WO2016177269A1

WO2016177269A1 - Compound topical drug for treating and/or preventing male-pattern alopecia

Info

Publication number: WO2016177269A1
Application number: PCT/CN2016/079562
Authority: WO
Inventors: 谢秉权
Original assignee: 谢秉权
Priority date: 2015-05-05
Filing date: 2016-04-18
Publication date: 2016-11-10
Also published as: CN104887685A

Abstract

Disclosed is a compound topical drug for treating male-pattern alopecia. The matrix (solvent) carrier of the drug comprises the following weight percentages of active ingredients: 0.01-0.8% of a finasteride, and 1-6% of a minoxidil. The compound topical drug further comprises a grape seed extract.

Description

Compound external medicine for treating and/or preventing male pattern hair loss

Technical field

The invention relates to the field of hair growth technology, in particular to a compound external medicine for treating and/or preventing male pattern hair loss

Background technique

There are many types of hair loss from the perspective of etiology, including male pattern hair loss, pathological hair loss, chemical hair loss, physical hair loss, nutritional hair loss, obesity alopecia, hereditary alopecia, neurological hair loss, etc. The symptoms are the same, and the treatment is different for a variety of different reasons.

Male pattern alopecia, also known as androgenetic alopecia (AGA), is a progressive hair loss disease that occurs after puberty and puberty. At present, male pattern hair loss is the most common disease, and its incidence is related to heredity and androgen. Mental and psychological factors can induce and aggravate the disease. In male male hair loss, the hair on the forehead and the top of the head is softened and shortened, and the hairline of the forehead is receded and the hair at the top of the head disappears. On the other hand, in the female type of hair loss, the hairline is generally changed, but the hair of the head centered on the top of the head and the forehead is thinned. Clinically divided into front mode, typical mode and top mode. The incidence of the disease is significantly different in different races, with a higher incidence of Caucasians and lower blacks and yellows. The latest epidemiological survey in China shows that the prevalence of this disease in China is 21.3%, the female prevalence is 6.0%, and there is a trend of increasing year by year.

As a drug that can be used in the treatment of male pattern hair loss, there are vasodilators such as minoxidil, caproammonium and various extracts, androgen inhibitors such as finasteride, estrogen and estradiol. An estrogen such as progesterone, ketoconazole, pentadecane, CTP (6-benzylaminopurine), total flavanone, adenosine, etc. as an antifungal agent. The drugs currently used more are 5% Minoxidil Topical Solution and Finasteride Oral.

The main component of the minoxidil solution is 6-(1-piperidinyl)-2,-4-pyrimidinediamine, 3-oxide, which It is a peripheral vasodilator that acts directly on the hair follicle, increases the proliferation and differentiation of the hair follicle epithelium, and stimulates the hair follicle to grow hair. At the same time, minoxidil acts as a potassium channel activator. Minoxidil increases potassium ion permeability and prevents calcium ions from entering cells. In the presence of calcium ions, epidermal growth factor inhibits hair growth.

Finasteride is a terpenoid, a class II 5 reductase inhibitor originally used to treat prostate disease. Finasteride is a synthetic 4 nitrogen steroid complex that prevents testosterone from being converted to diazotestosterone for the purpose of treating AGA. It is the first oral treatment approved by the US FDA for the treatment of AGA. medicine.

However, at present, in the treatment of male pattern hair loss, even if a combination treatment including oral finasteride or a solution of minoxidil is used, wherein each active compound is a separate preparation, a sufficient therapeutic effect cannot be obtained. Moreover, oral finasteride has side effects such as erectile dysfunction and ejaculation disorder, and the symptoms recur immediately upon discontinuation of use.

Summary of the invention

Therefore, the present invention provides a compound external preparation which exhibits a clear therapeutic effect and has few side effects, in view of the problems in the use of a single preparation for male type hair loss.

