A 5α-reductase inhibitor and its preparation method and application

Abstract

The present invention discloses a 5α-reductase inhibitor and its preparation method and application, and relates to the field of cosmetic technology. The present invention achieves the inhibition of 5α-reductase through the synergistic effect between the components, and at the same time, the pH of the 5α-reductase inhibitor is coordinated and adjusted by controlling the amount of each component, so that it does not cause irritation to the skin and does not destroy the skin microecological balance. In addition, the 5α-reductase inhibitor of the present invention also has the effects of purifying and converging pores and soothing the skin, achieving the comprehensive effects of soothing, oil control, and acne removal. The inhibition rate of 5α-reductase by the 5α-reductase inhibitor of the present invention to 5α-reductase is 53.45-76.71%, which fundamentally regulates sebum secretion, inhibits acne generation, and has an excellent effect of improving the oily acne state of the skin.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and more specifically, to a 5α-reductase inhibitor and a preparation method and application thereof. Background Art

[0002] The main reason for the vigorous secretion of sebaceous glands is the increase in the activity level of 5α-reductase in the skin tissue, which leads to abnormal activity of sebaceous glands. The growth and differentiation of sebaceous glands are regulated by androgens. Under the catalysis of specific enzymes such as 5α-reductase, androgens bind to androgen receptors of sebaceous glands, producing a series of programmed changes, such as DNA replication and protein synthesis, which ultimately lead to enhanced secretion function of sebaceous glands and excessive oil secretion. Therefore, inhibiting the activity of 5α-reductase can fundamentally reduce the secretion of skin oil.

[0003] At present, there are many products on the market that can regulate the secretion of skin oil, and solve the problem of oily, acne-prone and sensitive skin by controlling oil. However, existing products still have problems such as repeated acne removal and poor oil control effects, and are unable to inhibit the activity of 5α-reductase and fundamentally regulate the secretion of skin oil.

[0004] The prior art discloses a mild oil-controlling acne-removing essence, which can inhibit the activity of 5α-reductase to a certain extent and achieve an oil-control effect. However, bactericides such as quaternary ammonium salt-73 are also added to the essence, which can easily destroy the bacterial flora of the skin and damage the microecological balance of the skin. Summary of the invention

[0005] In order to overcome the defects and shortcomings of existing products that destroy the skin microecological balance while inhibiting the activity of 5a-reductase, the present invention provides a 5a-reductase inhibitor, which synergistically achieves the inhibition of 5α-reductase activity while maintaining the skin microecological balance by controlling the dosage of each component and the content of the active ingredient.

[0006] Another object of the present invention is to provide a method for preparing the above 5α-reductase inhibitor.

[0007] Another object of the present invention is to provide use of the above 5α-reductase inhibitor in cosmetics.

[0008] Another object of the present invention is to provide a lotion for improving oily skin and acne.

[0009] Another object of the present invention is to provide a method for preparing the above-mentioned skin acne-improving emulsion.

[0010] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0011] A 5α-reductase inhibitor, comprising a first component, a second component and a third component;

[0012] The first component includes milk thistle extract and witch hazel hydrosol; the second component includes tea tree hydrosol and Melaleuca alternifolia leaf oil; the third component includes medicinal pore fungus;

[0013] The weight ratio of the first component to the second component is (0.06-19):1;

[0014] The weight ratio of the first component to the third component is (0.1-48):1;

[0015] The content of Melaleuca alternifolia leaf water in the tea tree hydrosol is ≥ 99%;

[0016] The content of terpinen-4-ol in the Melaleuca alternifolia leaf oil is ≥35%;

[0017] The content of silybin in the milk thistle extract is 50-70%.

[0018] It should be noted that:

[0019] The main components of the 5α-reductase inhibitor of the invention are milk thistle extract and witch hazel hydrosol.

[0020] The milk thistle extract contains silybin active ingredient, which contains a large amount of flavonoids, can stimulate cell metabolism, accelerate local microcirculation, and has strong antioxidant properties, which are 10 times that of vitamin E. The content of silybin in the milk thistle extract used in the present invention is 50-70%, and the silybin content can provide an excellent antioxidant environment and reduce the 5α-reductase level and DHT (dihydrotestosterone) level of the skin.

[0021] North American witch hazel hydrosol contains tannins, polyphenol compounds and volatile oils, which can competitively inhibit the activity of 5α-reductase.

[0022] The addition of the second component can synergistically enhance the inhibition rate of the first component on 5α-reductase. Among them, the tea tree hydrosol contains more than 99% of Melaleuca alternifolia leaf water, which can soften aging cells, allowing the first component to better act on skin cells, synergistically inhibit 5α-reductase, and participate in regulating the pH state of the skin to avoid irritation to the skin.

[0023] If the ratio of the first component to the second component is too large, that is, the dosage of the first component is too high, it is easy to weaken the synergistic enhancement effect of the second component. At the same time, the inhibition of 5α-reductase by the first component will not be further improved, resulting in a decrease in the 5α-reductase inhibition rate. If the dosage of the second component is too high, it will also reduce the inhibitory effect on 5α-reductase.

[0024] The present invention selects Melaleuca alternifolia leaf oil with a terpinene-4-ol content of ≥35%, which can better act on the skin to sterilize, reduce the overexpression of cytokines, and alleviate inflammatory response, cooperate with the first component to inhibit the activity of 5α-reductase, further control the secretion of skin oil, and regulate the ecological balance of skin microecology.

