An anti-acne cream comprising azelaic acid and a method for its preparation

Abstract

The application discloses an anti-acne cream containing azelaic acid, and preparation raw materials at least include azelaic acid powder 1-20 parts, silicone oil 10-30 parts, wherein the silicone oil at least includes alkyl polysiloxane with carbon atom number greater than or equal to 6. The application can make azelaic acid form a uniformly dispersed solution by using a polyol combination of butanediol, glycerol and pentanediol, and the polyol has less skin irritation, thereby avoiding the skin irritation problem caused by using ethanol as a solvent. Furthermore, the combination of cyclotrisiloxane, cyclopentasiloxane and cyclohexasiloxane is introduced to form a silicone oil-ethanol system, thereby improving the stability of the emulsion system and avoiding precipitation in high and low temperature environments and light environments.

Description

TECHNICAL FIELD

[0001] The present application relates to an anti-acne cream containing azelaic acid and a preparation method thereof, and relates to the field of A61K, in particular to the field of cosmetic preparations. BACKGROUND

[0002] Azelaic acid, also known as rhododendrol, CAS 123-99-9, can inhibit the growth of skin bacteria and Propionibacterium acnes in hair follicles, inhibit the activity of active oxygen free radicals, has bactericidal and anti-inflammatory effects, and can reduce the synthesis of filamentous keratin and prevent hyperkeratosis of hair follicles. It has a competitive inhibitory effect on 5α-reductase. It is widely used in functional cosmetics to improve common acne, blackheads and other skin problems. However, high concentrations of azelaic acid have certain irritant properties on the skin, especially for sensitive skin, which can easily cause skin redness and swelling. In addition, azelaic acid is easily soluble in organic solvents such as alcohols, and has low solubility in water. It is easy to precipitate in low-temperature environments. The stability of azelaic acid in powder form used in cosmetics is not good, the transdermal absorption effect is not good, and the bioavailability is low. Therefore, it is crucial to develop a composition that improves the stability of azelaic acid and reduces the skin irritation of azelaic acid

[0003] Chinese invention patent CN 111544381A discloses a skin topical administration composition containing azelaic acid, and gives a microemulsion composition with azelaic acid in a dissolved state, which can enhance the transdermal absorption of azelaic acid. The stable emulsion is prepared at room temperature, but the stability in low-temperature or high-temperature environments is not good. Chinese invention patent CN202010743287.2 discloses a topical compound formula for treating acne and a preparation method thereof, which introduces menthol, lauric azone, pyrithione zinc and other substances to make azelaic acid and solvent co-dissolve. However, the introduction of such substances can cause certain irritation to the skin, and the composition can only maintain phase equilibrium at room temperature, and can easily separate in light or low-temperature environments. SUMMARY

[0004] In order to reduce the irritation of high-concentration azelaic acid to the skin and improve the stability of azelaic acid in high and low temperature and light environments, the first aspect of the present application provides an anti-acne cream containing azelaic acid, and the preparation raw materials include at least azelaic acid powder 1-20 parts, silicone oil 10-30 parts, and the silicone oil includes at least alkyl polysiloxane with carbon atom number ≥6.

[0005] As a preferred embodiment, the silicone oil is a fatty hydrocarbon polysiloxane selected from one or a combination of cycloalkane polysiloxane and linear alkyl polysiloxane.

[0006] As a preferred embodiment, the silicone oil is selected from one or a combination of cyclopolymethylsiloxane, cyclopentamethylsiloxane, cyclohexasiloxane, dimethylpolysiloxane, polymethylsilsesquioxane, polydimethylcyclosiloxane, polymethylphenylsiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane.

[0007] As a preferred embodiment, the silicone oil is a combination of cyclopolymethylsiloxane, cyclopentamethylsiloxane, cyclohexasiloxane.

[0008] As a preferred embodiment, the preparation raw material of the anti-acne cream further comprises 1-5 parts of a surfactant, 5-20 parts of a humectant, 40-70 parts of a polyhydric alcohol, and 0.1-5 parts of a rheological modifier.

[0009] As a preferred embodiment, the surfactant is a polyethylene glycol modified silicone surfactant or a polyethylene glycol modified silicone ether surfactant, and the polyethylene glycol has a degree of polymerization of 9-15.

[0010] As a preferred embodiment, the surfactant is selected from one or a combination of PEG-10 dimethicone, PEG-12 dimethicone, PEG-11 methyl ether dimethicone.

