CN116421511A

CN116421511A - 5 alpha-reductase inhibitor and preparation method and application thereof

Info

Publication number: CN116421511A
Application number: CN202310208113.XA
Authority: CN
Inventors: 林泽强; 肖瑞光
Original assignee: Guangzhou Shancaoji Cosmetic Co ltd
Current assignee: Guangzhou Shancaoji Cosmetic Co ltd
Priority date: 2023-03-06
Filing date: 2023-03-06
Publication date: 2023-07-14

Abstract

The invention discloses a 5 alpha-reductase inhibitor, a preparation method and application thereof, and relates to the technical field of cosmetics. The invention realizes the inhibition of 5 alpha-reductase through the synergistic effect of the components, and simultaneously, the pH value of the 5 alpha-reductase inhibitor is cooperatively regulated by controlling the dosage of the components, so that the inhibitor does not cause stimulation to the skin and does not destroy the microecological balance of the skin. In addition, the 5 alpha-reductase inhibitor also has the effects of purifying and converging pores and relieving skin, and realizes the comprehensive effects of soothing the skin, controlling the oil and removing acnes. The inhibition rate of the 5 alpha-reductase inhibitor to the 5 alpha-reductase is 53.45-76.71%, so that sebum secretion is fundamentally regulated, vaccinia generation is inhibited, and the 5 alpha-reductase inhibitor has an excellent effect of improving the oilpox state of skin.

Description

5 alpha-reductase inhibitor and preparation method and application thereof

Technical Field

The invention relates to the technical field of cosmetics, in particular to a 5 alpha-reductase inhibitor and a preparation method and application thereof.

Background

The main reason for the vigorous secretion of sebaceous glands is that the abnormal activity of sebaceous glands is caused by the increase of the activity level of 5α -reductase in skin tissues, the growth and differentiation of sebaceous glands are regulated and controlled by male hormones, and under the catalysis of specific enzymes such as 5α -reductase and the like, the male hormones are combined with the male hormone receptors of the sebaceous glands to generate a series of programmed changes, such as the replication of DNA and the synthesis of protein, so that the secretion function of the sebaceous glands is finally enhanced, and the secretion of grease is excessive. Thus, inhibition of 5α -reductase activity can fundamentally reduce skin oil secretion.

At present, a plurality of products on the market have the effect of regulating and controlling skin grease secretion, and the problem of sensitive muscles of oilpox is solved by controlling oil, but the existing products still have the problems of repeated acne removing effect and poor oil control effect, and can not inhibit the activity of 5 alpha-reductase, so that the secretion of skin grease is fundamentally regulated.

The prior art discloses a mild oil control acne removal essence, which can inhibit the activity of 5 alpha-reductase to a certain extent to achieve the oil control effect, but a quaternary ammonium salt-73 and other bactericides are also added in the essence, so that the microbial community of the skin is easily damaged, and the micro-ecological balance of the skin is easily damaged.

Disclosure of Invention

The invention provides a 5 a-reductase inhibitor, which aims to overcome the defect and the defect that the existing product can destroy the microecological balance of skin while inhibiting the activity of 5 a-reductase, and the 5 a-reductase activity is cooperatively inhibited while the microecological balance of skin is maintained by controlling the dosage of each component and the content of active ingredients.

It is another object of the present invention to provide a method for preparing the above 5α -reductase inhibitor.

It is a further object of the present invention to provide the use of the above 5α -reductase inhibitors in cosmetics.

It is still another object of the present invention to provide an improved skin oil-pox emulsion.

The invention also aims to provide a preparation method of the skin-improving oil acne emulsion.

The above object of the present invention is achieved by the following technical scheme:

a 5α -reductase inhibitor comprising a first component, a second component, and a third component;

wherein the first component comprises Silybum marianum extract, hamamelis virginiana extract; the second component comprises tea tree hydrolat, melaleuca alternifolia leaf oil; the third component comprises medicinal layer porus;

the weight ratio of the first component to the second component is (0.06-19): 1;

the weight ratio of the first component to the third component is (0.1-48) 1;

the content of water of the melaleuca alternifolia leaves in the tea tree hydrolat is more than or equal to 99 percent;

the content of terpinen-4-ol in the melaleuca alternifolia oil is more than or equal to 35%;

the content of the silybin in the silybum marianum extract is 50-70%.

The following are to be described:

the main components of the 5 alpha-reductase inhibitor are silybum marianum extract and Hamamelis virginiana pure dew.

The silymarin extract contains silybin active ingredient which contains a large amount of flavonoids, can stimulate cellular metabolism and accelerate local microcirculation, and has strong oxidation resistance which is 10 times of vitamin E; the silybin content in the silybum marianum extract used in the invention is 50-70%, and the silybum marianum content can provide excellent antioxidation environment and reduce the 5 alpha-reductase level and DHT (dihydrotestosterone) level of the skin.

The Hamamelis virginiana hydroln contains tannic acid, polyphenol compounds and volatile oil, and can competitively inhibit the activity of 5 alpha-reductase.

The addition of the second component can synergistically enhance the inhibition of 5α -reductase by the first component. Wherein, tea tree hydrolat contains more than 99% of the water of the cajeput leaves of the mutually grown leaves, can soften aged cells, make the first component act on skin cells better, cooperate to inhibit 5 alpha-reductase, participate in regulating and controlling the pH state of the skin at the same time, avoid causing the stimulation to the skin.

