Pharmaceutical compositions containing androgen receptor inhibitors / antagonists, methods and uses

Abstract

Belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing an androgen receptor inhibitor / antagonist and a method and application thereof. The use of an androgen receptor inhibitor / antagonist, in particular a combination of a compound of formula I or a crystalline form D of a compound of formula I and minoxidil, improves the effects obtained by a single drug of the androgen receptor inhibitor / antagonist or minoxidil. Indeed, this improvement is synergistic in nature because the effect of improving or promoting hair growth is also greater than the effect obtained with either androgen receptor inhibitor / antagonist alone or minoxidil. The method not only is simple mixing use in physical significance, but also has a good treatment addition effect and has the advantage of good safety.

Description

Pharmaceutical compositions containing androgen receptor inhibitors / antagonists, methods and uses Citation of Related Applications The present invention claims priority to the invention patent entitled “Pharmaceutical compositions containing androgen receptor inhibitors / antagonists, methods and uses” and application number CN2023111578546 filed in China on September 8, 2023, and the invention patent application entitled “Pharmaceutical compositions containing androgen receptor inhibitors / antagonists, methods and uses” and application number CN2024101716421 filed in China on February 6, 2024. The entire contents of the above patent applications are incorporated herein by reference. Technical Field The present invention belongs to the field of medical technology, and in particular relates to a pharmaceutical composition with an androgen receptor inhibitor / antagonist and minoxidil as active ingredients, a method and a use thereof. Background Art Minoxidil is a potassium channel opener. This type of drug is often accompanied by reflex tachycardia and increased cardiac output when lowering blood pressure. It can also reduce or stop hair loss and promote hair regeneration. Among the drugs approved for the treatment of hair loss and alopecia areata in China, minoxidil has a good effect on promoting hair growth. The action pathways of minoxidil are as follows: stimulate the proliferation of hair follicle epithelial cells and prolong the hair growth period; promote angiogenesis, increase local blood supply, and provide nutrition for hair growth; open potassium ion channels, prevent calcium ions from flowing into cells, increase cell DNA synthesis and hair follicle cell proliferation. At present, there are many topical preparations of minoxidil on the market at home and abroad, and they are relatively safe. However, the main function of minoxidil is to improve microcirculation disorders and accelerate hair growth. It is a symptomatic treatment. Therefore, it is only effective for general alopecia areata and hair loss, and is not effective for more harmful alopecia totalis and alopecia universalis. Androgenic alopecia is an androgen-dependent hereditary disease and the most common type of hair loss in clinical practice, characterized by a progressive decrease in hair density. Male androgenic alopecia is also called male pattern baldness, and female androgenic alopecia is also called female pattern baldness. Androgenic alopecia is an autosomal dominant multi-gene disease. The sensitivity of the patient's local scalp hair follicles to androgens (mainly dihydrotestosterone) increases, resulting in miniaturization of hair follicles and thinning of hair shafts, with clinical manifestations of sparse and thinning hair. Chinese invention patent CN102757389B discloses a small molecule androgen receptor antagonist (chemical name is 4-(4,4-dimethyl-3-(6-methylpyridin-3-yl)-5-oxo-2-thioxoimidazolidin-1-yl)-3-fluoro-2-methoxybenzonitrile (as shown in Formula I), which is currently in the clinical research stage). In the prior art, minoxidil is usually used in combination with active ingredients of traditional Chinese medicine that can promote hair growth (such as publication number CN109010432A, publication number CN113712968A), or minoxidil is used in combination with 5a reductase inhibitor finasteride (publication number CN111973607A) and dutasteride (publication number CN109674762A). Most of these two or more drug combinations have the effect of promoting hair growth. Simply mixing them in a physical sense has limited effect. Therefore, it is particularly important to develop a product and method to improve the monotherapy effect of minoxidil or androgen receptor inhibitors / antagonists. Summary of the invention Problem that the invention aims to solve The primary purpose of the present invention is to provide a novel pharmaceutical composition for treating diseases or disorders related to androgen receptor activity and a therapeutic method and use thereof. Solutions for solving problems In a first aspect, a pharmaceutical composition is provided, comprising an androgen inhibitor / antagonist and minoxidil or a pharmaceutically acceptable excipient thereof. Further, the androgen inhibitor / antagonist includes clacotolone, nilutamide, enzalutamide, topilutamide, bicalutamide, flutamide, hydrochlorothiazide, spironolactone, niclosamide, revilutamide, darolamide, althiazine, apalutamide, deenlutamide, enobosarm, pukelumab, ANA-001, 18F-dihydrotestosterone, 2-hydroxyflutamide, AKP-009, ASC-J9, AZD5312, EG017, LY2452473, MK-0773, VK5211, bavdegalutamide, dimethandrolone undecanoate, seviteronel, inotron, zanotron, CP-COV03, FW-1022, APC-100, ARV-766, EM-5854, EPI-7386, MVI-118, ODM-204, TRC253, UT-34, ralaniten acetate, vosilasarm, FW-424, AC0176, AZD3514, BMS-641988, CB-03-10, CC-94676, DT-200, EZN-4176, GSK2849466, GSK971086, HP518, HRS-5041, HSK38008, MK-3984, ONC1-13B, PF-06260414, RO7656594, SXL01, TAS3681, TQB3720, TFF NIC, UNI911, FW-420, A031, AB001, AB006, AC-262536, ADA-308, AH-001, AR-V7 PROTAC, ARCC-4, ARD-2051, ARD-2128, ARD-2585, ARD-266, ARD-61, ARD-69, ASN-1780, ASR-600, BMS-564929, BWA-522, CA103, CB-03-04, CH4892280, CH5137291, CL-AR-100, CZ-212-3, DA-4210, EM 6537, HC-X022, HYG-410, HYG-420, HYG-430, HYG-440, ID119160021, IMB-A6, JMKX002992, JNJ-26146900, JNJ-28330835, JNJ-37654032, LG1 21071, LGD-2941, LGD-3303, LGD2226, LHJ-647, MTX-23, NUV-1156, NUV-1511, OLX104C, ONC2-13B, PARD-33, PF-0998425, PRX-304, RD162, RU 56187, RU 58642, RU 58841, RU 59063, SKLB-C2807, TD-802, VPC-13789, WS9761, XY-32, YM-175735, YM-92088, YM580, ZD3980, Zeta55, SCAI-502, XNTR-934, or XNTR-936. Preferably, the present invention provides a pharmaceutical composition comprising an androgen inhibitor / antagonist and minoxidil or a pharmaceutically acceptable excipient thereof, wherein the androgen inhibitor / antagonist is a compound of formula I or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, isotopic derivative or prodrug thereof, The present invention further provides a pharmaceutical composition comprising an androgen inhibitor / antagonist and minoxidil or a pharmaceutically acceptable excipient thereof, wherein the androgen inhibitor / antagonist is an anhydrous polymorph of the compound of formula I. Furthermore, the anhydrous polymorph of the compound of formula I has a crystalline form D, and the crystalline form D meets at least one of the following conditions: I. The XRPD spectrum of Form D comprises peaks at the following 2θ values: 5.3±0.2°, 10.7±0.2°, 13.5±0.2°, 15.1±0.2° and 21.3±0.2°; Preferably, the XRPD spectrum of the crystalline form D further comprises peaks at the following 2θ values: 12.0±0.2°, 12.7±0.2°, 14.8±0.2°, 16.4±0.2°, 17.3±0.2°, 20.3±0.2°, 24.2±0.2° and 24.8±0.2°; More preferably, the XRPD spectrum of the crystalline form D further comprises peaks at the following 2θ values: 19.7±0.2°, 22.5±0.2°, 23.1±0.2°, 27.3±0.2°, 28.5±0.2°, 29.7±0.2° and 32.3±0.2°; Further preferably, the XRPD spectrum of the crystalline form D is substantially consistent with Figure 1; II. The TGA spectrum of the crystalline form D shows a weight loss of about 1.6% at 150±1°C; Preferably, the TGA spectrum of the crystalline form D is substantially consistent with FIG. 2 ; and III. The DSC spectrum of the crystalline form D shows endothermic absorption at 167±1°C; Preferably, the DSC spectrum of the crystalline form D is substantially consistent with FIG. 2 . Furthermore, the anhydrous polymorph has a crystalline form C, and the crystalline form C meets at least one of the following conditions: I. The XRPD spectrum of Form C comprises peaks at the following 2θ values: 5.2±0.2°, 10.4±0.2°, 13.4±0.2°, 15.0±0.2°, 16.4±0.2° and 29.1±0.2°; Preferably, the XRPD spectrum of the crystalline form C further comprises peaks at the following 2θ values: 19.6±0.2°, 20.1±0.2°, 22.8±0.2° and 24.4±0.2°; More preferably, the XRPD spectrum of the crystalline form C further comprises peaks at the following 2θ values: 11.9±0.2°, 17.3±0.2°, 23.6±0.2°, 31.6±0.2° and 34.1±0.2°; Further preferably, the XRPD spectrum of the crystalline form C is substantially consistent with FIG6 ; II. The TGA spectrum of the crystalline form C shows a weight loss of about 1.6% at 150±1°C; Preferably, the TGA spectrum of the crystalline form C is substantially consistent with FIG. 7 ; and III. The DSC spectrum of the crystalline form C shows endotherms at 148±1°C, 167±1°C and 177±1°C; Preferably, the DSC spectrum of the crystalline form C is substantially consistent with FIG. 7 . Furthermore, the anhydrous polymorph has a crystalline form B, and the crystalline form B meets at least one of the following conditions: I. The XRPD spectrum of Form B comprises peaks at the following 2θ values: 7.3±0.2°, 9.9±0.2°, 12.5±0.2°, 16.5±0.2° and 17.1±0.2°; Preferably, the XRPD spectrum of the crystalline form B further comprises peaks at the following 2θ values: 13.1±0.2°, 20.3±0.2°, 24.0±0.2°, 25.2±0.2° and 26.7±0.2°; More preferably, the XRPD spectrum of Form B further comprises peaks at the following 2θ values: 21.3±0.2°, 27.8±0.2°, 28.6±0.2°, 29.5±0.2° and 31.3±0.2°; Further preferably, the XRPD spectrum of the crystalline form B is substantially consistent with FIG8 ; II. The TGA spectrum of the crystalline form B shows a weight loss of about 1.5% at 150±1°C; Preferably, the TGA spectrum of the crystalline form B is substantially consistent with FIG. 9 ; and III. The DSC spectrum of the crystalline form B shows endotherm at 177±1°C; Preferably, the DSC spectrum of the crystalline form B is substantially consistent with FIG. 9 . Furthermore, the anhydrous polymorph has a crystalline form A, and the crystalline form A meets at least one of the following conditions: The XRPD spectrum of Form A comprises peaks at the following 2θ values: 9.0±0.2°, 12.5±0.2°, 15.7±0.2°, 17.2±0.2°, 18.1±0.2° and 23.2±0.2°; Preferably, the XRPD spectrum of the crystalline form A further comprises peaks at the following 2θ values: 3.3±0.2°, 7.5±0.2°, 12.9±0.2°, 15.2±0.2°, 24.4±0.2°, 28.4±0.2° and 29.8±0.2°; More preferably, the XRPD spectrum of the crystalline form A further comprises peaks at the following 2θ values: 14.4±0.2°, 17.7±0.2°, 19.9±0.2°, and 21.8±0.2°; Further preferably, the XRPD spectrum of the crystalline form A is substantially consistent with FIG. 10 ; II. The TGA spectrum of the crystalline form A shows a weight loss of about 1.0% at 150±1°C; Preferably, the