CN113813224A - Novel azelaic acid gel and preparation method thereof - Google Patents

Novel azelaic acid gel and preparation method thereof Download PDF

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CN113813224A
CN113813224A CN202010570378.0A CN202010570378A CN113813224A CN 113813224 A CN113813224 A CN 113813224A CN 202010570378 A CN202010570378 A CN 202010570378A CN 113813224 A CN113813224 A CN 113813224A
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azelaic acid
novel
gel
urea
propylene glycol
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周丽娟
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/194Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
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    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/10Anti-acne agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02Local antiseptics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents

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Abstract

The invention relates to a novel azelaic acid gel and a preparation method thereof, belonging to the field of skin medicaments. The technical problem to be solved by the invention is to provide a novel azelaic acid gel, which comprises the following components in percentage by weight: 10-20% of azelaic acid, 0.5-2% of salicylic acid, 1-3% of ZEN, 50-73% of 1, 3-propylene glycol, 1-25% of urea and the balance of deionized water. Compared with the azelaic acid gel product without urea, the novel azelaic acid gel prepared by adopting the specific raw materials has better transparency, no precipitate, good stability, more refreshing skin feel, no separation of azelaic acid particles and better skin permeation. Can be used for treating or preventing acne, and improving the cure rate of acne patients.

Description

Novel azelaic acid gel and preparation method thereof
[ technical field ] A method for producing a semiconductor device
The invention relates to a novel azelaic acid gel and a preparation method thereof, belonging to the field of skin medicaments.
[ background of the invention ]
Acne is a chronic inflammatory skin disease of a pilosebaceous unit, mainly occurs to teenagers, has great influence on the psychology and the social interaction of the teenagers, and can be naturally relieved or healed after adolescence. The clinical manifestations are marked by the polymorphic skin lesions of face, such as acne, papule, pustule, and nodule.
According to the joint investigation of the national dermatosis association and the national teenager association, the following results are shown: the incidence of acne in China is on the trend of rising year by year, and more than 80% of people have the problem of acne in different degrees.
For the treatment of acne, patients with mild or moderate acne generally choose not to be treated or choose acne removing products on the market for treatment, and patients with severe acne can go to hospitals and acne removing institutions for treatment. The existing acne removing mechanism and product on the market can not completely remove acnes and have side effects. The acne removing in hospitals is not specific, the acne removing in beauty parlors is not professional, and according to the authority statistics of the Ministry of health of China, the complete cure rate of the acne in China is only 32.95 percent. Therefore, there is an urgent need for a drug that can improve the cure rate of acne.
Azelaic acid, also known as azelaic acid, is a white to yellowish monoclinic prism, acicular crystals or powder in appearance. Has antibacterial effect, and can directly inhibit and kill bacteria on skin surface and in hair follicle; competitively inhibiting the enzyme process producing dihydrotestosterone and reducing excessive skin oil induced by dihydrotestosterone; inhibiting the generation and action of active oxygen free radicals, and resisting inflammation. It is used for treating acne, rosacea, and pigmentation disorder. Has good permeability to skin, and can increase absorption function of skin. However, since it is easily decomposed at high temperature, it is not preferable to add it at high temperature when it is used. It is easily soluble in hot water, alcohol and part of polyhydric alcohol, and slightly soluble in cold water, ether and benzene.
At present, azelaic acid products are often made into paste, for example, patent application numbers 201610786026.2, 201210230433.7. Patent application No. 201810825807.7 for making gel.
Some of the patents make azelaic acid into paste products, which have heavy skin feel and poor permeability; the product prepared into the gel has poor stability, and azelaic acid particles are separated out at low temperature, so the improvement is needed.
[ summary of the invention ]
Aiming at the defects, the technical problem solved by the invention is to provide a novel azelaic acid gel, compared with cream, the gel is free of oily component addition, and urea component is added to complex azelaic acid to generate azelaic acid urea complex which is dissolved in propylene glycol, so that the stability of the novel azelaic acid gel is improved, and the urea belongs to a humectant which can enhance the hydration force of the horny layer of skin, increase the permeability of the medicine and has good effect of preventing or treating acne. The invention relates to a novel azelaic acid gel, which consists of the following components in percentage by weight: 10-20% of azelaic acid, 0.5-2% of salicylic acid, 1-3% of ZEN, 50-73% of 1, 3-propylene glycol, 1-25% of urea and the balance of deionized water.
Preferably, the novel azelaic acid gel consists of the following components in percentage by weight: 12-18% of azelaic acid, 12-23% of urea, 0.8-1.5% of salicylic acid, 1.5-2.5% of ZEN, 50-73% of 1, 3-propylene glycol and the balance of deionized water.
As a preferable scheme, the novel azelaic acid gel consists of the following components in percentage by weight: 15% of azelaic acid, 15% of urea, 2% of ZEN, 1% of salicylic acid, 55% of 1, 3-propylene glycol and 12% of deionized water.
The invention solves the second technical problem by providing the preparation method of the novel azelaic acid gel.
The invention relates to a preparation method of a novel azelaic acid gel, which comprises the following steps:
a. dispersing ZEN in 1, 3-propylene glycol, then uniformly mixing with deionized water, and heating to 80-90 ℃ to obtain gel A;
b. uniformly dispersing azelaic acid and urea in 1, 3-propylene glycol, and heating to 65-80 ℃ to obtain a transparent solution B;
c. dispersing salicylic acid in 1, 3-propylene glycol, and heating until the salicylic acid is dissolved to obtain a transparent solution C;
d. and mixing the gel A, the solution B and the solution C, stirring and uniformly mixing at 55-85 ℃, and then cooling to room temperature to obtain the novel azelaic acid gel.
Wherein, there is no time sequence among step a, step b and step c, step a may be performed first, step b may be performed first, step c may be performed first, or the three steps may be performed simultaneously. The gel A, the solution B and the solution C are mixed and stirred evenly at last.
The novel azelaic acid gel provided by the invention can be used for treating or preventing acne, so that the cure rate of acne patients is improved, and facial skin injury of the patients caused by the acne is reduced, thereby relieving physiological and psychological pains of the patients caused by the acne. Meanwhile, the treatment cost of the patient is reduced, and the medical expense is reduced.
