Anti-hair loss pharmaceutical composition, anti-hair loss cream and preparation method of anti-hair loss pharmaceutical composition and anti-hair loss cream

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to an anti-alopecia pharmaceutical composition, anti-alopecia cream and a preparation method of the anti-alopecia cream. The invention discloses an anti-hair loss pharmaceutical composition which comprises dimethyl curcumin, eriochin and vitamin E, wherein the mass ratio of the dimethyl curcumin to the eriochin to the vitamin E is (0.5-2): 1: (1-2). The pharmaceutical composition provided by the invention can enhance hair follicle cell viability, restore hair follicle activity and skin state, improve hair regeneration capacity and slow down the alopecia process through dual effects of degrading scalp hair follicle androgen receptors and promoting scalp blood circulation. Meanwhile, the treatment target of the pharmaceutical composition provided by the invention is an androgen receptor instead of androgen, so that the adverse reaction caused by influence of 5 alpha-reductase inhibitors such as finasteride on the androgen level is overcome, and the pharmaceutical composition has higher biological safety.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and in particular to an anti-hair loss medicinal composition and an anti-hair loss cream and a preparation method thereof. Background Art

[0002] Androgenetic Alopecia (AGA), also known as male pattern baldness or seborrheic alopecia, is characterized by progressive miniaturization of hair follicles in the frontal, temporal and top parts of the head, which eventually leads to hair loss. The androgen secreted by the human body is mainly testosterone (T). Testosterone is converted into dihydrotestosterone (DHT) under the action of 5α-reductase, and then binds to the androgen receptor in the target cell to form an androgen receptor complex. After the androgen receptor complex enters the nucleus, it transmits the extracellular androgen signal to DNA through a series of mechanisms, regulates the expression of specific genes, produces the biological effect of androgen, affects the growth of hair follicles, interferes with the normal growth and metabolism of hair follicle cells, shortens the growth phase of hair follicles and prolongs the resting phase, thereby promoting the occurrence and development of diseases such as AGA. Therefore, the abnormality of the androgen signaling pathway caused by abnormal androgens and receptors is the main factor leading to this disease.

[0003] There is still a lack of ideal treatment for androgenic alopecia. Only oral finasteride and topical minoxidil are approved for marketing. The vasodilator minoxidil can act on the proliferation and differentiation of hair follicle keratinocytes and induce the extension of their growth period. However, minoxidil mainly exerts its therapeutic effect through its metabolite minoxidil sulfate in the body. Therefore, the efficacy of the drug is affected by the difference in the activity of sulfotransferases in the patient's body. After the treatment of minoxidil is stopped, its effect weakens over time. Therefore, there are problems such as long treatment cycle and many adverse reactions. Some patients may experience adverse reactions such as itchy and dry skin, contact dermatitis and facial hirsutism after applying minoxidil. Given that androgens are an important factor affecting hair follicle development and are closely related to seborrheic alopecia, the current main treatment method is to block the conversion of testosterone (T) to dihydrotestosterone (DHT) through 5α-reductase inhibitors such as finasteride, reduce DHT production, and thus reduce its destructive effects on hair follicles, thereby alleviating hair loss. However, finasteride has strong side effects, including loss of libido and effects on fertility. Long-term use may also induce type 2 diabetes, non-alcoholic fatty liver disease, dry eyes, and potential renal dysfunction, which requires more caution when choosing 5α-reductase inhibitors.

[0004] How to inhibit the activation of androgen signals in scalp hair follicles without affecting androgen levels is an urgent problem that needs to be solved. This has great clinical significance for the development of new, safe and effective drugs for the prevention and treatment of androgenic alopecia. Summary of the invention

[0005] In view of the above existing technologies, such as 5α-reductase inhibitors, which affect androgen levels when treating hair loss, have serious adverse reactions, poor biosafety, and other problems, the present invention provides a pharmaceutical composition targeting androgen receptors, which has a non-androgen effect and does not affect the production of androgen, and thus can treat hair loss without affecting androgen levels. The present invention further provides the use of the aforementioned pharmaceutical composition in the preparation of anti-hair loss products, and provides an anti-hair loss cream containing the aforementioned pharmaceutical composition and a preparation method thereof, with the aim of solving the problems existing in the prior art or at least alleviating some of the problems in the prior art.