The ratio of the first component to the second component is too large, i.e., the amount of the first component is too high, so that the synergistic enhancement effect of the second component is easily weakened, and meanwhile, the inhibition of the first component on the 5 alpha-reductase is not further improved, so that the inhibition rate of the 5 alpha-reductase is reduced, and the amount of the second component is too high, so that the inhibition effect on the 5 alpha-reductase is reduced.

The invention selects the trans-living melaleuca alternifolia leaf oil with the terpinen-4-ol content of more than or equal to 35 percent, can better act on skin sterilization, reduce the over-expression of cell factors and reduce inflammatory reaction, and cooperates with the first component to inhibit the activity of 5 alpha-reductase, further control the secretion of skin grease and regulate the ecological balance of skin micro-ecology.

The third component is used as an auxiliary component, and the first component and the third component are compounded for use, so that the inhibition of the activity of 5 alpha-reductase is realized, pores are converged, and the skin is kept fresh. In addition, the inventors found that the effect of the medicinal layer porus, hamamelis and silybum marianum extract can be maximally exerted by controlling the weight ratio of the first component to the third component, so that the third component further enhances the inhibition of 5α -reductase by the first component.

In addition, the pH value of the silybum marianum extract is higher after the silybum marianum extract is dissolved, and the pH value of the 5 alpha-reductase inhibitor can be regulated and controlled by the components with lower pH values in cooperation with the tea tree hydrolat and the Hamamelis virginiana hydrolat, so that the pH value of the 5 alpha-reductase inhibitor can be ensured not to cause irritation to skin by controlling the dosage of each component.

The invention realizes the mild and effective inhibition of the activity of 5 alpha-reductase by compounding the first component, the second component and the third component containing specific effective components, and the three components cooperate with each other to jointly promote the inhibition effect on the 5 alpha-reductase.

The content of water of the melaleuca alternifolia leaves in the tea tree hydrolat, the content of terpinen-4-ol in melaleuca alternifolia leaf oil and the content of silybin in the silybum marianum extract are mass contents.

Specifically, the weight ratio of the first component to the second component is (0.06-13): 1, more specifically (0.06-10): 1.

Specifically, the first component comprises 0.02-3 parts of silybum marianum extract and 2-35 parts of Hamamelis virginiana hydrolat according to parts by weight; the second component comprises 3-30 parts of tea tree hydrolat and 0.02-2 parts of melaleuca alternifolia leaf oil; the third component comprises 0.8-15 parts of medicinal layer porus.

Preferably, the weight ratio of the first component to the second component is (0.3-3.5): 1, and the weight ratio of the first component to the third component is (3-4): 1.

Preferably, the first component comprises 0.02-0.5 part of silybum marianum extract and 3-10 parts of Hamamelis virginiana hydrolat in parts by weight; the second component comprises 3-10 parts of tea tree hydrolat and 0.04-0.5 part of melaleuca alternifolia leaf oil; the third component comprises 0.12-1.5 parts of medicinal layer porus.

Specifically, the pH of a 1% aqueous solution of the silybum marianum extract is 5-8.

The pH of the silybum marianum extract is controlled to be beneficial to further synergism with other components, and the pH of the 5 alpha-reductase inhibitor is regulated, so that the pH state of the skin is regulated better.

Specifically, the relative density of the tea tree hydrolat and water is 0.98-1.02.

Specifically, the relative density of the Hamamelis virginiana hydrolat and water is 0.995-1.005.

The relative densities of the tea tree hydrolat and the witch hazel hydrolat can influence the corresponding effects, and the control of the relative densities of the tea tree hydrolat and the witch hazel hydrolat is beneficial to further improving the effect of the first component and the second component on synergistically inhibiting the activity of 5 alpha-reductase.

The invention also provides a preparation method of the 5 alpha-reductase inhibitor, which comprises the following steps:

adding tea tree hydrolat, melaleuca alternifolia leaf oil, silybum marianum extract, hamamelis virginiana hydrolat and medicinal layer porus into PEG-40 hydrogenated castor oil, uniformly mixing, and filtering to obtain the 5 alpha-reductase inhibitor.

The PEG-40 hydrogenated castor oil is a solubilizer of the melaleuca alternifolia leaf oil, and the PEG-40 hydrogenated castor oil is added to promote the co-dissolution of the melaleuca alternifolia leaf oil and other components.

Specifically, the PEG-40 hydrogenated castor oil is used in an amount of 0.06-6 parts by weight, for example, 0.06, 0.12, 0.9, 1.5 and 6.

Specifically, the mixing is achieved by stirring at a speed of 40 to 50rpm/min.

The invention protects the application of the 5 alpha-reductase inhibitor in cosmetics.

According to the invention, through the synergistic effect of the components, the activity of 5 alpha-reductase is inhibited, the secretion of grease is reduced, meanwhile, the pH state of skin is regulated and controlled, pores are converged, skin moisture is kept, and the outlet formed by sebum secretion is reduced, so that a virtuous circle is formed, the capability of inhibiting 5 alpha-reductase of a product is greatly improved, the water-oil balance of the skin is conditioned, long-acting oil control is realized, the growth of acne is further inhibited, pores are converged, and the cosmetic is favorable for preventing and repairing the problem of skin oil acne.

The invention particularly provides an oil acne emulsion for improving skin, which comprises the 5 alpha-reductase inhibitor.

