Anti-aging and wound healing compounds
AssigneeKimberly-Clark Worldwide, Inc.
InventorsStephen Quirk, Sohail Malik, Julie M. Villanueva
Life of this patent
Estimating the term…
Abstract
The invention provides inhibitors of matrix metalloproteinases that are useful for encouraging the development of healthy skin and for treating wounds. The inhibitors are peptides having sequences related to cleavage regions of the proenzyme forms of matrix metalloproteinases. The peptide inhibitors of the invention can be formulated into therapeutic compositions, lotions, creams, skin covering and wound dressings that facilitate healing and healthy skin development, discourage scarring and wrinkling and ameliorate the effects of healing.
Claims73
A peptide comprising SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, or SEQ ID NO:17, wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A composition comprising a therapeutically effective amount of peptide of formula I and a pharmaceutically acceptable carrier:
- Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6 Xaa7-Xaa8-Xaa9 (I)
- wherein:
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A composition comprising a therapeutically effective amount of peptide of formula II and a pharmaceutically acceptable carrier:
- Xaa10-Xaa11-Xaa12Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (II)
- wherein:
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A composition comprising a therapeutically effective amount of peptide of formula III and a pharmaceutically acceptable carrier:
- Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (III)
- wherein
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A composition that comprises a therapeutically effective amount of peptide of formula IV and a pharmaceutically acceptable carrier:
- 18 Xaaa-Xaab-Xaac-Xaad-Xaae-Xaaf-Xaag-Xaah-Xaai-Xaaj-Xaak-XaaL- (IV) (SEQ ID NO:18) Xaam-Xaan-Xaao-Xaap-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6- Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14- Xaa15-Xaa16-Xaa17-Xaa18-Xaa19
- 19 Xaaa is proline;
- Xaa1 is proline;
- Xaab is glutamine or glutamic acid;
- Xaa2 is arginine;
- Xaac is threonine;
- Xaa3 is cysteine;
- Xaad is glycine;
- Xaa4 is glycine;
- Xaae is aspartic acid or glutamic Xaa5 is valine or asparagine;
- acid;
- Xaaf is leucine;
- Xaa6 is proline;
- Xaag is aspartic acid;
- Xaa7 is aspartic acid;
- Xaah is glutamine or serine;
- Xaa8 is valine or leucine;
- Xaai is asparagine or alanine;
- Xaa9 is alanine or glycine;
- Xaaj is threonine;
- Xaa10 is asparagine or arginine;
- Xaak is isoleucine or leucine;
- Xaa11 is tyrosine or phenylalanine;
- XaaL is glutamic acid or lysine;
- Xaa12 is asparagine or glutamine;
- Xaam is threonine or alanine;
- Xaa13 is phenylalanine or threonine;
- Xaan is methionine;
- Xaa14 is phenylalanine;
- Xaao is arginine;
- Xaa15 is proline or glutamic acid;
- Xaap is lysine or threonine;
- Xaa16 is arginine or glycine;
- Xaa17 is lysine or aspartic acid;
- Xaa18 is proline or leucine;
- Xaa19 is lysine;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A composition that comprises a therapeutically effective amount of peptide that comprises SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13, and a pharmaceutically acceptable carrier.