[0025] The third component is used as an auxiliary component. By compounding the first component and the third component, the pores can be tightened while inhibiting the activity of 5α-reductase, so that the skin remains fresh. In addition, the inventors have found that by controlling the weight ratio of the first component to the third component, the effects of the extracts of medicinal porphyra, witch hazel and milk thistle can be maximized, so that the third component further enhances the inhibition of 5α-reductase by the first component.

[0026] In addition, since the pH of milk thistle extract is relatively high after dissolution, it can cooperate with tea tree hydrosol and witch hazel hydrosol, which have lower pH components, to regulate the pH of 5α-reductase inhibitors. By controlling the dosage of each component, it can ensure that the pH of the 5α-reductase inhibitor will not cause irritation to the skin.

[0027] The present invention achieves mild and effective inhibition of 5α-reductase activity by compounding a first component, a second component and a third component containing specific effective ingredients. The three components cooperate with each other to jointly enhance the inhibitory effect on 5α-reductase.

[0028] The content of Melaleuca alternifolia leaf water in the tea tree hydrosol, the content of terpinene-4-ol in Melaleuca alternifolia leaf oil, and the content of silybin in milk thistle extract are mass contents.

[0029] Specifically, the weight ratio of the first component to the second component is (0.06-13):1, more specifically (0.06-10):1.

[0030] Specifically, by weight, the first component includes 0.02-3 parts of milk thistle extract and 2-35 parts of witch hazel hydrosol; the second component includes 3-30 parts of tea tree hydrosol and 0.02-2 parts of Melaleuca alternifolia leaf oil; and the third component includes 0.8-15 parts of medicinal pore fungus.

[0031] 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.

[0032] Preferably, by weight, the first component comprises 0.02-0.5 parts of milk thistle extract and 3-10 parts of witch hazel hydrosol; the second component comprises 3-10 parts of tea tree hydrosol and 0.04-0.5 parts of Melaleuca alternifolia leaf oil; and the third component comprises 0.12-1.5 parts of medicinal pore fungus.

[0033] Specifically, the pH of the 1% aqueous solution of the milk thistle extract is 5-8.

[0034] By controlling the pH of milk thistle extract, it is beneficial to further cooperate with other components, regulate the pH of 5α-reductase inhibitors, and better regulate the pH state of the skin.

[0035] Specifically, the relative density of the tea tree hydrosol and water is 0.98-1.02.

[0036] Specifically, the relative density of the witch hazel hydrosol and water is 0.995-1.005.

[0037] The relative density of the tea tree hydrosol and the witch hazel hydrosol will affect their corresponding efficacy. Controlling the relative density of the tea tree hydrosol and the witch hazel hydrosol will help to further enhance the effect of the first component and the second component in synergistically inhibiting the activity of 5α-reductase.

[0038] The present invention also protects a method for preparing the above-mentioned 5α-reductase inhibitor, comprising the following steps:

[0039] Tea tree hydrosol, Melaleuca alternifolia leaf oil, milk thistle extract, witch hazel hydrosol and medicinal pore fungus are added into PEG-40 hydrogenated castor oil, mixed evenly and filtered to obtain a 5α-reductase inhibitor.

[0040] The PEG-40 hydrogenated castor oil is a solubilizing agent for Melaleuca alternifolia leaf oil. The addition of PEG-40 hydrogenated castor oil promotes the co-solubility of Melaleuca alternifolia leaf oil and other components.

[0041] Specifically, the amount of PEG-40 hydrogenated castor oil used is 0.06-6 parts by weight, for example, 0.06, 0.12, 0.9, 1.5, 6.

[0042] Specifically, the mixing is achieved by stirring at a speed of 40 to 50 rpm / min.

[0043] The present invention protects the use of the above 5α-reductase inhibitor in cosmetics.

[0044] The present invention inhibits the activity of 5α-reductase and reduces the secretion of oil through the synergistic effect of various components, and at the same time regulates the pH state of the skin, tightens pores and maintains skin moisture, and reduces the outlets formed by sebum secretion, thereby forming a virtuous circle, greatly improving the product's ability to inhibit 5α-reductase, regulating the water-oil balance of the skin, achieving long-term oil control, further inhibiting the growth of acne and tightening pores, and being used in cosmetics is beneficial to the prevention and repair of skin oil acne problems.

[0045] The present invention particularly protects an emulsion for improving skin oiliness and acne, wherein the emulsion comprises the above-mentioned 5α-reductase inhibitor.

[0046] The above-mentioned emulsion includes the 5α-reductase inhibitor of the present invention, which can well regulate the pH state of the skin, inhibit the activity of 5α-reductase, achieve oil control and acne removal without irritating the skin, and has both short-term and long-term oil control capabilities, and can effectively regulate the water-oil imbalance of the skin and the problems of enlarged pores, and the skin feels refreshing, while moisturizing the skin without giving the skin a heavy feeling, and is especially suitable for people with oily acne-sensitive skin. The 5α-reductase inhibitor of the present invention does not contain other strong bactericidal ingredients, and will not destroy the balance of the skin microecology.

[0047] Specifically, the mass content of the 5α-reductase inhibitor in the emulsion is 8-50%.

[0048] By controlling the content of 5α-reductase inhibitor in the lotion, the 5α-reductase inhibitor can better exert its corresponding efficacy, inhibit the activity of 5α-reductase, and make the lotion have a better oil control effect.

[0049] Specifically, a pH regulator, a thickener, oil, an emulsifier, a moisturizer, an antioxidant and an active preservative ingredient are added to the emulsion.