The 5 alpha-reductase inhibitor provided by the invention can well regulate and control the pH state of skin, inhibit the activity of 5 alpha-reductase, realize oil control and acne removal without causing irritation to skin, has the capabilities of short-acting oil control and long-acting oil control, can effectively regulate the problems of unbalanced skin water and oil and coarse pores, has fresh and cool skin feel, can not bring heavy feel to skin while preserving moisture, and is particularly suitable for oil acne sensitive muscle groups. The 5 alpha-reductase inhibitor does not contain other strong bactericidal components and does not destroy the balance of skin microecology.

Specifically, the mass content of the 5 alpha-reductase inhibitor in the emulsion is 8-50%.

By controlling the content of the 5 alpha-reductase inhibitor in the emulsion, the 5 alpha-reductase inhibitor can better exert the corresponding effect, inhibit the activity of 5 alpha-reductase and ensure that the emulsion has better oil control effect.

Specifically, a pH regulator, a thickener, grease, an emulsifier, a humectant, an antioxidant and a preservative active ingredient are added into the emulsion.

Specifically, the emulsifying agent is Montanan 68 and SL-1, wherein the mass ratio of Montanan 68 to SL-1 is 2:1.

When Montanan 68 and SL-1 are used as the emulsifier and the mass ratio of the Montanan 68 to SL-1 is 2:1, the emulsion effect of the emulsion can be better realized, and the skin feel of the emulsion product is improved.

Specifically, the pH regulator is arginine or aminomethylpropanol, wherein the weight part of the pH regulator is 0.02-2 parts, preferably 0.05-1 part.

Specifically, the thickening agent is one or two of acrylic acid (esters) and C10-30 alkanol acrylate cross-linked polymers, acrylamide-vinylformamide copolymer and acrylic acid (esters) and vinyl isodecanoate cross-linked polymers, and hydroxyethyl acrylate and sodium acryloyldimethyltaurate copolymer; wherein the weight portion of the thickener is 0.02-2 parts, preferably 0.1-0.8 parts.

Specifically, the grease is one or two of polydimethylsiloxane, isononyl isononanoate, caprylic/capric triglyceride, isohexadecane, isododecane and silicon elastomer; wherein the weight portion of the grease is 0.5-5 parts, preferably 1-4 parts.

Specifically, the humectant is one or more of butanediol, glycerol and trehalose.

Specifically, the molecular weight of the trehalose is 340-345.

Specifically, the antioxidant is one or more of aloe vera leaf juice, tuberose extract, beta-glucan, 10-hydroxydecanoic acid, allantoin and lime oil.

Specifically, the skin feel modifier component is silica, and the silica has elliptic specific surface area of > 15000 (cm) ² /cm ³ ) Silica with particle size less than 5 μm can absorb grease of about 5 times of the weight of the silica, is a good physical adsorbent and can regulate the skin feel effect of emulsion.

Specifically, the anti-corrosion active ingredient is one or two of 1, 2-hexanediol and p-hydroxyacetophenone.

The invention also provides a preparation method of the skin-improving oil acne emulsion, which comprises the following steps:

s1, dissolving deionized water, a thickening agent, an emulsifying agent and a humectant at 80-90 ℃ and uniformly mixing;

s2, adding grease, uniformly mixing, homogenizing and emulsifying at 80-90 ℃;

s3, adding a pH regulator, and uniformly mixing at 70-80 ℃;

s4, reducing the temperature to 55-65 ℃, adding the antioxidant which is mixed and dissolved in advance, and uniformly mixing;

s5, reducing the temperature to 40-50 ℃, adding the 5α -reductase inhibitor of any one of claims 1-3, and vacuum defoaming to obtain the skin-improving oil acne emulsion.

The skin-improving oil acne emulsion is prepared by an emulsification process, and the prepared emulsion has better emulsification effect by controlling the addition sequence and the mixing temperature of each component, and the functional components or the action activities of each component are not affected in the preparation process, so that an emulsion product with excellent comprehensive effects of comfort, oil control and acne removal is finally obtained.

Compared with the prior art, the invention has at least the following beneficial effects:

the invention provides a 5 alpha-reductase inhibitor, which realizes the inhibition of 5 alpha-reductase through the synergistic effect of all the components, and simultaneously, the pH of the 5 alpha-reductase inhibitor is cooperatively regulated by controlling the dosage of all the components, so that the 5 alpha-reductase inhibitor does not cause stimulation to the skin and does not destroy the microecological balance of the skin. In addition, the 5 alpha-reductase inhibitor also has the effects of purifying and converging pores and relieving skin, and realizes the comprehensive effects of soothing the skin, controlling the oil and removing acnes.

The inhibition rate of the 5 alpha-reductase inhibitor to 5 alpha-reductase is 53.45-76.71%, so that sebum secretion is fundamentally regulated, and the oil control effect is excellent; after the oil acne emulsion for improving skin is prepared, the short-acting oil control effect on skin for 8 hours is 68-152 ug sebum/cm ² The oil inhibition rate after 28 days of use is 26.15%; in addition, after 28 days of using the skin-improving oil acne emulsion provided by the invention, the acne skin damage area ratio is reduced by 77.59%, and the acne skin damage color a is reduced by 19.59%Has obvious acne removing effect.

Drawings

Fig. 1 is a skin oil content test chart of a long-acting oil control test.

Fig. 2 is a statistical chart of subjective evaluation of long-acting oil control test subjects.

Fig. 3 is a graph comparing ISGA scores at different time points in an anti-acne test.

Fig. 4 is a graph of acne lesions area to area ratio variation.

Fig. 5 is a graph showing changes in the skin lesion color a.

