Application of active matter and composition thereof

Abstract

The invention discloses an application of an active matter as a humectant. The active matter is characterized in that the active matter is a compound shown in the following structure: # imgabs0 #. The compound can be used as a cosmetic additive preparation.

Description

Technical Field

[0001] The present invention relates to the field of functional preparations, in particular, to functional preparations that can be used in the field of cosmetics / care products, and more particularly, to the use of diester of azelaic acid and a composition thereof in cosmetics for oil control, penetration promotion, solubilization and moisturizing. Background Art

[0002] As people's pursuit of spiritual life continues to improve, consumers are paying more and more attention to skin care, and the progress of cosmetic science research has further stimulated consumers' diversified demands for cosmetic efficacy.

[0003] At present, the mainstream oil-control ingredients on the market are α-hydroxy acids, mainly glycolic acid, salicylic acid, mandelic acid, lactic acid, etc. Although they can control oil very well, their acidity may irritate sensitive skin. At the same time, this type of acid can dissolve and lose a large amount of lipids between the sebum membrane and keratinocytes, causing side effects such as keratin exfoliation, dry and flaky skin, redness, itching, etc.

[0004] In addition, existing active ingredients have defects such as limited efficacy when used alone, difficulty in solubility and compatibility, low bioavailability, and poor transdermal absorption. Summary of the invention

[0005] The present invention aims to overcome the above-mentioned defects and provides a diester of azelaic acid, whose chemical name is 9-oxyylidene-9-(3,6-dioxaoctane-1-yloxy) nonanoic acid-3,6-dioxaoctane-1-yl ester, also known as bis-diethoxydiglycol azelaic acid ester, which is a new type of disubstituted azelaic acid ester compound. It can effectively inhibit the excessive secretion of oil in the sebaceous glands by competitively inhibiting 5-α reductase, thereby achieving a gentle and effective oil control effect. At the same time, it also has a moisturizing function and can promote the penetration and absorption of other active ingredients, thereby alleviating skin inflammation and discomfort caused by excessive oil secretion, while more comprehensively solving skin problems and achieving a gentle and efficient skin care experience. In addition, in our research, it was found that diester of azelaic acid also has the characteristics of a solubilizer, which can significantly improve the solubility of active ingredients, and effectively solves the defects of the existing active ingredients being limited in efficacy when used alone, solubility compatibility problems, low bioavailability, and poor transdermal absorption. Furthermore, in this study, it was found that the ingredient has a moisturizing effect, that is, the research of the present invention shows that diester of azelaic acid is a multifunctional preparation.

[0006] The present invention provides an application of an active substance as a moisturizer, characterized in that:

[0007] The above active substance is a compound shown in the following structure:

[0008]

[0009] The chemical name of the compound azelaic acid diester is: 9-oxyylidene-9-(3,6-dioxaoctane-1-yloxy)nonanoic acid-3,6-dioxaoctane-1-yl ester, also known as: bis-diethoxydiglycol azelaic acid ester.

[0010] The present invention provides an application of an active substance in a preparation for promoting the penetration and absorption of active ingredients, characterized in that:

[0011] The above active substance is a compound shown in the following structure:

[0012]

[0013] The active ingredient is selected from niacinamide, phenethyl resorcinol, 4-butyl resorcinol, resveratrol, glycyrrhizin, magnolol, tetrahydromagnoliol, capsaicin, ceramide NP, ceramide AP, ceramide AS, 10-hydroxydecanoic acid, hydroxyphenylpropionamide benzoic acid, dihydromyricetin, vitamin A and structural analogs of the above substances.

[0014] The present invention also provides an application of an active substance in a preparation for increasing the solubility of an active ingredient, characterized in that:

[0015] The above active substance is a compound shown in the following structure:

[0016]

[0017] The active ingredient is selected from phenylethylresorcinol, 4-butylresorcinol, resveratrol, glycyrrhizin, magnolol, tetrahydromagnoliol, capsaicin, ceramide NP, ceramide AP, ceramide AS, 10-hydroxydecanoic acid, hydroxyphenylpropionamidebenzoic acid, dihydromyricetin, vitamin A and structural analogs of the above substances.

[0018] The present invention also provides an application of an active substance in a multifunctional preparation as an oil control agent, a penetration enhancer, a solubilizer, and a moisturizer, characterized in that:

[0019] The above active substance is a compound shown in the following structure:

[0020]

[0021] In addition, the present invention also provides a composition, characterized in that:

[0022] Contains the following ingredients:

[0023] a) active ingredients, the content of which accounts for 0.1-90.0% of the total weight of the composition, preferably in the range of 0.1-20.0% by weight, 20.0-50.0% by weight, and the content and dosage of the components vary based on the differences in product properties;

[0024] b) A cosmetically acceptable carrier, the content of which accounts for 10.0-99.9% of the total weight of the composition, preferably in the range of 50.0-80.0% by weight, 80.0-99.9% by weight. The content and amount of the component may vary based on the properties of the product.

[0025] The above active substance is a compound shown in the following structure:

[0026]

[0027] Furthermore, the above composition is characterized by:

[0028] The above-mentioned cosmetically acceptable carrier is selected from at least one of the following categories i-iv:

[0029] i. a diol or triol having 3 to 10 carbon atoms;

[0030] ii. esters having 6 to 36 carbon atoms;

[0031] iii. branched and unbranched alkyl or alkenyl alcohols;

[0032] iv. Branched and unbranched hydrocarbons and waxes, cyclic or linear silicone oils and dialkyl ethers having 6 to 24 carbon atoms.