[0006] To achieve the above object, the present invention is specifically implemented through the following technical solutions:

[0007] The first aspect of the present invention provides an anti-hair loss pharmaceutical composition, comprising dimethylcurcumin, forskolin and vitamin E, wherein the mass ratio of the dimethylcurcumin, forskolin and vitamin E is 0.5-2:1:1-2.

[0008] Furthermore, the mass ratio of the dimethylcurcumin, the forskolin and the vitamin E is 1-2:1:2.

[0009] Furthermore, the mass ratio of the dimethylcurcumin, the forskolin and the vitamin E is 2:1:2.

[0010] The second aspect of the present invention provides the use of the anti-hair loss pharmaceutical composition as described above in the preparation of an anti-hair loss product.

[0011] Furthermore, the hair loss is androgenic alopecia.

[0012] The third aspect of the present invention provides an anti-hair loss cream, which includes 10-20% by mass of an oil-soluble component, 10-20% by mass of a water-soluble component, 0.05-0.5% by mass of an anti-hair loss pharmaceutical composition, 0.4-1.2% by mass of a pharmaceutical inclusion compound, 0.4-1% by mass of an emulsifier, and 0.04-0.12% by mass of a preservative, with the remainder being water.

[0013] Furthermore, the anti-hair loss cream comprises 17-19% by mass of an oil-soluble component, 10-11% by mass of a water-soluble component, 0.1-0.2% by mass of an anti-hair loss pharmaceutical composition, 0.6-1.0% by mass of a pharmaceutical inclusion compound, 0.6-1.0% by mass of an emulsifier and 0.06-0.1% by mass of a preservative, with the remainder being water.

[0014] Furthermore, the anti-hair loss cream comprises 18% by mass of an oil-soluble component, 10.44% by mass of a water-soluble component, 0.2% by mass of an anti-hair loss pharmaceutical composition, 0.8% by mass of a pharmaceutical inclusion compound, 0.8% by mass of an emulsifier and 0.08% by mass of a preservative, with the remainder being water.

[0015] Furthermore, the oil-soluble component includes vaseline, stearyl alcohol, glyceryl monostearate and glyceryl distearate, and the mass ratio of the vaseline, stearyl alcohol, glyceryl monostearate and glyceryl distearate is 10:5:4:4; and / or, the water-soluble component includes glycerol and 1,2-propylene glycol, and the mass ratio of the glycerol to the 1,2-propylene glycol is 6:7; and / or, the drug inclusion agent is β-cyclodextrin; and / or, the emulsifier is sodium lauryl sulfate; and / or, the preservative is ethyl paraben.

[0016] A fourth aspect of the present invention provides a method for preparing the anti-hair loss cream as described above, comprising the following steps:

[0017] S1, mixing the oil-soluble components, heating and melting, and obtaining an oil phase;

[0018] S2, adding the water-soluble component into water, heating and dissolving it to obtain an aqueous phase;

[0019] S3, mixing the pharmaceutical composition and the drug inclusion agent, adding water and grinding to obtain a drug inclusion compound;

[0020] S4, adding an emulsifier, a preservative and the drug inclusion compound to the aqueous phase, mixing well, to obtain a mixed aqueous phase;

[0021] S5, adding the oil phase to the mixed water phase, stirring and emulsifying to obtain a mixed emulsion;

[0022] S6. Condensing the mixed emulsion to obtain an anti-hair loss cream.

[0023] The advantages and positive effects of the present invention are:

[0024] The pharmaceutical composition provided by the present invention can enhance the activity of hair follicle cells through the dual effects of degrading the androgen receptors of the scalp hair follicles and promoting blood circulation in the scalp, restore the vitality of the hair follicles and the skin condition, improve the hair regeneration ability, and slow down the process of hair loss. At the same time, the therapeutic target of the pharmaceutical composition provided by the present invention is the androgen receptor rather than androgen, which overcomes the adverse reactions caused by the influence of 5α-reductase inhibitors such as finasteride on androgen levels and has higher biological safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments.