FIG. 6 is a graph comparing skin oil content after use of the emulsion of example 10 and a commercially available emulsion.

Fig. 7 is a graph showing the effect of repairing acne after 28 days of using the skin-improving oil-pox emulsion of the present invention.

Detailed Description

The tea tree hydrolat is purchased from silver valley fragrance technology Co., ltd, wherein the water content of the melaleuca alternifolia leaf is 99.6%, and the relative density is 1.00+/-0.02.

The melaleuca alternifolia oil 1 was purchased from Main Camp Natural Extracts Pty Ltd (MELALEUCA ALTERNIFOLIA) with a terpinen-4-ol content of 41.4%.

The melaleuca alternifolia leaf oil 2 was purchased from a green source natural perfume oil refinery (tea tree oil) in the Qingyuan area of Jian city, wherein the terpinen-4-ol content was 33.14%.

The silybum marianum extract is purchased from Guangdong graphene Biotechnology Co., ltd (silybum marianum extract), wherein the content of silybin is 65%, and the pH of a 1% aqueous solution is 5-8.

Silybum marianum extract 2 is purchased from Givaudan (IN-906400), wherein the content of silibinin is 29.7-36.3%, and the pH of 1% aqueous solution is 5-8.

Hamamelis virginiana is available from AMERICAN DISTILLING INC. (Witch Hazel Distillate with 1.0.0% Phenoxyyethanol) and has a relative density of 0.995 to 1.005.

The medicinal layer porus is purchased from Basoff (China) Limited company

LS 8865)。

The terpinen-4-ol content and the silybin content are measured by an HPLC mode.

The invention will be further described with reference to the following specific embodiments, but the examples are not intended to limit the invention in any way. Raw materials reagents used in the examples of the present invention are conventionally purchased raw materials reagents unless otherwise specified.

Examples 1 to 5

A 5α -reductase inhibitor, differing in the weight ratio of the first component, the second component and the third component.

First component in example 1: second component = 9.5:1; a first component: third component = 47.5:1;

first component in example 2: second component = 0.067:1; a first component: third component = 0.135:1;

first component in example 3: second component = 3.3:1; a first component: third component = 3.34:1;

first component in example 4: second component = 0.33:1; a first component: third component = 3.5:1;

first component in example 5: second component = 1.16:1; a first component: third component = 3.65:1;

see table 1 for specific formulations.

Table 1.5 formulation of alpha-reductase inhibitors (in parts by weight)

	Example 1	Example 2	Example 3	Example 4	Example 5
						Tea tree hydrolat	2	30	3	10	6
Melaleuca alternifolia leaf oil 1	2	0.02	0.04	0.5	0.3
						Silybum marianum extract 1	3	0.02	0.02	0.5	0.3
Hamamelis virginiana pure dew	35	2	10	3	7
						Phellinus linteus for medicine	0.8	15	3	1	2
PEG-40 hydrogenated castor oil	6	0.06	0.12	1.5	0.9

The preparation method of the 5 alpha-reductase inhibitor can refer to the following steps:

adding tea tree hydrolat, melaleuca alternifolia leaf oil, silybum marianum extract, hamamelis virginiana hydrolat and medicinal layer porus into PEG-40 hydrogenated castor oil, uniformly mixing, and filtering to obtain a 5 alpha-reductase inhibitor;

wherein, example 1 was solubilized by adding 6 parts of PEG-40 hydrogenated castor oil; example 2 solubilization by addition of 0.06 parts of PEG-40 hydrogenated castor oil; example 3 solubilization by adding 0.12 parts of PEG-40 hydrogenated castor oil; example 4 solubilization by adding 1.5 parts of PEG-40 hydrogenated castor oil; example 5 solubilization by adding 0.9 parts of PEG-40 hydrogenated castor oil;

the mixing was achieved by stirring at a speed of 45rpm/min.

Examples 6 to 10

An oil-acne-improving emulsion for skin comprises 5 alpha-reductase inhibitors of examples 1-5, respectively, with specific formulations shown in Table 2.

Table 2. Formula of skin-improving oil acne emulsion (in parts by weight)

The preparation method of the skin-improving oil-acne emulsion can be referred to as the following steps:

s1, adding deionized water, a thickening agent, an emulsifying agent and a humectant into an emulsifying pot, and uniformly stirring and dissolving at 82 ℃;

s2, uniformly mixing the grease, adding the grease into an emulsifying pot, homogenizing the grease for 3 minutes at the temperature of 82 ℃ at the rotating speed of 3000rpm, and preserving the heat for 10 minutes;

s3, adding a pH regulator, and stirring and dispersing uniformly at 75 ℃;

s4, reducing the temperature to 60 ℃, adding the pre-mixed and dissolved antioxidant into an emulsifying pot, and uniformly stirring and dissolving;

s5, the temperature is reduced to 45 ℃,5 alpha-reductase inhibitor is added, and the skin oil acne emulsion is obtained after vacuum defoaming.

Comparative examples 1 to 10

A5 alpha-reductase inhibitor is shown in Table 3 for specific components.

TABLE 35 alpha-reductase inhibitor formulations of comparative examples 1-10 (in parts by weight)

The preparation method of the 5α -reductase inhibitor is the same as that of example 1.

Comparative examples 11 to 20

An oil-acne-improving emulsion for skin, which has the same formulation as in example 10, except that the 5 a-reductase inhibitor corresponds to the 5 a-reductase inhibitor in each of the respective examples 1 to 10.