[0033] Furthermore, the above composition is characterized in that:

[0034] The cosmetically acceptable carrier is selected from glycerol, 1,2-propylene glycol, 1,3-propylene glycol, 2-methylpropane-1,3-diol, 1,2-butylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,3-pentanediol, 1,5-pentanediol, 2,4-pentanediol, 2-methylpentane-2,4-diol, 1,2-hexanediol, 1,6-hexanediol, 1,2-octanediol, dipropylene glycol, diethyl phthalate, diethylhexyl 2,6-naphthalene dicarboxylate, diisopropyl adipate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate , isooctyl stearate, isononyl stearate, isononyl isononanoate, 3,5,5-trimethylhexyl 3,5,5-trimethylhexyl, 2-ethylhexyl isononanoate, 2-ethylhexyl 3,5,5-trimethylhexyl, 2-ethylhexyl 2-ethylhexyl, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, cetearyl ethylhexanoate, stearyl heptanoate, stearyl octanoate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, oleyl oleate, erucyl erucate, 2-ethylhexyl isostearate, isotridecanol isononanoate, 2-ethylhexyl coconut oil, C benzoate 121-15-alkyl esters, cetyl palmitate, triethyl citrate, triacetin (triacetyl citrate), benzyl benzoate, benzyl acetate, vegetable oils (preferably olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil), triglycerides, in particular stearin, triisononanoin, laurin or medium-chain triglycerides with identical or different CC fatty acid groups (so-called medium-chain triglycerides, in particular caprylic / capric triglycerides such as caprylic triglyceride, capric triglyceride), decanol, decenol, caprylic alcohol, Octenol, dodecanol, dodecenol, octadienol, decanol, dodecadienol, oleyl alcohol, ricinoleyl alcohol, erucyl alcohol, stearyl alcohol, isostearyl alcohol, cetyl alcohol, lauryl alcohol, myristyl alcohol, arachidyl alcohol, linoleyl alcohol, linoleyl alcohol, hexyldecanol, octyldodecanol (especially 2-octyl-1-dodecanol), cetearyl alcohol, behenyl alcohol, jojoba oil, isoeicosane, dicaprylyl ether, mineral oil, petrolatum, squalane, squalene, cyclomethicone, decamethylcyclopentasiloxane, undecamethylcyclotrisiloxane, polydimethylsiloxane, polymethylphenylsiloxane, water.

[0035] Furthermore, the above composition is characterized in that:

[0036] Also includes,

[0037] The content of the fragrance with a ClogP value of 3-5 is 0.1-5.0% by weight of the total composition.

[0038] Furthermore, the above composition is characterized in that:

[0039] The above-mentioned flavoring agent is selected from α-amylcinnamaldehyde, α-hexylcinnamaldehyde, 2-phenoxyethyl isobutyrate, methyl dihydrojasmonate, 4,6,6,7,8,8-hexamethyl-1,3,4,6,7,8-hexahydrocyclopenta[g]benzopyran, benzyl salicylate, 2-methyl-3-(4-tert-butylphenyl)propanal, 4,7-bridged methylene-3a,4,5,6,7,7a-hexahydro-5-indenyl acetate and / or 4,7-bridged methylene-3a, 4,5,6,7,7a-hexahydro-6-indenyl acetate, styroyl acetate, octahydro-2,3,8,8-tetramethyl-2-naphthone and / or 2-acetyl-1,2,3,4,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalene, hexyl salicylate, 4-tert-butylcyclohexyl acetate, 2-tert-butylcyclohexyl acetate, a-ionone, 4-(4-hydroxy-4-methylpentyl)-3-cyclohexenal, (E)- and / or (Z)- 3-Methylcyclopentadecen-5-one, 15-cyclopentadecen-11-lactone and / or 15-cyclopentadecen-12-lactone, 15-cyclopentadecalactone, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethanone, brazilic acid ethylene glycol ester, 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-butene-1-ol, a-santalol, 2,2-dimethyl-3-(3-methyl)- At least one of (4aR,5R,7aS,9R)-octahydro-2,2,5,8,8,9a-hexamethyl-4H-4a,9-methyleneazulenone (5,6-d)-1,3-dioxole), 1-(2,2,6-trimethylcyclohexyl)hexan-3-ol, benzyl acetone, methyl cinnamate, and 3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan.

[0040] Furthermore, the above composition is characterized in that:

[0041] The above composition has at least one of the following uses:

[0042] A. Products for treating, protecting, caring for and cleaning the skin and / or hair;

[0043] B. As a makeup product;

[0044] C. As a cosmetic.

[0045] It can be in the following forms or selected from the following products:

[0046]

[0043] The invention relates to a composition comprising an alcoholic or aqueous / alcoholic solution, dispersion, suspension, emulsion (preferably a cream, lotion or milk of the W / O, O / W or multiple emulsion, PIT emulsion, emulsion foam, microemulsion, nanoemulsion, Pickering emulsion type), an ointment, a paste, a gel (preferably a hydrogel, a hydrodispersible gel, an oleogel), a balm, a serum, a powder, a wipe, an eau de toilette, a cologne, a perfume, a stick, a roll-on, a (pump) spray, an aerosol, a leave-on skin care composition (preferably a facial care composition), a leave-on insect repellent composition, a sunscreen composition, a skin lightening composition, a self-tanning composition, an after-sun repair preparation, a shaving or after-shave composition, a depilatory composition, a hair care composition (preferably a conditioner, a hair lotion, a hair tonic, a styling cream, a pomade, a styling aid (preferably a gel or wax)), a decorative cosmetic composition (preferably a face powder, an eyelid cream, an eyeliner, a lip balm), a deodorant and / or an antiperspirant composition.

[0047] Functions and effects of the present invention:

[0048] The present invention has successfully developed an azelaic acid diester active ingredient and the use of azelaic acid diester as a functional product for oil control, active ingredient penetration enhancement, solubilization and moisturizing. The ingredient or composition can significantly improve the bioavailability of other ingredients in the formula. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 . Histogram of the results of 5α-reductase activity inhibition rate of samples; when the t-test method is used for statistical analysis, compared with the BC group, the significance is indicated by *, P-value < 0.05 is indicated by *, and P-value < 0.01 is indicated by **. Compared with the azelaic acid group, the significance is indicated by ##, P-value < 0.05 is indicated by #, and P-value < 0.01 is indicated by ##.