[0026] Figure 1 These are representative images of the hair growth of mice in each group after 30 days of treatment in the examples of the present invention;

[0027] Figure 2These are representative images of H&E staining of dorsal skin sections of mice in each group of the present invention after treatment for 30 days. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with embodiments. The embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0029] Based on the information contained in the present invention, it is easy for those skilled in the art to make various changes to the precise description of the present invention without departing from the spirit and scope of the appended claims. It should be understood that the scope of the present invention is not limited to the defined processes, properties or components, because these embodiments and other descriptions are only for the purpose of illustrating specific aspects of the present invention. In fact, various changes that a person skilled in the art or related fields can obviously make to the embodiments of the present invention are covered within the scope of the appended claims.

[0030] In order to better understand the present invention but not to limit the scope of the present invention, all the numbers and other numerical values ​​used in the present invention to express the amount, percentage, etc. should be understood as modified by the word "about" in all cases. Therefore, unless otherwise specified, the numerical parameters listed in the specification and the appended claims are approximate values, which may be changed according to the different ideal properties to be obtained. Each numerical parameter should at least be regarded as obtained according to the reported significant figures and by conventional rounding methods.

[0031] In addition, it should be noted that, unless otherwise defined, in the context of the present invention, the scientific and technical terms used should have the meanings commonly understood by those of ordinary skill in the art. The meanings of the terms "comprise", "include", "contain", "have" and the like are non-restrictive, i.e., other steps and other ingredients that do not affect the result can be added. The term "and / or" should be regarded as a specific disclosure of each of the two specified features or components with or without the other. For example, "A and / or B" will be regarded as including the following situations: (i) A, (ii) B, and (iii) A and B.

[0032] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the technical principle and technical solution of the present invention are described in detail below.

[0033] An embodiment of the present invention provides an anti-hair loss pharmaceutical composition, comprising dimethylcurcumin, forskolin and vitamin E, wherein the mass ratio of the dimethylcurcumin, the forskolin and the vitamin E is 0.5-2:1:1-2.

[0034] Androgenic alopecia (AGA) is associated with overactive androgen signaling in scalp hair follicles. The biological activity of androgens is mediated by intracellular androgen receptors (AR), which are present in cells and tissues such as the epidermis, hair follicle keratinocytes, sebaceous glands, and sweat glands. Since AR plays an important role in androgen signaling, inhibiting the biological effects of AR is one of the ways to antagonize androgen signaling activation, and has potential for application in the treatment of hair loss.

[0035] Based on this, the present invention uses the androgen receptor (AR) inhibitor dimethyl curcumin in combination with the Chinese medicinal ingredients forskolin and vitamin E as a therapeutic drug. Dimethyl curcumin can inhibit the activation of the androgen receptor signaling pathway by degrading AR protein, reduce the negative impact of its androgen signal on hair follicles, and thus have a therapeutic effect on androgenic alopecia; Chinese medicinal ingredients forskolin and vitamin E can dilate blood vessels and improve scalp blood circulation, enhance scalp health and nourish hair. Therefore, the drug of the present invention can achieve the dual effects of inhibiting androgen signals and promoting blood circulation to synergistically improve hair regeneration ability, slow down the process of hair loss, and achieve better hair loss prevention and treatment effects. The efficacy of the pharmaceutical composition of the present invention was explored in a mouse model, and the results showed that the pharmaceutical composition of the present invention has the effect of regulating hair papilla cell activity and promoting hair papilla cell proliferation, which is conducive to restoring hair follicle vitality and skin condition, thereby promoting hair growth and effectively alleviating hair loss symptoms. At the same time, the therapeutic target provided by the present invention is androgen receptor rather than androgen. Compared with therapeutic drugs such as 5α-reductase inhibitors, it does not affect androgen levels, overcomes the adverse reactions caused by lowering androgen levels, has smaller side effects, and has higher biosafety.

[0036] The inhibitory effect of the dimethyl curcumin of the present invention on the activation of androgen signals plays a leading role in the hair growth process, and the dilation of blood vessels and the promotion of blood circulation of forskolin and vitamin E play an auxiliary role in the hair growth process. Properly increasing the dosage of dimethyl curcumin can significantly improve the hair growth effect. Therefore, preferably, the mass ratio of the dimethyl curcumin, the forskolin and the vitamin E is 1-2:1:2. More preferably, the mass ratio of the dimethyl curcumin, the forskolin and the vitamin E is 2:1:2.