The preparation method of the skin-improving oil-acne emulsion is the same as that of example 10.

Comparative examples 21 to 22

A5 alpha-reductase inhibitor is prepared in the same manner as in example 5 except that: in comparative example 1, melaleuca alternifolia leaf oil 2 was used; in comparative example 2, silybum marianum extract 2 was used.

Result detection

1. Inhibition 5 alpha-reductase inhibition test

Test sample: 5 alpha-reductase inhibitors of examples 1-5 and comparative examples 1-10.

Test principle: the secretion function of the sebaceous glands of oily skin is vigorous, the face is greasy, the skin is not easy to clean, and meanwhile, some corresponding skin diseases, such as acne vulgaris, seborrheic dermatitis and the like, are easy to occur. In view of the relationship between 5α -reductase and sebaceous glands, the inhibition effect of the test sample on 5α -reductase is generally detected to reflect the sebum regulation effect, so as to characterize the oil control effect of the test sample, and the higher the inhibition rate, the better the oil control effect.

An in vitro screening model of the 5 alpha-reductase inhibitor is established by utilizing an ultra-high performance liquid chromatography, and the inhibition activity of the skin-improving oilpox composite extract provided by the application on the 5 alpha-reductase is tested.

The experimental method comprises the following steps: extracting 5 alpha-reductase from SD rats, respectively preparing 5 alpha-reductase inhibitors of examples 1-5 and comparative examples 1-10, diluting the 5 alpha-reductase inhibitors with water to 100%, taking testosterone as a substrate, taking finasteride as a positive control, and measuring the change of testosterone concentration before and after reaction by using ultra-high performance liquid chromatography in a blank control group, and calculating the inhibition rate, wherein the calculation formula of the inhibition rate is as follows: inhibition ratio = (change in testosterone concentration in blank tube-change in testosterone concentration in sample tube)/change in testosterone concentration in blank tube × 100%

The specific test results inhibition rates are shown in the following table.

The results are shown in Table 4.

TABLE 4 inhibition of 5α -reductase by 5α -reductase inhibitors

As is clear from Table 4, the 5. Alpha. -reductase inhibitors of examples 1 to 5 had higher inhibition ratios to 5. Alpha. -reductase liquid than the 5. Alpha. -reductase inhibitors prepared in comparative examples 1 to 10, and the 5. Alpha. -reductase inhibitors of examples 1 to 5 had inhibition ratios to 5. Alpha. -reductase liquid of 53.45 to 76.71%, with the highest inhibition ratio of example 4 reaching 76.71%, which revealed that the oil control effect was optimal; the 5 alpha-reductase inhibitor can fully exert the oil control effect of the 5 alpha-reductase inhibitor through reasonable collocation and synergy of the active ingredients, and shows more excellent oil control effect than the combination form lacking any one component.

2. Skin closed type spot pasting experiment

Test site: normal skin on the dorsiflexion side of the forearm (10 sensitive myopes experimentally tested).

Test sample: skin-improving oil-pox emulsions of examples 6 to 10 and comparative examples 11 to 20.

The method comprises the following specific steps: cleaning the skin of a test part, taking 0.020 mL-0.025 mL of sample, placing the sample in a spot tester small chamber, firmly pasting skin spot test paper from bottom to top, pasting flat, and lightly pressing the skin spot test paper with a hand hall so as to discharge air.

Patch test time: 24 hours.

Observation time: 24 hours after application, the skin patch test consumables were removed and the results were observed at least 30 minutes later.

And (3) judging results:

1 (+ -) -suspicious reaction: only faint (unclear) erythema.

2 (+) -weak (blefree) positive reaction: erythema, infiltration, and possible minor erythema.

3 (++) -strong (blister) positive reaction: erythema, infiltration, papules are not small blisters.

4 (+ ++). Extremely-extreme positive reaction of (2): red swelling and bullae.

0 (-) -no reaction.

The results are shown in Table 5.

TABLE 5 results of the skin-improving oil-acne emulsion patch test

The test results in Table 5 show that only comparative example 7, one suspected reaction, and the rest of the subjects of examples 6 to 10 and comparative examples 11 to 20 showed no positive reaction. According to the specification of cosmetic safety technology (2015 edition), the test object does not cause adverse skin reaction to the subjects in the present batch. The formulation of the 5 alpha-reductase inhibitor and the emulsion thereof are mild and safe, do not generate irritation to skin, and are suitable for people

Selection 24 (6 persons divided into 1 panel) adult subjects (selected according to the requirements of the T/ZHCA 002-2018 inclusion test) under normal conditions, a single use test sample was used and the skin oil content was measured by the oil probe SM815 to evaluate the efficacy of the test sample in controlling oil.

The specific test steps are as follows: the face is divided into a left face area and a right face area, a sample group A or a sample group C is used for one area, a sample group B or a sample group D is used for one area, the sample groups are respectively symmetrical, the tested areas are named as A, B, C, D, and the tested areas are marked on the same positions of the forehead for testing.

Sample and specific method of use: randomly sequencing the skin-improving oil acne emulsions in examples 6-10 and comparative examples 11-20, respectively extracting 4 samples to be a group for testing, standing the test subject under the conditions of constant temperature and constant humidity for 20min, cleaning the forehead with clear water, smearing the samples according to the ratio of (2.0+/-0.1) mg/c square meter, completely absorbing, and measuring the skin grease content after 8 h; the subject was kept in a room at constant temperature of 22 ℃ during the test; and after the test is finished, counting the results, taking the average number, and analyzing.