[0050] Specifically, the emulsifiers are Montanan 68 and SL-1, wherein the mass ratio of Montanan 68 to SL-1 is 2:1.

[0051] When Montanan 68 and SL-1 are used as emulsifiers and the mass ratio of the two is 2:1, the emulsification effect of the emulsion can be better achieved and the skin feel of the emulsion product can be improved.

[0052] Specifically, the pH adjuster is arginine or aminomethyl propanol, wherein the weight portion of the pH adjuster is 0.02-2 parts, preferably 0.05-1 parts.

[0053] Specifically, the thickener is one or two of acrylic acid (ester) / C10-30 alkyl acrylate cross-linked polymer, ammonium acryloyldimethyltaurate / vinyl formamide copolymer, acrylic acid (ester) / vinyl isodecanoate cross-linked polymer, hydroxyethyl acrylate / sodium acryloyldimethyltaurate copolymer; wherein the weight proportion of the thickener is 0.02-2 parts, preferably 0.1-0.8 parts.

[0054] Specifically, the oil is one or two of polydimethylsiloxane, isononyl isononanoate, caprylic / capric triglyceride, isohexadecane, isododecane, and silicone elastomer; wherein the weight proportion of the oil is 0.5-5 parts, preferably 1-4 parts.

[0055] Specifically, the moisturizing agent is one or more of butylene glycol, glycerol and trehalose.

[0056] Specifically, the molecular weight of the trehalose is 340-345.

[0057] Specifically, the antioxidant is one or more of aloe vera leaf juice, tuberose extract, β-glucan, 10-hydroxydecanoic acid, allantoin, and lemon oil.

[0058] Specifically, the skin feel regulator component is silica, and the silica is elliptical with a specific surface area of ​​>15000 (cm 2 / cm 3 ), silica with a particle size of less than 5μm, can absorb about 5 times its own weight of oil, is a good physical adsorbent, and can adjust the skin feel of the lotion.

[0059] Specifically, the antiseptic active ingredient is one or two of 1,2-hexanediol and p-hydroxyacetophenone.

[0060] The present invention also protects a method for preparing the above-mentioned skin acne-improving lotion, comprising the following steps:

[0061] S1. Dissolve and mix deionized water, thickener, emulsifier and humectant at 80-90°C;

[0062] S2. After adding the oil, mix evenly, homogenize and emulsify at 80-90°C;

[0063] S3. Add pH adjuster and mix well at 70-80°C;

[0064] S4. Lower the temperature to 55-65°C, add the pre-mixed and dissolved antioxidant, and mix well;

[0065] S5. Lower the temperature to 40-50° C., add the 5α-reductase inhibitor according to any one of claims 1 to 3, and obtain a skin acne-improving lotion after vacuum degassing.

[0066] The skin oil acne improving emulsion of the present invention is prepared by an emulsification process. By controlling the addition order and mixing temperature of each component, the prepared emulsion can have a better emulsification effect, and the functional ingredients or activity of each component will not be affected during the preparation process, and finally an emulsion product with excellent comprehensive effects of soothing, oil control and removing acne is obtained.

[0067] Compared with the prior art, the present invention has at least the following beneficial effects:

[0068] The present invention provides a 5α-reductase inhibitor, which inhibits 5α-reductase through the synergistic effect of various components, and simultaneously coordinates the pH of the 5α-reductase inhibitor by controlling the dosage of various components, so that it does not irritate the skin and does not destroy the microecological balance of the skin. In addition, the 5α-reductase inhibitor of the present invention also has the effects of purifying and tightening pores and soothing the skin, achieving the comprehensive effects of soothing, oil control, and acne removal.

[0069] The 5α-reductase inhibitor of the present invention has an inhibition rate of 53.45-76.71% on 5α-reductase, which fundamentally regulates sebum secretion and has an excellent oil control effect. After being prepared into a lotion for improving skin oil acne, the short-term oil control effect on the skin for 8 hours is 68-152ug sebum / cm 2 , the oil inhibition rate after 28 days of use was 26.15%; in addition, after 28 days of using the skin oil acne improving emulsion of the present invention, the area ratio of acne lesions decreased by 77.59%, and the a* value of the acne lesion color decreased by 19.59%, which has a significant acne-removing effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0070] Figure 1 A test chart of skin oil content for long-term oil control test.

[0071] Figure 2 This is a statistical chart of the subjective evaluation of the subjects in the long-term oil control test.

[0072] Figure 3 This is a comparison chart of ISGA scores at different time points in the acne removal test.

[0073] Figure 4 This is a graph showing changes in the percentage of acne lesion area.

[0074] Figure 5 This is a graph showing the changes in the a* value of acne lesion color.

[0075] Figure 6 The figure is a comparison chart of skin oil content after using the emulsion of Example 10 and a commercially available emulsion.

[0076] Figure 7 This is a diagram showing the acne repair effect after using the skin oil acne improving lotion of the present invention for 28 days. DETAILED DESCRIPTION

[0077] Tea tree hydrosol was purchased from Yin Gu Aromatic Technology Co., Ltd., in which the water content of Melaleuca alternifolia leaves was 99.6% and the relative density was 1.00±0.02.

[0078] Melaleuca alternifolia leaf oil 1 was purchased from Main Camp Natural Extracts Pty Ltd (MELALEUCAALTERNIFOLIA), wherein the content of terpinen-4-ol was 41.4%.

[0079] Melaleuca alternifolia leaf oil 2 was purchased from Lvyuan Natural Spice Oil Refinery (tea tree oil) in Qingyuan District, Ji'an City, and the content of terpinene-4-ol was 33.14%.