[0050] Figure 2 .In vitro percutaneous penetration dynamics curves of each active substance; the horizontal axis is time and the vertical axis is the cumulative penetration amount (μg / cm 2 ).

[0051] Figure 3 .Branch chart of fluorescence intensity statistical results.

[0052] Figure 4 .Graphical analysis of sample and blank comparison results. DETAILED DESCRIPTION

[0053] The present invention is capable of various modifications and various embodiments, and therefore specific embodiments are illustrated and described in the accompanying drawings. However, this is not intended to limit the present invention to specific implementations, but should be understood to include all modifications, equivalents, and even substitutes that fall within the concept and technical scope of the present invention.

[0054] This embodiment provides the use of bis-diethoxydiglycol azelate in a multifunctional preparation as an oil control agent, penetration enhancer, solubilizer, and moisturizer. It is generally used as a product for treating, protecting, caring for, and cleaning the skin and / or hair, or as a makeup product, or as a cosmetic. The product form may be an alcoholic or aqueous / alcoholic solution, dispersion, suspension, emulsion (preferably a cream, lotion or milk of the W / O, O / W or multiple emulsion, PIT emulsion, emulsion foam, microemulsion, nanoemulsion, Pickering emulsion type), ointment, paste, gel (preferably a hydrogel, a hydrodispersible gel, an oil gel), balm, serum, powder, wipes, eau de toilette, cologne, perfume, stick, roll-on, (pump) spray, aerosol, leave-on skin care composition (preferably a facial care composition), leave-on insect repellent composition, sunscreen composition, skin lightening composition, self-tanning composition, after-sun repair preparation, shaving or after-shave composition, depilatory composition, hair care composition (preferably a conditioner, hair lotion, hair tonic, styling cream, pomade, styling aid (preferably a gel or wax)), decorative cosmetic composition (preferably a face powder, eyelid cream, eyeliner, lip gloss), deodorant and / or antiperspirant composition.

[0055] In this embodiment, the composition comprises 0.1-90.0% of bis-diethoxydiglycol azelaic acid ester by weight of the total composition, and 10.0-99.9% of a cosmetically acceptable carrier by weight of the total composition. Based on the difference in product properties, the component contents and dosages vary.

[0056] Cosmetically acceptable carriers include, for example, glycerol, 1,2-propylene glycol, 1,3-propylene glycol, 2-methylpropane-1,3-diol, 1,2-butylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,3-pentanediol, 1,5-pentanediol, 2,4-pentanediol, 2-methylpentane-2,4-diol, 1,2-hexanediol, 1,6-hexanediol, 1,2-octanediol, dipropylene glycol, diethyl phthalate, diethylhexyl 2,6-naphthalene dicarboxylate, diisopropyl adipate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate , isooctyl stearate, isononyl stearate, isononyl isononanoate, 3,5,5-trimethylhexyl 3,5,5-trimethylhexyl, 2-ethylhexyl isononanoate, 2-ethylhexyl 3,5,5-trimethylhexyl, 2-ethylhexyl 2-ethylhexyl, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, cetearyl ethylhexanoate, stearyl heptanoate, stearyl octanoate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, oleyl oleate, erucyl erucate, 2-ethylhexyl isostearate, isotridecanol isononanoate, 2-ethylhexyl coconut oil, C benzoate 12-15-alkyl esters, cetyl palmitate, triethyl citrate, triacetin, benzyl benzoate, benzyl acetate, vegetable oil, glyceryl stearate, triisononanoin, glyceryl laurate, caprylic / capric triglyceride, decyl alcohol, decenol, octanol, octenol, dodecanol, dodecenol, octadienol, decanol, dodecadienol, oleyl alcohol, ricinoleyl alcohol, erucyl alcohol, stearyl alcohol, isostearyl alcohol, cetyl alcohol, lauryl alcohol, myristyl alcohol, arachidyl alcohol, linoleyl alcohol, linoleyl alcohol, hexyldecyl alcohol, octyldodecanol, cetearyl alcohol, behenyl alcohol, jojoba oil, isoeicosane, dicaprylyl ether, mineral oil, petrolatum, squalane, squalene, cyclomethicone, decamethylcyclopentasiloxane, undecamethylcyclotrisiloxane, polydimethylsiloxane, polymethylphenylsiloxane, water, and the like cosmetic preparations commonly used in the art.

[0057] In addition, based on the needs of the product, a fragrance with a ClogP value of 3-5 can be added in an amount of 0.1-5.0% by weight of the total weight of the composition, such as: a-amyl cinnamaldehyde, a-hexyl cinnamaldehyde, 2-phenoxyethyl isobutyrate, methyl dihydrojasmonate, 4,6,6,7,8,8-hexamethyl-1,3,4,6,7,8-hexahydrocyclopenta[g]benzopyran, benzyl salicylate, 2-methyl-3-(4-tert-butylphenyl)propanal, 4,7-bridged methylene-3a,4,5, 6,7,7a-hexahydro-5-indenyl acetate and / or 4,7-methano-3a,4,5,6,7,7a-hexahydro-6-indenyl acetate, styroyl acetate, octahydro-2,3,8,8-tetramethyl-2-naphthyl acetonide and / or 2-acetyl-1,2,3,4,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalene, hexyl salicylate, 4-tert-butylcyclohexyl acetate, 2-tert-butylcyclohexyl acetate, α-ionone, 4-(4-hydroxy-4-methylpentyl)acetate, (E)- and / or (Z)-3-methylcyclopentadecen-5-one, 15-cyclopentadecen-11-lactone and / or 15-cyclopentadecen-12-lactone, 15-cyclopentadecen-1, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethanone, brazic acid ethylene glycol ester, 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-butene-1-ol, a-santalol, 2,2- At least one of dimethyl-3-(3-methylphenyl)-propanol, allyl heptanoate, 4-methylacetophenone, (4aR,5R,7aS,9R)-octahydro-2,2,5,8,8,9a-hexamethyl-4H-4a,9-methyleneazulenone(5,6-d)-1,3-dioxole), 1-(2,2,6-trimethylcyclohexyl)hexan-3-ol, benzyl acetone, methyl cinnamate, and 3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan.