The results are shown in Table 6.

TABLE 6 human body oil control test of skin-improving oil-pox emulsions of examples 6 to 10 and comparative examples 11 to 20

As can be seen from Table 6, the skin oil-acne-improving emulsions of examples 6 to 10 had a lower skin sebum oil content for 8 hours on skin than the skin oil-acne-improving emulsions of comparative examples 11 to 20, and had an oil control effect of 72 to 125ug sebum/cm on skin for 8 hours on skin ² In the middle, the skin-improving oil acne emulsion of example 6After 8 hours of use, the skin oil content was minimal, 72ug sebum/cm ² Therefore, the oil control effect is optimal; the oil control effect of the 5 alpha-reductase inhibitor can be fully exerted by reasonably matching and synergistically increasing the active ingredients, and the oil control effect is better than that of a combination form of components lacking any 5 alpha-reductase inhibitor, and the emulsion is proved to be capable of reducing the DHT (dihydrotestosterone) level of the skin.

4. Long-acting oil-controlling test for human body

Taking the skin-improving oil acne emulsion of the embodiment 10 for inspection, and performing long-acting oil control test on a human body by a third party.

The product use test method comprises the following steps:

after the face is cleaned, a proper amount of product is taken and evenly smeared on the face until the face is fully absorbed; each day is used for 28 days, 1 time in the morning and evening. During the trial, the subject prohibited the use of the oil-controlling, pore-affecting formulation; subjects prohibit infusion, injection, oral or other forms of intake of agents that affect oil control, affect pore testing; the subject is mainly subjected to indoor activities, and long-term exposure to outdoor illumination is avoided.

Subjective evaluation of the subjects:

subjects evaluate facial condition by mirror under natural light conditions in the human efficacy laboratory at 28 days (D28) return visit after product use and record scores; the product was scored for skin feel, mildness, effect and satisfaction with each subject using a scoring method, and then judged and recorded once per subject return visit.

Objective quantitative evaluation:

after a subject sits still for 30min in a constant temperature and humidity environment, detecting skin grease values before cleaning the face by using SM815 at a test part, uniformly cleaning the face, and sucking the face by using chipless facial tissues; after face cleaning for 30min, detecting skin oil value after face cleaning at the test part by using SM815, taking the measured value as a base line value (D0), and then dispensing the product and guiding the use method; subjects were asked to return to visit 28 days after product application (D28) and to conduct the same skin grease test.

Testing of the same subject was accomplished using the same instrument, the same tester, and keeping the test site and time consistent.

Cosmetic oil control efficacy evaluation was performed by 30 subjects using example 10 to improve the skin oil pox emulsion for 28 days.

The results are shown in tables 7, 8, 9 and FIG. 1 and FIG. 2.

TABLE 7 descriptive statistics of skin lipid content (μg/cm) ³ ，n＝30)

TABLE 8 analysis of skin lipid content differentiation (. Mu.g/cm) ³ ，xbar±s，n＝30)

Wherein a p value < 0.01 indicates a very significant difference.

Table 9. Evaluation results of skin feel and use effect of product (n=30)

Fig. 1 is a differential analysis of baseline to and return visit time point values for skin content using paired t-test and rank sum test, where p < 0.01. As can be seen from table 7, table 8 and fig. 1, the subject does not have adverse reaction cases after using the skin-improving oil pox emulsion of the invention, and the test product has higher safety; and the analysis of the oil content on the skin surface shows that after the product is used by a subject, the oil content on the skin surface measured before and after the face is cleaned has a descending trend at a return visit time point D28, and the oil content has a remarkable difference compared with a baseline value D0, because the emulsion contains the 5 alpha-reductase inhibitor provided by the invention, the levels of 5 alpha-reductase and DHT can be reduced, and the secretion of the oil on the skin is fundamentally controlled.

In addition, fig. 2 is a statistical chart of subjective evaluation of long-acting oil control test subjects; as can be seen from the subjective evaluation of the subjects in table 9 and fig. 2, after 28 days (D28), the average score is above 5 minutes, and more than 50% of the subjects in statistics give positive evaluation on the product mildness, moisturizing, oil control effect and satisfaction; at D28, 100% of subjects indicated acceptance of "feel product fresh and non-sticky" and "feel product well absorbed"; more than 90% of the subjects received acceptance that "the product was mild and non-irritating", "the product was perceived to reduce oil production from the facial skin" and "the skin was moist and smooth after application of the product" and that more than 90% of the subjects gave positive assessment of product satisfaction.

5. Human body acne removal test

The product use test method comprises the following steps:

after the face is cleaned, a proper amount of product is evenly spread on the acne part of the face until the whole face is absorbed; each day is used for 28 days, 1 time in the morning and evening. During the test period, subjects were prohibited from using anti-acne, oil control, anti-inflammatory and bacteriostatic formulations; subjects were prohibited from dropping, injecting, orally taking or otherwise ingesting agents that affect the anti-acne, oil control test; the subject is mainly subjected to indoor activities, and long-term exposure to outdoor illumination is avoided.

Semi-quantitative evaluation (doctor evaluation):

the dermatologist evaluates the skin lesions of the subject's face in the photographs before and after the subject uses the product. Scoring improvement of symptoms of skin lesions before and after use of the subject by ISGA (static comprehensive assessment) scale and calculating percent reduction of skin lesions; the percent skin loss reduction was calculated as follows:

percent skin loss reduction = (pre-product ISGA score-post-product ISGA score)/pre-product ISGA score x 100%

The acne removing effect of the product can be reflected by comparing the ISGA scores before and after use.