[0080] Milk thistle extract was purchased from Guangdong Gexin Biotechnology Co., Ltd. (milk thistle extract), wherein the content of silybin was 65%, and the pH of 1% aqueous solution was 5-8.

[0081] Milk thistle extract 2 was purchased from Givaudan (IN-906400), wherein the content of silybin was 29.7-36.3%, and the pH of 1% aqueous solution was 5-8.

[0082] Witch hazel was purchased from AMERICAN DISTILLING INC. (Witch Hazel Distillate with 1.0% Phenoxyethanol) and had a relative density of 0.995-1.005.

[0083] Medicinal pore fungus was purchased from BASF (China) Co., Ltd. LS 8865).

[0084] The above-mentioned terpinene-4-ol content and silybin content are measured by HPLC.

[0085] The present invention is further described below in conjunction with specific embodiments, but the embodiments do not limit the present invention in any form. Unless otherwise specified, the raw materials and reagents used in the embodiments of the present invention are conventionally purchased raw materials and reagents.

[0086] Examples 1 to 5

[0087] A 5α-reductase inhibitor, the difference being that the weight ratios of the first component, the second component and the third component are different.

[0088] In Example 1, the first component: the second component = 9.5:1; the first component: the third component = 47.5:1;

[0089] In Example 2, the first component: the second component = 0.067:1; the first component: the third component = 0.135:1;

[0090] In Example 3, the first component: the second component = 3.3:1; the first component: the third component = 3.34:1;

[0091] In Example 4, the first component: the second component = 0.33:1; the first component: the third component = 3.5:1;

[0092] In Example 5, the first component: the second component = 1.16:1; the first component: the third component = 3.65:1;

[0093] The specific formula is shown in Table 1.

[0094] Table 1.5 Alpha-reductase inhibitor formulations (by weight)

[0095] Example 1 Example 2 Example 3 Example 4 Example 5 Tea Tree Hydrosol 2 30 3 10 6 Melaleuca alternifolia leaf oil1 2 0.02 0.04 0.5 0.3 Milk Thistle Extract1 3 0.02 0.02 0.5 0.3 Witch Hazel Hydrosol 35 2 10 3 7 Medicinal pore fungus 0.8 15 3 1 2 PEG-40 Hydrogenated Castor Oil 6 0.06 0.12 1.5 0.9

[0096] The preparation method of the above 5α-reductase inhibitor can refer to the following steps:

[0097] Tea tree hydrosol, Melaleuca alternifolia leaf oil, milk thistle extract, witch hazel hydrosol and medicinal phytomycetes are added to PEG-40 hydrogenated castor oil, mixed evenly and filtered to obtain a 5α-reductase inhibitor;

[0098] In which, 6 parts of PEG-40 hydrogenated castor oil were added to Example 1 for solubilization; 0.06 parts of PEG-40 hydrogenated castor oil were added to Example 2 for solubilization; 0.12 parts of PEG-40 hydrogenated castor oil were added to Example 3 for solubilization; 1.5 parts of PEG-40 hydrogenated castor oil were added to Example 4 for solubilization; 0.9 parts of PEG-40 hydrogenated castor oil were added to Example 5 for solubilization;

[0099] The mixing was achieved by stirring at a speed of 45 rpm / min.

[0100] Embodiments 6 to 10

[0101] A skin acne-improving lotion comprises the 5α-reductase inhibitors of Examples 1 to 5, respectively. The specific formula is shown in Table 2.

[0102] Table 2. Formula of skin acne-improving lotion (by weight)

[0103]

[0104] The preparation method of the above-mentioned skin acne-improving lotion can refer to the following steps:

[0105] S1. Add deionized water, thickener, emulsifier and humectant into an emulsifying pot and stir to dissolve evenly at 82°C;

[0106] S2. Mix the oil and fat evenly, add it into the emulsifier, homogenize it at 82°C, at a speed of 3000 rpm for 3 minutes, and keep it warm for 10 minutes;

[0107] S3. Add pH adjuster and stir to disperse evenly at 75°C;

[0108] S4. Lower the temperature to 60°C, add the pre-mixed and dissolved antioxidant into the emulsifying pot, and stir to dissolve evenly;

[0109] S5. The temperature is lowered to 45°C, a 5α-reductase inhibitor is added, and the skin acne-improving lotion is obtained after vacuum degassing.

[0110] Comparative Examples 1 to 10

[0111] A 5α-reductase inhibitor, the specific components of which are shown in Table 3.

[0112] Table 3. 5α-reductase inhibitor formulations of Comparative Examples 1 to 10 (by weight)

[0113]

[0114] The preparation method of the above 5α-reductase inhibitor is the same as that in Example 1.

[0115] Comparative Examples 11 to 20

[0116] A skin acne-improving lotion, the formula of which is the same as that of Example 10, except that the 5α-reductase inhibitors correspond to the 5α-reductase inhibitors in Examples 1 to 10 respectively.

[0117] The preparation method of the above-mentioned skin acne improving lotion is the same as that of Example 10.

[0118] Comparative Examples 21-22

[0119] A 5α-reductase inhibitor, the formula of which is the same as that of Example 5, except that: Comparative Example 1 uses 2% Melaleuca alternifolia leaf oil; Comparative Example 2 uses 2% Silybum marianum extract.

[0120] Results

[0121] 1. Test of 5α-reductase inhibition rate

[0122] Test samples: 5α-reductase inhibitors of Examples 1 to 5 and Comparative Examples 1 to 10.