[0037] Another embodiment of the present invention provides the use of the anti-hair loss pharmaceutical composition as described above in the preparation of an anti-hair loss product.

[0038] Optionally, the hair loss is androgenic alopecia.

[0039] According to actual needs, the anti-hair loss pharmaceutical composition of the present invention can be prepared into a patch, tincture, cream, emulsion, ointment, gel and spray. The anti-hair loss product can be a shampoo, a hair conditioner, a hair care solution, a hair care essential oil, a hair care essence, a hair care oil, a hair care lotion, a scalp hair nourishing product, a scalp cream, a hair care gel, a hair spray or a hair care mask, etc.

[0040] In order to improve the absorption efficiency and bioavailability of the pharmaceutical composition of the present invention, in a preferred embodiment, the present invention provides a cream.

[0041] Specifically, another embodiment of the present invention provides an anti-hair loss cream comprising the anti-hair loss pharmaceutical composition as described above, wherein the anti-hair loss cream comprises 10-20% by mass of an oil-soluble component, 10-20% by mass of a water-soluble component, 0.05-0.5% by mass of a pharmaceutical composition, 0.4-1.2% by mass of a pharmaceutical inclusion agent, 0.4-1% by mass of an emulsifier and 0.04-0.12% by mass of a preservative, and the remainder is water.

[0042] Preferably, the anti-hair loss cream comprises 17-19% by weight of oil-soluble components, 10-11% by weight of water-soluble components, 0.1-0.2% of a pharmaceutical composition, 0.6-1.0% of a drug inclusion agent, 0.6-1.0% of an emulsifier and 0.06-0.1% of a preservative, and the remainder is water.

[0043] More preferably, the anti-hair loss cream comprises 18% by mass of an oil-soluble component, 10.44% by mass of a water-soluble component, 0.2% by mass of a pharmaceutical composition, 0.8% by mass of a drug inclusion agent, 0.8% by mass of an emulsifier and 0.08% by mass of a preservative, with the remainder being water.

[0044] Optionally, the oil-soluble component includes vaseline, stearyl alcohol, glyceryl monostearate and glyceryl distearate, and the mass ratio of the vaseline, stearyl alcohol, glyceryl monostearate and glyceryl distearate is 10:5:4:4.

[0045] Optionally, the water-soluble component includes glycerol and 1,2-propylene glycol, and the mass ratio of the glycerol to the 1,2-propylene glycol is 6:7.

[0046] Optionally, the drug inclusion agent is β-cyclodextrin. Dimethylcurcumin, forskolin and vitamin E are all hydrophobic components and can be included in the hydrophobic cavity of β-cyclodextrin, which is conducive to improving their dissolution efficiency in the aqueous phase, increasing the accumulation of active substances in hair follicle tissue, and improving bioavailability. In addition, β-cyclodextrin can play a protective role, which is conducive to improving the stability of hydrophobic active ingredients.

[0047] The present invention does not specifically limit the type of emulsifier. It is understood that the emulsifier is used to disperse the oil-soluble component in the form of droplets (micrometer level) in the aqueous phase to ensure that the water-soluble component and the oil-soluble component and the pharmaceutical composition of the present invention can coexist uniformly in a reaction system. Therefore, conventional substances that can make oil and water miscible can meet the requirements of the present invention. In some typical embodiments, the emulsifier is sodium dodecyl sulfate.

[0048] The present invention does not specifically limit the type of preservative, and the preservative is used to inhibit microbial activity and increase the shelf life of the cream. Therefore, conventional agents that prevent microbial infection and reproduction can meet the needs of the present invention. In some typical embodiments, the preservative is ethyl p-hydroxybenzoate.

[0049] Another embodiment of the present invention provides a method for preparing the anti-hair loss cream as described above, comprising the following steps:

[0050] S1, mixing the oil-soluble components, heating and melting, and obtaining an oil phase;

[0051] S2, adding the water-soluble component into water, heating and dissolving it to obtain an aqueous phase;

[0052] S3, mixing the pharmaceutical composition and the drug inclusion agent, adding water and grinding to obtain a drug inclusion compound;

[0053] S4, adding an emulsifier, a preservative and the drug inclusion compound to the aqueous phase, mixing well, to obtain a mixed aqueous phase;

[0054] S5, adding the oil phase to the mixed water phase, stirring and emulsifying to obtain a mixed emulsion;

[0055] S6. Condensing the mixed emulsion to obtain an anti-hair loss cream.

