New use of peptides derived from vasoactive intestinal peptide

Abstract

The present application provides a compound or a regioisomer, a stereoisomer or a pharmaceutically or cosmetically acceptable salt thereof for use in the treatment of vaginal laxity or a related disorder, said compound consisting essentially of 3 to 21 N-terminal amino acids having the following peptide sequence: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 1), wherein: X 4 , X 5 , X 9 , X 11 and / or X 13 each independently represents an amino acid selected from the group consisting of Ala, Val, lie, Gly, Asn, Ser, Thr, Tyr and Leu; said peptide sequence is optionally coupled to a group Y, or said peptide sequence is optionally coupled to a group -Lys-Y when the C-terminal amino acid is not Lys; and Y represents one or more molecules of latanoprost and / or one or more lipids selected from the group consisting of: vitamin A, vitamin E, cholesterol, and a fatty acid comprising one or more carboxylic acid groups, 1 to 50 carbons, and / or one or more rings, said lipid being linear or branched, saturated or unsaturated with 1 to 10 carbon-carbon double bonds, and / or substituted with 1 to 10 -OH groups, or a derivative of any of these lipids.

Description

Technical Field

[0001] This invention relates to the use of peptides (some of which are novel peptides) in human medicine for the treatment of vaginal laxity and related conditions. Background Technology

[0002] Vaginal laxity (VL) can be defined as vaginal loosening that may occur after pregnancy and / or vaginal delivery, but it can also be caused by pelvic surgery, menopause, and aging.

[0003] Although this condition is not well defined and may be underestimated, it is known to cause decreased pelvic sensation during intercourse, negatively impacting the quality of sexual life, as well as other problems such as urinary incontinence, vaginal dryness, and skin laxity.

[0004] Vulvovaginal laxity (VL) can be treated with so-called 'vaginal rejuvenation,' which aims to restore the appearance and / or function of the vagina. This is typically performed surgically (vaginoplasty; usually by a plastic surgeon, urologist, or gynecologist) and / or non-invasively using energy-based (radiofrequency or laser) devices designed to promote tissue remodeling. Patients who have undergone vaginoplasty repair targeting the vaginal opening have reported improved sexual function.

[0005] However, there remains a significant unmet clinical need for drugs that can be used for direct, immediate treatment of VL.

[0006] Vasoactive intestinal peptide (VIP) is an endogenous peptide hormone composed of 28 amino acid residues. It belongs to the glucagon / peptide secretin superfamily and is synthesized in many tissues, including the intestine, pancreas, and hypothalamus.

[0007] VIP has many known biological functions, including vasodilation that causes hypotension, bronchodilation (which, together with pulmonary vasodilation and bronchial secretion, promotes ventilation and protects against acute lung injury (ALI)), stimulation of glycogenolysis and gluconeogenesis, and stimulation of glands in the endocrine and neuroendocrine systems to release a variety of hormones.

[0008] According to clinicaltrials.gov, human studies have been conducted to test VIP in the treatment of Covid-19.

[0009] It is also known that VIP can relax the smooth muscles of the respiratory and gastrointestinal systems, as well as the smooth muscles of the male and female reproductive systems. In particular, VIP causes relaxation of the smooth muscle tubes and cervix, inhibits uterine muscle contraction, and increases uterine blood flow and vaginal lubrication in the female reproductive system.

[0010] Gourlet and others Peptides Previous reports summarized in 17,825 (1996) that VIP cannot be significantly shortened at the C-terminus without loss of binding affinity of the resulting peptide. Onoue et al. in Life Sciences A follow-up publication in 74,1465 (2004) reported that receptor binding activity decreased significantly in proportion to the reduction of C-terminal amino acid residues, with VIP(1-22) and VIP(1-21) exhibiting minimal binding activity even at high concentrations. These authors concluded that at least 23 amino acid residues are required to protect VIP receptor binding activity.