The technical solution of the present invention is as follows:

A compound external preparation characterized in that the matrix carrier of the compound external preparation contains the following effective percentage by weight of active ingredient: finasteride 0.01-0.8%, and minoxidil 1-6%. Finasteride, a male hormone inhibitor, is administered orally in the prior art and was first approved for marketing in the United States in 1998. It is the first US FDA approved for the treatment of AGA. Oral treatment. The present inventors unexpectedly discovered that the route of administration of finasteride was changed during long-term experimentation and practice, and that finasteride and minoxidil were combined as a compound external medicine for treating hair loss, and the effect achieved by the patient was better than that of the patient. Oral administration of finasteride alone, topical minoxidil alone, or both oral finasteride and topical minoxidil is much better. In the compound external preparation of the present invention, the concentration of finasteride can not be less than 0.01%, otherwise the ideal therapeutic effect cannot be achieved, and it can not be higher than 0.8%, otherwise it will cause side effects such as loss of libido and testicular pain, and its weight. The percentage concentration is preferably 0.25-0.5%; the concentration of minoxidil can not be less than 1%, otherwise the treatment effect is not good, and can not be higher than 6%, otherwise it will cause blood pressure lowering, heart rate The side effect is reduced, and the weight percentage concentration thereof is preferably 2 to 5%.

As a preferred embodiment of the present invention, the compound external preparation further comprises the following effective percentage by weight of the active ingredient: grape seed extract 2 to 6%. The addition of grape seed extract can enhance the efficacy of the above-mentioned compound external use, the specific mechanism of which is still unclear, and may be related to grape seed extract containing various active substances such as antioxidants and vitamins, and may also be related to grape seed extract. Contains phytoestrogens.

The external drug of the present invention is not particularly limited as long as the preparation can be directly applied, sprayed or adhered to a desired site (affected part) of the skin. The form of the compound external preparation of the present invention is preferably an ointment, a cream, a gel, a lotion, a coating agent, an elixir, a liquid preparation or the like. From the viewpoint of easiness of coating, an ointment, a gel, a cream, and a liquid preparation are particularly preferable.

In another aspect, the invention also provides the use of a combination external medicament for the treatment and/or prevention of male pattern hair loss. As mentioned above, there are various causes and types of hair loss, and the compound external preparation of the present invention is particularly suitable for treating and/or preventing male pattern hair loss.

In the course of many years of practice, the inventors initially used a combination of finasteride or oral and minoxidil solution for the treatment of male type hair loss, but found that the combination therapy for multiple patients is not only limited in hair growth, but also partially The side effects of male patients are very obvious, causing some patients to stop treatment. Later, the present inventors unexpectedly discovered that the conventional oral preparation of finasteride was changed to external use, and combined with minoxidil to form a compound external preparation, which directly acts on hair follicles, both of which have a good pharmacological effect. Complementary and synergistic, the clinical effective rate of treatment of male pattern hair loss is 96%, and effectively avoids side effects such as erectile dysfunction and ejaculation disorder caused by oral finasteride.

DRAWINGS

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a graph showing the therapeutic effects of a compound external ointment using the present invention. Subject 1 was photographed toward the bottom of the photo. A is the hair of the subject 1 before application, and it can be clearly seen that there is almost no hair on the forehead and the top of the head; B is the same part of the hair of the subject 1 after applying the compound external ointment of the present invention for 2 months. A clear hair growth and hair growth were confirmed from the forehead to the top of the head; C was the same part of the hair of the subject 1 after applying the compound external ointment of the present invention for 4 months, and the forehead to the top of the head was basic and normal male. The hair density is equivalent.

Fig. 2 is a graph showing the therapeutic effect of the compound external drug gel of the present invention. Subject 2 was photographed towards the bottom of the photo. A is the hair of the subject 2 before application, it can be clearly seen that the hair on the forehead and the top of the head is sparse, and the scalp is obviously exposed; B is the same part of the subject 2 after applying the compound external gel of the present invention for 2 months. Hair, the hair density from the forehead to the top of the head is increased, but the scalp can still be seen; C is the hair of the same part of the subject 2 coated with the compound external gel of the invention for 5 months, the forehead to the head The top has been basically covered by hair.

Fig. 3 is a graph showing the therapeutic effect of the combination external cream of the present invention. Subject 3 was photographed towards the bottom of the photo. A is the hair of the forehead before the application of the subject 3, and it can be clearly seen that the forehead hair is sparse; B is the hair of the top of the head before the application of the subject 3, and it can be clearly seen that the hair on the top of the head is sparse and the scalp is obvious. Naked; C is the subject 3 after applying the compound external cream of the present invention for 3 months, the forehead hair has an increase in the forehead hair density; D is the subject 3 coated with the compound external cream of the present invention 3 The hair at the top of the head after the month has been covered with hair at the top of the head.

detailed description

The technical solutions of the present invention will be described clearly and completely hereinafter with reference to the specific embodiments. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. The following description of the at least one exemplary embodiment is merely illustrative and is in no way All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts are within the scope of the present invention.