[0011] As a preferred embodiment, the surfactant is PEG-10 dimethicone.

[0012] As a preferred embodiment, the humectant is selected from one or a combination of pseudo natural moisturizing factor, sugar humectant, amino acid humectant, natural extract humectant, and polymer humectant.

[0013] As a preferred embodiment, the polymer humectant is selected from one or a combination of polyether humectant, polyethylene glycol, polyglycerol, polypropylene glycol, and polysiloxane humectant.

[0014] As a preferred embodiment, the humectant is selected from one or a combination of PPG-12-butanol polyether-16, betaine, panthenol, polyglycerol-6, allantoin, nicotinamide, urea, and diglycerol.

[0015] As a preferred embodiment, the humectant is a combination of diglycerol, betaine, panthenol, and PPG-12-butanol polyether-16.

[0016] As a preferred embodiment, the polyhydric alcohol is selected from one or a combination of butanediol, 1,2-pentanediol, glycerol, dipropylene glycol, sorbitol, ethoxydiglycol, and xylitol.

[0017] As a preferred embodiment, the polyol is a combination of butanediol, glycerin, 1,2-pentanediol.

[0018] Applicants found in the experiment that the combination of butanediol, glycerin, and pentanediol, together with the combination of cyclomethicone, cyclopentasiloxane, and cyclohexasiloxane, can reduce the irritation of high-concentration azelaic acid composition and form a cream with excellent stability. The possible reason is that azelaic acid has bactericidal and anti-inflammatory effects, but high-concentration azelaic acid has certain irritation to the skin. The application has good dispersion effect on azelaic acid by adding a combination of multiple polyols, which can make azelaic acid uniformly dispersed in the solvent to form a uniform solution. Then the application uses a silicone oil-alcohol system, so that the uniformly dispersed azelaic acid solution can be wrapped in the silicone oil system, reducing the skin irritation of the azelaic acid solution, and the wrapped body of the combination of multiple siloxanes and the solution of polyols forms a stable emulsion system after homogenization and emulsification, improving the stability in high-temperature environment, low-temperature environment, and light, maintaining uniform texture, and preventing azelaic acid from precipitating.

[0019] As a preferred embodiment, the rheology modifier is selected from one or a combination of several of polydimethylsiloxane / vinyl dimethicone crosspolymer, silica, ethyl cellulose, lithium montmorillonite, sodium carboxymethyl cellulose, polyvinylpyrrolidone, sodium polyacrylate, and hydroxypropyl methyl cellulose.

[0020] As a preferred embodiment, the rheology modifier is a combination of polydimethylsiloxane / vinyl dimethicone crosspolymer and silica.

[0021] As a preferred embodiment, the preparation raw material of the anti-acne cream further includes other trace ingredients acceptable in cosmetics.

[0022] As a preferred embodiment, the preparation raw material of the anti-acne cream further includes bisabolol and ginger (ZINGIBER OFFICINALE) root extract.

[0023] The second aspect of the application provides a preparation method of an anti-acne cream containing azelaic acid, comprising the following steps:

[0024] (1) uniformly mix azelaic acid powder, polyol, and humectant, and heat to 65-85°C to obtain phase A;

[0025] (2) uniformly mix silicone oil, surfactant, and rheology modifier to obtain phase B;

[0026] (3) slowly pour phase A into phase B and homogenize and emulsify at 2500 rpm for 5-10 minutes to obtain the anti-acne cream.

[0027] Compared with the prior art, the present application has the following beneficial effects:

[0028] (1) The azaleic acid-containing acne cream described in the present application can make azaleic acid form a uniformly dispersed solution by using a polyol combination of butanediol, glycerol, and pentanediol, and the polyol has less skin irritation, thereby avoiding the skin irritation problem caused by ethanol as a solvent.

[0029] (2) The azaleic acid-containing acne cream described in the present application can form a silicone oil-alcohol system by introducing a combination of cyclomethicone, cyclopentamethicone, and cyclohexasiloxane, thereby improving the stability of the emulsion system and avoiding precipitation in high and low temperature environments and under light.

