A high-concentration azelaic acid cream and its preparation process

Abstract

The present invention relates to the field of C07C51 / 285, and in particular to a high-concentration azelaic acid cream and a preparation process thereof, wherein the raw materials for preparation include: phase A, phase B, and phase C; the raw materials for preparation of phase A include: a solvent; the raw materials for preparation of phase B include: a polyether-based silicone polymer; and the raw materials for preparation of phase C include: azelaic acid. The azelaic acid content of the cream prepared by the present invention is as high as 20wt%. At this concentration, the high stability currently available in the prior art is achieved, and the cream remains stable for 30 days in an environment of 45°C and -10°C, without a sense of gravel or demulsification.

Description

Technical Field

[0001] The invention relates to the field of C07C51 / 285, and in particular to a high-concentration azelaic acid cream and a preparation process thereof. Background Art

[0002] Azelaic acid (also known as azelaic acid) can inhibit the proliferation of Propionibacterium acnes, and can also competitively inhibit the enzyme that produces dihydrotestosterone, reducing the excessive skin oil induced by dihydrotestosterone. At the same time, azelaic acid can also inhibit the activity of tyrosinase, so azelaic acid preparations are often used to make products for removing acne and acne marks. Azelaic acid is insoluble in water and oil at room temperature. There are two commonly used preparation technologies in the prior art. One is a nearly anhydrous system with polyols as solvents, and the other is to neutralize and ionize azelaic acid with alkali to increase water solubility. The products prepared by the two processes have poor skin feel and cannot fully exert the effect of azelaic acid.

[0003] CN112220741A discloses azelaic acid gel, its preparation method and application. An alcohol system is used as a solvent. The prepared azelaic acid gel can be used to treat acne. However, on the one hand, alcohol increases skin irritation, and on the other hand, the prepared colloid has a poor skin feel.

[0004] CN1611212 discloses azelaic acid cream and a preparation method thereof, which uses water as a solvent and adds an emulsifier to adjust the dispersibility. However, as the ambient temperature changes, the properties of the emulsifier change, resulting in changes in the stability of the cream.

[0005] It can be seen that both methods in the prior art have certain problems. The present invention specifically provides a high-concentration azelaic acid cream with good stability. Summary of the invention

[0006] The first aspect of the present invention provides a high-concentration azelaic acid cream, the preparation raw materials including: phase A, phase B, and phase C; the preparation raw materials of phase A include: solvent; the preparation raw materials of phase B include: polyether-based silicone polymer; the preparation raw materials of phase C include: azelaic acid.

[0007] As a preferred embodiment, the solvent is water and propylene glycol mixed in a weight ratio of (15-20):1.

[0008] As a preferred embodiment, the raw materials for preparing phase A also include: a thickener.

[0009] As a preferred embodiment, in the raw materials for preparing the phase A, the weight ratio of the solvent to the thickener is (52-56):1.

[0010] The present invention does not impose any particular limitation on the thickener, and includes but is not limited to hydrolyzed corn starch and sodium chloride.

[0011] As a preferred embodiment, the raw materials for preparing the C phase include: bisabolol; the bisabolol accounts for 0.2 wt % of the weight of azelaic acid.

[0012] As a preferred embodiment, the weight ratio of phase A, phase B and phase C is (9-12):(2-6):(2-6).

[0013] As a preferred embodiment, the viscosity (25° C.) of the polyether-based silicone polymer is less than 2300 mPa.s.

[0014] The solubility of azelaic acid in water is extremely low, and the effective dose is relatively high. It has poor storage stability, is easy to change color, and has many clinical research and development problems. In the prior art, low-concentration azelaic acid creams have little effect, and the addition of high-concentration azelaic acid can easily cause uneven dispersion and a gritty feeling and demulsification effect. The applicant found that when a certain amount of polyether-based silicone polymer is added to the system, the dispersion effect of azelaic acid can be significantly improved, especially when the viscosity of the polyether-based silicone polymer is less than 2300mPa.s, the prepared cream has no gritty feeling. It is speculated that the reason is that the polyether-based silicone polymer can increase the repulsion between azelaic acid molecules and inhibit the agglomeration of azelaic acid.