Techniques and methods known to those of ordinary skill in the relevant art may not be discussed in detail, but where appropriate, the technical industry methods and when deemed part of the authorization specification.

The compound external preparation of the present invention contains finasteride, minoxidil and grape seed extract as an active ingredient or a main drug, and can be known or known by blending a pharmaceutically acceptable base and various additives as needed. The method is easily obtained.

The gelling agent of the present invention may be any of a hydrogel, an anhydrous gel or a low water content gel comprising a swellable gel forming material. Further, it may be any of a hydrogel base and a liquid gel base, but is preferably a transparent hydrogel having an inorganic or organic polymer as a matrix.

The ointment preparation of the present invention may be any of an oil-based base and a water-soluble base, and any of them may be easily obtained according to a known method. An oily base such as petrolatum is excellent in irritation, odorlessness, skin protection, softening action, skin removal, granulation formation, and epithelialization promoting action. The water-soluble base is an ointment based on a polyethylene glycol base, and has a strong effect of absorbing and removing aqueous secretions.

The cream of the present invention may be an oil-in-water base (O/W) (snow cream) or a water-in-oil base (W/O) (cold cream). The oil-in-water base has less oil-soluble components than the water-soluble component, and has an advantage that the white color of the cream disappears when applied. It has good stretchability, good use of sweaty skin, and excellent cosmetic properties. In addition, it is also excellent in absorbability to the skin, and is therefore suitable for chronic hypertrophic lesions. The water-in-oil type base has a water-soluble component as compared with the oil-soluble component, and has a cooling action when spread and applied to the skin, and thus is sometimes referred to as a cold paste.

The liquid preparation of the present invention is prepared by dissolving finasteride, minoxidil, and grape seed extract as active ingredients in ethanol, propylene glycol, polyethylene glycol, water, or the like as a base, and preferably A liquid preparation of an aqueous solution obtained by dissolving in physiological saline. In addition to physiological saline, the aqueous solution may be mixed with a small amount of an organic base such as ethanol, propylene glycol or polyethylene glycol.

When the compound external preparation of the present invention is produced, various base agents, humectants, ultraviolet absorbers, alcohols, chelating agents, pH adjusters, preservatives, thickeners, colorants, perfumes, and the like may be blended in any combination. Fillers, excipients, disintegrants, extenders, binders, coating agents, solubilizers, suspending agents, buffers, stabilizers, preservatives, surfactants, antioxidants, dispersants, emulsifiers , solvent, cosolvent, etc. Further, in addition to finasteride, minoxidil, and grape seed extract as a main drug component, various drugs such as vitamins, skin softening agents, and the like may be appropriately blended as needed.

Example 1

The effective active ingredient of the present embodiment was 0.3% by weight of finasteride and 5% by weight of minoxidil, and the substrate was treated with petrolatum, liquid paraffin, glyceryl monostearate, glycerin, propylene carbonate and Tween 80.

First dissolve the two effective active ingredients in propylene carbonate; then add a total amount of 5 to 70 Vaseline, a total of 8 to 12 liquid paraffin, a total amount of 5 to 10% of glyceryl monostearate and an appropriate amount of Tween 80 mixed heating to 80 ~ 85 ° C; and the propylene carbonate solution was added to homogenization, stirring to form an ointment.

Example 2

The effective active ingredient of the present embodiment comprises 0.5% by weight of finasteride and 2% by weight of minoxidil, and the substrate is cetyl alcohol, petrolatum, liquid paraffin, glyceryl monostearate, glycerin, propylene carbonate, emulsifier, Preservatives and purified water. Firstly, the two effective active ingredients are dissolved in propylene carbonate; the total amount is 8-12% of cetyl alcohol, the total amount is 5-10% of vaseline, and the total amount is 8-12% of liquid paraffin, the total amount is 5~ 10% of glyceryl monostearate and an appropriate amount of preservative and emulsifier are mixed and heated to 80-85 ° C as an oil phase; a total amount of 0.5-5% glycerin is mixed with an appropriate amount of purified water and heated to 80-85 ° C as The aqueous phase; and the aqueous phase, the oil phase, and the propylene carbonate solution are mixed and homogenized, and uniformly stirred to form a cream.