[0011] We have now unexpectedly discovered that topically applied VIP analogues containing significantly fewer than 23 N-terminal amino acid residues demonstrate significant clinical benefit in the treatment of VL. Summary of the Invention

[0012] According to a first aspect of the invention, a compound and regioisomers, stereoisomers, or pharmaceutically or cosmetically acceptable salts of such compounds are provided for treating VL or related disorders, said compound consisting essentially of 3 to 21 N-terminal amino acids having the following peptide sequence: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 1) in: X 4 X 5 X 9 X 11 and / or X 13 Each of the following amino acids is independently selected: Ala, Val, Ile, Gly, Asn, Ser, Thr, Tyr, and Leu; The peptide sequence is optionally coupled to the group Y, or when the C-terminal amino acid is not Lys, the peptide sequence is optionally coupled to the group -Lys-Y; and Y represents one or more latanoprost molecules and / or one or more lipids selected from: vitamin A, vitamin E, cholesterol, and fatty acids containing one or more carboxylic acid groups, 1 to 50 carbons, and / or one or more rings, or derivatives of any of these lipids, said lipids being linear or branched, saturated or unsaturated with 1 to 10 carbon-carbon double bonds and / or substituted with 1 to 10 -OH groups; The compounds used for the purposes described herein, their regioisomers, stereoisomers, and salts are hereinafter referred to as 'compounds of the present invention'.

[0013] In some embodiments, the peptide sequence of the compound of the present invention is: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys (SEQ ID No: 2); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val (SEQ ID No: 3); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala (SEQ ID No: 4); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met (SEQID No: 5); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13-Arg-Lys-Gln (SEQ IDNo: 6); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ ID No:7); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No: 8); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 9); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg (SEQ ID No: 10); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 (SEQ ID No: 11); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr (SEQ ID No: 12); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 (SEQ ID No: 13); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp (SEQ ID No: 14); His-Ser-Asp-X 4-X 5 -Phe-Thr (SEQ ID No: 15); His-Ser-Asp-X 4 -X 5 -Phe (SEQ ID No: 16); His-Ser-Asp-X 4 -X 5 (SEQ ID No: 17); His-Ser-Asp-X 4 (SEQ ID No: 18); or His-Ser-Asp (SEQ ID No: 19), Any sequence in the sequence may be optionally coupled to the group Y, or optionally coupled to the group -Lys-Y when the C-terminal amino acid is not Lys.

[0014] More preferably, the compounds of the present invention include those having the following peptide sequences: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met (SEQID No: 5); or His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 9), for example: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln (SEQ IDNo: 6); or His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No: 8), and, especially His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ ID No:7), Any sequence in the sequence may be optionally coupled to the group Y, or optionally coupled to the group -Lys-Y when the C-terminal amino acid is not Lys.

[0015] Optional Y group (i.e., one or more latanoprosts) Z )-7-[(1 R ,2 R ,3 R 5 S )-3,5-dihydroxy-2-[(3 R A molecule or one or more lipids of the present invention may be covalently bound to one or more amino acid segments of the peptide in the compound of the invention via an amide bond formed between the corresponding carboxylic acid residue of Y and one or more free -NH2 residues present in the amino acid of the peptide. This includes coupling at the N-terminus of the peptide sequence and / or at the -NH2 group of one or more Lys amino acids present elsewhere in the sequence.

[0016] Optional Y groups may be covalently bound to one or more amino acid segments of the peptide in the compounds of the invention via ester bonds formed between the corresponding -OH residues in, for example, serine, threonine, and / or tyrosine and one or more free carboxylic acid residues in which Y may be present, and / or via ester bonds formed between the corresponding -OH residues in Y and the free carboxylic acid group at the C-terminus of the peptide sequence.

[0017] Similarly, the -Lys-Y group is covalently attached to the amino acid fragment at the C-terminus of the peptide sequence of the compound of the present invention via an amide bond formed between the corresponding -NH2 residue of the Lys fragment and the free carboxylic acid residue in the relevant amino acid present at the C-terminus of the peptide sequence.

[0018] The compounds of the present invention that may be mentioned include those in which Y is absent, such that the compounds of the present invention are isolated peptide compounds consisting essentially of any of the aforementioned peptide sequences or regioisomers, stereoisomers or pharmaceutically or cosmetically acceptable salts of the compounds.