The results are shown in Table 10 and FIG. 3.

Table 10. Comparison of ISGA score values before and after use (xbar±s, n=30)

Time point	ISGA scoring	p-value (compared with D0)
			D0	2.10±0.76	/
D28	1.83±0.83	＜0.05

Wherein a p value < 0.05 indicates a significant difference in results.

Fig. 3 is a comparison of ISGA scores at different time points by differential analysis of the values at baseline and return visit of the ISGA scores using a rank sum test analysis, where x represents p < 0.05. As can be seen by combining table 10 and fig. 3, the ISGA skin loss score showed a decreasing trend after use of the product compared to D0, and the percentage reduction of skin loss after 28 days of use was 12.7% with a significant difference (p < 0.05) from D0.

Analysis of acne skin lesions area:

the red region image shot by the VISIA-CR is subjected to spot analysis in an ImageProplus software skin comprehensive analysis module, so that the area ratio of acne skin lesions in the AOI selected region can be calculated; the acne removing effect of the product can be reflected by comparing the change of the acne skin lesion area ratio before and after use.

The more the acne area ratio is reduced at different return visit time points compared with the baseline value (D0) before use, the better the acne skin damage improving effect is, and the better the acne removing effect of the acne treatment product is indicated.

Acne skin area reduction rate = (acne area before use of product-acne area after use of product) acne area before use of product%

The results are shown in Table 11, table 12 and FIG. 4.

Table 11 descriptive statistics of acne lesions area ratio (%, n=30)

Time point	The number of people	Average value of	Standard deviation of	Standard error	Minimum value	Maximum value	Median of
								D0	30	31.45	8.07	1.47	19.65	52.41	30.62
D28	30	7.05	12.79	2.34	0.00	48.72	0.90

Table 12 analysis of acne lesions area ratio variability (%, xbar±s, n=30)

Time point	Mean ± standard deviation	p-value (compared with D0)
			D0	31.45±8.07	/
D28	7.05±12.79	＜0.01

Wherein a p value < 0.01 indicates that the difference is extremely significant.

Fig. 4 shows the change in acne lesion area ratio obtained by differential analysis of the baseline and return visit values of the acne lesion area ratio using paired t-test analysis, where p < 0.01 is expressed. As can be seen in combination with tables 11, 12 and fig. 4, the acne lesions area ratio showed a decreasing trend after using the product compared to D0, 77.59% after 28 days of use, with a very significant difference compared to the baseline value (D0), and the acne lesions area ratio after using the product was lower than D0.

Acne skin lesion color a value analysis:

the red region Image shot by the VISIA-CR is subjected to color analysis in an Image Proplus software skin comprehensive analysis module, the color of the skin sore skin loss in the AOI selected region can be calculated, and the three-base color stimulus values (L, a and b) determined by the international committee of illumination are adopted in the software to quantify the skin color. In the chromaticity of L, a and b, the larger the value of a is, the more the color is biased to red, the smaller the color is biased to green, and the acne removing effect of the product can be reflected by comparing the change of the value of a of the skin damage color of the acne before and after use.

The more the value of the acne a at different return visit time points is reduced compared with the baseline value (D0) before use, the better the improvement effect of acne skin lesions is, and the better the acne removing effect of the acne product is indicated.

Reduction rate of acne lesions a = (pre-product acne a = (post-product acne a =)/pre-product acne a = 100%)

The results are shown in Table 13 and Table 14, and FIGS. 5 and 7.

Table 13 descriptive statistics of acne skin lesions colour a values (n=30)

Time point	The number of people	Average value of	Standard deviation of	Standard error	Minimum value	Maximum value	Median of
								D0	30	13.82	3.56	0.65	6.95	21.86	13.23
D28	30	11.11	3.35	0.61	5.59	22.35	11.22

Table 14. Analysis of the differences in the values of the skin lesions of acne (xbar±s, n=30)

Time point	Mean ± standard deviation	p-value (compared with D0)
			D0	13.82±3.56	/
D28	11.11±3.35	＜0.01

Fig. 5 is a graph showing changes in the values of D0 and D28 of the skin lesion color a by differential analysis using paired t-test analysis, wherein p < 0.01. As can be seen in combination with tables 13, 14 and fig. 5, the acne skin lesion color a values showed a decreasing trend after the product was used, 19.59% decrease after 28 days of use, a very significant difference compared to D0, and the acne skin lesion color a values were below the baseline values after the product was used.

The test results show that after the skin oil acne emulsion is used for 28 days, ISGA score can be reduced, overall acne skin damage condition of the face can be improved, acne skin damage area ratio and acne skin damage color a value can be reduced, acne skin damage area is reduced, acne skin damage color is improved, acne removal effect is achieved, in subjective evaluation, more than 50% of subjects statistically evaluate skin feel, acne removal effect, mildness and satisfaction degree of the product positively, and the product has acne removal effect.

6. Human body short-acting oil control test and comparison of commercial samples

Taking the skin-improving oil acne liquid of the embodiment 10 for inspection, and performing a short-term oil control test on a third party.

The testing steps are as follows:

the subjects cleaned their faces with the facial cleansing product and wiped dry with dry facial tissues and allowed to sit still in a laboratory at 21±1 ℃ at 50±10%rh for 30min; 31 mixed oily skin and forehead skin grease content inclusion values greater than 120ug/cm are selected ² ；

The laboratory technician divides the forehead of the subject into left, middle and right 6 areas, uses products in the Z1 and Z4 sample areas, uses no products in the Z2 and Z5 areas as blank control areas, uses bidding in the Z3 and Z6 control areas, and each area is 2cm multiplied by 2cm.