[0015] Preferably, the polyether-based silicone polymer includes at least one of cetyl PEG / PPG-10 / 1 polydimethylsiloxane, PEG PG coconut oil glucoside polydimethylsiloxane, lauryl polyglycerol, methoxy PEG propyl trimethoxy silane, and lauryl PEG polydimethylsiloxane.

[0016] Further preferably, the polyether-based silicone polymer is cetyl PEG / PPG-10 / 1 polydimethylsiloxane, and the viscosity (25° C.) is 1500-2300 mPa.s.

[0017] As a preferred embodiment, the raw materials for preparing the phase B also include: branched alkyl carboxylic acid polyglycerol ester emulsifier and monohydric alcohol monobasic acid ester emollient.

[0018] In order to reduce the dry skin effect caused by azelaic acid, the weight ratio of the branched alkyl carboxylic acid polyglycerol ester emulsifier to the monohydric alcohol monobasic acid ester emollient is 1: (10-15).

[0019] As a preferred embodiment, the branched alkyl carboxylic acid polyglycerol ester emulsifier includes at least one of polyglyceryl-4 isostearate, polyglyceryl-3 isostearate, polyglyceryl-5 isostearate, polyglyceryl-10 isostearate and polyglyceryl isopalmitate.

[0020] Preferably, the branched alkyl carboxylic acid polyglycerol ester emulsifier is polyglyceryl-4 isostearate.

[0021] As a preferred embodiment, the monohydric alcohol monobasic acid ester emollient includes at least one of cetearyl ethylhexanoate, isotridecanol isononanoate, nonyl octanoate, octyl isovalerate, and butyl linoleate.

[0022] Preferably, the monohydric alcohol monobasic acid ester emollient is cetearyl ethylhexanoate.

[0023] The applicant found that when the weight ratio of branched alkyl carboxylic acid polyglycerol ester emulsifier and monohydric alcohol monoacid emollient is 1: (10-15), not only can the high temperature stability of the cream be achieved, but also the irritation of azelaic acid to the wound skin can be reduced, and the moisturizing effect can be achieved.

[0024] As a preferred embodiment, the weight ratio of the polyether-based silicone polymer, the branched alkyl carboxylic acid polyglycerol ester emulsifier and the monohydric alcohol monoacid ester emollient is (1.5-2.5):1:(10-15).

[0025] As a preferred embodiment, the raw materials for preparing the phase B also include: an antibacterial agent and a moisturizer.

[0026] The present invention does not specifically limit the antibacterial agent, and includes but is not limited to caprylhydroxamic acid.

[0027] As a preferred embodiment, the moisturizing agent includes polysiloxane and fatty alcohol.

[0028] Preferably, the weight ratio of the polysiloxane to the fatty alcohol is (2-4):(7-9).

[0029] As a preferred embodiment, the viscosity (25° C.) of the polysiloxane is 800-1200 cps.

[0030] Preferably, the polysiloxane includes at least one of polydimethylsiloxane, polymethyl (3-mercaptopropyl) siloxane, lauryl polymethylsiloxane, hexyl polymethylsiloxane, and diphenyl hexamethylsiloxane.

[0031] In order to achieve the effect of forming a film on the skin surface, the polysiloxane is polydimethylsiloxane.

[0032] As a preferred embodiment, the fatty alcohol includes at least one of tridecyl stearate, 2,3-hydroxypropyl linoleate, 2,3-dihydroxypropyl stearate, isotridecanol isononanoate, and 2-ethylhexanoate isobutyl.

[0033] Preferably, the fatty alcohol is tridecyl stearate.

