IP Library › Granted Patent US 12,419,824
Granted Patent B2
US 12,419,824 · App. 17/427,364 · Granted Sep 23, 2025

Compounds useful for the treatment and/or care of the skin, hair, nails and/or mucous membranes

Inventors: Mauricio Valerio Santiago (Cadiz, ES); Consuelo García Hernández (Murcia, ES); Núria Almiñana Doménech (Barcelona, ES); Albert Soley Astals (Barcelona, ES)
Assignee: Lubrizol Advanced Materials, Inc.
A61K8/64A61Q19/06A61Q19/08C07K5/1021C07K7/06A61K38/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,419,824
App. No.
17/427,364
Granted
Sep 23, 2025
Kind
B2
Abstract

A compound of formula (I) R 1 -W m -X n -AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -Y p -Z q -R 2 , a stereoisomer and/or cosmetically acceptable salt thereof, and a method of treatment using the compound are described. In the compound, AA 1 is Asp, Gly, Asn, Gln, Ala or no amino acid; AA 2 is Val, Ile, Leu or Ala; AA 3 is Tyr, Phe, Trp, Lys, Arg or His; AA 4 is Lys, Arg, His, Pro or Val; AA 5 is Asn, Asp, Gln or no amino acid; AA 6 is Thr, Ala, Ser or no amino acid. The compounds are useful for the treatment of the symptoms of skin aging and, in particular, for the treatment of skin wrinkles, the treatment of a sagging appearance of the skin, and/or the reduction of facial asymmetry.

Claims (111)

1. A compound selected from the group consisting of:

(R 1 -[SEQ ID NO. 1]-R 2 )

R 1 -Asp-Val-Tyr-Lys-R 2 ;

(R 1 -[SEQ ID NO. 2]-R 2 )

R 1 -Ala-Leu-Lys-Pro-Asn-Thr-R 2 ;

(R 1 -[SEQ ID NO. 3]-R 2 )

R 1 -Glu-Val-Tyr-Lys-R 2 ;

(R 1 -[SEQ ID NO. 4]-R 2 )

R 1 -Asp-Ile-Tyr-Lys-R 2 ;

(R 1 -[SEQ ID NO. 5]-R 2 )

R 1 -Asp-Val-Phe-Lys-R 2 ;

(R 1 -[SEQ ID NO. 6]-R 2 )

R 1 -Asp-Val-Tyr-Arg-R 2 ;

(R 1 -[SEQ ID NO. 7]-R 2 )

R 1 -Asn-Val-Tyr-Lys-R 2 ;

(R 1 -[SEQ ID NO. 8]-R 2 )

R 1 -Asp-Leu-Tyr-Lys-R 2 ;

(R 1 -[SEQ ID NO. 9]-R 2 )

R 1 -Ala-Asp-Val-Tyr-Lys-R 2 ;

(R 1 -[SEQ ID NO. 10]-R 2 )

R 1 -Asp-Val-Tyr-Lys-Ala-R 2 ;

(R 1 -[SEQ ID NO. 15]-R 2 )

R 1 -Glu-Ile-Tyr-Lys-R 2 ;

(R 1 -[SEQ ID NO. 18]-R 2 )

R 1 -Glu-Ile-Tyr-Arg-R 2 ;

(R 1 -[SEQ ID NO. 19]-R 2 )

R 1 -Glu-Ile-Phe-Arg-R 2 ;

(R 1 -[SEQ ID NO. 22]-R 2 )

R 1 -Ala-Leu-Arg-Pro-Asn-Thr-R 2 ;

(R 1 -[SEQ ID NO. 23]-R 2 )

R 1 -Ala-Leu-Lys-Val-Asn-Thr-R 2 ;

(R 1 -[SEQ ID NO. 30]-R 2 )

R 1 -Leu-Lys-Pro-Asn-Thr-R 2 ;

(R 1 -[SEQ ID NO. 31]-R 2 )

R 1 -Ala-Leu-Lys-Pro-Asn-R 2 ;

(R 1 -[SEQ ID NO. 32]-R 2 )

R 1 -Gly-Ile-Lys-Pro-Asn-Thr-R 2 ;