A wound dressing that comprises a peptide of the formula I:
- Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6 Xaa7-Xaa8-Xaa9 (I)
- wherein:
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A wound dressing that comprises a peptide of the formula II:
- Xaa10-Xaa11-Xaa12Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (II)
- wherein:
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A wound dressing that comprises a peptide of formula III:
- 20 Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11- Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (III)
- wherein:
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A wound dressing that comprises a peptide of formula IV:
- 21 Xaaa-Xaab-Xaac-Xaad-Xaae-Xaaf-Xaag-Xaah-Xaai-Xaaj-Xaak-XaaL- (IV) (SEQ ID NO:18) Xaam-Xaan-Xaao-Xaap-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6- Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14- Xaa15-Xaa16-Xaa17-Xaa18-Xaa19
- wherein:
- 22 Xaaa is proline;
- Xaa1 is proline;
- Xaab is glutamine or glutamic acid;
- Xaa2 is arginine;
- Xaac is threonine;
- Xaa3 is cysteine;
- Xaad is glycine;
- Xaa4 is glycine;
- Xaae is aspartic acid or glutamic Xaa5 is valine or asparagine;
- acid;
- Xaaf is leucine;
- Xaa6 is proline;
- Xaag is aspartic acid;
- Xaa7 is aspartic acid;
- Xaah is glutamine or serine;
- Xaa8 is valine or leucine;
- Xaai is asparagine or alanine;
- Xaa9 is alanine or glycine;
- Xaaj is threonine;
- Xaa10 is asparagine or arginine;
- Xaak is isoleucine or leucine;
- Xaa11 is tyrosine or phenylalanine;
- XaaL is glutamic acid or lysine;
- Xaa12 is asparagine or glutamine;
- Xaam is threonine or alanine;
- Xaa13 is phenylalanine or threonine;
- Xaan is methionine;
- Xaa14 is phenylalanine;
- Xaao is arginine;
- Xaa15 is proline or glutamic acid;
- Xaap is lysine or threonine;
- Xaa16 is arginine or glycine;
- Xaa17 is lysine or aspartic acid;
- Xaa18 is proline or leucine;
- Xaa19 is lysine;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A wound dressing that comprises a peptide comprising SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13, wherein the peptide can inhibit a matrix metalloproteinase or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A lotion for treating skin to reduce the effects of aging that comprises a peptide of the formula I:
- Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6 Xaa7-Xaa8-Xaa9 (I)
- wherein:
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A lotion for treating skin to reduce the effects of aging that comprises a peptide of the formula II:
- Xaa10-Xaa11-Xaa12 Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (II)
- wherein:
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A lotion for treating skin to reduce the effects of aging that comprises a peptide of formula III:
- Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (III)
- wherein:
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A lotion for treating skin to reduce the effects of aging that comprises a peptide of formula IV:
- 23 Xaaa-Xaab-Xaac-Xaad-Xaae-Xaaf-Xaag-Xaah-Xaai-Xaaj-Xaak-XaaL- (IV) (SEQ ID NO:18) Xaam-Xaan-Xaao-Xaap-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6- Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14- Xaa15-Xaa16-Xaa17-Xaa18-Xaa19
- wherein:
- 24 Xaaa is proline;
- Xaa1 is proline;
- Xaab is glutamine or glutamic acid;
- Xaa2 is arginine;
- Xaac is threonine;
- Xaa3 is cysteine;
- Xaad is glycine;
- Xaa4 is glycine;
- Xaae is aspartic acid or glutamic Xaa5 is valine or asparagine;
- acid;
- Xaaf is leucine;
- Xaa6 is proline;
- Xaag is aspartic acid;
- Xaa7 is aspartic acid;
- Xaah is glutamine or serine;
- Xaa8 is valine or leucine;
- Xaai is asparagine or alanine;
- Xaa9 is alanine or glycine;
- Xaaj is threonine;
- Xaa10 is asparagine or arginine;
- Xaak is isoleucine or leucine;
- Xaa11 is tyrosine or phenylalanine;
- XaaL is glutamic acid or lysine;
- Xaa12 is asparagine or glutamine;
- Xaam is threonine or alanine;
- Xaa13 is phenylalanine or threonine;
- Xaan is methionine;
- Xaa14 is phenylalanine;
- Xaao is arginine;
- Xaa15 is proline or glutamic acid;
- Xaap is lysine or threonine;
- Xaa16 is arginine or glycine;
- Xaa17 is lysine or aspartic acid;
- Xaa18 is proline or leucine;
- Xaa19 is lysine;
- and
- wherein the peptide can inhibit matrix metalloproteinase-2 or the peptide can stimulate cellular proliferation of fibroblasts or keratinocytes.
A lotion that comprises a peptide comprising SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13, wherein the peptide can inhibit a matrix metalloproteinase.