Example 3

The effective active ingredient of the present embodiment comprises 5% by weight of finasteride, 1% by weight of minoxidil and 2% by weight of grape seed extract, and the matrix carrier is carbomer, propylene carbonate, ethanol, propylene glycol, EDTA-2Na, and antiseptic. Agent, neutralizer and purified water. First, the three effective active ingredients are dissolved in a total of 5-20 propylene carbonate, ethanol, propylene glycol mixture, and preservative is added; 0.05%-2% EDTA-2Na is dissolved in an appropriate amount of purified water. Add 1-10% of the total amount of carbomer to swell into a gel; add the above solution to the sol and stir evenly, adjust the pH to 5-7 with an appropriate amount of neutralizing agent, and mix uniformly to form a gel.

Example 4

The effective active ingredient of this example employs 0.01% by weight of finasteride, 6% by weight of minoxidil and 6% by weight of grape seed extract, and the matrix carrier uses propylene carbonate, a cosolvent, glycerin, a skin softening agent and ethanol. Firstly, the three effective active ingredients are dissolved in a total of 2-20% of a mixture of propylene carbonate and a cosolvent, and a total amount of 10-15% of glycerin and an appropriate amount of skin softening agent are dissolved in ethanol. After all the ingredients have been dissolved, an appropriate amount of ethanol is added until the total amount of the pharmaceutical preparation is stirred to form an elixir.

Example 5

The effective active ingredient of this example employs 0.8% by weight of finasteride, 2% by weight of minoxidil and 4% by weight of grape seed extract, and the substrate carrier is a solubilizer, propylene carbonate, glycerin, a film former and purified water. Firstly, the three effective active ingredients are dissolved in a mixture of a solubilizer and propylene carbonate, and the film-forming agent is swollen into a gel with an appropriate amount of purified water, and then a total amount of 5 to 30% of glycerin is added and mixed, and two of them are dissolved. A mixture of effective active ingredients is added to the swollen gel, and an appropriate amount of purified water is added until the total weight of the pharmaceutical preparation is stirred to form a coating agent.

Performance statistics

Method of use: After the scalp is cleaned, the compound external preparation of the present invention is applied or sprayed on the scalp without hair or hair, and the affected area of the drug is applied by hand massage. Once a day, each time you take the medicine three times, and with hand massage, to promote blood circulation, enhance the permeability of the liquid, improve the treatment effect.

Through the clinical study of 160 male patients with alopecia, the medical history, condition, gender and age were selected, including 136 males and 24 females, aged from 18 to 68 years, with a course of 1 to 170 months. 30 days is a course of treatment, the effective rate of 2 to 3 courses can reach 80%; the effective rate can reach 90% after 4 courses; the efficiency of 5 to 6 courses can reach 96%.

Table 1: Clinical effect of the compound external preparation of the present invention on 160 male and female patients

Specific case

Subject 1, Mr. Huang, 38 years old, almost all of the hair on the forehead and the top of the head fell off, and the mental stress was high. He had been seeking medical treatment for several years and was still ineffective. The compound external preparation of the present invention is coated, and after nearly four courses of treatment, and with the ideological work, the forehead to the top of the head is substantially equal to the hair density of normal men. The specific effect comparison chart is shown in Figure 1.

Subject 2, Mr. Zeng, 41 years old, with thin hair on the forehead and top of the head, and the scalp is barely exposed. According to the introduction of others, the compound external preparation of the present invention is coated, and the forehead and the top of the head are basically covered by hair after nearly 5 courses of treatment, and the external image is obviously better. The specific effect comparison chart is shown in Figure 2.

Subject 3, Mr. Zhao, 45 years old, had thin hair on the forehead and top of the head, and the scalp was barely exposed. The compound external preparation of the present invention is coated, and the forehead and the top of the head are substantially covered by hair after nearly three courses of treatment. The specific effect comparison chart is shown in Figure 3.

Claims

A compound external preparation characterized in that the matrix carrier of the compound external preparation contains the following effective percentage by weight of active ingredient: finasteride 0.01-0.8%, and minoxidil 1-6%.
The compound external preparation according to claim 1, wherein the compound external preparation further comprises the following effective percentage by weight of the active ingredient: grape seed extract 2 to 6%.
The compound external preparation according to claim 1 or 2, wherein the compound external preparation is an ointment, a cream, a gel or a liquid preparation.
The use of the compound external preparation according to claim 1 or 2 for treating and/or preventing male pattern hair loss.
The use of the compound external preparation according to claim 3 for treating and/or preventing male pattern hair loss.