Oxa acids and related compounds for treating skin conditions

• US 5,847,003 A
• Filed: 06/04/1996
• Issued: 12/08/1998
• Est. Priority Date: 06/04/1996
• Status: Expired due to Term

• Current Assignee: Avon Products Incorporated (Natura &Co Holding SA)
• Original Assignee: Avon Products Incorporated (Natura &Co Holding SA)
• Inventors: Ptchelintsev, Dmitri, Kalafsky, Robert, Scancarella, Neil
• Primary Examiner(s): SPIVACK, PHYLLIS G
• Application Number:
  US08/658,089
• Time in Patent Office: 917 Days
• Field of Search: 514/558, 514/560, 514/559, 514/532, 514/544, 514/546, 514/549
• US Class Current: 514/532
• CPC Class Codes: A61K 2800/244 Endothermic; Cooling; Cooling sensation
• CPC Class Codes: A61K 2800/28 Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 8/365 Hydroxycarboxylic acids; Ketocarboxylic acids
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61K 8/42 Amides
• CPC Class Codes: A61K 8/44 Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
• CPC Class Codes: A61K 8/46 containing sulfur A61K8/44 takes precedence
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/007 : Preparations for dry skin
• CPC Class Codes: A61Q 19/02 : for chemically bleaching or whitening the skin
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations
• CPC Class Codes: A61Q 5/006 : Antidandruff preparations
• CPC Class Codes: A61Q 5/12 : Preparations containing hair conditioners

Abstract

Described are the use of compounds of Formula (I) depicted below, as active principals for treating skin conditions and compositions containing these compounds, ##STR1## where R₄ is (CR₅ R₆ --CR₇ R₈ --X₁)_n --CR₉ R₁₀ R₁₁ ; n is an integer from 1 to 18; R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are, independently, hydrogen or substituents selected from alkyls, alkenyls, oxa-alkyls, aralkyls and aryls; and X, X₁, Y and Z are, independently, oxygen.

Claims

1. A topical composition comprising a topical vehicle and a compound of Formula (I):

##STR4## wherein, R₄ is (CR₅ R₆ --CR₇ R₈ --X₁)_n --CR₉ R₁₀ R₁₁ ;

n is an integer from 1 to 18;

R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉, R₁₀, and R₁₁ are, independently, hydrogen or substituents selected from the group consisting of alkyls, alkenyls, oxa-alkyls, aralkyls, aryls, cycloalkyls and cycloalkenyls;

and X, X₁, Y and Z are O.

2. The composition of claim 1 wherein said compound of Formula (I) comprises about 0.1 to about 95 wt % of said composition, and wherein n in said compound is an integer from 2 to 12.

3. The composition of claim 2, wherein said topical vehicle is selected from the group consisting of gels, lotions and creams.

4. The composition of claim 3, wherein said topical vehicle is comprised of ingredients selected from the group consisting of ammonium hydroxide, cetearyl alcohol/Ceteareth-20, EDTA, glycerin, glyceryl monostearate, hydroxyethyl cellulose, imidazolidilyl urea, methyl paraben, myristyl myristate, octyl palmitate and propylene glycol.

5. The composition of claim 3, wherein said composition comprises about 0.1 wt % to about 20 wt % 3,6,9-trioxadecanoic acid;

said vehicle comprises;

(a) about 2 wt % to about 10 wt % glycerin;

(b) about 1 wt % to about 10 wt % propylene glycol;

(c) about 0.1 wt % to about 2 wt % hydroxyethyl cellulose;

(d) about 0.1 wt % to about 1 wt % imidazolidilyl urea;

(e) about 0.01 wt % to about 2 wt % disodium-EDTA; and

has a pH of about 7.0 or less.

6. The composition of claim 3, wherein said composition comprises about 0.1 wt % to about 20 wt % 3,6,9-trioxadecanoic acid;

said vehicle comprises;

(a) about 1 wt % to about 10 wt % glycerin;

(b) about 1 wt % to about 10 wt % propylene glycol;

(c) about 1 wt % to about 10 wt % octyl palmitate;

(d) about 1 wt % to about 10 wt % myristyl myristate;

(e) about 1 wt % to about 6 wt % cetearyl alcohol/Ceteareth-20;

(f) about 0.5 wt % to about 6 wt % glyceryl monostearate;

(g) about 0.1 wt % to about 2 wt % hydroxyethyl cellulose;

(h) about 0.1 wt % to about 1 wt % imidazolidilyl urea;

(i) about 0.05 wt % to about 0.5 wt % methyl paraben;

(j) about 0.01 wt % to about 2 wt % disodium-EDTA; and

has a pH of about 7.0 or less.