[0123] Test principle: The secretion function of sebaceous glands in oily skin is relatively strong, the face feels greasy and difficult to clean, and it is also prone to some corresponding skin diseases, such as acne vulgaris and seborrheic dermatitis. In view of the relationship between 5α-reductase and sebaceous glands, the inhibitory effect of the test sample on 5α-reductase is usually tested to reflect the sebum regulation effect, so as to characterize the oil control effect of the test sample. The higher the inhibition rate, the better the oil control effect.

[0124] An in vitro screening model for 5α-reductase inhibitors was established using ultra-high performance liquid chromatography to test the inhibitory activity of the combined extract for improving skin oiliness and acne provided in the present application on 5α-reductase.

[0125] Experimental method: 5α-reductase was extracted from SD rats, and the 5α-reductase inhibitors of Examples 1 to 5 and Comparative Examples 1 to 10 were respectively prepared and diluted with water to 100% as an inhibitor, testosterone was used as a substrate, finasteride was used as a positive control, and a blank control group was used. The change in testosterone concentration before and after the reaction was determined by ultra-high performance liquid chromatography, and the inhibition rate was calculated, wherein the inhibition rate was calculated as follows: Inhibition rate = (change in testosterone concentration in the blank tube - change in testosterone concentration in the sample tube) / change in testosterone concentration in the blank tube × 100%

[0126] The specific test results and inhibition rates are shown in the table below.

[0127] The results are shown in Table 4.

[0128] Table 4. Inhibition rate of 5α-reductase inhibitors on 5α-reductase

[0129]

[0130]

[0131] As can be seen from Table 4, the inhibition rate of the 5α-reductase inhibitors of Examples 1 to 5 on the 5α-reductase liquid is higher than that of the 5α-reductase inhibitors prepared in Comparative Examples 1 to 10. The inhibition rates of Examples 1 to 5 on the 5α-reductase liquid are between 53.45% and 76.71%, among which the inhibition rate of Example 4 is the highest, reaching 76.71%, which shows that its oil control effect is the best; the 5α-reductase inhibitor of the present invention can give full play to the oil control effect of the 5α-reductase inhibitor through reasonable combination of the active ingredients and synergistic enhancement, and shows a better oil control effect than the combination form lacking any one component.

[0132] 2. Skin occlusive patch test

[0133] Test site: normal skin on the flexor side of the forearm (10 people with sensitive skin were tested in the experiment).

[0134] Test samples: the skin acne-improving lotions of Examples 6 to 10 and Comparative Examples 11 to 20.

[0135] The specific steps are: clean the skin of the test area, take 0.020mL~0.025mL of sample, put it in the small chamber of the spot tester, stick the skin spot test paper firmly and flatly from bottom to top, and press it lightly with your hand a few times to expel the air.

[0136] Patch test time: 24 hours.

[0137] Observation time: 24 hours after application, remove the skin spot test consumables and observe the results after at least 30 minutes.

[0138] Result judgment:

[0139] 1(+-)-Questionable reaction: only faint (indistinct) erythema.

[0140] 2(+) - weak (non-blistering) positive reaction: erythema, infiltration, possible small red rash.

[0141] 3(++)--Strong (vesicular) positive reaction: erythema, infiltration, papules but not vesicles.

[0142] 4 (+++) - Extreme positive reaction: redness, swelling and bullae.

[0143] 0(-)--No response.

[0144] The results are shown in Table 5.

[0145] Table 5. Results of the patch test on the lotion for improving skin oiliness and acne

[0146]

[0147] The test results in Table 5 show that among the subjects of Examples 6 to 10 and Comparative Examples 11 to 20, only Comparative Example 7 showed a suspicious reaction, and the rest showed no positive reactions. According to the "Technical Specifications for Safety of Cosmetics" (2015 edition), the test substance will not cause adverse skin reactions in this batch of subjects. This shows that the formula of the 5α-reductase inhibitor and its emulsion of the present invention is mild and safe, does not irritate the skin, and is suitable for

[0148] 24 (6 people divided into 1 group) adult subjects (selected according to the requirements of T / ZHCA002-2018 inclusion test) were selected to use the test sample once under normal conditions, and the skin oil content was measured by the oil probe SM815 to evaluate the effectiveness of the test sample in oil control.

[0149] The specific test steps are as follows: divide the face into two areas, one area uses sample group A or C, and the other area uses sample group B or D, which are symmetrical. The test areas are named A, B, C, and D, and are marked at the same position on the forehead for testing.

[0150] Samples and specific usage methods: The skin acne-improving lotions in Examples 6 to 10 and Comparative Examples 11 to 20 were randomly sorted, and 4 samples were respectively selected as a group for testing. The subjects sat quietly for 20 minutes under constant temperature and humidity conditions, and then washed their foreheads with clean water. The sample was applied at a concentration of (2.0±0.1) mg / c㎡ and the skin oil content was measured after complete absorption for 8 hours. During the test, the subjects stayed in a room with a constant temperature of 22°C. After the test, the statistical results were averaged and analyzed.

[0151] The results are shown in Table 6.