A method for promoting healthy skin development that comprises administering a therapeutically effective amount of a peptide of formula I:
- Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6 Xaa7-Xaa8-Xaa9 (I)
- wherein:
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- and
- wherein the peptide is capable of inhibiting the activity of a matrix metalloproteinase or of promoting the growth of fibroblasts or keratinocytes.
A method for promoting healthy skin development that comprises administering a therapeutically effective amount of a peptide of formula II:
- Xaa10-Xaa11-Xaa12 Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (II)
- wherein:
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and
- wherein the peptide is capable of inhibiting the activity of a matrix metalloproteinase or of promoting the growth of fibroblasts or keratinocytes.
A method for promoting healthy skin development that comprises administering a therapeutically effective amount of a peptide of formula III:
- 25 Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11- Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (III)
- wherein:
- Xaa1, Xaa4, and Xaa6 are separately each apolar amino acids;
- Xaa2 is a basic amino acid;
- Xaa3 is a cysteine-like amino acid;
- Xaa5 is a polar or aliphatic amino acid;
- Xaa7 is an acidic amino acid;
- Xaa8 is an aliphatic or polar amino acid;
- Xaa9 is an aliphatic, apolar or basic amino acid;
- Xaa10 is a polar, acidic, basic or apolar amino acid;
- Xaa11 is a polar or aromatic amino acid;
- Xaa12 is a polar, basic, aliphatic or apolar amino acid;
- Xaa13 is an aromatic, aliphatic, polar or acidic amino acid;
- Xaa14 is an aromatic, apolar or polar amino acid;
- Xaa15 is an apolar or acidic amino acid;
- Xaa16 is a basic, a polar or an apolar amino acid;
- Xaa17 is a basic, a polar, an aliphatic, an apolar or an acidic amino acid;
- Xaa18 is an apolar or an aliphatic amino acid;
- Xaa19 is a basic or an aliphatic amino acid;
- and
- wherein the peptide is capable of inhibiting the activity of a matrix metalloproteinase or of promoting the growth of fibroblasts or keratinocytes.
A method for promoting healthy skin development that comprises administering a therapeutically effective amount of a peptide of formula IV:
- 26 Xaaa-Xaab-Xaac-Xaad-Xaae-Xaaf-Xaag-Xaah-Xaai-Xaaj-Xaak-XaaL- (SEQ ID NO:18) Xaam-Xaan-Xaao-Xaap-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6- Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14- +01 Xaa15-Xaa16-Xaa17-Xaa18-Xaa19 (IV)
- wherein:
- 27 Xaaa is proline;
- Xaa1 is proline;
- Xaab is glutamine or glutamic acid;
- Xaa2 is arginine;
- Xaac is threonine;
- Xaa3 is cysteine;
- Xaad is glycine;
- Xaa4 is glycine;
- Xaae is aspartic acid or glutamic Xaa5 is valine or asparagine;
- acid;
- Xaaf is leucine;
- Xaa6 is proline;
- Xaag is aspartic acid;
- Xaa7 is aspartic acid;
- Xaah is glutamine or serine;
- Xaa8 is valine or leucine;
- Xaai is asparagine or alanine;
- Xaa9 is alanine or glycine;
- Xaaj is threonine;
- Xaa10 is asparagine or arginine;
- Xaak is isoleucine or leucine;
- Xaa11 is tyrosine or phenylalanine;
- XaaL is glutamic acid or lysine;
- Xaa12 is asparagine or glutamine;
- Xaam is threonine or alanine;
- Xaa13 is phenylalanine or threonine;
- Xaan is methionine;
- Xaa14 is phenylalanine;
- Xaao is arginine;
- Xaa15 is proline or glutamic acid;
- Xaap is lysine or threonine;
- Xaa16 is arginine or glycine;
- Xaa17 is lysine or aspartic acid;
- Xaa18 is proline or leucine;
- Xaa19 is lysine;
- and
- wherein the peptide is capable of inhibiting the activity of a matrix metalloproteinase or of promoting the growth of fibroblasts or keratinocytes.
Dependencies are inferred from the claim text.