[0030] (3) The azaleic acid-containing acne cream described in the present application further introduces farnesol and ginger root extract raw materials, which can further soothe the skin, synergistically act with azaleic acid, achieve anti-inflammatory and antibacterial effects, reduce skin irritation, and repair acne-damaged skin. BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 is an azaleic acid acne cream with a mass percentage of 15% of commercially available azaleic acid;

[0032] Figure 2 is an azaleic acid acne cream of Example 3;

[0033] Figure 3 is the average erythema index content increase and decrease rate (%) before and after use. DETAILED DESCRIPTION

[0034] Example 1

[0035] An azaleic acid-containing acne cream, the preparation raw materials of which include azaleic acid powder 5 parts, silicone oil 13 parts, surfactant 3 parts, humectant 13 parts, polyol 63.5 parts, rheology modifier 2 parts, farnesol 0.5 parts, and ginger root extract 0.05 parts by weight.

[0036] The silicone oil is a combination of cyclomethicone, cyclopentamethicone, and cyclohexasiloxane, with a weight ratio of 8:3:2, cyclomethicone is purchased from CM TECH, model HM-CM01, cyclopentamethicone is purchased from SHIN-ETSU, model KF 995, and cyclohexasiloxane is purchased from HRS Co., Ltd., model HRC-C6.

[0037] The surfactant is PEG-10 dimethicone, which is purchased from KCC, model SERASOL SC86A.

[0038] The humectant is a combination of diglycerin, betaine, panthenol, PPG-12-buteth-16 in a weight ratio of 2:3:3:5, PPG-12-buteth-16 is purchased from Dow Chemical, model UCON50-HB-660.

[0039] The polyol is a combination of 1,2-butanediol, glycerin, 1,2-pentanediol in a weight ratio of 42.5:20:1.

[0040] The rheology modifier is a combination of dimethicone / vinyl dimethicone crosspolymer and silica in a weight ratio of 1:1, dimethicone / vinyl dimethicone crosspolymer is purchased from CHEMSIL, model SPECSIL K-13.

[0041] The ginger root extract is purchased from BIOSPECTRUM.

[0042] A preparation method of an anti-acne cream containing azelaic acid, comprising the following steps:

[0043] (1) uniformly mix azelaic acid powder, polyol, humectant, and heat to 75°C to obtain phase A;

[0044] (2) uniformly mix silicone oil, surfactant, and rheology modifier to obtain phase B;

[0045] (3) slowly pour phase A into phase B, homogenize and emulsify at 2500 rpm for 8 minutes to obtain the anti-acne cream.

[0046] Example 2

[0047] An anti-acne cream containing azelaic acid, the specific steps are the same as those of Example 1, except that azelaic acid powder is 7.5 parts, polyol is 60 parts, and silicone oil is 14 parts.

[0048] The silicone oil is a combination of cyclomethicone, cyclopentasiloxane, and cyclohexasiloxane in a weight ratio of 8:4:2.

[0049] The polyol is a combination of 1,2-butanediol, glycerin, 1,2-pentanediol in a weight ratio of 50:9:1.

[0050] Example 3

[0051] An anti-acne cream containing azelaic acid, the specific steps are the same as those of Example 1, except that silicone oil is 17 parts, humectant is 11 parts, and polyol is 61.5 parts,

[0052] The silicone oil is a combination of cyclomethicone, cyclopentasiloxane, and cyclohexasiloxane in a weight ratio of 8:6:3.

[0053] The moisturizing agent is a combination of diglycerin, betaine, panthenol, PPG-12-butanol polyether-16, with a weight ratio of 0:3:3:5;

[0054] The polyol is a combination of 1,2-butanediol, glycerol, 1,2-pentanediol, with a weight ratio of 55.5:5:1.

[0055] Example 4

[0056] An anti-acne cream containing azelaic acid, the specific steps are the same as in Example 1, except that azelaic acid powder is 10 parts, silicone oil is 12 parts, moisturizing agent is 11 parts, polyol is 61.5 parts,

[0057] The silicone oil is a combination of cyclomethicone, cyclopentamethicone, cyclohexasiloxane, with a weight ratio of 8:3:1;

[0058] The moisturizing agent is a combination of diglycerin, betaine, panthenol, PPG-12-butanol polyether-16, with a weight ratio of 0:3:3:5;

[0059] The polyol is a combination of 1,2-butanediol, glycerol, 1,2-pentanediol, with a weight ratio of 59.5:1:1.