(R 1 -[SEQ ID NO. 34]-R 2 )

R 1 -Ala-Ile-Arg-Pro-Asn-Thr-R 2 ;

(R 1 -[SEQ ID NO. 34]-R 2 )

R 1 -Gly-Val-Arg-Pro-Asn-Thr-R 2 ;

(R 1 -[SEQ ID NO. 40]-R 2 )

R1-Ala-Leu-Lys-Pro-Gln-Thr-R 2 ;

and combinations thereof;

wherein R 1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl and R 5 —CO—, wherein R 5 is selected from the group consisting of H, a non-cyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl and heteroarylalkyl;

R 2 is selected from the group consisting of —NR 3 R 4 , —OR 3 , —SR 3 , wherein R 3 and R 4 are independently selected from a group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl and aralkyl; and

R 1 and R 2 are not amino acids.

2. A compound according to claim 1 , wherein R 1 is selected from the group consisting of H and R 5 —CO—, wherein R 5 is selected from the group consisting of C 1 -C 18 alkyl, C 2 -C 24 alkenyl, C 3 -C 24 cycloalkyl; and R 2 is —NR 3 R 4 or —OR 3 wherein R 3 and R 4 are independently selected from the group consisting of H and C 1 -C 16 alkyl.

3. A compound according to claim 1 , wherein the compound is selected from the group consisting of:

(PEP1, Ac-[SEQ ID NO. 1]-NH 2 )

Ac-Asp-Val-Tyr-Lys-NH 2 ;

(PEP2, H-[SEQ ID NO. 2]-NH 2 )

H-Ala-Leu-Lys-Pro-Asn-Thr-NH 2 ;

and combinations thereof.

4. A composition comprising a cosmetically effective quantity of a compound of claim 1 , and at least one cosmetically acceptable excipient or adjuvant.

5. A combination of a compound according to claim 1 and at least one of Botulinum toxin and the peptide of sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH 2 (Ac-[SEQ ID NO. 41]-NH 2 .

6. A compound selected from the group consisting of:

(PEP3, Palm-[SEQ ID NO. 1]-NH 2 )

Palm-Asp-Val-Tyr-Lys-NH 2 ;

(PEP4, Ac-[SEQ ID NO. 2]-OH)

Ac-Asp-Val-Tyr-Lys-OH;

(PEP5, H-[SEQ ID NO. 2]-NH 2 )

H-Asp-Val-Tyr-Lys-NH 2 ;

(PEP7, Ac-[SEQ ID NO. 3]-NH 2 )

Ac-Glu-Val-Tyr-Lys-NH 2 ;

(PEP8, Ac-[SEQ ID NO. 4]-NH 2 )

Ac-Asp-Ile-Tyr-Lys-NH 2 ;

(PEP9, Ac-[SEQ ID NO. 5]-NH 2 )

Ac-Asp-Val-Phe-Lys-NH 2 ;

(PEP10, Ac-[SEQ ID NO. 6]-NH 2 )

Ac-Asp-Val-Tyr-Arg-NH 2 ;

(PEP11, Ac-[SEQ ID NO. 7]-NH 2 )

Ac-Asn-Val-Tyr-Lys-NH 2 ;

(PEP12, Ac-[SEQ ID NO. 8]-NH 2 )

Ac-Asp-Leu-Tyr-Lys-NH 2 ;

(PEP13, Palm-[SEQ ID NO. 3]-NH 2 )

Palm-Glu-Val-Tyr-Lys-NH 2 ;

(PEP14, Ac-[SEQ ID NO. 9]-NH 2 )

Ac-Ala-Asp-Val-Tyr-Lys-NH 2 ;

(PEP15, Ac-[SEQ ID NO. 10]-NH 2 )

Ac-Asp-Val-Tyr-Lys-Ala-NH 2 ;

(PEP20, Ac-[SEQ ID NO. 15]-NH 2 )

Ac-Glu-Ile-Tyr-Lys-NH 2 ;

(PEP23, Ac-[SEQ ID NO. 18]-NH 2 )

Ac-Glu-Ile-Tyr-Arg-NH 2 ;

