# US 10,117,821 B2 · Topical lightening composition and methods of use thereof

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- Number: US 10,117,821 B2
- Document ID: US10117821B2
- Status: Granted
- Kind: B2
- Application number: 14/379,520
- Filed: 2014-02-26
- Published: 2016-08-18
- Granted: 2018-11-06
- Earliest claimed: 2013-03-12
- Assignees: Avon Products, Inc.
- Applicants: Avon Products, Inc.
- Inventors: Arvind N. Shah; Uma Santhanam; Sungham Yim
- Web page: https://patentgrep.com/patent/US10117821B2

## CPC

- A61K 8/675: {Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde (tocopheryl nicotinate A61K8/678)}
- A61K 8/06: Emulsions
- A61K 8/46: containing sulfur (A61K8/44 takes precedence)
- A61Q 19/02: for chemically bleaching or whitening the skin
- A61Q 19/08: Anti-ageing preparations
- A61K 2800/49: Solubiliser, Solubilising system
- A61K 2800/592: Mixtures of compounds complementing their respective functions
- A61K 2800/596: Mixtures of surface active compounds
- A61K 2800/782: Enzyme inhibitors; Enzyme antagonists
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## Abstract

Embodiments of the invention are generally directed to compositions comprising lightening agents, nicotinamide and 3,3′-thiodipropanoic acid, in a cosmetically acceptable vehicle, articles of manufacture, and methods of use thereof. The compositions and methods of described herein are effective to lighten an area of skin in need of lightening, such as but not limited to, a subject having overall dark complexion, pigmented skin discoloration, freckles, age spots, liver spots, sun damage, tans, pigmented acne marks, scars, pigmented birthmarks, hyperpigmentation, post-inflammatory hyperpigmentation, post-injury hyperpigmentation, melasma, cholasma, after-burn scar, nail stain, yellowing of skin, dark circles under eyes, and the like. The composition may include additional ingredients accordingly for a colored cosmetic, moisturizer, cleanser, toner, and the like.

## Claims

### Claim 1

A topical composition for reducing pigmentation in human skin, comprising: (i) 3,3′-thiodipropionic acid, or a salt or ester thereof, and (ii) nicotinamide, or salt thereof, or melanosome-transfer inhibiting derivative thereof, and (iii) a cosmetically or dermatologically acceptable vehicle,
wherein the 3,3′-thiodipropionic acid, or salt or ester thereof, is present in an effective amount ranging from about 0.1% (w/w) to about 2.5% (w/w) based on the total weight of the composition and the nicotinamide, or salt thereof, or melanosome-transfer inhibiting derivative thereof, is present in an effective amount ranging from about 0.01% (w/w) to about 1% (w/w) based on the total weight of the composition, and
wherein the effective amount of 3,3′-thiodipropionic acid, or salt or ester thereof, and effective amount of nicotinamide, or salt thereof, or melanosome-transfer inhibiting derivative thereof together provide at least 25% greater relative reduction in melanin synthesis than either component alone.

### Claim 2 (depends on 1)

The composition according to claim 1, wherein the composition comprises an ester of 3,3′-thiodipropionic acid having the structure of the structure of formula I:
wherein R1 and R2 are independently selected from hydrogen, a group L, or a group Ra, where Ra is independently at each occurrence an aliphatic C1-20 hydrocarbon radical; an aromatic C6-12 hydrocarbon radical; a C6-20 alkyl-aryl hydrocarbon radical; a C6-20 aryl-alkyl hydrocarbon radical; or a heteroaromatic radical, each of the foregoing being optionally substituted with a group R or with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen;
wherein L is a group of the form —X1—(CR*2)n—X2—(CR*2)m—X3—; wherein X1, X2, and X3 are independently at each occurrence a bond, —O—, —NRN—, —S—, —(OCH2CH2)p—, —CH2CH2O)q—, or a group R*, wherein “p” and “q” are independently an integer from 1 to 10, and “n” and “m”are independently an integer from 0 to 10;
R is independently at each occurrence selected from hydrogen, —F; —Cl; —Br; —I; —OH, —OR*; —NH2; —NHR*; —N(R*)2; —N(R*)3; —N(R*)—OH; —N(→O)(R*)2; —O—N(R*)2; —N(R*)—O—R*; —N(R*)—N(R*)2; —C═N—R*; —N═C(R*)2; —C═N—N(R*)2; —C(═NR*)—N(R*)2; —SH; —SR*; —CN; —NC; —(C═O)—R*; —CHO; —CO2H; —CO2−; —CO2R*; —(C═O)—S—R*; —O—(C═O)—H; —O—(C═O)—R*; —S—(C═O)—R*; —(C═O)—NH2; —(C═O)—N(R*)2; —(C═O)—NHNH2; —O—(C═O)—NHNH2; —(C═S)—NH2; —(C═S)—N(R*)2; —N(R*)—CHO; —N(R*)—(C═O)—R*; —(C═NR)—O—R*; —O—(C═NR*)—R*, —SCN; —NCS; —NSO; —SSR*; —N(R*)—C(═O)—N(R*)2; —N(R*)—C(═S)—N(R*)2; —SO2—R*; —O—S(═O)2—R*; —S(═O)2—OR*; —N(R*)—SO2—R*; —SO2—N(R*)2; —O—SO3−; —O—S(═O)2—OR*; —O—S(═O)—OR*; —O—S(═O)—R*; —S(═O)—OR*; —S(═O)—R*; —NO; —NO2; —NO3; —O—NO; —O—NO2; —N3; —N2—R*; —N(C2H4); —Si(R*)3; —CF3; —O—CF3; —PR*2; —O—P(═O)(OR*)2; —P(═O)(OR*)2; perfluoroalkyl; an aliphatic C1-C12 hydrocarbon radical; a C6-C12 aromatic hydrocarbon radical; a C5-C12 heteroaryl radical;
RN and R* are selected independently from hydrogen or a saturated, partially saturated, or aromatic C1-C20 hydrocarbon radical, optionally substituted with a group R or with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen;
with the proviso that at least one of R1 and R2 is a group L or R*; and salts thereof.