TGA spectrum of the crystalline form A is substantially consistent with Figure 11; and III. The DSC spectrum of the crystalline form A shows endothermicity at 160±1°C and 177±1°C, and exothermicity at 162±1°C; Preferably, the DSC spectrum of the crystalline form A is substantially consistent with FIG. 11 . The present invention further provides a pharmaceutical composition: comprising administering to the individual a therapeutically effective amount of an androgen inhibitor / antagonist on a continuous daily regimen until progression of a disease or disorder associated with androgen receptor activity or unacceptable toxicity; and / or, the androgen inhibitor / antagonist is administered in an amount of 0.05% (0.5 mg / mL or mg / g) to 10% (100 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist is administered in an amount of 0.25% (2.5 mg / mL or mg / g) to 1% (10 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist is administered in an amount of 0.1 mg / day to 1000 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 0.5 mg / day to 100 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 1 mg / day to 50 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 1.8 mg / day, 2.5 mg / day, 3.6 mg / day, 5 mg / day, 7.2 mg / day, 10 mg / day, 20 mg / day; and / or, the androgen inhibitor / antagonist is administered in a QD or BID manner; And / or, the androgen inhibitor / antagonist is administered in an amount of 0.25% (2.5 mg / mL or mg / g), 0.5% (5 mg / mL or mg / g) or 1% (10 mg / mL or mg / g) QD or BID. The present invention further provides a pharmaceutical composition: comprising administering to the individual a therapeutically effective amount of minoxidil or a pharmaceutically acceptable excipient thereof on a continuous daily regimen until progression of a disease or disorder associated with androgen receptor activity or unacceptable toxicity; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2 mg / day to 500 mg / day; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 14.4 mg / day, 20 mg / day, 36 mg / day, 40 mg / day, 44 mg / day, 50 mg / day, or 100 mg / day; and / or, the minoxidil or a pharmaceutically acceptable excipient thereof is administered in an amount of 0.1% (1 mg / mL or mg / g) to 15% (150 mg / mL or mg / g); And / or, the minoxidil or its pharmaceutically acceptable excipient is 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g) And / or, the minoxidil is administered in a QD or BID manner; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2% (20 mg / mL or mg / g) or 5% (50 mg / mL or mg / g) QD or BID. In a second aspect, the present invention provides the pharmaceutical composition of the first aspect, which is used for preventing, alleviating and / or treating diseases or conditions related to androgen receptor activity. Preferably, the disease or disorder associated with androgen receptor activity is selected from prostate cancer, benign prostatic hyperplasia, acne, hirsutism, excess sebum and androgenic alopecia. In a third aspect, the present invention provides use of the pharmaceutical composition described in the first aspect in the preparation of a medicament for preventing, alleviating and / or treating diseases or conditions associated with androgen receptor activity. Preferably, the disease or disorder associated with androgen receptor activity is selected from prostate cancer, benign prostatic hyperplasia, acne, hirsutism, excess sebum and androgenic alopecia. In a fourth aspect, the present invention provides a method for preventing, alleviating and / or treating diseases or conditions associated with androgen receptor activity, comprising the following steps: administering a preventive, alleviating and / or therapeutically effective amount of the pharmaceutical composition described in the first aspect to an individual in need thereof. Preferably, the disease or disorder associated with androgen receptor activity is selected from prostate cancer, benign prostatic hyperplasia, acne, hirsutism, excess sebum and androgenic alopecia. And / or, the androgen inhibitor / antagonist and minoxidil contained in the pharmaceutical composition are co-formulated or separately formulated, and administered in combination, simultaneously, or at intervals. In a fifth aspect, the present invention provides a pharmaceutical composition for preventing, alleviating and / or treating male pattern baldness, comprising a compound of formula I or a crystalline form D of the compound of formula I and minoxidil or a pharmaceutically acceptable excipient thereof, Preferably, the pharmaceutical composition: The method comprises administering a therapeutically effective amount of an androgen inhibitor / antagonist (a compound of Formula I or a crystalline form D of the compound of Formula I) to a subject on a continuous daily regimen until a disease or condition associated with androgen receptor activity progresses or unacceptable toxicity occurs; and / or, the androgen inhibitor / antagonist (compound of Formula I or crystalline form D of the compound of Formula I) is administered in an amount of 0.05% (0.5 mg / mL or mg / g) to 10% (100 mg / mL or mg / g); And / or, the androgen inhibitor / antagonist (compound of formula I or crystalline form D of compound of formula I) is 0.25% (2.5 mg / mL or mg / g) to 1% (10 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist (compound of formula I or crystalline form D of compound of formula I) is administered in an amount of 0.1 mg / day to 1000 mg / day; and / or, the androgen inhibitor / antagonist (compound of Formula I or crystalline form D of the compound of Formula I) is administered in an amount of 0.5 mg / day to 100 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 1 mg / day to 50 mg / day; And / or, the androgen inhibitor / antagonist (compound of Formula I or crystalline form D of the compound of Formula I) is administered in an amount of 1.8 mg / day, 2.5 mg / day, 3.6 mg / day, 5 mg / day, 7.2 mg / day, 10 mg / day, or 20 mg / day; And / or, the androgen inhibitor / antagonist (compound of formula I or crystalline form D of compound of formula I) is administered in a QD or BID manner; And / or, the androgen inhibitor / antagonist (compound of Formula I or compound of Formula I Form D) is administered in an amount of 0.25% (2.5 mg / mL or mg / g), 0.5% (5 mg / mL or mg / g) or 1% (10 mg / mL or mg / g) QD or BID. comprising administering to the individual a therapeutically effective amount of minoxidil or a pharmaceutically acceptable excipient thereof on a continuous daily regimen until progression of a disease or disorder associated with androgen receptor activity or unacceptable toxicity; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2 mg / day to 500 mg / day; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 14.4 mg / day, 20 mg / day, 36 mg / day, 40 mg / day, 44 mg / day, 50 mg / day, or 100 mg / day; and / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 0.1% (1 mg / mL or mg / g) to 15% (150 mg / mL or mg / g); and / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); And / or, the minoxidil is administered in a QD or BID manner; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2% (20 mg / mL or mg / g) or 5% (50 mg / mL or mg / g) QD or BID. More preferably, in the pharmaceutical composition: And / or, the compound of formula I and minoxidil are administered in combination, wherein the combined administration is selected from: simultaneous administration, independent formulation and co-administration, or independent formulation and sequential administration; And / or, the administration route of the compound of formula I and minoxidil is selected from oral administration, parenteral administration, topical administration, and transdermal administration; preferably, the administration route is selected from topical administration and transdermal administration; and / or, administering a therapeutically effective amount of the compound of formula I to the individual on a continuous daily regimen until male pattern baldness disease or condition progression or unacceptable toxicity; And / or, preparing a preparation containing the compound of formula I, wherein the specification of the compound of formula I in the preparation is about 0.05% (0.5 mg / mL or mg / g) to 10% (100 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, a gel, preferably a liquid preparation (such as a tincture). Preferably, preparing a solution of the compound of formula I, wherein the specification of the compound of formula I in the solution is about 0.25% (2.5 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); and / or, the compound of formula I is administered in an amount of about 0.1 mg / day to about 1000 mg / day; and / or, the compound of formula I is administered in an amount of about 0.5 mg / day to about 100 mg / day; and / or, the compound of formula I is administered in an amount of about 1 mg / day to about 50 mg / day; and / or, the compound of formula I is administered in an amount of about 1.8 mg / day, about 2.5 mg / day, about 3.6 mg / day, about 5 mg / day, about 7.2 mg / day, about 10 mg / day, about 20 mg / day; And / or, the compound of formula I is administered in a QD or BID manner; And / or, a solution of the compound of formula I is prepared, wherein the specification of the compound of formula I in the solution is about 0.25% (2.5 mg / mL), 0.5% (5 mg / mL) or 1% (10 mg / mL), and the solution is administered in a QD or BID manner, or in a topically administered manner, and each administration of the solution is about 1 mL. comprising administering to the individual a therapeutically effective amount of minoxidil on a continuous daily regimen until progression of the androgenetic alopecia disease or condition or unacceptable toxicity; and / or, the minoxidil is administered in an amount of about 2 mg / day to about 500 mg / day; and / or, the minoxidil is administered in an amount of about 14.4 mg / day, about 20 mg / day, about 36 mg / day, about 40 mg / day, about 44 mg / day, about 50 mg / day, about 100 mg / day; And / or, preparing a preparation containing minoxidil, wherein the specification of minoxidil in the preparation is about 0.1% (1 mg / mL or mg / g) to 15% (150 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, or a gel, preferably a liquid preparation, a foam, or an aerosol; and / or, preparing a preparation containing minoxidil for administration in a manner such that the minoxidil content in the preparation is about 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, or a gel, preferably a liquid preparation, a foam, or an aerosol; And / or, the minoxidil is administered in a QD or BID manner; and / or, preparing a solution, foam or aerosol containing minoxidil for administration in a manner such that the minoxidil content in the formulation is about 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); And / or, a solution, foam or aerosol of minoxidil is prepared, with the minoxidil content in the preparation being about 2% (20 mg / mL or mg / g) or 5% (50 mg / mL or mg / g), the solution being administered in a QD or BID manner, or in a topical manner, with each administration of about 1 mL of the solution. And / or, liquid preparations of the compound of formula I and minoxidil are separately prepared, and the preparation of the