USE OF MATRIX METALLOPROTEINASE INHIBITORS IN SKIN CARE
First Claim
1. A cosmetic method of skin care, the method comprising steps of:
- applying to the skin of a subject a cosmetically effective amount of a matrix metalloproteinase (MMP) inhibitor in a cosmetically suitable vehicle in order to improve the appearance of skin, wherein the MMP inhibitor is of one of the formulae;
whereinX is O or S; and
each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;
and at least one of R1, R2, R3, and R4 is not hydrogen;
or a cosmetically acceptable form thereof.
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Accused Products
Abstract
The application of matrix metalloproteinase (MMP) inhibitors to the skin inhibits the degradation of proteins found in the skin including collagen, elastin, and other basement membrane and extracellular matrix protein. MMP inhibitors may be used in both cosmetic compositions and pharmaceutical compositions for application to skin. MMP inhibitors are formulated with a cosmetically suitable vehicle or pharmaceutically acceptable excipient for application to the skin as creams, lotions, ointments, solutions, face masks, etc. As cosmetics, the inventive MMP inhibitor compositions are applied to the skin to prevent or reduce the appearance of wrinkles, pigmentation changes, loss of elasticity, or other effects associated with aging or sun damage. As pharmaceuticals, the inventive MMP inhibitor compositions may also be applied to the skin to treat or prevent a skin disease (e.g., proliferative disease, inflammatory disease).
166 Citations
92 Claims
-
1. A cosmetic method of skin care, the method comprising steps of:
-
applying to the skin of a subject a cosmetically effective amount of a matrix metalloproteinase (MMP) inhibitor in a cosmetically suitable vehicle in order to improve the appearance of skin, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a cosmetically acceptable form thereof.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
-
-
3. The cosmetic method of claim 2, wherein X is O.
-
4. The cosmetic method of claim 1, wherein the MMP inhibitor is:
-
5. The cosmetic method of claim 1, wherein the MMP inhibitor is:
-
6. The cosmetic method of claim 1, wherein the MMP inhibitor is:
-
7. The cosmetic method of claim 1, wherein the MMP inhibitor is:
-
8. The cosmetic method of claim 1, wherein the step of applying is repeated at least daily.
-
9. The cosmetic method of claim 1, wherein the step of applying is repeated at least twice daily.
-
10. The cosmetic method of claim 1 further comprising applying to the skin of the subject a retinoid.
-
11. The cosmetic method of claim 1 further comprising applying to the skin of the subject a sunscreen.
-
12. The cosmetic method of claim 1 further comprising applying to the skin of the subject an antioxidant.
-
13. A pharmaceutical method of treating skin, the method comprising steps of:
-
administering to the skin of a subject a therapeutically effective amount of a matrix metalloproteinase (MMP) inhibitor in a pharmaceutically acceptable excipient in order to treat a skin condition, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a pharmaceutically acceptable form thereof.- View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)
-
-
15. The pharmaceutical method of claim 14, wherein X is O.
-
16. The pharmaceutical method of claim 13, wherein the MMP inhibitor is:
-
17. The pharmaceutical method of claim 13, wherein the MMP inhibitor is:
-
18. The pharmaceutical method of claim 13, wherein the MMP inhibitor is:
-
19. The pharmaceutical method of claim 13, wherein the MMP inhibitor is:
-
20. The pharmaceutical method of claim 13, wherein the step of administering is repeated at least weekly.
-
21. The pharmaceutical method of claim 13, wherein the step of administering is repeated at least daily.
-
22. The pharmaceutical method of claim 13, wherein the step of administering is repeated at least twice daily.
-
23. The pharmaceutical method of claim 13, wherein the amount of MMP inhibitor applied is effective to decrease the degradation of collagen in the treated skin by at least 25%.
-
24. The pharmaceutical method of claim 13, wherein the amount of MMP inhibitor applied is effective to decrease the degradation of collagen in the treated skin by at least 50%.
-
25. The pharmaceutical method of claim 13, wherein the amount of MMP inhibitor applied is effective to decrease the degradation of collagen in the treated skin by at least 75%.
-
26. The pharmaceutical method of claim 13, wherein the amount of MMP inhibitor applied is effective to decrease the degradation of collagen in the treated skin by at least 90%.
-
27. The pharmaceutical method of claim 13, wherein the amount of MMP inhibitor applied is effective to increase or prevent the decrease of procollagen levels.
-
28. The pharmaceutical method of claim 13, wherein the amount of MMP inhibitor applied is effective to stimulate the formation of new collagen.