[0056] It is understandable that although the steps S1-S3 are limited in order in the embodiment of the present invention, this order limitation is only for the purpose of description, and the three steps have no substantial order relationship. That is, step S1 can be performed first, then step S2, and then step S3; or step S2 can be performed first, then step S1 or S3; or steps S1-3 can be performed simultaneously.

[0057] The present invention includes the pharmaceutical composition into a pharmaceutical inclusion agent by grinding with water, which can greatly improve the stability, effectiveness and bioavailability of hydrophobic active ingredients (dimethylcurcumin, forskolin and vitamin E), then dissolves the hydrophobic active ingredients in an aqueous phase, mixes the oil phase with the aqueous phase in the presence of an emulsifier to prepare an oil-in-water emulsion, and finally condenses to obtain an ointment. The ointment is prepared in the form of an ointment and applied on the skin surface of a patient, which is conducive to transdermal absorption, improves drug utilization efficiency, and enhances drug efficacy.

[0058] In steps S1-S2, the melting temperature of the oil-soluble component and the dissolving temperature of the water-soluble component are adaptively adjusted according to the selected reagents. Generally speaking, heating to 70-80° C. can effectively melt or dissolve the aforementioned components.

[0059] The present invention is further described below in conjunction with specific examples. The experimental methods in the following examples without specifying specific conditions are generally carried out according to the conditions recommended by the manufacturer.

[0060] The dimethyl curcumin (CAS No.: 60831-46-1) used in the following examples was purchased from Aladdin Reagents, item number A126049; forskolin (also known as forskolin, CAS No.: 66575-29-9) was purchased from Aladdin Reagents, item number F127328; vitamin E (CAS No.: 59-02-9) was purchased from Aladdin Reagents, item number T433011; finasteride (CAS No.: 98319-26-7) was purchased from McLean Biotechnology, item number F829929. The remaining reagents were purchased from Sinopharm Group unless otherwise specified. All reagents used were analytically pure unless otherwise specified.

[0061] Example 1-Example 4

[0062] The anti-hair loss cream containing dimethylcurcumin, forskolin and vitamin E as medicinal ingredients in this embodiment includes 18% by weight of an oil-soluble component, 10.44% by weight of a water-soluble component, 0.12-0.2% by weight of a pharmaceutical composition, 0.8% by weight of a drug inclusion compound, 0.8% by weight of an emulsifier and 0.08% by weight of a preservative, and the remainder being water.

[0063] The preparation method comprises the following steps:

[0064] Preparation of oil phase: weigh 78.3g of medical vaseline into a beaker, add 3.91g of octadecyl alcohol and 3.13g of mono- and distearic glyceryl, heat to 75°C to melt, stir evenly and set aside;

[0065] Preparation of aqueous phase: Weigh 48.1 g of glycerol and 56.1-56.2 g of 1,2-propylene glycol respectively, add into ultrapure water, heat to 75°C and dissolve for later use;

[0066] Preparation of drug inclusion complex: Weigh 0.2-0.8g of dimethyl curcumin, 0.4g of forskolin and 0.4-0.8g of vitamin E respectively, mix well, add 1g of β-cyclodextrin, then add 1g of water, and grind thoroughly with a mortar, so that dimethyl curcumin, forskolin and vitamin E are included into the hydrophobic cavity of β-cyclodextrin under the action of external force;

[0067] Preparation of mixed aqueous phase: Add the drug inclusion compound prepared above, 8.0 g of sodium dodecyl sulfate and 0.1 g of ethyl p-hydroxybenzoate into a beaker, add water to 75° C. to dissolve, and obtain a mixed aqueous phase;

[0068] Oil-water mixing: add 180 g of the uniformly stirred oil phase to 820 g of the mixed water phase, and stir and emulsify with a glass rod at room temperature to form a mixed emulsion;

[0069] Cream preparation: Condensing the mixed emulsion to obtain the anti-hair loss cream.