compound of formula I with a strength of about 0.25% (2.5 mg / mL), 0.5% (5 mg / mL) or 1% (10 mg / mL) is administered in combination with the preparation of minoxidil with a strength of about 2% (20 mg / mL) or 5% (50 mg / mL); preferably, the frequency of administration of the compound of formula I and minoxidil is QD or BID, and the route of administration is topical administration; preferably, each administration is about 1 mL. In certain technical solutions of the present application, the pharmaceutical composition comprises: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), and the specification of minoxidil is about 2% (20 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD. Preferably, the compound of formula I and minoxidil are administered simultaneously; and / or each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 5 mg / day, and the minoxidil is administered at a dose of 20 mg / day. In certain technical solutions of the present application, the pharmaceutical composition comprises: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.25% (2.5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD. Preferably, the compound of formula I and minoxidil are administered simultaneously. And / or, each administration frequency is about 1 mL, that is, the compound of formula I is administered at about 2.5 mg / day, and the minoxidil is administered at 50 mg / day. In certain technical solutions of the present application, the pharmaceutical composition comprises: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD. Preferably, the compound of formula I and minoxidil are administered simultaneously; and / or the dosing frequency is about 1 mL per administration, that is, the compound of formula I is administered at a dose of about 5 mg / day, and the minoxidil is administered at a dose of 50 mg / day. In certain technical solutions of the present application, the pharmaceutical composition comprises: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 1% (10 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD. Preferably, the compound of formula I and minoxidil are administered simultaneously; and / or each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 10 mg / day, and the minoxidil is administered at a dose of 50 mg / day. In certain technical schemes of the present application, the pharmaceutical composition comprises: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.25% (2.5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of BID. Preferably, the compound of formula I and minoxidil are administered in an intermittent manner; and / or each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 5 mg / day, and the minoxidil is administered at a dose of 100 mg / day. In certain technical solutions of the present application, the pharmaceutical composition comprises: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of BID. Preferably, the compound of formula I and minoxidil are administered in an intermittent manner; and / or the dosing frequency is about 1 mL per administration, that is, the compound of formula I is administered in an amount of about 10 mg / day and the minoxidil is administered in an amount of 100 mg / day. Preferably, in the above-mentioned pharmaceutical composition, the weight percentage of the compound of formula I or the anhydrous polymorph of the compound of formula I (form D) is 1.0%-99.0%, for example, it can be 10.0%-80.0%, 20%-80%, 25%-80%, 25%-70%, 25%-65%, 25%-60%, 25%-55%, 25%-50%, 30%-50%, 35%-50% or 40%-50%. In a sixth aspect, the present invention provides a method for preventing, alleviating and / or treating male pattern baldness, comprising the following steps: administering a preventive, alleviating and / or therapeutically effective amount of a compound of formula I and minoxidil to an individual in need thereof; And / or, in the method, the compound of formula I and minoxidil are administered in combination, wherein the combined administration is selected from: simultaneous administration, independent formulation and co-administration, or independent formulation and sequential administration; And / or, in the method, the administration route is selected from oral administration, parenteral administration, topical administration, and transdermal administration; preferably, in the method, the administration route is selected from topical administration and transdermal administration; and / or, comprising administering to the individual a therapeutically effective amount of a compound of Formula I on a continuous daily regimen until progression of the androgenetic alopecia disease or condition or unacceptable toxicity; And / or, a preparation containing the compound of formula I is prepared and administered in a manner that the compound of formula I in the preparation has a specification of about 0.05% (0.5 mg / mL or mg / g) to 10% (100 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, a gel, preferably a liquid preparation (such as a tincture). Preferably, a solution of the compound of formula I is prepared and administered in a manner that the compound of formula I in the solution has a specification of about 0.25% (2.5 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); and / or, the compound of formula I is administered in an amount of about 0.1 mg / day to about 1000 mg / day; and / or, the compound of formula I is administered in an amount of about 0.5 mg / day to about 100 mg / day; and / or, the compound of formula I is administered in an amount of about 1 mg / day to about 50 mg / day; and / or, the compound of formula I is administered in an amount of about 1.8 mg / day, about 2.5 mg / day, about 3.6 mg / day, about 5 mg / day, about 7.2 mg / day, about 10 mg / day, about 20 mg / day; And / or, the compound of formula I is administered in a QD or BID manner; And / or, a solution of the compound of formula I is prepared, wherein the concentration of the compound of formula I in the solution is about 0.25% (2.5 mg / mL), 0.5% (5 mg / mL) or 1% (10 mg / mL), the dosage frequency is QD or BID, and the administration route is topical administration, with each administration frequency being about 1 mL. comprising administering to the individual a therapeutically effective amount of minoxidil on a continuous daily regimen until progression of the androgenetic alopecia disease or condition or unacceptable toxicity; and / or, the minoxidil is administered in an amount of about 2 mg / day to about 500 mg / day; and / or, the minoxidil is administered in an amount of about 14.4 mg / day, about 20 mg / day, about 36 mg / day, about 40 mg / day, about 44 mg / day, about 50 mg / day, about 100 mg / day; and / or, preparing a preparation containing minoxidil for administration in a manner in which the minoxidil specification in the preparation is about 0.1% (1 mg / mL or mg / g) to 15% (150 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, or a gel, preferably a liquid preparation, a foam, or an aerosol; and / or, preparing a preparation containing minoxidil for administration in a manner such that the minoxidil specification in the preparation is about 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, or a gel, preferably a liquid preparation, a foam, or an aerosol; And / or, the minoxidil is administered in a QD or BID manner; and / or, preparing a solution, foam or aerosol containing minoxidil for administration in a manner that the minoxidil concentration in the formulation is about 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); And / or, a solution, foam or aerosol of minoxidil is prepared, with a minoxidil specification of about 2% (20 mg / mL or mg / g) or 5% (50 mg / mL or mg / g) in the preparation, a dosing frequency of QD or BID, and a local administration route of administration, with each administration frequency of about 1 mL. And / or, liquid preparations of the compound of formula I and minoxidil are separately prepared, and the compound of formula I with a strength of about 0.25% (2.5 mg / mL), 0.5% (5 mg / mL) or 1% (10 mg / mL) is used in combination with a minoxidil with a strength of about 2% (20 mg / mL) or 5% (50 mg / mL); preferably, the compound of formula I and minoxidil are administered QD or BID, and the administration route is topical administration; preferably, each administration is about 1 mL. In certain technical schemes of the present application, in the method: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), and the specification of minoxidil is about 2% (20 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; preferably, the compound of formula I and minoxidil are administered simultaneously; and / or, each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 5 mg / day, and the minoxidil is administered at a dose of 20 mg / day. In certain technical schemes of the present application, in the method: liquid preparations of the compound of formula I and minoxidil are separately prepared, the specification of the compound of formula I is about 0.25% (2.5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; preferably, the compound of formula I and minoxidil are administered simultaneously; and / or, each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 2.5 mg / day, and the minoxidil is administered at a dose of 50 mg / day. In certain technical solutions of the present application, in the method: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); And / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; preferably, the compound of formula I and minoxidil are administered simultaneously; and / or, the dosing frequency is about 1 mL per administration, that is, the compound of formula I is administered at a dose of about 5 mg / day and the minoxidil is administered at a dose of 50 mg / day. In certain technical schemes of the present application, in the method: liquid preparations of the compound of formula I and minoxidil are separately prepared, the specification of the compound of formula I is about 1% (10 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; preferably, the compound of formula I and minoxidil are administered simultaneously; and / or, each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 10 mg / day, and the minoxidil is administered at a dose of 50 mg / day. In certain technical schemes of the present application, in the method: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.25% (2.5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of BID; preferably, the compound of formula I and minoxidil are administered in an intermittent manner; and / or, each administration in the dosing frequency is about 1 mL, that is, the compound of formula I is administered in an amount of about 5 mg / day, and the minoxidil is administered in an amount of 100 mg / day. In certain technical schemes of the present application, in the method: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of BID; preferably, the compound of formula I and minoxidil are administered in an intermittent manner; and / or, each administration in the dosing frequency is about 1 mL, that is, the compound of formula I is administered in an amount of about 10 mg / day, and the minoxidil is administered in an amount of 100 mg / day. Preferably, in the method, the weight percentage of the compound of formula I is 1.0%-99.0%, for example, it can be 10.0%-80.0%, 20%-80%, 