[0019] The term 'consistently composed of a specific peptide sequence and / or N-terminal amino acids' should be understood to mean that the relevant sequence includes only the amino acids (or those amino acids) of that sequence along with other features and / or components that do not substantially affect the essential and novel characteristics of the sequence.

[0020] When Y is present, it can represent one or more lipids, in which case the lipids can be selected from: palmitic acid, stearic acid, oleic acid, octadecanoic acid, docosahexaenoic acid and leukotriene B4 (LTB4), or any derivatives of these lipids.

[0021] Other preferred compounds of the present invention include those comprising, but not limited to, polyunsaturated fatty acids or derivatives thereof. In such embodiments, the derivative may be a specific pro-inflammatory mediator (SPM).

[0022] Other preferred compounds of the present invention also include those in which one or more lipids include derivatives of fatty acids, such as glycerolipids, glycerophospholipids, sphingolipids, or glycolipids.

[0023] Other preferred compounds of the present invention also include those comprising palmitic acid or a derivative thereof. In such embodiments, the derivative may be phosphatidylserine, or more preferably, 1,2-dipalmitoyl-sn-glycerol-3-phosphatidyl-1-serine (DPPS). In such embodiments, the derivative may be phosphatidylethanolamine, or more preferably, 1,2-dipalmitoyl-sn-glycerol-3-phosphatidylethanolamine (DPPE).

[0024] Other preferred compounds of the present invention include those comprising stearic acid or a derivative thereof. In such embodiments, the derivative may be 1,2-distearate-sn-glycerol-3-phosphoryl-1-serine.

[0025] Other preferred compounds of the present invention include those comprising oleic acid or a derivative thereof. In such embodiments, the derivative may be 1,2-dioleoyl-sn-glycerol-3-phosphoryl-L-serine.

[0026] Other preferred compounds of the present invention include those comprising hexadecanoic acid ethanol (PEA).

[0027] Other preferred compounds of the present invention include those selected from vitamin E, vitamin A, and cholesterol, or any derivatives of these lipids. In such embodiments, the cholesterol derivative may be cholesterol-acetic acid.

[0028] Other preferred compounds of the invention include those in which the lipid is a fatty acid as defined above, the fatty acid comprising 1 to 5 -OH groups, for example 1 to 2 -OH groups. In other embodiments, the fatty acid may have 1 to 10 rings, for example 1 to 8 rings.

[0029] The compounds of the present invention that may be mentioned include those in which Y represents at least one lipid as defined above.

[0030] Therefore, the compounds of the present invention that may be mentioned include: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 20); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 21); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 22); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm) (SEQ ID No: 23); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13-Arg-Lys-Gln-Lys(Palm)(SEQ ID No: 24); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm) (SEQ IDNo: 25); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ ID No:26); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No: 27); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Lys(Palm) (SEQ ID No: 28); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-Lys(Palm) (SEQ ID No: 29); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Lys(Palm) (SEQ ID No: 30); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-Lys(Palm) (SEQ ID No: 31); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Lys(Palm) (SEQ ID No: 32); His-Ser-Asp-X 4 -X 5 -Phe-Lys(Palm) (SEQ ID No: 33); His-Ser-Asp-X 4 -X 5 -Lys(Palm) (SEQ ID No: 34); His-Ser-Asp-X 4 -Lys(Palm) (SEQ ID No: 35); or His-Ser-Asp-Lys(Palm) (SEQ ID No: 36).

[0031] More preferred compounds of the present invention include: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm) (SEQ ID No: 23), or His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No: 27); for example: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Lys(Palm)(SEQ ID No: 24) or His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ ID No:26); and, especially His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm) (SEQ IDNo: 25).

[0032] In alternative embodiments, the compounds of the present invention that may be mentioned include: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 37); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 38); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 39); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 40); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13-Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 41); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 42); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys (SEQ ID No: 43); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 44); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val (SEQ ID No: 45); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala (SEQ ID No: 46); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9-Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 47); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met(SEQ ID No: 48); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Lys(Palm) (SEQ ID No: 49); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln (SEQ ID No: 50); or His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Lys(Palm) (SEQ ID No: 51).