(PEP24, Ac-[SEQ ID NO. 19]-NH 2 )

Ac-Glu-Ile-Phe-Arg-NH 2 ;

(PEP27, Ac-[SEQ ID NO. 2]-OH)

Ac-Ala-Leu-Lys-Pro-Asn-Thr-OH;

(PEP30, H-[SEQ ID NO. 22]-NH 2 )

H-Ala-Leu-Arg-Pro-Asn-Thr-NH 2 ;

(PEP31, H-[SEQ ID NO. 23]-NH 2 )

H-Ala-Leu-Lys-Val-Asn-Thr-NH 2 ;

(PEP40, H-[SEQ ID NO. 30]-NH 2 )

H-Leu-Lys-Pro-Asn-Thr-NH 2 ;

(PEP41, H-[SEQ ID NO. 31]-NH 2 )

H-Ala-Leu-Lys-Pro-Asn-NH 2 ;

(PEP42, H-[SEQ ID NO. 32]-NH 2 )

H-Gly-Ile-Lys-Pro-Asn-Thr-NH 2 ;

(PEP44, H-[SEQ ID NO. 34]-NH 2 )

H-Ala-Ile-Arg-Pro-Asn-Thr-NH 2 ;

(PEP46, H-[SEQ ID NO. 36]-NH 2 )

H-Gly-Val-Arg-Pro-Asn-Thr-NH 2 ;

(PEP50, H-[SEQ ID NO. 40]-NH 2 )

H-Ala-Leu-Lys-Pro-Gln-Thr-NH 2 -);

and combinations thereof.

7. A composition comprising a cosmetically effective quantity of a compound of claim 6 , and at least one cosmetically acceptable excipient or adjuvant.

8. A method of treatment and/or care of the skin, of a subject comprising administering a compound according to claim 6 to the skin, of the subject, wherein the treatment and/or care comprises at least one of:

reduction of skin wrinkles; a stimulation of collagen synthesis; a reduction of collagen loss;

an improvement or maintenance of skin firmness; an increase of the volume of adipose tissue;