[0034] The second aspect of the present invention provides a method for preparing a high-concentration azelaic acid cream, comprising the following steps:

[0035] 1. Add the raw materials of phase A into the preparation pot, heat and stir evenly;

[0036] 2. Add the raw materials of phase B into the water phase pot, heat and stir evenly;

[0037] 3. Pour the raw materials prepared in the water phase pot into the preparation pot, start homogenization, cool down, add the raw materials prepared in phase C, and start homogenization;

[0038] 4. After the physical and chemical indexes are tested, the material is cooled and discharged.

[0039] The physical and chemical indicators include but are not limited to viscosity.

[0040] Compared with the prior art, the present invention has the following beneficial effects:

[0041] 1. The cream prepared by the present invention has a nonanedioic acid content of up to 20wt%. At this concentration, it achieves the high stability currently available in the prior art and remains stable for 30 days in an environment of 45°C and -10°C without any gritty feeling or demulsification.

[0042] 2. In addition to the good healing effect, the cream of the present invention also has a good moisturizing effect on wounded skin, solving the problem of dry skin caused by azelaic acid.

[0043] 3. The cream of the present invention has good film-forming property and remains on the wound surface for a long time. DETAILED DESCRIPTION

[0044] Example 1

[0045] The first aspect of this embodiment provides a high-concentration azelaic acid cream, the preparation raw materials include: phase A, phase B, phase C;

[0046] By weight, the raw materials for preparing phase A include: 54.4 parts of solvent, 1.8 parts of thickener;

[0047] The solvent is water and propylene glycol mixed in a weight ratio of 7:1.

[0048] The thickener is a mixture of hydrolyzed corn starch and sodium chloride in a weight ratio of 1:0.8.

[0049] By weight, the raw materials for preparing phase B include: 2 parts of polyether-based silicone polymer, 1 part of branched alkyl carboxylic acid polyglycerol ester emulsifier, 12 parts of monohydric alcohol monobasic acid ester emollient, 8 parts of moisturizer, and 0.6 parts of antibacterial agent.

[0050] The polyether-based silicone polymer is cetyl PEG / PPG-10 / 1 polydimethylsiloxane with a viscosity (25° C.) of 1500-2300 mPa.s, purchased from Shanghai Bioho Chemical Co., Ltd.

[0051] The branched alkyl carboxylic acid polyglycerol ester emulsifier is polyglycerol-4 isostearate, which was purchased from Binzhou Jinsheng New Material Technology Co., Ltd.

[0052] The monohydric alcohol monobasic acid ester emollient is cetearyl ethylhexanoate.

[0053] The moisturizing agent is a mixture of polydimethylsiloxane and tridecyl stearate in a weight ratio of 3:5.

[0054] The polydimethylsiloxane was purchased from Dow Chemical.

[0055] The antibacterial agent is caprylhydroxamic acid.

[0056] By weight, the raw materials for preparing phase C include: 20 parts of azelaic acid and 0.2 parts of bisabolol.

[0057] The second aspect of this embodiment provides a method for preparing a high-concentration azelaic acid cream, comprising the following steps:

[0058] 1. Add the raw materials of phase A into the preparation pot, heat to 80℃ and stir evenly;

[0059] 2. Add the prepared materials of phase B into the water phase pot, heat to 80℃ and stir evenly;

[0060] 3. Pour the raw materials prepared in the water phase pot into the preparation pot, start homogenization for 5 minutes, cool to 48°C, add the raw materials prepared in phase C, and start homogenization for 10 minutes;

[0061] 4. After viscosity testing, cool down and discharge the material.

[0062] Comparative Example 1

[0063] The first aspect of this comparative example provides a high-concentration azelaic acid cream, and the specific implementation method is the same as that of Example 1, except that, based on parts by weight, the polyether-based silicone polymer is replaced with 0 parts.

