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JP-2026514509-A - Dicarboxylic acid concentrate

JP2026514509AJP 2026514509 AJP2026514509 AJP 2026514509AJP-2026514509-A

Abstract

A substantially anhydrous dermatological concentrate comprising: (a) a long-chain alkyldicarboxylic acid having 6 to 12 carbon atoms and having low solubility in water, selected from the group consisting of adipic acid, azelaic acid, sebacic acid, and dodecanediic acid; and (b) an amidoamine. The substantially anhydrous dermatological concentrate may contain salicylic acid.

Inventors

  • グルーバー，ジェームズ ヴィンセント
  • チェン，シャン
  • フォンディー，パチャラダ
  • キム，ユラー

Assignees

  • ヴァンテージ スペシャルティ イングリーディエンツ，インコーポレイテッド

Dates

Publication Date
20260511
Application Date
20240416
Priority Date
20230427

Claims (20)

  1. (a) Long-chain alkyldicarboxylic acids selected from the group consisting of adipic acid, azelaic acid, sebacic acid, and dodecanediic acid, which have low solubility in water and 6 to 12 carbon atoms; and (b) Amidoamines; A substantially anhydrous dermatological concentrate consisting essentially of two components, When the ratio of a:b is 1:9 to 1:1, and the substantially anhydrous dermatological concentrate is added to water or a hydrophilic carrier, a clear solution is formed with a pH of less than 7 and in which no long-chain alkyldicarboxylic acid precipitates are visible to the naked eye. A virtually anhydrous dermatological concentrate.
  2. The substantially anhydrous dermatological concentrate according to claim 2, wherein the ratio of a:b is 1:4 to 2:3.
  3. The substantially anhydrous dermatological concentrate according to claim 2, wherein the amidoamine is fatty acid amidopropyldimethylamine.
  4. The substantially anhydrous dermatological concentrate according to claim 3, wherein the fatty acid amidopropyldimethylamine is cocamidopropyldimethylamine.
  5. The substantially anhydrous dermatological concentrate according to any one of claims 1 to 4, wherein the long-chain alkyldicarboxylic acid is azelaic acid.
  6. A method for producing a topical product containing a long-chain alkyldicarboxylic acid at a concentration of at least 0.5% by weight, based on the total weight of the topical product, comprising the step of adding a substantially anhydrous dermatological concentrate according to any one of claims 1 to 5 to a hydrophilic carrier.
  7. The method according to claim 6, wherein the topical product contains a long-chain alkyldicarboxylic acid at a concentration of at least 1% by weight.
  8. The method according to claim 7, wherein the topical product contains a long-chain alkyldicarboxylic acid at a concentration of at least 5% by weight.
  9. (a) A long-chain alkyldicarboxylic acid selected from the group consisting of adipic acid, azelaic acid, sebacic acid, and dodecanediic acid, which has low solubility in water and has 6 to 12 carbon atoms; (b) with salicylic acid; (c) with amidoamine; A substantially anhydrous dermatological concentrate essentially derived from, (i) a and b are present in a total amount up to 60% by weight of the substantially anhydrous dermatological concentrate; (ii) The ratio of b:c is 3:7 to 3:2; (iii) When the substantially anhydrous dermatological concentrate is added to water or a hydrophilic carrier, a clear solution is formed having a pH of less than 6 and in which (x) long-chain alkyl dicarboxylic acid precipitates and (y) salicylic acid precipitates are not visible to the naked eye; A virtually anhydrous dermatological concentrate.
  10. The substantially anhydrous dermatological concentrate according to claim 9, wherein the amidoamine is fatty acid amidopropyldimethylamine.
  11. The substantially anhydrous dermatological concentrate according to claim 10, wherein the fatty acid amidopropyldimethylamine is cocamidopropyldimethylamine.
  12. A substantially anhydrous dermatological concentrate according to any one of claims 9 to 11, wherein the ratio of b:c is 2:3 to 11:9.
  13. The substantially anhydrous dermatological concentrate according to claim 12, wherein the alkylamide alkylamine is fatty acid amidopropyldimethylamine.
  14. The substantially anhydrous dermatological concentrate according to claim 13, wherein the fatty acid amidopropyldimethylamine is cocamidopropyldimethylamine.
  15. The substantially anhydrous dermatological concentrate according to any one of claims 9 to 14, wherein the long-chain alkyldicarboxylic acid is azelaic acid.
  16. A method for producing a topical product containing a long-chain alkyl dicarboxylic acid and salicylic acid, comprising the step of adding a substantially anhydrous dermatological concentrate according to any one of claims 9 to 15 to a hydrophilic carrier, wherein the topical product contains salicylic acid at a concentration of up to 5% based on the total weight of the topical product.
  17. The method according to claim 16, wherein the topical product is used for the treatment of acne and contains salicylic acid at a concentration of 0.5% to 2.0% based on the total weight of the topical product.
  18. The method according to claim 16, wherein the topical product is applied to the scalp and contains salicylic acid at a concentration of 1.8% to 3.0% based on the total weight of the topical product.
  19. A topical product comprising a substantially anhydrous dermatological concentrate according to any one of claims 1 to 5 or 9 to 15, a hydrophilic carrier, and one or more surfactants.
  20. A topical product according to claim 19, which does not contain sulfates.