an alleviation of adipose tissue loss; a reduction of skin roughness; and an improvement in skin smoothness.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 15, 2021
From: VALERIO, MAURICIO; GARCIA HERNANDEZ, CONSUELO; ALMINANA, NURIA; SOLEY, ALBERT
To: LUBRIZOL ADVANCED MATERIALS, INC.
Reel/Frame 057489/0650 →
Priority Claims (1)
EP 19382092 · Feb 8, 2019 · regional
Continuity (1)
Related Publication 20220183950A1 · Jun 16, 2022
References Cited (74)
US 5370996A · Metz · 1994 [cited by examiner]
US 7660677B2 · Tanuma et al. · 2010 [cited by applicant]
US 7736639B2 · Bam et al. · 2010 [cited by applicant]
US 8058016B2 · Nordstedt et al. · 2011 [cited by applicant]
US 8669089B2 · Helbert et al. · 2014 [cited by applicant]
US 8865651B2 · Otte et al. · 2014 [cited by applicant]
US 9493522B2 · Wells et al. · 2016 [cited by applicant]
US 9597274B2 · Idkowiak-Baldys et al. · 2017 [cited by applicant]
US 9725483B2 · García et al. · 2017 [cited by applicant]
US 9771392B2 · Ferrer Montiel et al. · 2017 [cited by applicant]
US 10107820B2 · Reilly et al. · 2018 [cited by applicant]
US 20070249528A1 · Weston · 2007 [cited by applicant]
US 20100008654A1 · Hsu · 2010 [cited by applicant]
US 20110182905A1 · Takada et al. · 2011 [cited by applicant]
US 20120276049A1 · Stern et al. · 2012 [cited by applicant]
US 20130183702A1 · Bossmann et al. · 2013 [cited by applicant]
US 20160132631A1 · Bremel et al. · 2016 [cited by applicant]
US 20180369115A1 · Alminana Domenech et al. · 2018 [cited by applicant]
US 20220096657A1 · Paul et al. · 2022 [cited by applicant]
EP 1992332A1 · 2008 [cited by applicant]
JP 2004081178 · 2004 [cited by applicant]
JP 2008502311A · 2008 [cited by applicant]
KR 20180108988A · 2018 [cited by applicant]
WO WO9209628A1 · 1992 [cited by applicant]
WO WO2004087188A1 · 2004 [cited by applicant]
WO WO2004091517A2 · 2004 [cited by applicant]
WO WO2009064399A1 · 2009 [cited by applicant]
WO WO2010021822A2 · 2010 [cited by applicant]
WO WO2011044452A2 · 2011 [cited by applicant]
WO WO2011082376A1 · 2011 [cited by applicant]
WO WO2011119484A1 · 2011 [cited by applicant]
WO WO2011157966A1 · 2011 [cited by applicant]
WO WO2013049830A2 · 2013 [cited by applicant]
WO WO2013156493A1 · 2013 [cited by applicant]
WO WO2014200910A2 · 2014 [cited by applicant]
WO WO2015074048A1 · 2015 [cited by applicant]
WO WO2016025516A1 · 2016 [cited by examiner]
WO WO2016204841A1 · 2016 [cited by applicant]
WO WO2017100421A1 · 2017 [cited by applicant]
WO WO2017189963A1 · 2017 [cited by applicant]
WO WO2018071640A1 · 2018 [cited by applicant]
Albericio, F., et al., “Preparation and application of the 5-(4-(9-fluorenylmethyloxycarbonyl) aminomethyl-3,5-dimethoxy-phenoxy)valeric-acid (PAL) handle for the solid-phase synthesis of C-terminal peptide amides under… [cited by applicant]
Atherton, B., et al., “Solid Phase Peptide Synthesis: A practical approach,” IRL Oxford University Press, pp. 1-61 (1989). [cited by applicant]
Barlos, K., et al., “Darstellung geschützter Peptid-Fragmente unter Einsatz substituierter Triphenylmethyl-Harze,” Tetrahedron Lett., 30, 3943-3946 (1989), English Abstract only. [cited by applicant]
Barlos, K., et al., “Veresterung von partiell geschützten Peptid-Fragmenten mit Harzen. Einsatz von 2-Chlorotritylchlorid zur Synthese von Leu1-Gastrin I,” Tetrahedron Lett., 30, 3947-3951 (1989), English Abstract only. [cited by applicant]
Berge, S.M., et al., “Pharmaceutical Salts,” J. Pharm. Sci., 66, pp. 1-19 (1977). [cited by applicant]
Bodanzsky, M., et al., “The practice of Peptide Synthesis,” pp. 75-126, Springer Verlag, Berlin (1994). [cited by applicant]
Christensen, T., “A Qualitative Test for Monitoring Coupling Completeness in Solid Phase Peptide Synthesis Using Chloranil,” Acta Chem. Scand., 33B, pp. 763-766 (1979). [cited by applicant]
Davis, J. et al. “MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response,” Nature Communications, vol. 6: 10084, pp. 1-14 (2015). [cited by applicant]
Goldberg, A. et al. “Skin Rejuvenation with Non-Invasive Pulsed Electric Fields,” Nature Scientific Reports, vol. 5:10187, pp. 1-18 (2015). [cited by applicant]
Hipler, U.C, et al., “Biofunctional Textiles and the Skin” in Curr. Probl. Dermatol. v.33, pp. 35-41 (Hipler U.C. and Elsner P., eds.) S. Karger AG, Basel, Switzerland (2006). [cited by applicant]