[0060] Performance test

[0061] 1. Stability test: Examples 1-4 were respectively packaged in colorless transparent plastic wide-mouth bottles (not open). The glass bottles were respectively placed at -7, 4, 25, 27, 45℃, and under light (room temperature 25℃) conditions, and observed for 2 months; the degree of change was represented by 0-3, 0 for no obvious change in texture, 1 for acceptable slight changes (such as slight change in viscosity), 2 for unacceptable changes (such as obvious thickening, precipitation), and 3 for severe changes (such as severe volume reduction, layering, crystal precipitation). The test results are shown in Table 1. No azelaic acid precipitation was observed, and the product texture remained stable

[0062] 2. Safety test: 60 subjects were selected, and Example 3 was taken in the patch tester, and the control hole was the blank control group (Example 3 without azelaic acid); the patch tester with the test substance was attached to the flexor of the forearm of the test personnel, and the palm was pressed lightly to make it evenly attached to the skin for 24 hours; the skin irritation and sensitization were observed at 30 min, 24 h, and 48 h after the test substance patch tester was removed according to Table 5, and the observation results were recorded. The test results are shown in Table 3, and Table 2 is the skin reaction grading standard for skin occlusive patch test.

[0063] 3. Anti-acne and anti-redness human test: 60 volunteers with facial acne were selected and randomly divided into two groups, 30 people in each group. Example 3 and commercially available azelaic acid cream with 15% content were used for testing respectively. After washing the face with facial cleanser, the subjects rested for 15 minutes in a constant temperature and humidity room. Before using the product, the target acne was photographed using C-CUBE (PIXIENCE, France). The product was applied in the morning and evening every day, and the face of the subjects was photographed after 1d, 2d and 3d of product use. The images were captured and analyzed using software, and in 2D mode, redness was observed for vascular formation, inflammation or erythema. Through picture judgment, the lower the hemoglobin concentration, the better the anti-acne effect. The test results are shown in Figures 1-3 .

[0064] Figure 1 Example 3 is the azelaic acid anti-acne cream with 15% content commercially available; Figure 2 Example 3 is the azelaic acid anti-acne cream with 15% content commercially available; Figure 3 is the average redness index content increase and decrease rate (%) before and after use.

[0065] As can be seen from the figure, the anti-acne cream provided by the present application has better anti-acne and anti-redness effect although the azelaic acid content is lower.

[0066] Table 1

[0067]

[0068] Table 2

[0069]

[0070]

[0071] Table 3

[0072]

Claims

1. An anti-acne cream comprising azelaic acid, characterized in that, The preparation raw material comprises at least by weight parts: azelaic acid powder 5-10 parts, silicon oil 10-30 parts, surfactant 1-5 parts, humectant 5-20 parts, polyol 40-70 parts, rheological modifier 0.1-5 parts, the silicon oil comprises at least alkyl polysiloxane with carbon atom number≥6; The polyol is a combination of butanediol, glycerol and 1,2-pentanediol; The silicon oil is a combination of cyclotetrasiloxane, cyclopentasiloxane and cyclohexasiloxane.

2. The acne cream comprising azelaic acid according to claim 1, characterized in that, The surfactant is polyethylene glycol modified siloxane surfactant or polyethylene glycol modified siloxane ether surfactant, and the polyethylene glycol has a polymerization degree of 9-15.

3. The acne cream comprising azelaic acid according to claim 1, characterized in that, The humectant is selected from one or a combination of several of pseudo natural moisturizing factor, sugar humectant, amino acid humectant, natural extract humectant and polymer humectant.

4. The acne cream comprising azelaic acid according to claim 3, characterized in that, The polymer humectant is selected from one or a combination of several of polyether humectant, polyethylene glycol, polyglycerol, polypropylene glycol and polysiloxane humectant.

5. The acne cream comprising azelaic acid according to claim 1, characterized in that, The rheological modifier is selected from one or a combination of several of dimethicone / vinyl dimethicone crosspolymer, silica, ethyl cellulose, lithium montmorillonite, sodium carboxymethyl cellulose, polyvinylpyrrolidone, sodium polyacrylate and hydroxypropyl methyl cellulose.

6. A process for the preparation of an anti-acne cream comprising azelaic acid according to any one of claims 1 to 5, characterized in that, The method comprises the following steps: (1) uniformly mixing azelaic acid powder, polyol and humectant, and heating to 65-85℃ to obtain phase A; (2) uniformly mixing silicon oil, surfactant and rheological modifier to obtain phase B; (3) slowly adding phase A into phase B, and homogenizing and emulsifying at 2500 rpm for 5-10 minutes to obtain the acne-removing cream.

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