7. The composition of claim 3, wherein said composition comprises about 0.1 wt % to about 20 wt % 3,6,9-trioxadecanoic acid;

said vehicle comprises;

(a) about 2 wt % to about 10 wt % glycerin;

(b) about 1 wt % to about 10 wt % octyl palmitate;

(c) about 1 wt % to about 10 wt % myristyl myristate;

(d) about 1 wt % to about 7 wt % cetearyl alcohol/Ceteareth-20;

(e) about 1 wt % to about 10 wt % propylene glycol;

(f) about 1 wt % to about 6 wt % glyceryl monostearate;

(g) about 0;

1 wt % to about 2 wt % hydroxyethyl cellulose;

(h) about 0.1 wt % to about 1 wt % imidazolidilyl urea;

(i) about 0.05 wt % to about 0.5 wt % methyl paraben;

(j) about 0.01 wt % to about 2 wt % disodium-EDTA; and

has a pH of about 7.0 or less.

8. The composition of claim 1 further comprising a mixture of two or more different compounds of Formula (I).

9. The composition of claim 1, wherein said subtituents are selected from the group consisting of methyl, ethyl, propyl, isopropyl, buytl, isobutyl, hexyl, heptyl, octyl, nonyl, dodecanyl, methoxy, ethoxy, propoxy, butoxy, cyclohexenyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, cyclobutyl and cyclohexyl.

10. The composition of claim 1 wherein R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉, R₁₀, and R₁₁ of said compound are each hydrogen.

11. The composition of claim 1, wherein said compound is selected from the group consisting of 3,6-dioxaheptanoic acid;

7,7-dimethyl-3,6-dioxaheptanoic acid;

3,6-dioxaheptanoic acid ethyl ester;

3,6-dioxaheptanoic acid dodecyl ester;

2-phenyl-3,6-dioxaheptanoic acid;

2-benzyl-3,6-dioxaheptanoic acid;

2-methyl-3,6-dioxaheptanoic acid;

3,6,9-trioxadecanoic acid;

2-phenyl-3,6,9-trioxadecanoic acid;

2-benzyl-3,6,9-trioxadecanoic acid;

2-decyl-3,6,9-trioxadecanoic acid;

3,6,9,12-tetraoxatridecanoic acid;

3,6,9,12,15-pentaoxahexadecanoic acid;

2-methyl-3,6,9-trioxadecanoic acid;

10,10-dimethyl-3,6,9-trioxadecanoic acid;

2-ethyl-3,6,9,12-tetraoxatridecanoic acid;

10-phenyl-3,6,9-trioxadecanoic acid;

3,6,9-trioxadecanoic acid ethyl ester;

10,10-dimethyl-3,6,9-trioxadecanoic acid ethyl ester;

10,10-dimethyl-3,6,9-trioxadecanoic acid heptadecanyl ester; and

mixtures thereof.

12. The composition of claim 1 further comprising at least one active selected from the group consisting of antifungals, vitamins, sunscreens, retinoids, antiallergenic agents, depigmenting agents, anti-inflammatory agents, anesthetics, surfactants, moisturizers, exfolients, emulsifiers, stabilizers, preservatives, antiseptics, emollients, thickeners, lubricants, humectants, chelating agents, fragrances, colorants and skin penetration enhancers.

13. The composition of claim 2, wherein said composition comprises up to about 60 wt % of said compound of Formula (I) and has a pH of less than 7.0.

14. The composition of claim 13, wherein said topical vehicle comprises up to about 95 wt % of water;

up to about 30 wt % of an emollient; and

up to about 20 wt % of an emulsifier.

15. The composition of claim 14, wherein said compound is selected from the group consisting of 3,6-dioxaheptanoic acid, 3,6,9-trioxadecanoic acid, 3,6,9,12-tetraoxatridecanoic acid and 3,6,9,12,15-pentaoxahexadecanoic acid;

said emollient is selected from the group consisting of mineral oil, petrolatum, paraffin, ceresin, ozokerite, microcrystalline wax, perhydrosqualene, dimethyl polysiloxanes, methylphenyl polysiloxanes, silicone-glycol copolymers, triglyceride esters, acetylated monoglycerides, ethoxylated glycerides, alkyl esters of fatty acids, fatty acids and alcohols, lanolin and lanolin derivatives, polyhdric alcohol esters, sterols, beeswax derivatives, polyhydric alcohols and polyethers, and amides of fatty acids; and

said emulsifier is selected from the group consisting of sorbitans, alkoxylated fatty alcohols, alkylpolyglycosides, soaps, alkyl sulfates, monoalkyl and dialkyl phosphates, alkyl sulphonates, and acyl isothionates.