[0070] In the embodiment of the present invention, since the oil phase and water phase components have little effect on the therapeutic effect of the pharmaceutical composition, the embodiment of the present invention does not separately discuss the hair growth effect under the change of the ratio of the above-mentioned components, and only uses the oil-soluble components including medical vaseline, stearyl alcohol, monostearate glyceryl and distearate glyceryl in a mass ratio of 10:5:4:4, and the water-soluble components including glycerol and 1,2-propylene glycol in a mass ratio of 6:7 as an example for explanation.

[0071] Examples 1-4 are intended to explore the effect of the ratio of each active ingredient in the pharmaceutical composition on the therapeutic effect of the pharmaceutical composition, specifically:

[0072] In Example 1, the mass ratio of dimethylcurcumin, forskolin and vitamin E is 1:1:1;

[0073] In Example 2, the mass ratio of dimethylcurcumin, forskolin and vitamin E is 1:1:2;

[0074] In Example 3, the mass ratio of dimethylcurcumin, forskolin and vitamin E is 0.5:1:2;

[0075] In Example 4, the mass ratio of dimethylcurcumin, forskolin and vitamin E is 2:1:2.

[0076] Comparative Example 1-Comparative Example 6

[0077] The preparation methods of the comparative examples are basically the same as those of the embodiments, except that the medicinal components are different. Comparative Examples 1-6 lack one or two of the medicinal compositions of the present invention, respectively, to explore the synergistic hair growth and cell proliferation promoting effects of the medicinal compositions of the present invention.

[0078] The formulas of Examples 1-4 and Comparative Examples 1-6 and the proportions of each functional component are shown in Tables 1-2, respectively.

[0079] Table 1 Component contents of mixed aqueous phases of Examples 1-4 and Comparative Examples 1-6 (unit: g)

[0080]

[0081] Table 2 Proportion of functional components in Examples 1-4 and Comparative Examples 1-6

[0082] Oil soluble components Water soluble components Emulsifier preservative Medicinal ingredients β-Cyclodextrin water total Example 1 18.00％ 10.44％ 0.80％ 0.08％ 0.120％ 0.80％ 69.76％ 100％ Example 2 18.00％ 10.44％ 0.80％ 0.08％ 0.160％ 0.80％ 69.72％ 100％ Example 3 18.00％ 10.44％ 0.80％ 0.08％ 0.140％ 0.80％ 69.74％ 100％ Example 4 18.00％ 10.44％ 0.80％ 0.08％ 0.200％ 0.80％ 69.68％ 100％ Comparative Example 1 18.00％ 10.44％ 0.80％ 0.08％ 0.000％ 0.80％ 69.88％ 100％ Comparative Example 2 18.00％ 10.44％ 0.80％ 0.08％ 0.040％ 0.80％ 69.84％ 100％ Comparative Example 3 18.00％ 10.44％ 0.80％ 0.08％ 0.040％ 0.80％ 69.84％ 100％ Comparative Example 4 18.00％ 10.44％ 0.80％ 0.08％ 0.040％ 0.80％ 69.84％ 100％ Comparative Example 5 18.00％ 10.44％ 0.80％ 0.08％ 0.080％ 0.80％ 69.80％ 100％ Comparative Example 6 18.00％ 10.44％ 0.80％ 0.08％ 0.080％ 0.80％ 69.80％ 100％ Comparative Example 7 18.00％ 10.44％ 0.80％ 0.08％ 0.080％ 0.80％ 69.80％ 100％

[0083] Test Case

[0084] 1. Mouse hair growth experiment

[0085] This example aims to conduct a mouse hair growth experiment on the anti-hair loss cream prepared in the examples and comparative examples.

[0086] Animal strain: C57BL / 6 mice, male, 6-8 weeks old.

[0087] Animal model: The probability of androgenic alopecia in mice is extremely low (<1%), so exogenous androgens are needed to accelerate hair loss and disease progression. Exogenous androgens include dihydrotestosterone (DHT) and testosterone, and the effect of dihydrotestosterone is significantly better than testosterone. This model was first established by Murata and has been improved. Depilatory cream is used to remove hair from the back, and DHT (1 mg / mouse / day) is injected subcutaneously at multiple points for 21 days to induce the model. This model is also the most widely used model for drug evaluation.