[0152] Table 6. Human oil control test of the skin acne-improving emulsions of Examples 6 to 10 and Comparative Examples 11 to 20

[0153]

[0154]

[0155] As can be seen from Table 6, the skin oil acne improving lotions of Examples 6 to 10 have a short-term effect on the skin sebum content for 8 hours, which is lower than that of the skin oil acne improving lotions of Comparative Examples 11 to 20. The oil control effect on the skin for 8 hours is between 72 and 125 ug sebum / cm 2 Among them, the skin oil acne improving lotion of Example 6 had the least amount of skin oil after 8 hours of use, which was 72ug sebum / cm 2 , thus it can be known that its oil control effect is the best; this shows that the skin oil acne improving emulsion of the present invention can give full play to the oil control effect of 5α-reductase inhibitors through reasonable combination of various active ingredients and synergistic enhancement, and has a better oil control effect than the combination of components lacking any 5α-reductase inhibitors, which also proves that the emulsion can reduce the DHT (dihydrotestosterone) level of the skin.

[0156] 4. Human long-term oil control test

[0157] The skin acne improving lotion of Example 10 was sent for inspection and a third party conducted a long-term oil control test on humans.

[0158] Product use test method:

[0159] After cleansing, apply an appropriate amount of the product evenly on the face until it is fully absorbed; use once a day in the morning and evening for 28 consecutive days. During the trial, subjects are prohibited from using oil-control or pore-affecting preparations; subjects are prohibited from dripping, injecting, orally or otherwise taking preparations that affect oil control or pore testing; subjects are mainly indoors and avoid long-term exposure to outdoor light.

[0160] Subjective evaluation of the subjects:

[0161] During the follow-up visit 28 days (D28) after using the product, the subjects evaluated their facial condition through a mirror under natural light conditions in the human efficacy laboratory and recorded the scores. Using the scoring method, the products were scored from four aspects: skin feel, mildness, usage effect and usage satisfaction. Then a judgment was made and a record was made for each subject during the follow-up visit.

[0162] Objective quantitative evaluation:

[0163] After the subjects sat quietly in a constant temperature and humidity environment for 30 minutes, SM815 was used to detect the skin oil value before cleansing on the test site, and then the face was cleaned uniformly and dried with a chip-free facial tissue; 30 minutes after facial cleansing, SM815 was used to detect the skin oil value after cleansing on the test site, and the measured value was used as the baseline value (D0), and then the product was distributed and the usage was instructed; 28 days after the subjects used the product (D28), they needed to return for a visit and undergo the same skin oil test.

[0164] The test on the same subject is completed using the same instrument and the same tester, and the test site and time are kept consistent.

[0165] The oil control efficacy of the cosmetic was evaluated by using the skin acne improving lotion of Example 10 on 30 subjects for 28 consecutive days.

[0166] The results are shown in Tables 7, 8, 9 and Figure 1 , Figure 2 shown.

[0167] Table 7. Descriptive statistics of skin oil content (μg / cm 3 , n = 30)

[0168]

[0169] Table 8. Analysis of differences in skin oil content (μg / cm 3 , xbar±s, n=30)

[0170]

[0171] Among them, p value < 0.01 indicates a very significant difference.

[0172] Table 9. Evaluation results of product skin feel and use effect (n=30)

[0173]

[0174] Figure 1 Paired t-test and rank sum test were used to analyze the difference between the baseline and return time points of skin content, where ** indicates p < 0.01. Figure 1It can be seen that no adverse reactions occurred after the subjects used the skin acne improving lotion of the present invention, and the test product has high safety; and the analysis of the skin surface oil content showed that after the subjects used the product, the skin surface oil content measured before and after cleaning the face showed a downward trend at the follow-up time point D28, and there was a significant difference compared with the baseline value D0. This is because the lotion contains the 5α-reductase inhibitor of the present invention, which can reduce the levels of 5α-reductase and DHT, and fundamentally control the skin oil secretion.

[0175] also, Figure 2 This is a statistical chart of subjective evaluation of subjects in the long-term oil control test; combined with Table 9 and Figure 2 The subjective evaluation of the subjects showed that after 28 days of use (D28), the mean score was above 5 points, and statistically more than 50% of the subjects gave positive comments on the mildness, moisturizing, oil control effect and satisfaction of the product; at D28, 100% of the subjects agreed with "the product feels refreshing and not sticky" and "the product feels well absorbed"; more than 90% of the subjects agreed with "the product is mild and non-irritating", "the product feels that it can reduce oiliness of facial skin" and "the skin feels hydrated and smooth after using the product", and more than 90% of the subjects gave positive comments on product satisfaction.

[0176] 5. Human acne test

[0177] The skin acne improving lotion of Example 10 was sent for inspection and a third party conducted a long-term oil control test on humans.

[0178] Product use test method:

[0179] After cleansing, apply an appropriate amount of the product evenly to the acne areas on the face until the whole face is absorbed; use once in the morning and evening every day for 28 consecutive days. During the trial, the subjects are prohibited from using acne-removing, oil-controlling, anti-inflammatory and antibacterial preparations; the subjects are prohibited from dripping, injecting, orally or otherwise taking preparations that affect acne-removing and oil-control tests; the subjects are mainly indoor activities and avoid long-term exposure to outdoor light.

[0180] Semi-quantitative evaluation (doctor's evaluation):

[0181] Dermatologists evaluated the subjects' facial acne lesions in the photos before and after using the product. The ISGA (Investigator Static Global Assessment) scale was used to score the improvement of the subjects' lesion symptoms before and after use, and the percentage of lesion reduction was calculated; the percentage of lesion reduction was calculated as follows:

[0182] Skin lesion reduction percentage = (ISGA score before using the product - ISGA score after using the product) / ISGA score before using the product × 100%

[0183] By comparing the ISGA scores before and after use, the acne-removing effect of the product can be reflected.