16. A method of treating skin conditions caused by, accompanied with or exacerbated by abnormal desquamation, comprising applying to said skin conditions an effective amount of a compound of Formula (I):

##STR5## wherein, R₄ is (CR₅ R₆ --CR₇ R₈ --X₁)_n --CR₉ R₁₀ R₁₁ ;

n is an integer from 1 to 18;

R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉, R₁₀, and R₁₁, are, independently, hydrogen or substituents selected from the group consisting of alkyls, alkenyls, oxa-alkyls, aralkyls, aryls, cycloalkyls and cycloalkenyls;

and X, X₁, Y and Z are O.

17. The method of claim 16 wherein said compound is combined with a suitable topical vehicle in a topical composition.

18. The method of claim 17 wherein said compound of Formula (I) comprises about 0.1 to about 95 wt % of said composition, and wherein n in said compound is an integer from 2 to 12.

19. The method of claim 16 further comprising, applying to said skin an effective amount of a mixture of two or more different compounds of Formula (I).

20. The method of claim 16 wherein said non-hydrogen substituents of said compound are selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, hexyl, heptyl, octyl, nonyl, dodecanyl, methoxy, ethoxy, propoxy, butoxy, cyclohexenyl, hydroxymethyl, hydroxyethyl, hydroxypropyl, cyclobutyl and cyclohexyl.

21. The method of claim 16 wherein R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉, R₁₀, and R₁₁ of said compound are each hydrogen.

22. The method of claim 16, wherein said compound is selected from the group consisting of 3,6-dioxaheptanoic acid;

7,7-dimethyl-3,6-dioxaheptanoic acid;

3,6-dioxaheptanoic acid ethyl ester;

3,6-dioxaheptanoic acid dodecyl ester;

2-phenyl-3,6-dioxaheptanoic acid;

2-benzyl-3,6-dioxaheptanoic acid;

2-methyl-3,6-dioxaheptanoic acid;

3,6,9-trioxadecanoic acid;

2-phenyl-3,6,9-trioxadecanoic acid;

2-benzyl-3,6,9-trioxadecanoic acid;

2-decyl-3,6,9-trioxadecanoic acid;

3,6,9,12-tetraoxatridecanoic acid;

3,6,9,12,15-pentaoxahexadecanoic acid;

2-methyl-3,6,9-trioxadecanoic acid;

10,10-dimethyl-3,6,9-trioxadecanoic acid;

2-ethyl-3,6,9,12-tetraoxatridecanoic acid;

10-phenyl-3,6,9-trioxadecanoic acid;

3,6,9-trioxadecanoic acid ethyl ester;

10,10-dimethyl-3,6,9-trioxadecanoic acid ethyl ester;

10,10-dimethyl-3,6,9-trioxadecanoic acid heptadecanyl ester; and

mixtures thereof.

23. The method of claim 16 further comprising at least one active selected from the group consisting of antifungals, vitamins, sunscreens, retinoids, antiallergenic agents, depigmenting agents, anti-inflammatory agents, anesthetics, surfactants, moisturizers, exfolients, emulsifiers, stabilizers, preservatives, antiseptics, emollients, thickeners, lubricants, humectants, chelating agents, fragrances, colorants and skin penetration enhancers.

24. The method of claim 16, wherein said skin conditions to be treated are selected from the group consisting of dry skin, ichthyosis, palmar and plantar hyperkeratoses, dandruff, lichen simplex chronicus, Dariers disease, keratoses, lentigines, age spots, melasmas, blemished skin, acne, psoriasis, eczema, pruritis, inflammatory dermatoses, striae distensae, warts, calluses, signs of dermatological aging, skin wrinkles, fine wrinkles around the mouth area, irregular pigmentation, sallowness, loss of skin resilience and elasticity, disorders associated with nails, cuticles and hair such as ingrown hair, folliculitis and Pseudo-folliculitis barbae.