25%-80%, 25%-70%, 25%-65%, 25%-60%, 25%-55%, 25%-50%, 30%-50%, 35%-50% or 40%-50%. Effects of the Invention The present invention provides a pharmaceutical composition, method and use with androgen receptor inhibitor / antagonist and minoxidil as active ingredients. It has been surprisingly found that the use of androgen receptor inhibitor / antagonist, especially the combination of formula I compound or formula I compound crystalline form D and minoxidil improves the effect obtained by the single drug of androgen receptor inhibitor / antagonist or minoxidil. In fact, this improvement is synergistic in nature, because the effect of improving or promoting hair growth is also greater than the effect obtained by using a single androgen receptor inhibitor / antagonist or minoxidil. This method is not only a simple mixed use in a physical sense, but also has a good therapeutic additive effect and the advantage of good safety. BRIEF DESCRIPTION OF THE DRAWINGS FIG1 is an XRPD spectrum of an anhydrous polymorph having crystalline form D of the compound of formula I; FIG2 is a TGA / DSC spectrum of an anhydrous polymorph having crystalline form D of the compound of formula I; FIG3 is a DVS diagram of an anhydrous polymorph having crystalline form D of the compound of Formula I; FIG4 is an XRPD spectrum of an anhydrous polymorph having crystalline form D of the compound of Formula I before and after a DVS experiment; FIG5 is an XRPD spectrum of the stability test of the anhydrous polymorph having crystalline form D of the compound of formula I; FIG6 is an XRPD spectrum of an anhydrous polymorph having Form C of the compound of Formula I; FIG7 is a TGA / DSC spectrum of an anhydrous polymorph having Form C of the compound of Formula I; FIG8 is an XRPD spectrum of an anhydrous polymorph having Form B of the compound of Formula I; FIG9 is a TGA / DSC spectrum of an anhydrous polymorph having Form B of the compound of Formula I; FIG10 is an XRPD spectrum of an anhydrous polymorph having Form A of the compound of Formula I; FIG11 is a TGA / DSC spectrum of an anhydrous polymorph having Form A of the compound of Formula I; Figure 12 is a schematic diagram of the main observation indicators of mice; Figure 13 is a schematic diagram of the hair growth experiment of mice in groups G1-G8; FIG14 is a comparison of hair scores of mice in groups G1-G8; Figure 15 is a comparison of the body weight results of mice in groups G1-G8; Figure 16 is a schematic diagram of hair growth in mice in groups G1-G8; FIG17 is a comparison of hair scores of mice in groups G1-G8; FIG. 18 is a comparison chart of the body weight results of mice in groups G1-G8. DETAILED DESCRIPTION Unless otherwise defined, scientific and technical terms used herein have the meanings commonly understood by one of ordinary skill in the art. Unless otherwise specified, singular forms of words such as "a", "an" and "the" appearing herein include their corresponding plural references unless the context clearly indicates otherwise. For example, when reference is made to "a" crystalline form or polymorph, one or more different crystalline forms or polymorphs are included, and when reference is made to "the" method, equivalent steps and methods known to those of ordinary skill in the art are included. Unless otherwise specified, the term "comprising" and its variants, such as "containing" and "including", appearing in this document indicate that the set not only includes one or more integers, steps or combinations thereof explicitly disclosed, but also does not exclude any other integers, steps or combinations thereof. At the same time, in certain cases, the term "comprising" appearing in this document can be replaced by the term "containing", "including" or "having". Unless otherwise specified, the terms "effective amount", "therapeutically effective amount" or "pharmaceutically effective amount" as used herein refer to an amount of a therapeutic agent sufficient to alleviate one or more aspects of a condition. The result can be a reduction and / or alleviation of the signs, symptoms or causes of a disease, or any other desired change in a biological system. For example, an "effective amount" for therapeutic use includes the amount of a therapeutic agent described herein. The composition of the present invention prevents, alleviates and / or treats androgen receptor activity related diseases or conditions clinically significantly reduce the amount required. For example, for a given aspect (e.g., incidence length), the therapeutically effective amount will show an increase or decrease of 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90% or at least 100%. The therapeutic effect can also be expressed as a "fold" increase or decrease. For example, the therapeutically effective amount can be at least 1.2 times, 1.5 times, 2 times, 5 times or more times the effect of the control. Suitable "effective amount" in any individual case can be determined by using technology such as dose escalation research. Unless otherwise specified, the pharmaceutical composition comprising the androgen inhibitor / antagonist of the present invention can be administered to an individual / subject / patient in need thereof by oral, inhalation, rectal, parenteral or topical routes. For oral administration, the pharmaceutical composition can be a solid preparation (such as tablets, powders, granules, capsules, etc.) or a liquid preparation (such as water-based or oil-based suspensions or other liquid preparations, such as syrups, solutions, etc.). For parenteral administration, the pharmaceutical composition can be a solution, a suspension, a lyophilized powder, etc. The pharmaceutical composition can be a single unit with a precise dose. In addition, the pharmaceutical composition can further include additional pharmacologically active ingredients. Unless otherwise specified, "treatment" as used herein (and as known in the art) also generally includes any method for obtaining a beneficial or desired result (including a clinical result) for a subject's condition. Beneficial or desired clinical results include, but are not limited to, alleviating or relieving one or more symptoms or conditions, reducing the extent of the disease, stabilizing (i.e., not worsening) the disease state, preventing the spread or spread of the disease, delaying or slowing the progression of the disease, improving or alleviating the disease state, reducing the disease, and alleviating whether partial or complete and whether detectable or undetectable. In other words, "treatment" as used herein includes any cure, improvement, or prevention of a disease. Treatment can prevent the occurrence of a disease; inhibit the spread of a disease; alleviate the symptoms of a disease, completely or partially remove the underlying cause of the disease, shorten the duration of the disease, or a combination thereof. Unless otherwise specified, the term "disease" refers to any deviation from normal health in mammals, and includes states when disease symptoms are present, as well as conditions where deviations (e.g., infection, gene mutation, genetic defects, etc.) have occurred but symptoms have not yet manifested. According to the present invention, the methods disclosed herein are suitable for use in patients, who are members of the vertebrate class, including but not limited to primates, livestock, and domestic pets (e.g., companion animals). Typically, the patient is a human patient. Unless otherwise specified, the terms "topical application" or "topical application" as used herein are used interchangeably and include application of a composition to the upper and / or lower eyelid margins, eyebrow area, scalp or face. Topical application or application results in delivery of an active agent to a localized area of ​​the skin or body. Unless otherwise indicated, abbreviations used herein have their conventional meanings in the fields of chemistry, biology or pharmacy. As used herein, unless otherwise specified, the phrase "pharmaceutically acceptable salt" refers to salts of an active compound that possess the same pharmacological activity as the active compound and are biologically and otherwise beneficial. Unless otherwise specified, the term "about" in this disclosure means that the error is within ±5%. The terms QD and BID respectively indicate that the dosing frequency is once a day and twice a day. It should be understood that the dosing frequency can be adjusted to meet the daily dosage. The frequency may be, for example, once a day, twice a day, once every two days, or once every three days. For the crystal forms in this article, only the characteristic peaks in the XRPD spectrum (i.e., the most characteristic, significant, unique and / or repeatable diffraction peaks) are summarized, while other peaks can be obtained from the spectrum by conventional methods. The above characteristic peaks can be repeated within the error limit (the error range is ± 0.2°). In the present invention, the androgen inhibitor / antagonist or minoxidil is administered in an amount of 0.25% (2.5 mg / mL or mg / g) to 1% (10 mg / mL or mg / g), where 1% means that 1 mL (liquid preparation, such as tincture) or 1 g preparation (solid preparation or semisolid preparation, such as gel) contains 10 mg of androgen inhibitor / antagonist or minoxidil; the rest of the description is similar. Male pattern baldness refers to androgenetic alopecia (androgenetic alopecia AGA), which can be male or female androgenetic alopecia. In the present application, it is especially directed to male androgenetic alopecia, for example, male androgenetic alopecia patients of grade IIIv-V according to Hamilton-Norwood classification. Source of Minoxidil in the Examples of the Present Invention Minoxidil (CAS 38304-91-5) is known for its effects in slowing or preventing hair loss and promoting hair regrowth. It is available without a prescription for the treatment of androgenetic alopecia, as well as other hair loss treatments, but measurable changes disappear within a few months after treatment is discontinued. The minoxidil preparation of the present invention is commercially available, such as from Shanghai MacLean Biochemical Technology Co., Ltd. Minoxidil has the following structure: or a pharmaceutically acceptable excipient thereof. The minoxidil with a concentration of 50 mg / mL (specification: 60 ml: 3 g) and 20 mg / mL (specification: 60 ml: 1.2 g) in the present invention was purchased from Shanxi Zhendong Anxin Biopharmaceutical Co., Ltd. Source of dihydroxytestosterone DHT in the embodiment of the present invention Dihydrotestosterone is a steroid hormone secreted by the testicles. It is the main androgen in the human body and is related to the development of male secondary sexual characteristics. It is the main androgen produced by interstitial cells of the testicles. It belongs to C10 steroids. After entering the circulating blood, most of it is bound to the sex hormone binding protein (SHBG) in the plasma, and a very small part is in a free state. The present invention uses DHT to simulate androgen-mediated hair loss, which can be obtained commercially, such as purchased from Suzhou Shengnuokang Biotechnology Co., Ltd. Sources of the compounds of formula I in the embodiments of the present invention According to the CN102757389B specification, page 50