[0058] The following is a combination of the above schemes as Experimental Example 1 to test performance and other items.

[0059] Example 1. Preparation of an oil-controlling moisturizing gel

[0060] (1) Weigh the raw materials required for oil control condensation according to the table below.

[0061] (2) The preparation method of the oil-control moisturizing gel is as follows: ① The raw materials of phase A are mixed evenly, and heated at 85°C with stirring until completely dissolved. ② Cool down to 65°C, add the raw materials of phase B, and stir to dissolve. ③ Cool down to 45°C, add the raw materials of phase C, and stir evenly to obtain the oil-control moisturizing gel.

[0062]

[0063] Example 1 Comparative Example 1.

[0064] (1) Weigh the raw materials required for oil control condensation according to the table below.

[0065] (2) The preparation method of the oil-control moisturizing gel is as follows: ① The raw materials of phase A are mixed evenly, and heated at 85°C with stirring until completely dissolved. ② The temperature is lowered to 65°C, and the raw materials of phase B are added, and stirred to dissolve. Comparative Example 1 is obtained.

[0066]

[0067] Example 1 Comparative Example 2.

[0068] (1) Weigh the raw materials required for oil control condensation according to the table below.

[0069] (2) The preparation method of the oil-control moisturizing gel is as follows: ① The raw materials of phase A are mixed evenly, and heated at 85°C with stirring until completely dissolved. ② Cool down to 65°C, add the raw materials of phase B, and stir to dissolve. ③ Cool down to 45°C, add the raw materials of phase C, and stir evenly to obtain Comparative Example 2.

[0070]

[0071] Example 1 Comparative Example 3.

[0072] (1) Weigh the raw materials required for oil control condensation according to the table below.

[0073] (2) The preparation method of the oil-control moisturizing gel is as follows: ① The raw materials of phase A are mixed evenly, and heated at 85°C with stirring until completely dissolved. ② Cool down to 65°C, add the raw materials of phase B, and stir to dissolve. ③ Cool down to 45°C, add the raw materials of phase C, and stir evenly to obtain Comparative Example 3.

[0074]

[0075] Example 2.

[0076] 2-1. Test on the oil control effect of bis-diethoxydiglycol azelaic acid ester

[0077] 2.1 Mechanism and efficacy

[0078] By competitively inhibiting 5-α reductase (i.e. inhibiting the conversion of excessive testosterone into dihydrotestosterone), it inhibits excessive secretion of oil in the sebaceous glands and achieves an oil-control effect.

[0079] 2.2 Test Purpose and Basis

[0080] This test is based on the 5α-reductase inhibition rate test and is carried out according to the "Biochemical Experimental Method Based on 5α-Reductase Inhibition Rate Detection" to evaluate the oil control effect of the sample.

[0081] 2.3 Test materials

[0082] 2.3.1 Samples and reagents

[0083] Test product: Bis-diethoxydiglycol azelaic acid ester (English trade name is -PE Plus, the Chinese product name is Plus)(Source: Keqin Laboratory), azelaic acid, 5α-reductase, finasteride, testosterone, and NADPH.

[0084] 2.3.2 Main equipment

[0085] ELISA instrument, water-tight constant temperature incubator, high-speed desktop refrigerated centrifuge

[0086] 2.4 Test Method

[0087] 2.4.1 Test Grouping

[0088]

[0089] 2.4.25 α-Reductase Inhibition Assay

[0090] (1) Sample tube: Add 1 mL sample working solution, 1 mL enzyme solution, 1 mL NADPH solution and 1 mL testosterone solution into a test tube, set up 3 parallel tubes, shake gently, use a pipette to take 200 μL into a 96-well ELISA plate, put it into the ELISA reader for detection, and measure the absorbance at 340 nm, which is the first measurement value A. 样品0 After the sample is incubated at 37°C for 20 minutes, it is placed in an ELISA reader for detection. The absorbance value at 340 nm is the second measurement value A. 样品20 .

[0091] (2) Enzyme tube: Add 1 mL PBS solution, 1 mL enzyme solution, 1 mL NADPH solution and 1 mL testosterone solution into a test tube. Set up 3 parallel tubes. Gently shake. Use a pipette to transfer 200 μL into a 96-well ELISA plate. Place the plate in an ELISA reader for detection. Measure the absorbance at 340 nm, which is the first measurement value A. 酶0 After the sample is incubated at 37°C for 20 minutes, it is placed in an ELISA reader for detection. The absorbance value at 340 nm is the second measurement value A. 酶20 ; Perform blank and positive control tests at the same time.

[0092] 2.4.3 Calculation formula

[0093]

[0094] 2.5 Test results, see Figure 1 .

[0095] Compared with the BC group, the inhibitory effect of the PC group on 5α-reductase activity increased significantly, indicating that the positive control of this test was effective. -PE Plus and azelaic acid have a significant inhibitory effect on 5α-reductase activity at concentrations of 1mg / mL, 5mg / mL, 10mg / mL, and 50mg / mL. -PE plus had a better inhibitory effect on 5α-reductase activity than the azelaic acid group.