[0033] The compounds of the present invention that may be mentioned include: Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 52); Palm-His-Ser-Asp-X 4 -X5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys (SEQ ID No: 53); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val (SEQ ID No: 54); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala (SEQ ID No: 55); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met(SEQ ID No: 56); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln (SEQID No: 57); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ IDNo: 58); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X11 -Arg-X 13 -Arg (SEQ ID No:59); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 60); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg (SEQ ID No: 61); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 (SEQ ID No: 62); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr (SEQ ID No: 63); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 (SEQ ID No: 64); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp (SEQ ID No: 65); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr (SEQ ID No: 66); Palm-His-Ser-Asp-X 4 -X 5 -Phe (SEQ ID No: 67); Palm-His-Ser-Asp-X 4 -X 5 (SEQ ID No: 68); Palm-His-Ser-Asp-X 4 (SEQ ID No: 69); or Palm-His-Ser-Asp (SEQ ID No: 70).

[0034] More preferably, the compounds of the present invention also include: Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met(SEQ ID No: 56); or Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 60), for example Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln (SEQ ID No: 57); or Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No:59), and, especially Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ IDNo: 58).

[0035] The compounds of the present invention that may be mentioned include: Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 71); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 72); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 73); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 74); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 75); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13-Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 76); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 77); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys (SEQ ID No: 78); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 79); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 80); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val (SEQ ID No: 81); Palm-His-Ser-Asp-X 4 -X5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 82); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 83); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala (SEQ ID No: 84); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 85); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 86); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met (SEQ ID No: 87); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm) (SEQ ID No: 88); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Lys(Palm) (SEQ ID No: 89); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln(SEQ ID No: 90); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Lys(Palm) (SEQ ID No: 91); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Lys(Palm) (SEQ ID No: 92); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)(SEQ ID No: 93); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ IDNo: 94); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No:95); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Lys(Palm) (SEQ ID No:96); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-Lys(Palm) (SEQ ID No: 97); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Lys(Palm) (SEQ ID No: 98); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-Lys(Palm) (SEQ ID No: 99); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Lys(Palm) (SEQ ID No: 100); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Lys(Palm) (SEQ ID No: 101); Palm-His-Ser-Asp-X 4 -X 5-Lys(Palm) (SEQ ID No: 102); Palm-His-Ser-Asp-X 4 -Lys(Palm) (SEQ ID No: 103); or Palm-His-Ser-Asp-Lys(Palm) (SEQ ID No: 104).

[0036] More preferred compounds of the present invention include: Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met (SEQ ID No: 87); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm) (SEQ ID No: 88); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Lys(Palm) (SEQ ID No: 89); or Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No:95), for example Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln(SEQ ID No: 90); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Lys(Palm) (SEQ ID No: 91); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Lys(Palm) (SEQ ID No: 92); or Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ IDNo: 94), and, especially Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)(SEQ ID No: 93).

[0037] According to other aspects of the invention, isolated compounds consisting substantially of any of the peptide sequences defined by any of SEQ IDs Nos: 7, 8, 9 or by any of SEQ IDs Nos: 11 to 104 are provided, as well as regioisomers, stereoisomers, and pharmaceutically or cosmetically acceptable salts of such compounds.

[0038] Specific compounds that may be mentioned in this regard include isolated compounds consisting substantially of any one of the peptide sequences having SEQ IDs Nos: 7, 8, 9 or having any one of SEQ IDs Nos: 23 to 25, any one of SEQ IDs Nos: 56 to 60, or any one of SEQ IDs Nos: 87-95, as well as regioisomers, stereoisomers, and pharmaceutically or cosmetically acceptable salts of such compounds.