[0425] To the content disclosed in paragraph

[0427] , the title compound is prepared in a substantially colloid or viscous state, the title compound is dissolved in DMSO, and water is added dropwise to precipitate The solid was collected by filtration and the filter cake was dried under reduced pressure at 40-50°C to obtain the compound of formula I in solid form. Preparations of compounds of formula I with different concentrations can be completed by referring to the technical teachings in CN202310219411.9, which the applicant hereby incorporates in its entirety into this application. Sources of the anhydrous polymorphs of the compound of formula I in the present invention A, B, C, D According to the contents disclosed in Examples 1-4 of the specification of WO2022199577A1, anhydrous polymorphs having crystal forms A, B, C, and D were prepared. The androgen inhibitor / antagonist in Example 1 of the present invention is preferably a compound of formula I or crystalline form D. Experimental materials and experimental animals of the present invention Any solvent commonly used in the art can be used as a solvent for the pharmaceutical composition of the present invention for administration of the pharmaceutical combination comprising an androgen inhibitor / antagonist and minoxidil. The invention is further described by the following non-limiting examples. Experimental Example 1: In vivo efficacy experiment Experimental design 100 mice were deeply anesthetized. The hair on the back of the mice was shaved with an animal shaver. Then, depilatory cream (Veet https: / / item.jd.com / 6291245.html) was evenly applied on the skin surface of the mice. After standing for 7-10 minutes, the hair was gently shaved against the direction of the hair with a depilatory razor. Finally, the depilatory cream remaining on the skin surface was thoroughly washed with wet wipes to avoid burning the mouse skin. The main observation indicators of this experiment are shown in Figure 12 ((hair scoring literature: Biomolecules & Therapeutics, 17 (3), 241-248 (2009))), and are described as follows: (0 points: no darkening of skin color in all areas; 1 point: darkening of gray skin color areas; 2 points: short hair is visible; 3 points: sparse hair; 4 points: dense hair; 5 points: complete hair growth). After shaving, the mice were photographed and scored three times a week until the end of the experiment. Experimental methods 100 mice were deeply anesthetized. The hair on the back of the mice was first shaved with an animal shaver. Then, the depilatory cream was evenly applied on the skin surface of the mice. After standing for 7-10 minutes, the hair was gently shaved off in the opposite direction of the hair with a depilatory razor. Finally, the depilatory cream remaining on the skin surface was thoroughly washed with wet wipes to avoid burning the mouse skin. This experiment was divided into 8 groups as shown in Table 1. The administration of DHT and the test substance (compound of formula I, minoxidil) started on the second day of hair removal, counted as day 1 (the day of hair removal was counted as day 0). 64 mice in good condition were randomly selected into the group. Table 1 Experimental groups The solvent in Table 2 refers to a mixture of diethylene glycol monoethyl ether, anhydrous ethanol, propylene glycol, and purified water. According to the grouping, the corresponding dosage, test substance concentration and administration volume in Table 1, DHT, minoxidil and the compound of formula I were topically applied to the back of the mice treated according to the above experimental design and experimental method. In the combined administration of the compound of formula I and minoxidil in groups G7 and G8, one of the drugs was used first and then the other drug, and the time interval between the administration of the two drugs did not exceed 1 minute. Starting from the first day of administration, body weight and hair anagen scores were measured and recorded twice a week and photographed until the end of the experiment. The results of day 23 are shown in Figure 13. Scoring was performed according to the experimental design. Experimental Results The results are shown in Figure 14, Table 2, and Table 3. Corresponding to Table 1, G1 is the vehicle control group, G2 is the DHT modeling group, G3 is the 2% (20 mg / mL) minoxidil monotherapy group, G4 is the 5% (50 mg / mL) minoxidil monotherapy group, G5 is the 0.5% (5 mg / mL) compound of formula I monotherapy group, G6 is the 1.0% (10 mg / mL) compound of formula I monotherapy group, G7 is the 0.5% (5 mg / mL) compound of formula I combined with 2% (20 mg / mL) minoxidil combination group, and G8 is the 1.0% (10 mg / mL) compound of formula I combined with 5% (50 mg / mL) minoxidil combination group. The results show that the combined administration of minoxidil and the compound of formula I can promote hair growth. Compared with the single-drug group, the combined drug has a stronger effect in promoting hair growth and has a synergistic effect. answer. As shown in FIG15 , during the administration period, the test substance had no effect on the body weight of mice and had good safety. Table 2 Mouse hair score Table 3 Statistical values ​​of mouse hair scores *p<0.05, **p<0.01*, ***p<0.001 Experimental Example 2: In vivo efficacy experiment 120 mice were deeply anesthetized, and the hair on the back of the mice was shaved with an animal shaver, and then depilatory cream (Veet https: / / item.jd.com / 6291245.html) Apply the cream evenly on the mouse skin surface, let it stand for 7-10 minutes, then use a hair removal razor to gently shave the hair in the opposite direction of the hair. Finally, use a wet wipe to thoroughly wash off the hair removal cream remaining on the skin surface to avoid burning the mouse skin. This experiment was divided into 8 groups as shown in Table 4. The administration of DHT and the test substance (compound of formula I, minoxidil) started on the second day of hair removal, counted as day 1 (the day of hair removal was counted as day 0). 86 mice in good condition were randomly selected into the group. The main observation indicators of this experiment are shown in Figure 12 ((hair scoring literature: Biomolecules & Therapeutics, 17 (3), 241-248 (2009))), and are described as follows: (0 points: no darkening of skin color in all areas; 1 point: darkening of gray skin color areas; 2 points: short hair is visible; 3 points: sparse hair; 4 points: dense hair; 5 points: complete hair growth). After shaving, the mice were photographed and scored three times a week until the end of the experiment. Table 4 Experimental groups The solvent in Table 4 refers to a mixture of diethylene glycol monoethyl ether, anhydrous ethanol, propylene glycol, and purified water. According to the grouping in Table 4, and the corresponding dosage, test substance concentration, and administration volume, DHT, minoxidil, and the compound of formula I were topically applied to the back of the mice treated according to the above experimental design and experimental method. G6, G7, G8 The compound of formula I and minoxidil in the group are administered in combination, wherein one of the drugs is administered first and then the other, and the time interval between the two drugs does not exceed 1 minute. Starting from the first day of administration, body weight and hair anagen scores were measured and recorded twice a week and photographed until the end of the experiment. The results of day 21 are shown in Figure 16. Scoring was performed according to the experimental design. Experimental Results The results are shown in Figure 17, Table 5 and Table 6. Corresponding to Table 4, G1 is the vehicle control group, G2 is the DHT modeling group, G3 is the 5% (50 mg / ml) minoxidil monotherapy group, G4 is the 0.25% (2.5 mg / ml) compound of formula I monotherapy group, G5 is the 0.5% (5 mg / ml) compound of formula I monotherapy group, G6 is the 0.25% (2.5 mg / ml) compound of formula I and 5% (50 mg / ml) minoxidil combination group, G7 is the 0.5% (5 mg / ml) compound of formula I and 5% (50 mg / ml) minoxidil combination group, and G8 is the 1.0% (10 mg / ml) compound of formula I and 5% (50 mg / ml) minoxidil combination group. The results showed that the combined administration of minoxidil and the compound of formula I can promote hair growth. Compared with the single-drug group, the combined drug has a stronger effect in promoting hair growth and has a synergistic effect. As shown in FIG18 , during the administration period, the test substance had no effect on the body weight of mice and had good safety. Table 5 Mouse hair score Table 6 Statistical values ​​of mouse hair scores *p<0.05, **p<0.01*, ***p<0.001 Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention, which shall all be included in the scope of protection of the present invention.