Compared with the prior art, the invention has the following beneficial effects:
compared with the azelaic acid gel product without urea, the novel azelaic acid gel prepared by adopting the specific raw materials has better transparency, no precipitate, good stability, more refreshing skin feel, no separation of azelaic acid particles and better skin permeation. Can be used for treating or preventing acne, and improving the cure rate of acne patients.
The novel azelaic acid gel of the invention is a formula (relative cream) without oil component addition. After the oily skin is used, the burden on the skin is not increased, pores are not blocked, and the hidden danger of acne is not generated; for the skin with acne, because of the strong penetration of urea and azelaic acid, the gel-like azelaic acid is simpler and easier than the paste-like penetration, and does not need more grease for dissolution and penetration assistance, thereby avoiding the corresponding side effect caused by the excessive introduction of oily substances; in the later anti-acne period, the follicular canal needs to be unblocked to facilitate the discharge of grease and other metabolites, azelaic acid is used for diminishing inflammation and sterilizing, the follicular canal is unblocked, the discharge problem is solved smoothly, and the possibility of recurrence of acne is reduced.
The novel azelaic acid gel provided by the invention has the advantages of simple components, antibacterial effect, simple preparation method and low cost.
[ detailed description ] embodiments
The invention relates to a novel azelaic acid gel, which consists of the following components in percentage by weight: 10-20% of azelaic acid, 0.5-2% of salicylic acid, 1-3% of ZEN, 50-73% of 1, 3-propylene glycol, 1-25% of urea and the balance of deionized water.
Wherein ZEN is polyacrylate cross-linked polymer-6, produced by French Saibek corporation, under the trade name Sepimax ZEN.
Salicylic acid is a fat-soluble organic acid, is white crystalline powder, exists in willow bark, beautyberry leaves and betula in nature, can be used as a cosmetic preservative, has the functions of removing sweat odor, relieving itching and swelling, relieving pain and diminishing inflammation and the like besides the functions of antisepsis and sterilization, can soften and peel off cutin and reduce pore blockage, and has a good effect on adolescent acne and common acne, and the dosage of the salicylic acid is preferably 0.5-2%. A specific amount of salicylic acid is mixed with azelaic acid, which has a synergistic effect and can improve the treatment effect of acne.
Urea is a good moisturizing ingredient, exists in the horny layer of the skin, and belongs to the main ingredient of the natural moisturizing factor NMF of the skin. Urea has the effects of moisturizing the skin and softening the cutin, so that the problem of acne can be solved by preventing the stratum corneum from blocking the pores. In the invention, azelaic acid and urea are subjected to a complex reaction when heated in a propylene glycol solution to generate an azelaic acid-urea complex which is easily dissolved in the propylene glycol solution, so that the stability of the formula is increased, and the urea is used as a moisture retention component to improve the moisture retention and make the skin feel fresh.
Preferably, the novel azelaic acid gel consists of the following components in percentage by weight: 12-18% of azelaic acid, 12-23% of urea, 0.8-1.5% of salicylic acid, 1.5-2.5% of ZEN, 50-73% of 1, 3-propylene glycol and the balance of deionized water.
As a preferable scheme, the novel azelaic acid gel consists of the following components in percentage by weight: 15% of azelaic acid, 15% of urea, 2% of ZEN, 1% of salicylic acid, 55% of 1, 3-propylene glycol and 12% of deionized water.
The invention solves the second technical problem by providing the preparation method of the novel azelaic acid gel.
The invention relates to a preparation method of a novel azelaic acid gel, which comprises the following steps:
a. dispersing ZEN in 1, 3-propylene glycol, then uniformly mixing with deionized water, and heating to 80-90 ℃ to obtain gel A;
b. uniformly dispersing azelaic acid and urea in 1, 3-propylene glycol, and heating to 65-80 ℃ to obtain a transparent solution B;
c. dispersing salicylic acid in 1, 3-propylene glycol, and heating until the salicylic acid is dissolved to obtain a transparent solution C;
d. and mixing the gel A, the solution B and the solution C, stirring and uniformly mixing at 55-85 ℃, and then cooling to room temperature to obtain the novel azelaic acid gel.
Wherein, there is no time sequence among step a, step b and step c, step a may be performed first, step b may be performed first, step c may be performed first, or the three steps may be performed simultaneously. The gel A, the solution B and the solution C are mixed and stirred evenly at last.
The novel azelaic acid gel provided by the invention can be used for treating or preventing acne, so that the cure rate of acne patients is improved, and facial skin injury of the patients caused by the acne is reduced, thereby relieving physiological and psychological pains of the patients caused by the acne. Meanwhile, the treatment cost of the patient is reduced, and the medical expense is reduced.
The following examples are provided to further illustrate the embodiments of the present invention and are not intended to limit the scope of the present invention. The raw materials used in the examples were:
ZEN: purchased from french seebeck;
urea: purchased from west longus science, inc;
azelaic acid: purchased from inspiring science and technology development ltd in Shanghai;
salicylic acid: purchased from remote chemical agents, ltd, Tianjin;
1, 3-propanediol: corn sources, available from dupont, usa;
example 1
A novel azelaic acid gel is prepared according to the following steps:
a. dispersing ZEN in 1, 3-propylene glycol, then uniformly mixing with deionized water, and heating to 80-90 ℃ to obtain gel A;
b. uniformly dispersing azelaic acid and urea in 1, 3-propylene glycol, and heating to 65-80 ℃ to obtain a transparent solution B;
c. dispersing salicylic acid in 1, 3-propylene glycol, and heating until the salicylic acid is dissolved to obtain a transparent solution C;
d. and mixing the gel A, the solution B and the solution C, stirring and uniformly mixing at 55-85 ℃, and then cooling to room temperature to obtain the novel azelaic acid gel.
Wherein the formula of each raw material is shown in table 1.
TABLE 1
Figure BSA0000211784660000061
Figure BSA0000211784660000071
Example 2 and comparative examples 1 to 2 are shown in Table 2.
TABLE 2
Figure BSA0000211784660000072
When the samples of examples 1 to 2 and comparative examples 1 to 2 were placed in a refrigerator and observed at a temperature of 5 ℃ for 1 month, it was found that examples 1 to 2 remained transparent, whereas comparative examples 1 to 2 had granular azelaic acid crystals precipitated, indicating that the samples produced according to examples 1 to 2 had good stability.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention, and all equivalent changes and modifications made based on the features and principles described in the claims of the present invention are included in the scope of the present invention.