[0039] In any of the above peptide sequences, X 4 X 5 X 9 X 11 and / or X 13 Any of (if present) and each of them can represent Ala, Val, Ile, Gly, Asn, Ser, Thr, Tyr and / or Leu. However, it is preferred that: X 4 It means Gly or Ala; X 5 Indicates Ile or Val; X 9 Indicates Ser or Asn; X 11 Indicates Ser or Thr; and / or X 13 This indicates Tyr or Leu.

[0040] According to other aspects of the invention, isolated compounds consisting of peptide sequences defined as follows are provided: (i) any one of SEQ IDs Nos: 7, 8, 9, or SEQ IDs Nos: 11 to 104, and regioisomers, stereoisomers, and pharmaceutically or cosmetically acceptable salts of such compounds; or more preferably... (ii) isolated compounds substantially composed of any one of the peptide sequences having SEQ IDs Nos: 7, 8, 9 or having any one of SEQ IDs Nos: 23 to 25, any one of SEQ IDs Nos: 56 to 60, or any one of SEQ IDs Nos: 87-95; and especially (iii) Any one of SEQ IDs Nos: 7, 25, 58, and 93. Where X 4 Represents Gly or (preferably) Ala, X 5 Val, X 9 Represents Asn, X 11 Indicates Thr, X 13 This refers to Leu, as well as the regioisomers, stereoisomers, and pharmaceutically or cosmetically acceptable salts of this compound.

[0041] In this respect, other compounds of the present invention that may be mentioned include: His-Ser-Asp-Gly-Ile-Phe (SEQ ID No: 105); His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (SEQ IDNo: 107); Palm-His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (SEQID No: 108); His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (Palm) (SEQ ID No: 109).

[0042] As used in this application, His represents histidine, Ser represents serine, Asp represents aspartic acid, Phe represents phenylalanine, Thr represents threonine, Tyr represents tyrosine, Arg represents arginine, Lys represents lysine, Gln represents glutamine, Met represents methionine, Ala represents alanine, Val represents valine, Gly represents glycine, Ile represents isoleucine, Asn represents asparagine, Leu represents leucine, and Palm represents palmitic acid.

[0043] Whether in salt form or other forms, the compounds of this invention include regioisomers within the amino acids of the peptide (e.g., the Tyr moiety), as well as mixtures of such regioisomers. For example, Tyr includes not only tyrosine (4-hydroxyphenylalanine), but also 2-hydroxyphenylalanine and 3-hydroxyphenylalanine.

[0044] Similarly, in addition to the standard central carbon atom of the amino acids in the compounds of this invention (which is generally, but not limited to, the L-configuration), some amino acids in the sequence also include other chiral carbon atoms. All these stereoisomers and mixtures thereof (including racemic mixtures) are included within the scope of this invention.

[0045] The compounds of this invention may be in salt form. Salts that may be mentioned include pharmaceutically acceptable and / or cosmetically acceptable salts, such as pharmaceutically acceptable and / or cosmetically acceptable acid addition salts and base addition salts. Such salts can be formed by conventional techniques, for example by reacting the compound of this invention with an equivalent or greater amount of a suitable acid or base, optionally in a solvent or in a medium in which the salt is insoluble, and then removing the solvent or medium using standard techniques (e.g., vacuum, lyophilization, or filtration). Salts can also be prepared, for example, by exchanging the counterion of the compound of this invention in salt form with another counterion using a suitable ion exchange resin.

[0046] Preferred salts include, for example, acetates, hydrochlorides, trifluoroacetates, hydrogen sulfates, maleates, methanesulfonates, toluenesulfonates, alkaline earth metal salts such as calcium and magnesium salts, or alkali metal salts such as sodium and potassium salts. Most preferably, the compounds of the present invention can be in the form of acetates.

[0047] The compounds of the present invention can be prepared using conventional techniques, such as standard amino acid coupling techniques using standard coupling reagents and solvents, as described below. The compounds of the present invention can be synthesized from available starting materials using appropriate reagents and reaction conditions. In this regard, those skilled in the art will particularly refer to BM Trost and I. Fleming's "..." Comprehensive Organic Synthesis "Pergamon Press, 1991. Other references that may be used include: J.A. Joule, K. Mills, and GF. Smith's " Heterocyclic Chemistry ", 3rd edition, published by Chapman & Hall; AR Katritzky, CW Rees and EFV Scriven's " Comprehensive Heterocyclic Chemistry II ", Pergamon Press, 1996; and " Science of Synthesis ”, Volume 9-17 (Hetarenes and Related Ring Systems), Georg Thieme Verlag, 2006.