[0088] Dosage regimen: After the hair loss model was established, the model mice were divided into 5 groups, 5 mice in each group. The first group was the control group, which was treated with a blank cream (without dimethyl curcumin, forskolin and vitamin E) once a day; the remaining groups were treated with the creams of Examples 1-4 and Comparative Examples 1-6, once a day, applying 1-5 mL for 5 minutes; after 30 days of treatment, photos were taken to observe the hair growth on the depilated back, and the average hair coverage of the depilated area of ​​each group was calculated. In addition, the mice were killed after the experiment, and the back skin was taken for histopathological analysis.

[0089] The condition of the mice was observed and recorded during the 30-day dosing period. There was no redness, swelling, allergy or hair loss on the mouse skin, and the mice were in normal mental state. They ate, drank water and moved around normally. There were no adverse reactions such as anorexia, diarrhea, weight loss, etc., and the mice had a relatively high biosafety.

[0090] Figure 1Representative images of each group of mice after 30 days of treatment are shown, and the average hair coverage rate is statistically shown in Table 3 according to the hair coverage of the depilatory area on the back of the mice. According to the above results, the cream of the control group does not contain drugs and has basically no hair growth effect. The dimethyl curcumin cream prepared in Comparative Example 1 has a significant hair growth effect, and has a certain hair growth effect compared to the forskolin cream and vitamin E cream prepared in Comparative Examples 2 and 3, proving that the hair growth effect of dimethyl curcumin is more significant than the hair growth effect of forskolin or vitamin E alone; in addition, the creams of Comparative Examples 4 and 6 add forskolin or vitamin E on the basis of adding dimethyl curcumin, showing a significant hair growth effect, while the forskolin and vitamin E compound cream of Comparative Example 5 shows a slight hair growth effect, which shows that the inhibitory effect of dimethyl curcumin on androgens plays a leading role in the hair growth process, and the vasodilation and blood circulation promotion of forskolin and vitamin E play an auxiliary role in the hair growth process, and forskolin and vitamin E have the effect of synergistically promoting dimethyl curcumin. Therefore, the hair growth ability of the creams of dimethyl curcumin, forskolin and vitamin E in different proportions in Examples 1-4 of the present invention is greatly improved. In addition, the mass ratios of dimethyl curcumin, forskolin and vitamin E of 1:1:2 and 2:1:2 show better hair growth effect than 0.5:1:2, which further illustrates that dimethyl curcumin plays a leading role in the hair growth process. The formula with the best hair growth effect is the group with a mass ratio of dimethyl curcumin, forskolin and vitamin E of 2:1:2.

[0091] Table 3 Average hair coverage of Examples 1-4 and Comparative Examples 1-6

[0092]

[0093] Figure 2 Representative images of H&E staining of the back skin sections of each group of mice are shown. It can be seen that the thickness of the mouse skin treated with the dimethyl curcumin cream prepared in Comparative Example 1 is significantly increased compared with the control group and the forskolin group and vitamin E group of Comparative Examples 2-3, and the diameter of the hair papilla is also larger; the thickness of the mouse skin treated with the dimethyl curcumin, forskolin cream prepared in Comparative Example 4 and the dimethyl curcumin and vitamin E cream prepared in Comparative Example 6 and the diameter of the hair papilla are larger than the forskolin and vitamin E cream prepared in Comparative Example 5. This result further shows that dimethyl curcumin plays a leading role in the hair growth cream. The cream prepared by Example 1, dimethyl curcumin, forskolin, and vitamin E have a more excellent effect of promoting the proliferation of hair papilla cells, restoring hair follicle cells and skin vitality, and thus, it is excellent in hair growth.

[0094] 2. Hormone level detection

[0095] This example aims to compare the effects of dimethylcurcumin on the androgen dihydrotestosterone (DHT) in mice.

[0096] Animal strain: C57BL / 6 mice, male, 6-8 weeks old.

[0097] Dosage scheme: Healthy mice were divided into 3 groups, 5 mice in each group. The first group was a blank control group, treated with a blank cream once a day; the second group was treated with the anti-hair loss cream prepared in Example 1, 1-5 mL was applied for 5 minutes; the third group was a positive control group, treated with finasteride by oral gavage, the dosage of finasteride was 4 mg / kg, dissolved in a PBS solution containing 10% (w / v) DMSO.