[0096] 2.6 Conclusion

[0097] Compared with the control group, the samples -PE Plus and azelaic acid at concentrations of 1mg / mL, 5mg / mL, 10mg / mL, and 50mg / mL have a significant inhibitory effect on 5α-reductase activity, and have an oil control effect. -PEPlus has better oil control effect than azelaic acid.

[0098] 2-2. Effect evaluation of experimental example 1 and comparative examples 1-3

[0099] 2.7. Evaluation method: 80 volunteers (volunteer selection criteria: oily skin, oily T zone) were recruited, and each group consisted of 20 volunteers (10 males and 10 females), who used the products of Example 1, Comparative Example 1, Comparative Example 2, and Comparative Example 3 respectively. The prescribed frequency of use was: use twice a day, the test time was 30 days, and the evaluation was carried out 12 hours after the last use.

[0100] 2.8. Evaluation items

[0101] 2.8.1. Oil removal performance

[0102] Commercially available oil-absorbing paper was used to wipe the forehead, and the paper was divided into levels I (less than 5%), II (5-10%), III (10-20%), IV (20-30%) to V (greater than 30%) according to the degree of oil absorption.

[0103] The test results are as follows:

[0104] Level I Level II Level III Level IV V-Class Experimental Example 1 17 people 2 people 1 person 0 people 0 people Comparative Example 1 0 people 0 people 6 people 11 people 3 people Comparative Example 2 11 people 3 people 5 people 1 person 0 people Comparative Example 3 9 people 6 people 4 people 1 person 0 people

[0105] Example 3. Experiment on promoting the penetration of poorly soluble components

[0106] 3.1 Experimental Purpose and Description

[0107] Compare bis-diethoxydiglycol azelaic acid ester (English trade name is -PE Plus, the Chinese product name is Plus) (Source: Keqin Laboratory) and ethoxydiglycol, PPG-24-glyceryl polyether-24 glyceryl resveratrol, phenethyl resorcinol, glycyrrhizin, tetrahydromagnanol, capsaicin, ceramide NP, ceramide AP, ceramide AS, 10-hydroxydecanoic acid, hydroxyphenylpropionamide benzoic acid, dihydromyricetin, and vitamin A promote the permeation skin absorption rate.

[0108] 3.2 Materials and samples

[0109] High performance liquid chromatography, Strat-M skin membrane, Franz-type diffusion cell, phosphate buffered saline (PBS), ultrapure water, acetonitrile (CH3CN)

[0110] sample: -PE Plus (Source: Keqin Laboratory), PPG-24-glyceryl polyether-24, ethoxydiglycol.

[0111] 3.3 Experimental plan

[0112] 3.3.1 Preparation of samples for permeation enhancement

[0113] The preparation methods of the embodiments and comparative examples are as follows: according to the active substances (resveratrol, phenethyl resorcinol, niacinamide, glabridin, tetrahydromagnanol, capsaicin, ceramide NP, ceramide AP, ceramide AS, 10-hydroxydecanoic acid, hydroxyphenylpropionamide benzoic acid, dihydromyricetin, vitamin A), the penetration enhancer ( -PE Plus, ethoxydiglycol, PPG-24-glycerol polyether-24 glycerol), water = 0.1:10: the remainder of the mass percentage concentration configuration of the test solution totaling 39 groups.

[0114] 3.3.2 Testing

[0115] (1) Before the experiment, the Strat-M skin membrane was fixed in a Franz-type diffusion tank with a diffusion area of ​​0.785 cm 2 , place 0.4g of test sample at the upper drug application end, and place 3 parallel portions of PBS solution containing 50% CH3CN at the lower drug receiving end, with constant temperature 35±1℃ magnetic stirring to balance the concentration distribution in the drug receiving end.

[0116] (2) Take 0.2 mL of sample from the receiving pool at 0.5 h, 1.0 h, 2.0 h, 3.0 h, and 4.0 h, filter through a 0.22 μm microporous filter membrane, and inject 20 μL into a high performance liquid chromatograph for analysis.

[0117] (3) Calculate the cumulative penetration of active ingredients (in terms of active substances) at the four sampling points (μg / cm 2 ), the in vitro percutaneous penetration dynamic curve is as follows Figure 2 shown.

[0118] 3.4 Experimental Results

[0119] Taking active ingredients as indicators, at the same concentration, The resveratrol permeation in the -PE Plus group was higher than that in the +ethoxydiglycol and +PPG-24-glycerol groups, and the difference in permeation gradually widened over time, indicating that -PE Plus can increase the transdermal absorption rate and bioavailability of active ingredients, and is superior to PPG-24-glyceryl polyether-24 and ethoxydiglycol.

[0120] Example 4. Experiment on promoting the penetration of water-soluble components

[0121] 4.1 Experimental Purpose and Basis

[0122] This experiment is based on a 3D epidermal skin model According to the 3D epidermal skin model Study the penetration behavior of samples and conduct tests to evaluate the skin penetration behavior of the samples to be tested.

[0123] 4.2 Test materials

[0124] 4.2.1 Samples and reagents

[0125] Bis-diethoxydiglycol azelaic acid ester (English trade name is -PE Plus, the Chinese product name is Plus) (source: Keqin Laboratory), EpiGrowth culture medium, PBS buffer solution, sodium fluorescein, 4% paraformaldehyde tissue fixative.

[0126] 4.2.2 Main equipment

[0127] CO2 incubator (Thermo, 150I), clean bench (Sujing Antai, SW-CJ-1F), fluorescence microscope (Olympus, BX43).

[0128] 4.3 Test Method

[0129] 4.3.1 Test Grouping

[0130] The test group information is shown in the following table:

[0131]

[0132] 4.4 Test steps

[0133] 1) According to the trademark test group, transfer the model to a 6-well plate (add 0.9 mL of model culture medium in advance) and mark the test group number on the 6-well plate.