Description

Background of the Invention: Azelaic acid is a dicarboxylic acid found in whole grains such as wheat, rye, and barley, and is produced by Malassezia furfur, a commensal yeast that is part of the human skin microbiome. Azelaic acid has been reported in scientific literature to exhibit antibacterial, keratolytic, comedone-improving, and antioxidant effects. This is because it inhibits protein synthesis in microbial cells, reducing the thickness of the stratum corneum. For the treatment of inflammatory papules and pustules in acne vulgaris and mild to moderate rosacea, two different formulations with varying strengths are available: a 20% active ingredient cream (AZELEX®) and a 15% active ingredient gel or foam (FINACEA®). A low-concentration 10% active ingredient "non-prescription" formulation is marketed as a cosmetic brightener to improve dullness, uneven skin tone, and rough texture. Other reported dermatological benefits of azelaic acid include suppression of sebum production in the sebaceous glands and reduction of hair loss or thinning, due to its competitive inhibitory effect on the reduction of testosterone to dihydrotestosterone. Two representative non-prescription skincare products containing azelaic acid are THE ORDINARY® 10% Azelaic Acid Suspension and PAULA’S CHOICE® 10% Azelaic Acid Booster (which also contains 0.5% salicylic acid). U.S. Patent No. 6,734,210 (expired) describes the difficulty in solubilizing azelaic acid. Water only "slightly dissolves" azelaic acid to a maximum of 0.24% by weight (w/w), a concentration that is "unlikely" to be clinically effective. Isopropanol is considered a "good" solvent, but is deemed "unsatisfactory" because it can cause drying. Ethanol destabilizes azelaic acid at "room temperature," resulting in a "completely ineffective composition." U.S. Patents 4,713,394 and 4,885,282 similarly characterize the instability of azelaic acid when dissolved in ethyl alcohol. In July 2020, Azeco Cosmeceuticals published a "Technical Information File" providing guidelines for formulations using azelaic acid and a general solution to the limited solubility of azelaic acid in aqueous systems (i.e., incorporating azelaic acid into the final formulation using a "pre-mixture"). According to Azeco, the "simplest" "pre-mixture" is formed by dissolving azelaic acid in ethanol or isopropanol. However, Azeco notes that since these alcohols are undesirable in many dermatological formulations, diols, namely propanediol (e.g., available from DuPont Tate & Lyle Bio Products Company, LLC, Wilmington, Delaware under the trademark Zemea®), 1,3-butylene glycol, and pentylene glycol (e.g., available from Minasolve SAS, Beuvry-La-Foret, France under the trademark Pentiol Green+), are used instead. Azeco's formulation guidelines also comment that "glycerin and glycerin/water mixtures are suitable solvent systems; [however] the maximum concentration of water in this solvent mixture is not adequately defined and has not been reported in the literature." Brief explanation of the drawing The following shows comparative results of enzyme-linked immunosorbent assay (ELISA) for tumor necrosis factor α (TNF-α) after application of the substantially anhydrous dermatological concentrate of the present invention. The following shows comparative results of enzyme-linked immunosorbent assay (ELISA) for tumor necrosis factor α (TNF-α) after application of the substantially anhydrous dermatological concentrate of the present invention. The following shows comparative ELISA results for caspase-1 (CASP-1) after application of the substantially anhydrous dermatological concentrate of the present invention. Detailed Description of the Invention In the disclosure of this invention, "low solubility in water" means less than 30 g/L in water at 25°C. See Fiume, MM et al, “Final Report of the Cosmetic Ingredient Review Expert Panel on the Safety Assessment of Dicarboxylic Acids, Salts, and Esters” International Journal of Toxicology 31(Supplement 1)5S-76S(2012)(DOI:10.1177/1091581812447203). In the description of the concentrates in the disclosure of the present invention, "substantially anhydrous" is understood to mean that no water other than the water of hydration contained in the components of the substantially anhydrous dermatological concentrates of the disclosure of the present invention has been added to the concentrate. Typically, the water content of the concentrate is less than 1.0% by weight, preferably less than 0.5% by weight, and more preferably less than 0.1% by weight. The term "dermatological" is understood to mean that the product is suitable for topical application to the skin, hair, or scalp of mammals. The first essential component of the substantially anhydrous dermatological concentrate disclosed in this invention is a dicarboxylic acid with low water solubility. These acids are linear alkyl chains with functionalized terminals, separated from each other by 4 to 10 carbon atoms. Preferred dicar