[0064] The second aspect of this comparative example provides a method for preparing a high-concentration azelaic acid cream, and the specific implementation method is the same as that of Example 1.

[0065] Comparative Example 2

[0066] The first aspect of this comparative example provides a high-concentration azelaic acid cream, and the specific implementation method is the same as Example 1, except that the polyether-based silicone polymer is cetyl PEG / PPG-10 / 1 polydimethylsiloxane with a viscosity (25°C) of 3400-7400mPa.s, which is purchased from Shanghai Hengchen Industrial Co., Ltd.

[0067] The second aspect of this comparative example provides a method for preparing a high-concentration azelaic acid cream, and the specific implementation method is the same as that of Example 1.

[0068] Comparative Example 3

[0069] The first aspect of this comparative example provides a high-concentration azelaic acid cream, and the specific implementation method is the same as that of Example 1, except that, based on parts by weight, the branched alkyl carboxylic acid polyglycerol ester emulsifier is replaced with 0 parts.

[0070] The second aspect of this comparative example provides a method for preparing a high-concentration azelaic acid cream, and the specific implementation method is the same as that of Example 1.

[0071] Comparative Example 4

[0072] The first aspect of this comparative example provides a high-concentration azelaic acid cream, and the specific implementation method is the same as Example 1, except that the branched alkyl carboxylic acid polyglycerol ester emulsifier is polyglycerol-10 pentastearate, which is purchased from Wuhan Xinxin Jiali Biotechnology Co., Ltd.

[0073] The second aspect of this comparative example provides a method for preparing a high-concentration azelaic acid cream, and the specific implementation method is the same as that of Example 1.

[0074] Performance Testing

[0075] Viscosity test method: The sample is kept at a constant temperature of 25°C for 24 hours and measured using a NDJ-5S rotary digital viscometer produced by Shanghai Yueping.

[0076] Stability test method: The creams of the embodiment and the comparative example were placed in -10°C environment for 30 days and 45°C environment for 30 days respectively, and after returning to room temperature, the state changes were observed to see if there was any water precipitation or water-oil separation.

[0077] .

Claims

1. A high concentration azelaic acid cream, characterized in that: The preparation raw materials include: phase A, phase B and phase C; By weight, the raw materials for preparing phase A include: 54.4 parts of solvent and 1.8 parts of thickener; The solvent is water and propylene glycol mixed in a weight ratio of 7:1; The thickener is a mixture of hydrolyzed corn starch and sodium chloride in a weight ratio of 1:0.8; The raw materials for preparing phase B include, by weight: 2 parts of polyether-based silicone polymer, 1 part of branched alkyl carboxylic acid polyglycerol ester emulsifier, 12 parts of monohydric alcohol monobasic acid ester emollient, 8 parts of moisturizer and 0.6 parts of antibacterial agent; The polyether silicone polymer is cetyl PEG / PPG-10 / 1 polydimethylsiloxane, and has a viscosity of 1500-2300 mPa.s at 25°C; The branched alkyl carboxylic acid polyglycerol ester emulsifier is polyglyceryl-4 isostearate; The monohydric alcohol monobasic acid ester emollient is cetearyl ethylhexanoate; The moisturizer is a mixture of polydimethylsiloxane and tridecyl stearate in a weight ratio of 3:5; The antibacterial agent is caprylhydroxamic acid; By weight, the raw materials for preparing phase C include: 20 parts of azelaic acid and 0.2 parts of bisabolol; The preparation method of the high-concentration azelaic acid cream comprises the following steps: (1) Add the raw materials of phase A into the preparation pot, heat to 80°C and stir evenly; (2) Add the raw materials of phase B into the water phase pot, heat to 80°C and stir evenly; (3) Pour the raw materials prepared in the water phase pot into the preparation pot, start homogenization for 5 minutes, cool to 48°C, add the raw materials prepared in phase C, and start homogenization for 10 minutes; (4) After viscosity testing, cool down and discharge the material.