[0134] 2) Take 25 μL of the sample and add it to the surface of the model, so that the sample is evenly distributed on the surface of the model, and place it in a CO2 incubator (37°C, 5% CO2) for incubation for 24 hours.

[0135] 3) Penetration detection: After the drug incubation, the model was fixed and frozen into sections, and the sections were photographed and the fluorescence intensity values ​​were calculated.

[0136] 4) Statistical analysis of results: GraphPad Prism was used for plotting, and the results were expressed as Mean ± SD. The t-test was used for statistical analysis between groups. All statistical analyses were two-tailed. P < 0.05 was considered to be significantly different, and P < 0.01 was considered to be extremely significantly different.

[0137] 4.4 Test Results

[0138] The fluorescence intensity analysis results of the samples are shown in Figure 3 As shown. The IOD value results show that based on the 3D epidermal skin model At 6h and 24h, compared with the previous time point, the samples of fluorescein sodium -100ppm, The cumulative amount of fluorescent substances in the -PE Plus+Sodium Fluorescein-2%+100ppm group increased significantly.

[0139] 4.5 Conclusion

[0140] The results of fluorescence microscopy showed that at 6h and 24h, the samples were -PE Plus + sodium fluorescein -2% + 100ppm group has a significant increase in the accumulation of fluorescent substances, indicating that -PE Plus promotes the penetration of sodium fluorescein.

[0141] Example 5. A method comprising - Preparation of PE Plus solution

[0142] (1) Weigh the required raw materials according to the table below.

[0143] (2) Stir and dissolve to obtain -PE Plus aqueous solution, set aside.

[0144] Table 2% -PE Plus Solution

[0145]

[0146] Example 6. Moisturizing effect test

[0147] 6.1 Safety Testing - Skin Patch Test

[0148] Test substance: 2% obtained in Example 5 -PE Plus aqueous solution.

[0149] Negative control: filter

[0150] Number of participants: 30, half male and half female, aged between 20 and 55 years old, all meeting the criteria for subjects.

[0151] Test process: 30 subjects met the test criteria. The samples of the test subjects were placed in the small chamber of the spot tester, with a dosage of about 0.020mL-0.025mL, and no substance was placed in the control well; the spot tester with the test substance was applied to the back or curved side of the forearm of the subject with a low-allergenic tape, and the palm of the hand was gently pressed to make it evenly applied to the skin for 24 hours; after removing the spot tester with the test substance, the skin reaction was observed according to the standards shown in Table 5 at 30 minutes, 24 hours and 48 hours, and the observation results were recorded. The grading standards are shown in the following table:

[0152]

[0153] The test results are shown in the following table:

[0154]

[0155] As can be seen from the above table, the 2% obtained in Example 5 of the present invention -PE Plus aqueous solution is non-irritating to the skin.

[0156] 6.2 Human clinical trials

[0157] 6.2.1 Test Purpose: To evaluate whether the cosmetic has moisturizing effect by measuring the moisture content of the stratum corneum of the test (test) area and the control (blank) area at multiple time points.

[0158] Reference method: QB / T 4256-2011 Guidelines for the evaluation of moisturizing efficacy of cosmetics

[0159] 6.2.2 Test object: obtained in Example 7 -PE Plus aqueous solution

[0160] 6.2.3 Test equipment

[0161] Corneometer (Courage & Khazaka, Germany) for testing the moisture content of the stratum corneum; 10-100 μL pipette.

[0162] 6.2.4 Test environment

[0163] Environmental requirements: Temperature: 21.0℃±1.0℃; Humidity: 50%±10%;

[0164] 6.2.5 Requirements for subjects

[0165] 6.2.5.1 Have signed the informed consent form and voluntarily participate in this test

[0166] All subjects received verbal and paper informed consent in accordance with local laws and regulations. Informed consent explains the nature, purpose and potential risks of participating in the study, and emphasizes the voluntary nature of participating in the test. Subjects can withdraw from the study at any time for any reason. All subjects can ask questions about the study and are given sufficient time to consider before signing. All informed consent must be signed before the start of the study.

[0167] 6.2.5.2 Selection criteria

[0168] ① Both men and women are welcome, but women are preferred;

[0169] ②Age 18 to 60 years old (at the start of the trial);

[0170] ③Those who have troubles such as dry skin on the inner forearm;

[0171] ④ The basic value of the capacitive skin moisture meter in the forearm test area is between 15 and 45 (Corneometer Unit, CU);

[0172] ⑤ The subjects should not be sensitive to commonly used cosmetics;

[0173] ⑥ The subject has not participated in other clinical studies in the past three months;

[0174] 6.2.5.3 Exclusion criteria

[0175] ① Use of antihistamines in the past week or immunosuppressants in the past month;

[0176] ② Any anti-inflammatory drugs have been used in the tested area in the past two months;

[0177] ③ Patients with insulin-dependent diabetes;

[0178] ④ Patients with respiratory diseases who are receiving treatment;

[0179] ⑤ Women who are breastfeeding or pregnant;

[0180] ⑥ People with allergic constitution, allergic dermatitis, and skin diseases or a history of diseases;

[0181] ⑦ People who are receiving dermatological treatment, or subjects who have taken hydroxy acids, whitening and anti-aging drugs within one month;

[0182] ⑧ The test area has large birthmarks, scratches, white spots, pigmented moles, keloids and other skin manifestations that affect the test. In addition, the person in charge of the test judges that the population is not suitable as the subject of this test.

[0183] 6.2.5.4 Restrictions

[0184] ①During the test, drinking hot water and spicy food are prohibited;

[0185] ②During the test, frequent entry and exit of the constant temperature and humidity room is prohibited;

[0186] ③During the test, it is prohibited to cover the inner side of the forearm or touch the test area;

[0187] 6.2.5.5 Screening failure, subject dropout and replacement

[0188] The subjects who were not included in the study were those who signed the informed consent but failed to be included in the study because they did not meet the inclusion / exclusion criteria.