Claims (4)

1. A novel azelaic acid gel comprises the following components by weight percent: 10-20% of azelaic acid, 0.5-2% of salicylic acid, 1-3% of ZEN, 50-73% of 1, 3-propylene glycol, 1-25% of urea and the balance of deionized water.
2. The novel azelaic acid gel of claim 1 wherein: the paint consists of the following components in percentage by weight: 12-18% of azelaic acid, 12-23% of urea, 0.8-1.5% of salicylic acid, 1.5-2.5% of ZEN, 50-73% of 1, 3-propylene glycol and the balance of deionized water.
3. The novel azelaic acid gel of claim 1 wherein: the paint consists of the following components in percentage by weight: 15% of azelaic acid, 15% of urea, 2% of ZEN, 1% of salicylic acid, 55% of 1, 3-propylene glycol and 12% of deionized water.
4. The preparation method of the novel azelaic acid gel as claimed in any one of claims 1 to 3, which is characterized by comprising the following steps:
a. dispersing ZEN in 1, 3-propylene glycol, then uniformly mixing with deionized water, and heating to 80-90 ℃ to obtain gel A;
b. uniformly dispersing azelaic acid and urea in 1, 3-propylene glycol, and heating to 65-80 ℃ to obtain a transparent solution B;
c. dispersing salicylic acid in 1, 3-propylene glycol, and heating until the salicylic acid is dissolved to obtain a transparent solution C; d. and mixing the gel A, the solution B and the solution C, stirring and uniformly mixing at 55-85 ℃, and then cooling to room temperature to obtain the novel azelaic acid gel.
CN202010570378.0A 2020-06-19 2020-06-19 Novel azelaic acid gel and preparation method thereof Pending CN113813224A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116370325A (en) * 2023-03-23 2023-07-04 上海科黛生物科技有限公司 Transparent azelaic acid gel and preparation method and application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116370325A (en) * 2023-03-23 2023-07-04 上海科黛生物科技有限公司 Transparent azelaic acid gel and preparation method and application thereof

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Application publication date: 20211221