[0048] The compounds of the present invention can be isolated from their reaction mixtures and, if necessary, purified using conventional techniques known to those skilled in the art. Therefore, the method for preparing the compounds of the present invention as described in this application may include the isolation and optional purification of the compounds of the present invention as a final step.

[0049] Those skilled in the art will understand that, in the methods described above and below, the functional groups of the intermediate compound may need to be protected by protecting groups. Protection and deprotection of functional groups can be carried out before or after the reaction.

[0050] Protecting groups can be applied and removed using techniques well known to those skilled in the art and described below. For example, standard deprotection techniques can be used to chemically convert the protected compound / intermediate described in this application into an unprotected compound. The type of chemistry involved will determine the need for and type of protecting groups, as well as the sequence of synthesis. The use of protecting groups is fully described in ' Protective Groups in Organic Synthesis ', 5th edition, TW Greene & PGM Wutz, Wiley-Interscience (2014), the contents of which are incorporated herein by reference.

[0051] The compounds of this invention are used as human and animal medicines. Therefore, they are labeled as pharmaceuticals (and / or in veterinary science), but they can also be used as cosmetics and / or as part of medical devices, as well as in everyday disinfectant products.

[0052] The compounds of the present invention may also possess pharmacological activity; therefore, certain pharmaceutically acceptable (e.g., 'protected') derivatives of the compounds of the present invention may exist or be prepared as having no such activity, but they may be administered and subsequently metabolized or chemically transformed to form the compounds of the present invention. Such compounds (which may possess some pharmacological activity, provided that such activity is significantly lower than that of the active compounds to which they are metabolized / converted) may therefore be referred to as 'prodrugs' of the compounds of the present invention.

[0053] As described in this application, references to prodrugs include compounds that, upon administration, form an experimentally detectable amount of the compound of the present invention within a predetermined time. All prodrugs of the compounds of the present invention are included within the scope of this invention.

[0054] The compounds of this invention are specifically used to treat VL and related disorders.

[0055] Those skilled in the art will understand that the term 'VL' includes any of the following conditions: a condition characterized by measurable loosening of the vagina (e.g., at the vaginal opening), or a condition characterized by a loss of elasticity and strength of the vagina and / or surrounding tissues. In the context of this invention, the term VL also includes a patient's perception of such loosening, which may be caused by a variety of factors, including childbirth, menopause, aging, genetics, pelvic surgery, etc. Measurement of VL may be related to pelvic floor muscle strength, sexual function, and / or the perception of a sexual partner.

[0056] Furthermore, the compounds of the present invention can be used as part of a vaginal restoration procedure, thereby restoring the aesthetic appearance and / or function of the vagina. The compounds of the present invention can therefore be used as part of a vaginal restoration procedure in conjunction with surgical procedures that promote tissue remodeling (vaginoplasty) and / or energy-based (radiofrequency or laser) devices.

[0057] In this respect, the compounds of the present invention can provide medium- to long-term therapeutic benefits, resulting in improved vaginal lumen (VL), wherein vaginal function is improved or corrected during sexual intimacy and / or intercourse. This can thus be used to increase the sensitivity of female reproductive organs and enhance sexual arousal.

[0058] The compounds of the present invention can additionally and / or in alternative embodiments treat vaginal lumen-related disorders. For example, the compounds of the present invention can be administered with the intention of inducing vaginal contractions shortly (e.g., immediately) before sexual intimacy and / or intercourse, in order to improve vaginal function and / or increase the sensitivity of female reproductive organs and enhance sexual arousal, even in subjects who do not directly suffer from vaginal lumen.