### Claim 3 (depends on 2)

The composition according to claim 2, wherein R1 and R2 are each independently selected from C1-20 aliphatic hydrocarbon radicals.

### Claim 4 (depends on 3)

The composition according to claim 3, wherein the 3,3′-thiodipropionic acid, or salt or ester thereof comprises di-lauryl-3,3′-thiodipropionate.

### Claim 5 (depends on 1)

The composition according to claim 1, wherein said melanosome-transfer inhibiting derivative of nicotinamide has the structure of the structure of formula II:
wherein “n” is an integer 0 or 1;
Z is selected from the group consisting of O, S, NH, and NRN;
G and Q are independently selected from the group consisting of hydrogen, RN, —COR, —CO2R, —C(═O)NHR, —C(═O)NR2, —PO3R, —S(O)mR, —NHR, —N═CHR, —NR(C═O)R; and —NRCO2R;
where “m” is 0, 1, or 2; and wherein G and Q may together form a 3-6 membered heterocyclic ring; and where Z and G may together form a 5 or 6-member heterocylic ring;
X and Y are independently selected from groups R; and where X and Y may together to form 4-6 membered ring;
R is independently at each occurrence selected from hydrogen, —F; —Cl; —Br; —I; —OH, —OR*; —NH2; —NHR*; —N(R*)2; —N(R*)3+; —N(R*)—OH; —N(→O)(R*)2; —O—N(R*)2; —N(R*)—O—R*; —N(R*)—N(R*)2; —C═N—R*; —N═C(R*)2; —C═N—N(R*)2; —C(═NR*)—N(R*)2; —SH; —SR*; —CN; —NC; —(C═O)—R*; —CHO; —CO2H; —CO2−; —CO2R*; —(C═O)—S—R*; —O—(C═O)—H; —O—(C═O)—R*; —S—(C═O)—R*; —(C═O)—NH2; —(C═O)—N(R*)2; —(C═O)—NHNH2; —O—(C═O)—NHNH2; —(C═S)—NH2; —(C═S)—N(R*)2; —N(R*)—CHO; —N(R*)—(C═O)—R*; —(C═NR)—O—R*; —O—(C═NR*)—R*, —SCN; —NCS; —NSO; —SSR*; —N(R*)—C(═O)—N(R*)2; —N(R*)—C(═S)—N(R*)2; —SO2—R*; —O—S(═O)2—R*; —S(═O)2—OR*; —N(R*)—SO2—R*; —SO2—N(R*)2; —O—SO3−; —O—S(═O)2—OR*; —O—S(═O)—OR*; —O—S(═O)—R*; —S(═O)—OR*; —S(═O)—R*; —NO; —NO2; —NO3; —O—NO; —O—NO2; —N3; —N2—R*; —N(C2H4); —Si(R*)3; —CF3; —O—CF3; —PR*2; —O—P(═O)(OR*)2; —P(═O)(OR*)2; perfluoroalkyl; an aliphatic C1-C12 hydrocarbon radical; a C6-C12 aromatic hydrocarbon radical; and a C3-C12 heteroaryl radical;
RN and R* are selected independently from hydrogen or a saturated, partially saturated, or aromatic C1-C20 hydrocarbon radical, optionally substituted with a group R or with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen;
or a salt thereof.

### Claim 6 (depends on 1)

The composition according to claim 1, wherein the 3,3′-thiodipropionic acid, or a salt or ester thereof, and the nicotinamide, or salt or derivative thereof, are present in a ratio ranging from about 5:1 (w/w) to about 1:5 (w/w) based on the total weight of the composition.

### Claim 7 (depends on 1)

The composition according to claim 1, wherein the 3,3′-thiodipropionic acid, or a salt or ester thereof and the nicotinamide, or salt or derivative thereof, are present in a ratio of about 10:1 (w/w) based on the total weight of the composition.

### Claim 8 (depends on 1)

The topical composition according to claim 1, wherein the cosmetically or dermatologically acceptable vehicle comprises a water-in-oil, oil-in-water, water-in-silicone, silicone-in-water, polyol-in-silicone, or silicone-in-polyol emulsion, and further comprises from about 0.001% to about 20% by weight of an emulsifier.

### Claim 9 (depends on 1)

A method of reducing pigmentation in human skin, comprising topically applying to an area of skin the composition according to claim 1.

### Claim 10 (depends on 9)

The method according to claim 9, wherein said composition is applied to the skin at least once daily for a period of one week or more.

### Claim 11 (depends on 9)

The method according to claim 9, wherein said composition is applied to the skin at least once daily for a period of one four weeks or more.

### Claim 12 (depends on 3)

The method according to claim 3, wherein the skin suffers from one or more of dark complexion, pigmented skin discoloration, pigmented birthmarks, hyperpigmentation, post-inflammatory hyperpigmentation, post-injury hyperpigmentation, freckles, age spots, liver spots, sun damage, tans, pigmented acne marks, scars, melasma, cholasma, after-burn scars, nail stains, yellowing of skin, or dark circles under eye.