Marking a sample area, a blank control area and a control area, wherein the sample area, the blank control area and the control area are fixedly distributed in the left, middle and right forehead calibration areas, so that the positions of all the sample area, the blank control area and the control area reach balance in statistics, and the initial oil content value has no significant difference;

a laboratory technician tests the skin grease content basic value of each corresponding area of the forehead of the subject (all marked areas are uniformly rubbed with alcohol before measurement);

the laboratory technician uses the test sample in the sample area according to the product use requirement, the use amount is 2mg/cm ² ；

The control area is a blank area and no sample was used.

The laboratory technicians respectively correspond to the skin grease content data values of the corresponding areas of the forehead of the test subject after using the sample for T0h before using the sample, 4 hours after using the sample for T4h and 8 hours after using the sample.

The laboratory technician again tests the skin grease content data value of each corresponding area of the forehead of the subject.

The test results are shown in Table 15 and FIG. 6.

TABLE 15 skin oil content (mean) at different time points for different groups

	T0h	T4h	T8h
				Sample area	6	107	141
Blank control area	7	157	221
				Control area	7	136	194

Fig. 6 is a graph of skin lipid content for different groups at different time points, where p < 0.05 is shown. As can be seen by combining table 14 and fig. 6, the skin lipid content of 31 subjects in the sample area was increased by 101 at 4 hours after using the sample, with a significant difference compared to before using the sample; the skin grease content of 31 subjects in the blank control area is improved by 150, and compared with the skin grease content before using the sample, the skin grease content is obviously different; the skin lipid content of 31 subjects in the control area was increased by 129, with a significant difference compared to that before the sample was used. The skin grease content of 31 subjects in the sample area is improved by 135 hours after the sample is used, and compared with the skin grease content before the sample is used, the skin grease content is obviously different; the skin grease content of 31 subjects in the blank control area is improved by 214, and compared with the skin grease content before using the sample, the skin grease content is obviously different; the skin lipid content of 31 subjects in the control area was increased by 187, with a significant difference compared to that before the sample was used.

The test results show that the oil inhibition rate of 8 hours is as high as 35.74% by using the skin-improving oil acne emulsion disclosed by the invention, and the oil inhibition rate is better than the short-acting oil control capacity of the commercial emulsion.

7. Sample sensory testing

10 panelists who had received the sensitive oilpox muscles were selected and tested with the skin-improving oilpox emulsion samples of examples 6 to 10, respectively. The test subjects scored the samples from the following criteria, with higher scores (0-10 scores), better evaluation and higher acceptance, and the result was a random blind average for the group of 10 test subjects, as shown in table 16.

TABLE 16 sensory testing of skin-improving oil-pox emulsions of examples 6-10

	Oil control and no greasiness	Light and fresh	No mud rubbing	Fitting with skin	Preference degree
						Example 6	7.3	7.9	8.6	8.2	7.9
Example 7	8.3	7.7	8.3	8.7	8.3
						Example 8	6.8	7.3	6.1	7.0	6.4
Example 9	9.0	8.2	7.2	7.8	7.6
						Example 10	8.7	9.2	9.5	9.1	9.1

As can be seen from the results in table 16, the test person rated the example 10 of the skin-improving oil-pox emulsion products of examples 6 to 10 according to the invention the highest; furthermore, no irritation, sensitivity, or discomfort occurred for all the testers.

It is to be understood that the above examples of the present invention are provided by way of illustration only and not by way of limitation of the embodiments of the present invention. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. Any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the invention are desired to be protected by the following claims.

Claims

1. A 5α -reductase inhibitor comprising a first component, a second component, and a third component;

the weight ratio of the first component to the third component is (0.1-48) 1;

the content of the silybin in the silybum marianum extract is 50-70%.

2. The 5α -reductase inhibitor of claim 1, wherein the weight ratio of the first component to the second component is (0.3-3.5): 1 and the weight ratio of the first component to the third component is (3-4): 1.

3. The 5α -reductase inhibitor of claim 2, wherein the first component comprises, in parts by weight, 0.02-0.5 parts of silybum marianum extract, 3-10 parts of witch hazel hydrolat; the second component comprises 3-10 parts of tea tree hydrolat and 0.04-0.5 part of melaleuca alternifolia leaf oil; the third component comprises 0.12-1.5 parts of medicinal layer porus.

4. The 5α -reductase inhibitor as claimed in claim 1 wherein the 1% aqueous solution of silybum marianum extract has a pH of 5 to 8.

5. The 5α -reductase inhibitor of claim 1 wherein the tea tree hydrolat has a relative density to water of from 0.98 to 1.02.

6. The 5α -reductase inhibitor of claim 1, wherein the relative density of the witch hazel hydrolat to water is between 0.995 and 1.005.

7. A method of preparing a 5α -reductase inhibitor as claimed in any one of claims 1 to 6, comprising the steps of:

8. Use of a 5α -reductase inhibitor as claimed in any one of claims 1 to 6 in cosmetics.

9. An oil-pox improving emulsion comprising the 5α -reductase inhibitor of any one of claims 1 to 6.

10. The skin-improving oil pox emulsion according to claim 9, wherein the mass content of the 5 alpha-reductase inhibitor in the emulsion is 8 to 50%.