[0189] If a subject leaves after randomization or group assignment, it is considered to be dropped out. If a subject does not complete the study for any reason, it is considered to be dropped out and no additional supplement will be made.

[0190] Shedding Guidelines:

[0191] Subject dropout consent: Subjects can withdraw at any time for any reason (according to the Helsinki Declaration);

[0192] Adverse event / serious adverse event: any event that the investigator believes is detrimental to the subjects if the trial is continued;

[0193] Not following the protocol;

[0194] Subjects were lost to follow-up;

[0195] Other reasons: Reasons for other subjects to withdraw.

[0196] In other cases, the investigator believes that continued participation in the trial would be disadvantageous to the subject;

[0197] This commission is terminated.

[0198] The CRF form must be filled in until the screening fails or drops out. All subjects who end the trial early must be recorded on the flow sheet by the investigator or research team.

[0199] 6.2.6 Observation and test areas

[0200] 31 volunteers were randomly selected from the inner skin of the left / right forearm as the experimental group and the control group. Single trial test.

[0201] 6.2.7 Observation and test items

[0202] Instrumental tests were performed on the subjects four times before use, 2h after use, 4h after use, and 8h after use.

[0203] ① Water content of stratum corneum: Use Corneometer to test 3 times and take the average value.

[0204] ②Parameter explanation: The higher the value, the higher the water content of the skin's stratum corneum.

[0205] ③Result determination: After using the product, the increase in moisture content of the stratum corneum in the test area is significantly higher than that in the blank area, indicating that the test sample has a moisturizing effect.

[0206] 6.2.8 Test process

[0207] ① At the first visit, the experiment was explained to the subjects and they signed the informed consent form.

[0208] ② Before the test on the inner forearm of the visiting subject Do not use any products (cosmetics or topical medicines), Do not contact water. Before the test, the subjects need to clean the inner forearms of both hands uniformly, and the cleaning method is to wipe them clean with dry tissue paper. The measurement area should be marked on the inner forearms of both hands of the subjects. The test area should be at least 3cm*3cm. Multiple areas can be marked on the same arm at the same time, and the interval between each test area should be at least 1cm.

[0209] ③Screen the subjects participating in the trial according to the trial requirements.

[0210] ④ After the qualified subjects clean the test area, they should rest in a constant temperature and humidity room for 30 minutes without drinking water or beverages. The forearm is exposed and placed in the test state, and remain relaxed. After 30 minutes, the instrument test is carried out, and the moisture content of the stratum corneum is measured with a Corneometer. The sample application area and the blank control area should be randomly distributed in the marked areas of the left and right arms to ensure that the positions of all products and blank areas are statistically balanced. The sample is measured at (2.0±0.1)mg / cm 2 Apply the sample once with the dosage specified, apply the sample evenly on the test area with latex finger cots, and record the actual amount of sample applied.

[0211] ⑤After adjusting the instrument according to the instrument manual, measure the product area and the blank control area. First, measure the initial value of each test area (before using the sample), and then measure the skin moisture content of the sample area and the blank control area after the set time of 2h, 4h, and 8h.

[0212] 6.2.9 Data Statistical Analysis Methods

[0213] GraphPad Prism software was used to perform descriptive statistics on each measurement value, including quantity, mean, standard deviation, minimum, median and maximum value.

[0214] Calculate the difference between the initial value of each test area and the measured value at other time points, and then use this difference to statistically analyze the differences between the product area and the blank control area at different time points.

[0215] If the test data is normally distributed, the t-test method is used for statistical analysis; if the test data is non-normally distributed, the rank sum test method is used for statistical analysis. The statistical method significance level p<0.050.

[0216] 6.2.10 Test results

[0217] The test results of stratum corneum moisture content are shown in the table below, and the data comparison chart is shown in Figure 4 .

[0218]

[0219] 6.2.11 Conclusion

[0220] According to QB / T 4256-2011 Guidelines for Evaluation of Moisturizing Effect of Cosmetics, -PE Plus aqueous solution was tested.

[0221] The test subjects (31 people) used the test sample once, and the test results of the sample area and the blank control area showed that:

[0222] 1. After using the test sample for 2 hours, compared with not using any product, the moisture content of the stratum corneum increased significantly (P<0.001), indicating that the test sample has a 2-hour moisturizing effect.

[0223] 2. Compared with not using any product, the moisture content of the stratum corneum increased significantly after using the test sample for 4 hours (P<0.001), indicating that the test sample has a 4-hour moisturizing effect.

[0224] 3. After using the test sample for 8 hours, compared with not using any product, the moisture content of the stratum corneum increased significantly (P<0.001), indicating that the test sample has an 8-hour moisturizing effect.

[0225] Although the above description is centered on the embodiment, it is only an example and does not limit the present invention. It is clear to those skilled in the art that various modifications and applications not illustrated above can be made within the scope of the essential characteristics of the present embodiment. For example, each component specifically shown in the embodiment can be implemented after being modified. Moreover, various differences related to such modifications and applications should be interpreted as being included in the scope of the present invention as defined in the attached claims.

Claims

1. The use of the active substance as a moisturizer, characterized in that: The active substance is a compound shown in the following structure: 。 2. The use of an active substance in a preparation for promoting the penetration and absorption of an active ingredient, characterized in that: The active substance is a compound shown in the following structure: ； The active ingredient is selected from niacinamide, phenethylresorcinol, 4-butylresorcinol, resveratrol, glabridin, magnolol, tetrahydromagnols, capsaicin, ceramide NP, ceramide AP, ceramide AS, 10-hydroxydecanoic acid, hydroxyphenylpropionamide benzoic acid, dihydromyricetin, vitamin A and structural analogs of the above substances.