Claims

1. A pharmaceutical composition comprising an androgen inhibitor / antagonist and minoxidil or a pharmaceutically acceptable excipient thereof.

2. The pharmaceutical composition according to claim 1, wherein the androgen inhibitor / antagonist comprises clacoterone, nilutamide, enzalutamide, topiluamide, bicalutamide, flutamide, hydrochlorothiazide, spironolactone, niclosamide, revilutamide, darolamide, althiazide, apalutamide, deenlutamide, enobosarm, pukelumab, ANA-001, 18F-dihydrotestosterone, 2-hydroxyflutamide, AKP-009, ASC-J9, AZD5312, EG017, LY2452473, MK-0773, VK5211, bavdegalutamide, dimethandrolone undecanoate, seviteronel, inotron, zanotron, CP-COV03, FW-1022, APC-100, ARV-766, EM-5854, EPI-7386, MVI-118, ODM-204, TRC253, UT-34, ralaniten acetate, vosilasarm, FW-424, AC0176, AZD3514, BMS-641988, CB-03-10, CC-94676, DT-200, EZN-4176, GSK2849466, GSK971086, HP518, HRS-5041, HSK38008 , MK-3984, ONC1-13B, PF-06260414, RO7656594, SXL01, TAS3681, TQB3720, TFFNIC, UNI911, FW-420, A031, AB001, AB006, AC-262536, ADA-308, AH-001, AR-V7PROTAC, ARCC-4, ARD-2051, ARD-2128, ARD-2585, ARD-266, ARD-61, ARD-69, ASN-1780, ASR-600, BMS-564929, BWA-522, CA103, CB-03-04, CH4892280, CH5137291, CL-AR-100, CZ-212-3, DA-4210, EM6537, HC-X022, HYG-410, HYG-420, HYG-430, HYG-440, ID119160021, IMB-A6, JMKX002992, JNJ-26146900, JNJ-28330835, JNJ-37654032, LG121071, LGD-2941, LGD-3303, LGD2226, LHJ-647, MTX-23, NUV-1156, NUV-1511, OLX104C, ONC2-13B, PARD-33, PF-0998425, PRX-304, RD162, RU56187, RU58642, RU58841, RU59063, SKLB-C2807, TD-802, VPC-13789, WS9761, XY-32, YM-175735, YM-92088, YM580, ZD3980, Zeta55, SCAI-502, XNTR-934, or XNTR-936.

3. A pharmaceutical composition comprising an androgen inhibitor / antagonist and minoxidil or a pharmaceutically acceptable excipient thereof, wherein the androgen inhibitor / antagonist is a compound of formula I or a pharmaceutically acceptable salt, stereoisomer, solvate, polymorph, isotopic derivative or prodrug thereof, Preferably, the androgen inhibitor / antagonist is an anhydrous polymorph of the compound of formula I.