[0098] After 15 days of administration to each group of mice, serum samples were collected to determine the dihydrotestosterone content. The determination method was performed according to the mouse dihydrotestosterone (DHT) ELISA kit (purchased from Jingkang Biological, catalog number JK-E3253). The dihydrotestosterone inhibition rate (%) before and after drug treatment was calculated. The results are shown in Table 4.

[0099] Table 4 Anti-hair loss cream of the present invention inhibits dihydrotestosterone

[0100] Group blank Anti-hair loss cream Finasteride Inhibition rate (%) - 0.5±0.02 12.4±0.81

[0101] By comparing the androgen regulation levels of the anti-hair loss cream of the present invention and finasteride, it was found that dimethyl curcumin and the like did not cause significant changes in the androgen level of mice, while taking finasteride significantly reduced the androgen level of mice, which shows that the anti-hair loss cream of the present invention has better biosafety.

[0102] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An anti-hair loss pharmaceutical composition, characterized in that: The invention comprises dimethyl curcumin, forskolin and vitamin E, wherein the mass ratio of the dimethyl curcumin, forskolin and vitamin E is 0.5-2:1:1-2.

2. The anti-hair loss pharmaceutical composition according to claim 1, characterized in that: The mass ratio of the dimethylcurcumin, the forskolin and the vitamin E is 1-2:1:

2.

3. The anti-hair loss pharmaceutical composition according to claim 2, characterized in that: The mass ratio of the dimethylcurcumin, the forskolin and the vitamin E is 2:1:

2.

4. Use of the anti-hair loss pharmaceutical composition according to any one of claims 1 to 3 in the preparation of an anti-hair loss product.

5. Use of the anti-hair loss pharmaceutical composition according to claim 4 in the preparation of an anti-hair loss product, characterized in that: The hair loss is androgenic alopecia.

6. An anti-hair loss cream, characterized in that: The invention comprises 10-20% by weight of an oil-soluble component, 10-20% by weight of a water-soluble component, 0.05-0.5% of the anti-hair loss pharmaceutical composition according to any one of claims 1 to 3, 0.4-1.2% of a pharmaceutical inclusion compound, 0.4-1% of an emulsifier and 0.04-0.12% of a preservative, and the balance is water.

7. The anti-hair loss cream according to claim 6, characterized in that The invention comprises 17-19% by weight of an oil-soluble component, 10-11% by weight of a water-soluble component, 0.1-0.2% of an anti-hair loss drug composition, 0.6-1.0% of a drug inclusion compound, 0.6-1.0% of an emulsifier and 0.06-0.1% of a preservative, and the balance is water.

8. The anti-hair loss cream according to claim 7, characterized in that: The composition comprises 18% by weight of an oil-soluble component, 10.44% by weight of a water-soluble component, 0.2% by weight of an anti-hair loss pharmaceutical composition, 0.8% by weight of a pharmaceutical inclusion compound, 0.8% by weight of an emulsifier, 0.08% by weight of a preservative, and the remainder being water.

9. The anti-hair loss cream according to claim 6, characterized in that: The oil-soluble component comprises vaseline, stearyl alcohol, glyceryl monostearate and glyceryl distearate, and the mass ratio of the vaseline, stearyl alcohol, glyceryl monostearate and glyceryl distearate is 10:5:4:4; And / or, the water-soluble component includes glycerol and 1,2-propylene glycol, and the mass ratio of the glycerol to the 1,2-propylene glycol is 6:7; And / or, the drug inclusion agent is β-cyclodextrin; And / or, the emulsifier is sodium lauryl sulfate; And / or, the preservative is ethyl paraben.

10. A method for preparing an anti-hair loss cream, characterized in that: For preparing the anti-hair loss cream according to any one of claims 6 to 9, the preparation method comprises the following steps: S1, mixing the oil-soluble components, heating and melting, and obtaining an oil phase; S2, adding the water-soluble component into water, heating and dissolving it to obtain an aqueous phase; S3, mixing the anti-hair loss pharmaceutical composition and the pharmaceutical inclusion compound, adding water and grinding to obtain a pharmaceutical inclusion compound; S4, adding an emulsifier, a preservative and the drug inclusion compound to the aqueous phase, mixing well, to obtain a mixed aqueous phase; S5, adding the oil phase to the mixed water phase, stirring and emulsifying to obtain a mixed emulsion; S6. Condensing the mixed emulsion to obtain an anti-hair loss cream.

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