Jennings, J.A. “Regulation of gene expression in response to continuous low intensity direct current electrical fields,” Doctoral Thesis, Birmingham Alabama, pp. 1-208 (2007) (Abstract only). [cited by applicant]
Kaiser, E., et al., “Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides,” Anal. Biochem., 34, pp. 595-598 (1970). [cited by applicant]
Kern, H., et al. “Electrical stimulation counteracts muscle decline in seniors,” Frontiers in Aging Neuroscience, vol. 6 (189), pp. 1-11 (2014). [cited by applicant]
Kullmann, W., “Proteases as catalysts for enzymic syntheses of opioid peptides,” J. Biol. Chem., 255(17), pp. 8234-8238 (1980). [cited by applicant]
Lionakis, et al., “Development of a Ligand-Directed Approach to Study the Pathogenesis of Invasive Aspergillosis,” Infection and Immunity, American Society for Microbiology, vol. 73, No. 11, pp. 7747-7758 (Nov. 2005). [cited by applicant]
Lloyd-Williams, P., et al., “Chemical Approaches to the Synthesis of Peptides and Proteins,” pp. 19-93, CRC, synthesis in solution, enzymatic synthesis, Boca Raton, FL, USA (1997). [cited by applicant]
Lloyd-Williams, P., et al., “Convergent Solid-Phase Peptide Synthesis,” Tetrahedron, 49(48), pp. 11065-11133 (1993). [cited by applicant]
Malatesta, M. et al., “Muscleblind-like1 undergoes ectopic relocation in the nuclei of skeletal muscles in myotonic dystrophy and sarcopenia,” European Journal of Histochemistry, vol. 57:e15, pp. 86-92 (2013). [cited by applicant]
Malatesta, M. et al. “RNA transcription and maturation in skeletal muscle cells are similarly impaired in myotonic dystrophy and sarcopenia: the ultrastructural evidence”, (2014), Frontiers in Aging Neuroscience, vol. 6… [cited by applicant]
Malcolm, R.K., et al., “Controlled release of a model antibacterial drug from a novel self-lubricating silicone biomaterial,” J. Cont. Release, 97(2), pp. 313-320 (2004). [cited by applicant]
Matsueda, G.R., et al., “A p-methylbenzhydrylamine resin for improved solid-phase synthesis of peptide amides,” Peptides, 2, pp. 45-50 (1981). [cited by applicant]
Nelson, G., “Application of microencapsulation in textiles,” Int. J. Pharm., 242(1-2), pp. 55-62 (2002). [cited by applicant]
Rink, H., “Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin,” Tetrahedron Lett., 28, pp. 3787-3790 (1987). [cited by applicant]
Roberts, D.C., et al., “Unusual amino acids in peptide synthesis,” in The Peptides, vol. 5, Chapter VI, pp. 341-449 (Gross E. and Meienhofer J., Eds.) Academic Press, New York, USA (1983). [cited by applicant]
Schaab, C.K., “Impregnating Fabrics with Microcapsules,” HAPPI, pp. 84-86 (May 1986). [cited by applicant]
Saniee, F. et al. “Consider of Micro-Current's effect to variation of Facial Wrinkle trend, Randomized Clinical Trial Study,” Life Science , vol. 9(3), pp. 1184-1189 (2012). [cited by applicant]
Stewart, J.M., et al., “Solid Phase Peptide Synthesis,” 2nd edition, pp. 1-20, Pierce Chemical Company, Rockford, Illinois (1984). [cited by applicant]
Wang, S.S., “p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycarbonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments,” J. Am. Chem. Soc., 95, pp. 1328-1333 (1973). [cited by applicant]
Wilkinson, et al., “Harry's Cosmeticology,” Seventh edition, pp. 50-73 and 757-799 (Wilkinson J.B., Moore R.J., eds.) Longman House, Essex, GB (1982). [cited by applicant]
CTFA International Cosmetic Ingredient Dictionary and Handbook, 12th Edition, vol. 3, pp. 3040-3065 (2008). [cited by applicant]
IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), Nomenclature and Symbolism for Amino Acids and Peptides, Recommendations 1983, Eur J. Biochem., 138, 9-37 (1984). [cited by applicant]
Varani, J. et al. “Decreased Collagen Production in Chronologically Aged Skin: Roles of Age-Dependent Alteration in Fibroblast Function and Defective Mechanical Stimulation,” American Journal of Pathology, vol. 168 (6),… [cited by applicant]
Wu, Jing-Tao et al., “Protein Digest Analysis by Pressurized Capillary Electrochromatography Using an Ion Trap Storage / Reflectron Time-of-Flight Mass Detector” Analytical Chemistry, vol. 69, No. 15, pp. 2-7 (1997). [cited by applicant]