4. The pharmaceutical composition according to claim 3, wherein the anhydrous polymorph of the compound of formula I has a crystalline form D, and the crystalline form D meets at least one of the following conditions: I. The XRPD spectrum of Form D comprises peaks at the following 2θ values: 5.3±0.2°, 10.7±0.2°, 13.5±0.2°, 15.1±0.2° and 21.3±0.2°; Preferably, the XRPD spectrum of the crystalline form D further comprises peaks at the following 2θ values: 12.0±0.2°, 12.7±0.2°, 14.8±0.2°, 16.4±0.2°, 17.3±0.2°, 20.3±0.2°, 24.2±0.2° and 24.8±0.2°; More preferably, the XRPD spectrum of the crystalline form D further comprises peaks at the following 2θ values: 19.7±0.2°, 22.5±0.2°, 23.1±0.2°, 27.3±0.2°, 28.5±0.2°, 29.7±0.2° and 32.3±0.2°; Further preferably, the XRPD spectrum of the crystalline form D is substantially consistent with Figure 1; II. The TGA spectrum of the crystalline form D shows a weight loss of about 1.6% at 150±1°C; Preferably, the TGA spectrum of the crystalline form D is substantially consistent with FIG. 2 ; and III. The DSC spectrum of the crystalline form D shows endothermic absorption at 167±1°C; Preferably, the DSC spectrum of the crystalline form D is substantially consistent with FIG. 2 ; Or the anhydrous polymorph has a crystalline form C, and the crystalline form C meets at least one of the following conditions: I. The XRPD spectrum of Form C comprises peaks at the following 2θ values: 5.2±0.2°, 10.4±0.2°, 13.4±0.2°, 15.0±0.2°, 16.4±0.2° and 29.1±0.2°; Preferably, the XRPD spectrum of the crystalline form C further comprises peaks at the following 2θ values: 19.6±0.2°, 20.1±0.2°, 22.8±0.2° and 24.4±0.2°; More preferably, the XRPD spectrum of the crystalline form C further comprises peaks at the following 2θ values: 11.9±0.2°, 17.3±0.2°, 23.6±0.2°, 31.6±0.2° and 34.1±0.2°; Further preferably, the XRPD spectrum of the crystalline form C is substantially consistent with FIG6 ; II. The TGA spectrum of the crystalline form C shows a weight loss of about 1.6% at 150±1°C; Preferably, the TGA spectrum of the crystalline form C is substantially consistent with FIG. 7 ; and III. The DSC spectrum of the crystalline form C shows endotherms at 148±1°C, 167±1°C and 177±1°C; Preferably, the DSC spectrum of the crystalline form C is substantially consistent with FIG. 7 . Or the anhydrous polymorph has a crystalline form B, and the crystalline form B meets at least one of the following conditions: I. The XRPD spectrum of Form B comprises peaks at the following 2θ values: 7.3±0.2°, 9.9±0.2°, 12.5±0.2°, 16.5±0.2° and 17.1±0.2°; Preferably, the XRPD spectrum of the crystalline form B further comprises peaks at the following 2θ values: 13.1±0.2°, 20.3±0.2°, 24.0±0.2°, 25.2±0.2° and 26.7±0.2°; More preferably, the XRPD spectrum of Form B further comprises peaks at the following 2θ values: 21.3±0.2°, 27.8±0.2°, 28.6±0.2°, 29.5±0.2° and 31.3±0.2°; Further preferably, the XRPD spectrum of the crystalline form B is substantially consistent with FIG8 ; II. The TGA spectrum of the crystalline form B shows a weight loss of about 1.5% at 150±1°C; Preferably, the TGA spectrum of the crystalline form B is substantially consistent with FIG. 9 ; and III. The DSC spectrum of the crystalline form B shows endotherm at 177±1°C; Preferably, the DSC spectrum of the crystalline form B is substantially consistent with FIG9 ; Or the anhydrous polymorph has a crystalline form A, and the crystalline form A meets at least one of the following conditions: The XRPD spectrum of Form A comprises peaks at the following 2θ values: 9.0±0.2°, 12.5±0.2°, 15.7±0.2°, 17.2±0.2°, 18.1±0.2° and 23.2±0.2°; Preferably, the XRPD spectrum of the crystalline form A further comprises peaks at the following 2θ values: 3.3±0.2°, 7.5±0.2°, 12.9±0.2°, 15.2±0.2°, 24.4±0.2°, 28.4±0.2° and 29.8±0.2°; More preferably, the XRPD spectrum of the crystalline form A further comprises peaks at the following 2θ values: 14.4±0.2°, 17.7±0.2°, 19.9±0.2° and 21.8±0.2°; Further preferably, the XRPD spectrum of the crystalline form A is substantially consistent with FIG. 10 ; II. The TGA spectrum of the crystalline form A shows a weight loss of about 1.0% at 150±1°C; Preferably, the TGA spectrum of the crystalline form A is substantially consistent with Figure 11; and III. The DSC spectrum of the crystalline form A shows endothermicity at 160±1°C and 177±1°C, and exothermicity at 162±1°C; Preferably, the DSC spectrum of the crystalline form A is substantially consistent with FIG. 11 .

5. The pharmaceutical composition according to any one of claims 1 to 4, comprising administering to the individual a therapeutically effective amount of an androgen inhibitor / antagonist on a continuous daily regimen until progression of a disease or disorder associated with androgen receptor activity or unacceptable toxicity; And / or, the individual is a male or female androgenic alopecia patient, preferably a male androgenic alopecia patient, further preferably a male androgenic alopecia patient with Hamilton-Norwood classification of IIIv-V; and / or, the androgen inhibitor / antagonist is administered in an amount of 0.05% (0.5 mg / mL or mg / g) to 10% (100 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist is administered in an amount of 0.25% (2.5 mg / mL or mg / g) to 1% (10 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist is administered in an amount of 0.1 mg / day to 1000 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 0.5 mg / day to 100 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 1.8 mg / day, 2.5 mg / day, 1.8 mg / day, 3.6 mg / day, 5 mg / day, 10 mg / day, 20 mg / day; and / or, the androgen inhibitor / antagonist is administered in a QD or BID manner; And / or, the androgen inhibitor / antagonist is administered in an amount of 0.25% (2.5 mg / mL or mg / g), 0.5% (5 mg / mL or mg / g) or 1% (10 mg / mL or mg / g) QD or BID.

6. The pharmaceutical composition according to any one of claims 1 to 5, comprising administering to the individual a therapeutically effective amount of minoxidil or a pharmaceutically acceptable excipient thereof on a continuous daily regimen until progression of a disease or disorder associated with androgen receptor activity or unacceptable toxicity; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2 mg / day to 500 mg / day; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 14.4 mg / day, 20 mg / day, 36 mg / day, 40 mg / day, 44 mg / day, 50 mg / day, or 100 mg / day; and / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 0.1% (1 mg / mL or mg / g) to 15% (150 mg / mL or mg / g); and / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); And / or, the minoxidil is administered in a QD or BID manner; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2% (20 mg / mL or mg / g) or 5% (50 mg / mL or mg / g) QD or BID.

7. The pharmaceutical composition according to any one of claims 1 to 6, for preventing, alleviating and / or treating diseases or conditions associated with androgen receptor activity; Preferably, the androgen receptor activity-related disease or disorder is selected from prostate cancer, benign prostatic hyperplasia, acne, hirsutism, excess sebum and androgenic alopecia; And / or, the patient of the related disease or condition is a male or female patient with androgenic alopecia, preferably a male patient with androgenic alopecia, and further preferably a male patient with androgenic alopecia of grade IIIv-V according to Hamilton-Norwood classification.

8. Use of the pharmaceutical composition according to any one of claims 1 to 6 in the preparation of a medicament for preventing, alleviating and / or treating diseases or conditions associated with androgen receptor activity; Preferably, the androgen receptor activity-related disease or disorder is selected from prostate cancer, benign prostatic hyperplasia, acne, hirsutism, excess sebum and androgenic alopecia; And / or, the patient of the related disease or condition is a male or female patient with androgenic alopecia, preferably a male patient with androgenic alopecia, and further preferably a male patient with androgenic alopecia of grade IIIv-V according to Hamilton-Norwood classification.

9. A method for preventing, alleviating and / or treating diseases or conditions associated with androgen receptor activity, comprising the following steps: administering a preventive, alleviating and / or therapeutically effective amount of the pharmaceutical composition according to any one of claims 1 to 6 to an individual in need thereof; Preferably, the androgen receptor activity-related disease or disorder is selected from prostate cancer, benign prostatic hyperplasia, acne, hirsutism, excess sebum and androgenic alopecia; And / or, the androgen inhibitor / antagonist and minoxidil contained in the pharmaceutical composition are co-formulated or separately formulated, and administered in combination, simultaneously, or at intervals; and / or, topically administering the pharmaceutical composition to an individual in need thereof; And / or, the individual is a male or female androgenic alopecia patient, preferably a male androgenic alopecia patient, and further preferably a male androgenic alopecia patient with Hamilton-Norwood classification of grade IIIv-V.

10. A pharmaceutical composition for preventing, alleviating and / or treating male pattern baldness, comprising a compound of formula I or a crystalline form D of the compound of formula I and minoxidil or a pharmaceutically acceptable excipient thereof, 11. The pharmaceutical composition according to claim 10, comprising administering to the individual a therapeutically effective amount of a compound of Formula I or a crystalline Form D of the compound of Formula I on a continuous daily regimen until a disease or disorder associated with androgen receptor activity progresses or unacceptable toxicity occurs; And / or, the individual is a male or female androgenic alopecia patient, preferably a male androgenic alopecia patient, further preferably a male androgenic alopecia patient with Hamilton-Norwood classification of IIIv-V; and / or, the androgen inhibitor / antagonist is administered in an amount of 0.05% (0.5 mg / mL or mg / g) to 10% (100 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist is administered in an amount of 0.25% (2.5 mg / mL or mg / g) to 1% (10 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist is administered in an amount of 0.1 mg / day to 1000 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 0.5 mg / day to 100 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 1 mg / day to 50 mg / day; and / or, the androgen inhibitor / antagonist is administered in an amount of 2.5 mg / day, 5 mg / day, 10 mg / day, or 20 mg / day; and / or, the androgen inhibitor / antagonist is administered in a QD or BID manner; and / or, the androgen inhibitor / antagonist is administered in an amount of 0.25% (2.5 mg / mL or mg / g), 0.5% (5 mg / mL or mg / g), or 1% (10 mg / mL or mg / g) QD or BID; comprising administering to the individual a therapeutically effective amount of minoxidil or a pharmaceutically acceptable excipient thereof on a continuous daily regimen until progression of a disease or disorder associated with androgen receptor activity or unacceptable toxicity; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2 mg / day to 500 mg / day; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 20 mg / day, 40 mg / day, 44 mg / day, 50 mg / day, or 100 mg / day; and / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 0.1% (1 mg / mL or mg / g) to 15% (150 mg / mL or mg / g); and / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); and / or, the androgen inhibitor / antagonist is administered in a QD or BID manner; And / or, the minoxidil or its pharmaceutically acceptable excipient is administered in an amount of 2% (20 mg / mL or mg / g) or 5% (50 mg / mL or mg / g) QD or BID.