3. Use of an active substance in a preparation for increasing the solubility of an active ingredient, characterized in that: The active substance is a compound shown in the following structure: ； The active ingredient is selected from phenylethylresorcinol, 4-butylresorcinol, resveratrol, glycyrrhizin, magnolol, tetrahydromagnoliol, capsaicin, ceramide NP, ceramide AP, ceramide AS, 10-hydroxydecanoic acid, hydroxyphenylpropionamide benzoic acid, dihydromyricetin, vitamin A and structural analogs of the above substances.

4. The use of active ingredients in a multifunctional preparation as an oil control agent, penetration enhancer, solubilizer, and moisturizer, characterized in that: The active substance is a compound shown in the following structure: 。 5. A composition, characterized in that: Contains the following ingredients: a) active matter, the content of which accounts for 0.1-90.0% of the total weight of the composition; b) a cosmetically acceptable carrier, the content of which accounts for 10.0-99.9% of the total weight of the composition; The active substance is a compound shown in the following structure: 。 6. A composition as claimed in claim 5, characterized in that: The cosmetically acceptable carrier is selected from at least one of the following categories i-iv: Diols or triols having 3 to 10 carbon atoms; Esters having 6 to 36 carbon atoms; iii. branched and unbranched alkyl or alkenyl alcohols; iv. Branched and unbranched hydrocarbons and waxes, cyclic or linear silicone oils and dialkyl ethers having 6 to 24 carbon atoms.

7. A composition as claimed in claim 5, characterized in that: The cosmetically acceptable carrier is selected from water, ethanol, glycerol, 1,2-propylene glycol, 1,3-propylene glycol, 2-methylpropane-1,3-diol, 1,2-butylene glycol, 1,3-butylene glycol, 1,2-pentanediol, 1,3-pentanediol, 1,5-pentanediol, 2,4-pentanediol, 2-methylpentane-2,4-diol, 1,2-hexanediol, 1,6-hexanediol, 1,2-octanediol, dipropylene glycol, diethyl phthalate, diethylhexyl 2,6-naphthalene dicarboxylate, diisopropyl adipate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, oleic acid n-Decyl stearate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 3,5,5-trimethylhexyl 3,5,5-trimethylhexyl, 2-ethylhexyl isononanoate, 2-ethylhexyl 3,5,5-trimethylhexyl, 2-ethylhexyl 2-ethylhexyl, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, cetearyl ethylhexanoate, stearyl heptanoate, stearyl octanoate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate, 2-ethylhexyl isostearate, isotridecanol isononanoate, 2-ethylhexyl coconut oil, C benzoate 12 -15-Alkyl Esters, Cetyl Palmitate, Triethyl Citrate, Triacetin, Benzyl Benzoate, Benzyl Acetate, Vegetable Oil, Glyceryl Stearate, Glyceryl Triisononanoate, Glyceryl Laurate, Caprylic / Capric Triglyceride, Decyl Alcohol, Decenol, Caprylic Alcohol, Octenol, Octenol, Dodecanol, Dodecanol, Octadienol, Decadienol, Dodecadienol, Oleyl Alcohol, Ricinoleyl Alcohol, Erucyl Alcohol, Stearyl Alcohol, Isostearyl Alcohol, Cetyl Alcohol, Lauryl Alcohol, Myristyl Alcohol, Arachidyl Alcohol, Linoleyl Alcohol, Linoleyl Alcohol, Hexyldecanol, Octyldodecanol, Cetearyl Alcohol, Behenyl Alcohol, Jojoba Oil, Isoicosane, Dicaprylyl Ether, Mineral Oil, Petrolatum, Squalane, Squalene, Cyclomethicone, Decamethylcyclopentasiloxane, Undecamethylcyclotrisiloxane, Dimethicone, Polymethylphenylsiloxane.

8. A composition as claimed in claim 5, characterized in that: Also includes, The content of the fragrance with a ClogP value of 3-5 is 0.1-5.0% by weight of the total composition.

9. A composition as claimed in claim 8, characterized in that: The fragrance is selected from α-amylcinnamaldehyde, α-hexylcinnamaldehyde, 2-phenoxyethyl isobutyrate, methyl dihydrojasmonate, 4,6,6,7,8,8-hexamethyl-1,3,4,6,7,8-hexahydrocyclopenta[g]benzopyran, benzyl salicylate, 2-methyl-3-(4-tert-butylphenyl)propanal, 4,7-thiadiazole-3a,4,5,6,7,7a-hexahydro-5-indenyl acetate and / or 4,7-thiadiazole-3a, 4,5,6,7,7a-hexahydro-6-indenyl acetate, styroyl acetate, octahydro-2,3,8,8-tetramethyl-2-naphthone and / or 2-acetyl-1,2,3,4,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalene, hexyl salicylate, 4-tert-butylcyclohexyl acetate, 2-tert-butylcyclohexyl acetate, a-ionone, 4-(4-hydroxy-4-methylpentyl)-3-cyclohexenal, (E)- and / or (Z)- 3-Methylcyclopentadecen-5-one, 15-cyclopentadecen-11-lactone and / or 15-cyclopentadecen-12-lactone, 15-cyclopentadecalactone, 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthyl)ethanone, brazilic acid ethylene glycol ester, 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-butene-1-ol, a-santalol, 2,2-dimethyl-3-(3-methyl)- At least one of (4aR,5R,7aS,9R)-octahydro-2,2,5,8,8,9a-hexamethyl-4H-4a,9-methyleneazulenone (5,6-d)-1,3-dioxole), 1-(2,2,6-trimethylcyclohexyl)hexan-3-ol, benzyl acetone, methyl cinnamate, and 3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan.

10. A composition according to any one of claims 5 to 9, characterized in that: The composition has at least one of the following uses; A. Products for treating, protecting, caring for and cleaning the skin and / or hair; B. As a makeup product; C. As a cosmetic.

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