[0184] The results are shown in Table 10 and Figure 3 .

[0185] Table 10. Comparison of ISGA scores before and after use (xbar±s, n=30)

[0186] Time ISGA Rating p value (compared with D0) D0 2.10±0.76 / D28 1.83±0.83 ＜0.05

[0187] Among them, p value < 0.05 indicates that the results are significantly different.

[0188] Figure 3 The ISGA scores at different time points were compared by using the rank sum test to analyze the difference between the baseline and follow-up values ​​of the ISGA scores, where * indicates p < 0.05. Figure 3 It can be seen that compared with D0, the ISGA skin lesion score showed a downward trend after using the product. After 28 days of use, the skin lesion reduction percentage was 12.7%, which was significantly different from D0 (p < 0.05).

[0189] Analysis of the proportion of acne lesion area:

[0190] The red area images taken by VISIA-CR can be analyzed by spots in the ImageProPlus software's comprehensive skin analysis module to calculate the area ratio of acne lesions in the AOI selection area; by comparing the changes in the area ratio of acne lesions before and after use, the acne-removing efficacy of the product can be reflected.

[0191] The more the acne area ratio at different follow-up time points decreases compared with the baseline value before use (D0), the better the improvement effect of acne lesions is, indicating that the acne removal effect of the product is better.

[0192] Acne lesion area ratio decrease rate = (acne area ratio before using the product - acne area ratio after using the product) / acne area ratio before using the product × 100%

[0193] The results are shown in Tables 11, 12 and Figure 4 .

[0194] Table 11. Descriptive statistics of acne lesion area ratio (%, n = 30)

[0195] Time Number of people average value Standard Deviation Standard error Minimum Maximum median 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

[0196] Table 12. Analysis of differences in the proportion of acne lesion area (%, xbar±s, n=30)

[0197] Time Mean ± SD p value (compared with D0) D0 31.45±8.07 / D28 7.05±12.79 ＜0.01

[0198] Among them, a p value of < 0.01 indicates that the difference is extremely significant.

[0199] Figure 4 The change in the percentage of acne lesion area was obtained by using paired t-test to analyze the difference between the baseline value and the follow-up value of the percentage of acne lesion area, where ** indicates p < 0.01. Figure 4 It can be seen that compared with D0, the proportion of acne lesion area showed a downward trend after using the product, and decreased by 77.59% after 28 days of use, which was significantly different from the baseline value (D0). The proportion of acne lesion area after using the product was lower than D0.

[0200] Analysis of a* value of acne lesion color:

[0201] The red area image taken by VISIA-CR can be analyzed by color in the comprehensive skin analysis module of Image ProPlus software to calculate the color of acne lesions in the AOI selection area. The software uses the three primary color stimulus values ​​(L*, a*, b*) determined by the International Illumination Commission to quantify skin color. In the L*, a*, and b* chromaticity, the larger the a* value, the more red the color tends to be, and the smaller the a* value, the more green the color tends to be. By comparing the changes in the a* value of the color of acne lesions before and after use, the acne removal effect of the product can be reflected.

[0202] The more the acne a* value at different follow-up time points decreases compared with the baseline value before use (D0), the better the improvement effect of acne lesions is, indicating that the acne removal effect of the product is better.

[0203] Acne lesion a* value reduction rate = (acne a* value before using the product - acne a* value after using the product) / acne a* value before using the product × 100%

[0204] The results are shown in Tables 13, 14 and Figure 5 , Figure 7 .

[0205] Table 13. Descriptive statistics of a* values ​​for acne lesion color (n=30)

[0206] Time Number of people average value Standard Deviation Standard error Minimum Maximum median 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

[0207] Table 14. Analysis of the difference in a* values ​​of acne lesion color (xbar±s, n=30)

[0208] Time Mean ± SD p value (compared with D0) D0 13.82±3.56 / D28 11.11±3.35 ＜0.01

[0209] Figure 5 The acne lesion color a* value change diagram is obtained by using paired t-test to analyze the difference between the D0 and D28 values ​​of the acne lesion color a* value, where ** indicates p < 0.01. Figure 5 It can be seen that the a* value of acne lesion color showed a downward trend after using the product, and decreased by 19.59% after 28 days of use, which was significantly different from D0. After using the product, the a* value of acne lesion color was lower than the baseline value.

[0210] The above test results show that after using the skin oil acne improving lotion of the present invention for 28 days, the ISGA score can be reduced, the overall facial acne lesions can be improved, the acne lesion area ratio and the a* value of the acne lesion color can be reduced, the acne lesion area can be reduced, the acne lesion color can be improved, and the acne lesion area can be reduced. The acne lesion color is improved, and the acne effect is achieved. In the subjective evaluation, more than 50% of the subjects gave positive comments on the product's skin feel, acne removal effect, mildness and satisfaction, indicating that the product has acne removal effect.

[0211] 6. Comparison of human short-term oil control test and commercial samples

[0212] The skin oil acne improving liquid of Example 10 was sent for inspection and a short-term oil control test was performed by a third party.

[0213] Test steps:

[0214] The subjects cleaned their faces with cleansing products and wiped their skin with dry tissues, and sat in a laboratory at a temperature of 21±1℃ and 50±10%RH for 30 minutes; 31 subjects with mixed and oily skin and forehead oil content greater than 120ug / cm were selected. 2 ;

[0215] Laboratory technicians divided the subject's forehead into six areas: left, middle and right. The product was used in the Z1 and Z4 sample areas, and no product was used in the Z2 and Z5 areas as blank control areas. Competing products were used in the Z3 and Z6 control areas. The area of ​​each area was 2cm×2cm.