12. The pharmaceutical composition according to claim 11, (1) The compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 0.5% (5 mg / mL or mg / g), and the minoxidil is administered in an amount of 2% (20 mg / mL or mg / g); and / or, the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 5 mg / day; and / or, the minoxidil is administered in an amount of 20 mg / day; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in a QD manner; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered simultaneously; Or, (2) the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 0.25% (2.5 mg / mL or mg / g), and the minoxidil is administered in an amount of 5% (50 mg / mL or mg / g); and / or, the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 2.5 mg / day; and / or, the minoxidil is administered in an amount of 50 mg / day; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in a QD manner; and / or, the compound of formula I or the crystalline form D of the compound of formula I Compound Form D and minoxidil are administered simultaneously; Or, (3) the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 0.5% (5 mg / mL or mg / g), and the minoxidil is administered in an amount of 5% (50 mg / mL or mg / g); and / or, the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 5 mg / day; and / or, the minoxidil is administered in an amount of 50 mg / day; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in a QD manner; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered simultaneously; Or, (4) the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 1% (10 mg / mL or mg / g), and the minoxidil is administered in an amount of 5% (50 mg / mL or mg / g); and / or, the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 10 mg / day; and / or, the minoxidil is administered in an amount of 50 mg / day; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in a QD manner; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered simultaneously; Or, (5) the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 0.25% (2.5 mg / mL or mg / g), and the minoxidil is administered in an amount of 5% (50 mg / mL or mg / g); and / or, the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 5 mg / day; and / or, the minoxidil is administered in an amount of 100 mg / day; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in a BID manner; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in an intermittent manner; Or, (6) the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 0.5% (5 mg / mL or mg / g), and the minoxidil is administered in an amount of 5% (50 mg / mL or mg / g); and / or, the compound of formula I or the crystalline form D of the compound of formula I is administered in an amount of 10 mg / day; and / or, the minoxidil is administered in an amount of 100 mg / day; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in a BID manner; and / or, the compound of formula I or the crystalline form D of the compound of formula I and minoxidil are administered in an intermittent manner.

13. A method for preventing, alleviating and / or treating male pattern baldness, comprising the following steps: administering a preventive, alleviating and / or therapeutically effective amount of a compound of formula I and minoxidil to an individual in need thereof; And / or, the individual is a male or female androgenic alopecia patient, preferably a male androgenic alopecia patient, further preferably a male androgenic alopecia patient with Hamilton-Norwood classification of IIIv-V; And / or, in the method, the compound of formula I and minoxidil are administered in combination, wherein the combined administration is selected from: simultaneous administration, independent formulation and co-administration, or independent formulation and sequential administration; And / or, in the method, the administration route is selected from oral administration, parenteral administration, topical administration, and transdermal administration; preferably, in the method, the administration route is selected from topical administration and transdermal administration; and / or, comprising administering to the individual a therapeutically effective amount of a compound of formula I on a continuous daily regimen until male pattern baldness disease or condition progression or unacceptable toxicity; and / or, preparing a preparation containing the compound of formula I, and administering it in a manner that the compound of formula I in the preparation has a specification of about 0.05% (0.5 mg / mL or mg / g) to 10% (100 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, a gel, preferably a liquid preparation (such as a tincture); preferably, preparing a solution of the compound of formula I, and administering it in a manner that the compound of formula I in the solution has a specification of about 0.25% (2.5 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); and / or, the compound of formula I is administered in an amount of about 0.1 mg / day to about 1000 mg / day; and / or, the compound of formula I is administered in an amount of about 0.5 mg / day to about 100 mg / day; and / or, the compound of formula I is administered in an amount of about 1 mg / day to about 50 mg / day; and / or, the compound of formula I is administered in an amount of about 1.8 mg / day, about 2.5 mg / day, about 3.6 mg / day, about 5 mg / day, about 7.2 mg / day, about 10 mg / day, about 20 mg / day; And / or, the compound of formula I is administered in a QD or BID manner; and / or, preparing a solution of the compound of formula I, wherein the compound of formula I in the solution is about 0.25% (2.5 mg / mL), 0.5% (5 mg / mL) or 1% (10 mg / mL), the dosage frequency is QD or BID, and the administration route is topical administration, and the dosage frequency is about 1 mL per administration; comprising administering to the individual a therapeutically effective amount of minoxidil on a continuous daily regimen until progression of the androgenetic alopecia disease or condition or unacceptable toxicity; and / or, the minoxidil is administered in an amount of about 2 mg / day to about 500 mg / day; and / or, the minoxidil is administered in an amount of about 14.4 mg / day, about 20 mg / day, about 36 mg / day, about 40 mg / day, about 44 mg / day, about 50 mg / day, about 100 mg / day; and / or, preparing a preparation containing minoxidil for administration in a manner in which the minoxidil specification in the preparation is about 0.1% (1 mg / mL or mg / g) to 15% (150 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, or a gel, preferably a liquid preparation, a foam, or an aerosol; and / or, preparing a preparation containing minoxidil for administration in a manner such that the minoxidil specification in the preparation is about 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); the preparation is a solid preparation, a liquid preparation (such as a tincture), a foam, an aerosol, or a gel, preferably a liquid preparation, a foam, or an aerosol; And / or, the minoxidil is administered in a QD or BID manner; and / or, preparing a solution, foam or aerosol containing minoxidil for administration in a manner that the minoxidil concentration in the formulation is about 2% (20 mg / mL or mg / g) to 5% (50 mg / mL or mg / g); and / or, preparing a solution, foam or aerosol of minoxidil, with a minoxidil concentration of about 2% (20 mg / mL or mg / g) or 5% (50 mg / mL or mg / g) in the preparation, a dosing frequency of QD or BID, and a route of administration of topical It is administered by topical administration, with a dosing frequency of about 1 mL per administration; And / or, liquid preparations of the compound of formula I and minoxidil are separately prepared, and the compound of formula I with a strength of about 0.25% (2.5 mg / mL), 0.5% (5 mg / mL) or 1% (10 mg / mL) is used in combination with a minoxidil with a strength of about 2% (20 mg / mL) or 5% (50 mg / mL); preferably, the compound of formula I and minoxidil are administered QD or BID, and the administration route is topical administration; preferably, each administration is about 1 mL.

14. The method according to claim 13, (1) In the method, liquid preparations of the compound of formula I and minoxidil are prepared separately, with the compound of formula I having a strength of about 0.5% (5 mg / mL) and the minoxidil having a strength of about 2% (20 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; and / or, each administration is about 1 mL, i.e., the compound of formula I is administered at a dosage of about 5 mg / day and the minoxidil is administered at a dosage of 20 mg / day; Or (2) the method wherein: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.25% (2.5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; and / or, each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 2.5 mg / day, and the minoxidil is administered at a dose of 50 mg / day; or (3) the method wherein: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; and / or, each administration is about 1 mL, i.e., the compound of formula I is administered at a dose of about 5 mg / day, and the minoxidil is administered at a dose of 50 mg / day; or (4) the method wherein: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 1% (10 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of QD; preferably, the compound of formula I and minoxidil are administered simultaneously; and / or, each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 10 mg / day, and the minoxidil is administered at a dose of 50 mg / day; or (5) the method wherein: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.25% (2.5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of BID; preferably, the compound of formula I and minoxidil are administered in an intermittent manner; and / or, each administration frequency is about 1 mL, that is, the compound of formula I is administered at a dose of about 5 mg / day, and the minoxidil is administered at a dose of 100 mg / day; or (6) the method wherein: liquid preparations of the compound of formula I and minoxidil are prepared separately, the specification of the compound of formula I is about 0.5% (5 mg / mL), and the specification of minoxidil is about 5% (50 mg / mL); and / or, the compound of formula I and minoxidil are administered at a dosing frequency of BID; preferably, the compound of formula I and minoxidil are administered at intervals of and / or, the administration frequency is about 1 mL each time, that is, the compound of formula I is administered in an amount of about 10 mg / day and the minoxidil is administered in an amount of 100 mg / day.

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