-
29. A pharmaceutical method of treating telangiectasia, the method comprising:
-
administering to the skin of a subject an amount of a matrix metalloproteinase (MMP) inhibitor sufficient to reduce the appearance of telangiectasia, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a pharmaceutically acceptable form thereof.- View Dependent Claims (30, 31)
-
-
32. A pharmaceutical method of treating coarse wrinkles, the method comprising:
-
administering to the skin of a subject an amount of a matrix metalloproteinase (MMP) inhibitor sufficient to reduce the appearance of coarse wrinkles, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a pharmaceutically acceptable form thereof.- View Dependent Claims (33, 34, 35)
-
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36. A cosmetic method decreasing the appearance of pore size in the skin, the method comprising:
-
administering to the skin of a subject an amount of a matrix metalloproteinase (MMP) inhibitor sufficient to reduce the apparent pore size, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a cosmetically acceptable form thereof.- View Dependent Claims (37, 38)
-
-
39. A cosmetic method of reducing the appearance of redness, the method comprising:
-
administering to the skin of a subject an amount of a matrix metalloproteinase (MMP) inhibitor sufficient to reduce the appearance of redness, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a cosmetically acceptable form thereof.- View Dependent Claims (40, 41)
-
-
42. A cosmetic method of reducing the appearance of coarse wrinkles, the method comprising:
administering to the skin of a subject an amount of a matrix metalloproteinase (MMP) inhibitor sufficient to reduce the appearance of coarse wrinkles. - View Dependent Claims (43, 44, 45)
-
46. A cosmetic method of reducing the appearance of pores in the skin, the method comprising:
administering to the skin of a subject an amount of a matrix metalloproteinase (MMP) inhibitor sufficient to reduce the appearance of pores in the skin. - View Dependent Claims (47, 48)
-
49. A cosmetic composition comprising:
-
a matrix metalloproteinase (MMP) inhibitor, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a pharmaceutically acceptable form thereof; and
a cosmetically acceptable excipient.- View Dependent Claims (50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78)
-
-
79. A cosmetic composition comprising water, disodium EDTA, carbomer, xantham gum, PEG-7 glyceryl cocoate, glycerin, butylated hydroxytoluene, dimethyl isosorbide, ceteraryl alcohol ceteareth-20, capryl/capric triglyceride, glyceryl stearate PEG-100 stearate, sodium hydroxide, phenoxyethanol, chlorphenesin, methylparaben, propylparaben, and an MMP inhibitor of formula:
-
80. A cosmetic composition comprising water, glycerin, sodium chloride, hyaluronic acid, echinacin, ascorbyl palmitate, tocopheryl acetate, BHT, PEG-4, PEG-7 glyceryl cocoate, cyclopentasiloxane, polysilicone 11, glyceryl laurate, cetyl PEG/PPG 10/1 dimethicone, PEG/PPG-18/18 dimethicone, dimethicone, vinyl dimethicone cross polymer, silica, phenoxyethanol, caprylyl glycol, sorbic acid, and an MMP inhibitor of formula:
-
81. A cosmetic composition comprising water, an antioxidant, a solubilizer, and an MMP inhibitor of formula:
-
82. A method of treating or preventing a skin disease, the method comprising steps of:
-
administering to a subject a therapeutically effective amount of a matrix metalloproteinase (MMP) inhibitor optionally in combination with a pharmaceutically acceptable excipient, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a pharmaceutically acceptable form thereof.- View Dependent Claims (83, 84, 85, 86, 87, 88, 89, 90)
-
-
91. A pharmaceutical composition comprising:
-
a matrix metalloproteinase (MMP) inhibitor, wherein the MMP inhibitor is of one of the formulae; wherein X is O or S; and each of R1, R2, R3, and R4 is independently hydrogen;
halogen;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
substituted or unsubstituted, branched or unbranched acyl;
substituted or unsubstituted, branched or unbranched aryl;
substituted or unsubstituted, branched or unbranched heteroaryl;
—
ORA;
—
C(═
O)RA;
—
CO2RA;
—
CN;
—
SCN;
—
SRA;
—
SORA;
—
SO2RA;
—
NO2;
—
N(RA)2;
—
NHC(O)RA;
—
C(O)NHRA;
—
CH2NHRA;
—
CH2C(═
O)NHRA;
or —
C(RA)3;
wherein each occurrence of RA is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an acyl moiety;
an aryl moiety;
a heteroaryl moiety;
alkoxy;
aryloxy;
alkylthio;
arylthio;
amino, alkylamino, dialkylamino, heteroaryloxy;
or heteroarylthio moiety;and at least one of R1, R2, R3, and R4 is not hydrogen;
or a pharmaceutically acceptable form thereof; anda pharmaceutically acceptable excipient. - View Dependent Claims (92)
-
Specification