[0216] Mark the sample area, blank control area and control area. The sample area, blank control area and control area are fixedly distributed in the left, middle and right forehead calibration areas to ensure that the positions of all sample areas, blank control areas and control areas are statistically balanced and there is no significant difference in the initial oil content values;

[0217] The laboratory technicians tested the basal values ​​of skin oil content in the corresponding areas of the subject's forehead (all marked areas were wiped with alcohol before measurement);

[0218] The laboratory technician applies the test sample to the sample area according to the product usage requirements, with a usage of 2mg / cm 2 ;

[0219] The control area is a blank area where no sample is used.

[0220] The laboratory technicians measured the skin oil content data values ​​of the corresponding areas on the forehead of the test subjects T0h before using the samples, T4h 4 hours after using the samples, and T8h 8 hours after using the samples.

[0221] The laboratory technicians once again tested the skin oil content data values ​​of the corresponding areas on the subject's forehead.

[0222] The test results are shown in Table 15 and Figure 6 .

[0223] Table 15. Skin oil content of different groups at different time points (mean)

[0224] T0h T4h T8h Sample area 6 107 141 Blank control area 7 157 221 Control area 7 136 194

[0225] Figure 6 The corresponding skin oil content of different groups at different time points, where * indicates p < 0.05. Figure 6 It can be seen that 4 hours after using the sample, the skin oil content of the 31 subjects in the sample area increased by 101, which was significantly different from before using the sample; the skin oil content of the 31 subjects in the blank control area increased by 150, which was significantly different from before using the sample; the skin oil content of the 31 subjects in the control area increased by 129, which was significantly different from before using the sample. 8 hours after using the sample, the skin oil content of the 31 subjects in the sample area increased by 135, which was significantly different from before using the sample; the skin oil content of the 31 subjects in the blank control area increased by 214, which was significantly different from before using the sample; the skin oil content of the 31 subjects in the control area increased by 187, which was significantly different from before using the sample.

[0226] The above test results show that the oil suppression rate of the skin oil acne improving emulsion of the present invention is as high as 35.74% in 8 hours, which is better than the short-term oil control ability of the commercially available emulsion.

[0227] 7. Sample sensory test

[0228] 10 testers with sensitive acne-prone skin were selected to try out the skin acne-prone lotion samples of Examples 6 to 10 respectively. The testers scored the samples based on the following indicators. The higher the score (0 to 10 points), the better the evaluation and the higher the acceptance. The results are the average values ​​of the random blind test of the 10 testers in this group, as shown in Table 16.

[0229] Table 16. Sensory test of the skin acne-improving lotion of Examples 6 to 10

[0230] Oil control and non-greasy Light and refreshing No mud Skin conformability Likeability 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

[0231] From the results in Table 16, it can be seen that the testers gave the highest evaluation to Example 10 of the skin acne-improving emulsion products of Examples 6 to 10 of the present invention; in addition, all the testers did not experience irritation, sensitivity, or discomfort.

[0232] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. 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 claims of the present invention.

Claims

1. A lotion for improving oily skin and acne, characterized in that: These include 5α-reductase inhibitors; The mass content of the 5α-reductase inhibitor in the emulsion is 8 to 50%; The 5α-reductase inhibitor comprises a first component, a second component, a third component and PEG-40 hydrogenated castor oil; The first component includes milk thistle extract and witch hazel hydrosol; the second component includes tea tree hydrosol and Melaleuca alternifolia leaf oil; the third component includes medicinal pore fungus; Wherein, the α-reductase inhibitor comprises, by weight, 0.02-3 parts of milk thistle extract, 3-10 parts of witch hazel hydrosol, 3-10 parts of tea tree hydrosol, 0.02-2 parts of Melaleuca alternifolia leaf oil, 0.8-15 parts of medicinal pore fungus; 0.06-6 parts of PEG-40 hydrogenated castor oil; 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 Melaleuca alternifolia leaf water in the tea tree hydrosol is ≥ 99%; The content of terpinen-4-ol in the Melaleuca alternifolia leaf oil is ≥35%; The content of silybin in the milk thistle extract is 50-70%.

2. The skin acne-improving lotion according to claim 1, characterized in that: 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 skin acne-improving lotion according to claim 2, characterized in that: In terms of weight, the first component includes 0.02-0.5 parts of milk thistle extract and 3-10 parts of witch hazel hydrosol; the second component includes 3-10 parts of tea tree hydrosol and 0.04-0.5 parts of Melaleuca alternifolia leaf oil; and the third component includes 0.12-1.5 parts of medicinal pore fungus.

4. The skin acne-improving lotion according to claim 1, characterized in that: The pH value of the 1% aqueous solution of the milk thistle extract is 5-8.

5. The skin acne-improving lotion according to claim 1, characterized in that: The relative density of the tea tree pure water and water is 0.98-1.

02.

6. The skin acne-improving lotion according to claim 1, characterized in that: The relative density of the witch hazel pure water and water is 0.995-1.

005.

7. The skin acne-improving lotion according to any one of claims 1 to 6, characterized in that: The preparation method of the 5α-reductase inhibitor comprises the following steps: Tea tree hydrosol, Melaleuca alternifolia leaf oil, milk thistle extract, witch hazel hydrosol and medicinal pore fungus are added into PEG-40 hydrogenated castor oil, mixed evenly and filtered to obtain a 5α-reductase inhibitor.

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