[0091] According to the results of microscopic observation, Examples 1-7 can effectively achieve the purpose of inhibiting drug crystallization under simulated use conditions (green rods are drug crystals, and a pure dark field black background indicates no drug crystals are precipitated), that is, the crystal inhibition combination works to inhibit the formation and growth of crystals of poorly soluble small drug molecules, forming a high-concentration drug reservoir, so that the drug is continuously released and penetrates the skin during the use of the preparation, thereby improving the efficacy.

[0092] Experimental Example 3 Comparative Study of In Vitro Transdermal Test

[0093] Test method: Franz diffusion cell method;

[0094] Instrument: LOGAN 918-12 Transdermal Diffusion Tester

[0095] Skin: Experimental pig skin, thickness 0.8-1mm, contact area 1.767cm 2, the integrity of the skin barrier was tested using the SKT transepidermal water loss meter provided by Beijing Hebang Xingye Scientific Instrument Co., Ltd.;

[0096] Receiving solution: physiological saline containing 1% polyoxyethylene 20 oleyl ether;

[0097] Receiving liquid temperature: 32±0.5℃;

[0098] Speed: 600rpm;

[0099] Sample: The preparations of Example 1, Example 2 and Comparative Example 1, Comparative Example 2 were evenly coated on the experimental pig skin, and the sample amount of each preparation was about 26.5 mg (15 mg / cm 2 , drug release area 1.767cm 2 ).

[0100] Diffusion cell volume: 12ml;

[0101] Sampling method: all sampling;

[0102] Sampling time points: 1h, 2h, 4h, 6h, 8h, 12h;

[0103] Sample analysis: LC / MS determination, calculation of cumulative permeation at each time point (Q, ng / cm 2 ) and flux (J, ng / cm 2 The test results are shown in Table 2.

[0104] Table 2 Cumulative permeation

[0105]

[0106]

[0107] The cumulative penetration data show that the cumulative penetration of Examples 1 and 2 at 12h is significantly higher than that of Comparative Examples 1 and 2, indicating that after the solvent evaporates, the crystal inhibitor of the present invention fully exerts its effect, and the drug forms a high-concentration drug reservoir in the crystal inhibitor, so that the drug is continuously released and penetrates the skin. In addition, the solvents in the composition, such as ethanol, propylene glycol and diethylene glycol monoethyl ether, have a good effect of promoting the percutaneous penetration of drugs in topical preparations; the glycerol in the composition has a moisturizing effect, can effectively delay the loss of skin moisture, has the effect of softening the stratum corneum, and can also promote drug penetration. Therefore, the present composition can effectively achieve the purpose of delaying crystallization and continuous percutaneous penetration, as shown in Table 3.

[0108] Table 3 Flux data comparison

[0109]

[0110] like Figure 4As shown, the results show that the flux of Examples 1 and 2 within 12 hours is significantly higher than that of Comparative Examples 1 and 2, indicating that the crystal inhibitor enables the composition to have excellent penetration promotion of external preparations and can take effect quickly, and it is expected to significantly improve the therapeutic effect.

[0111] In summary, the composition contains an inhibitor, which can greatly increase the drug concentration and the concentration difference on both sides of the skin, and promote the continuous release of the drug during use to exert its efficacy; the ethanol, propylene glycol and diethylene glycol monoethyl ether in the composition increase the diffusion ability of the drug in the skin and promote the continuous penetration of the drug through the stratum corneum, which is also beneficial for the drug to penetrate into the skin to exert its efficacy.

[0112] The above description is only a preferred embodiment of the present invention, but is not intended to limit the present invention. Those skilled in the art may make possible changes and modifications to the present invention using the technical contents disclosed above without departing from the scope of the technical solution of the present invention, or modify it into an equivalent embodiment of equivalent changes. Any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention shall fall within the protection scope of the technical solution of the present invention.

Claims

1. A topical composition containing a 5α-reductase inhibitor, characterized in that: The composition comprises 0.01% to 0.1% of dutasteride or a pharmaceutically acceptable salt thereof, 3% to 14% of a crystal inhibitor and 85.9% to 96.99% of a solvent, based on the total weight of the composition. Wherein, the crystal inhibitor is selected from one or more of Tween, HPMC, glycerol, sodium lauryl sulfate, polyvinyl pyrrolidone, polyethylene glycol, poloxamer, caprylic acid capric acid macrogol glyceride, The solvent is a mixture of one or more selected from lower monohydric alcohols having 1 to 4 carbon atoms, polyhydric alcohols, oleic acid, DMSO and water.

2. The topical composition containing a 5α-reductase inhibitor according to claim 1, characterized in that The crystal inhibitor is polyvinyl pyrrolidone, and its content is 3% to 9% of the total weight of the composition.

3. The topical composition containing a 5α-reductase inhibitor according to claim 1, characterized in that The crystal inhibitor is a mixture of Tween and polyvinyl pyrrolidone, wherein the amount of Tween is 1% to 5% of the total weight of the composition, and the amount of polyvinyl pyrrolidone is 2% to 9% of the total weight of the composition.

4. The topical composition containing a 5α-reductase inhibitor according to claim 1, characterized in that The lower monohydric alcohol having 1 to 4 carbon atoms includes methanol, ethanol, isopropanol and butanol, and the polyhydric alcohol includes ethylene glycol, propylene glycol, glycerol and diethylene glycol monoethyl ether.

5. The topical composition containing a 5α-reductase inhibitor according to claim 1, characterized in that The solvent is a mixture of one or more selected from diethylene glycol monoethyl ether, glycerol, ethanol, propylene glycol and water.

6. The topical composition containing a 5α-reductase inhibitor according to any one of claims 1 to 5, characterized in that: The composition is presented in the form of tincture, liniment, spray, aerosol, foam or external gel.

7. A method for preparing a topical composition containing a 5α-reductase inhibitor according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: adding the 5α-reductase inhibitor into a solvent at room temperature and stirring until dissolved; then mixing with a crystal inhibitor and stirring evenly until all dissolved to obtain a composition.

8. The preparation method according to claim 7, characterized in that: When the solvent is propylene glycol, glycerol, ethanol and water, the preparation method is as follows: The 5α-reductase inhibitor is added to ethanol at room temperature, stirred until dissolved, and then mixed with a crystal inhibitor, propylene glycol, glycerin and water, and stirred evenly until all dissolved to obtain a composition.

9. The preparation method according to claim 7, characterized in that: When the solvent is propylene glycol, diethylene glycol monoethyl ether, glycerol, ethanol and water, the preparation method is as follows: The 5α-reductase inhibitor is added to ethanol and diethylene glycol monoethyl ether at room temperature, and then mixed with a crystal inhibitor, propylene glycol, glycerin and water, and stirred evenly until all dissolved to obtain a composition.

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