[0059] In addition, the compounds of the present invention can also be used generally to treat frigidity and pelvic floor muscle dysfunction, such as pelvic organ prolapse (POP). POP can be defined as any obstruction of the descent of one or more pelvic organs from their normal position.

[0060] The compounds of this invention can also be used to treat certain respiratory and / or inflammatory diseases, such as asthma, erectile dysfunction in men (and women), blood pressure regulation, endocrine disorders, and / or to treat tumors.

[0061] According to other aspects of the invention, a method for treating VL or related disorders is provided, the method comprising administering a compound of the invention or a salt thereof to a patient in need of such treatment.

[0062] For the avoidance of doubt, in the context of this invention, the terms 'treatment', 'therapy', and 'therapy method' include therapeutic or palliative care for patients requiring treatment of VL and / or certain related disorders, as well as preventive treatment and / or diagnosis for patients susceptible to VL and / or certain related disorders.

[0063] 'Patients' include mammals (especially humans) who are patients.

[0064] According to the present invention, the compounds of the present invention can be administered locally or systemically in pharmaceutically acceptable dosage forms in the form of pharmaceutical formulations comprising the compounds, such as orally, intravenously or intra-arterially (including via intravascular and other perivascular devices / dosage forms (e.g., stents)), intramuscularly, through the skin, subcutaneously, via mucosa (e.g., sublingual or oral), rectally, intravaginally, intradermally, transdermally, via the nose, via the lungs (e.g., trachea or bronchi), for example by direct injection, or via any other parenteral route.

[0065] When administered directly to the whole body via the gastrointestinal tract, this administration can be used to treat one or more of the aforementioned disorders or conditions in one or more internal organs of a patient, including the stomach, intestines, pancreas, liver, spleen, bladder, vascular system, ovaries, prostate, preferably the heart, kidneys, and lungs.

[0066] The compounds of the present invention can be administered by intradermal injection, but are preferably applied topically in a pharmaceutically acceptable dosage form in the form of a pharmaceutical preparation containing the compound, for example, to the skin, or more preferably to mucosal surfaces, particularly the vaginal mucosa.

[0067] Pharmaceutically acceptable formulations used via the above-described routes of administration may therefore include compounds of the present invention mixed with pharmaceutically acceptable adjuvants, diluents, or carriers, wherein the pharmaceutically acceptable adjuvants, diluents, or carriers may be selected appropriately taking into account the intended route of administration and standard pharmaceutical practice. Such pharmaceutically acceptable carriers may be chemically inert to the active compound and may not have harmful side effects or toxicity under the conditions of use. Such pharmaceutically acceptable carriers may also allow for immediate or modified release of the compounds of the present invention.

[0068] Preferred delivery modes of the compounds of the present invention include local delivery to the skin and / or preferably to the vaginal mucosa in a suitable (e.g., pharmaceutically acceptable and locally acceptable) medium suitable for application to mucosal surfaces.

[0069] Suitable pharmaceutical formulations may be commercially available or prepared according to the techniques described in the literature below, such as Remington. The Science and Practice of Pharmacy ,twenty two nd edition, PharmaceuticalPress (2012), and Martindale - The Complete Drug Reference, 38 th Edition, Pharmaceutical Press (2014), and the references thereto, the relevant disclosures in all such documents are incorporated herein by reference. Alternatively, the preparation of suitable formulations comprising the compounds of the present invention can be carried out non-inventively by those skilled in the art using conventional techniques.

[0070] The compounds of the present invention are preferably administered in the form of liquid, gel, cream, lotion, essential oil, or powder. The compounds of the present invention may also be in the form of sanitary napkins, tampons, suppositories, capsules, or tablets.

[0071] Aqueous formulations may include emulsions, suspensions, and / or more preferably solutions, such as (optionally) buffered aqueous formulations (e.g., solutions), such as formulations containing physiological saline (e.g., solutions), phosphate formulations (e.g., solutions), acetate formulations (e.g., solutions), or borate formulations (e.g., solutions), or lyophilized powders that can be reconstituted with a medium such as an aqueous medium prior to use.

[0072] Such formulations may include other suitable excipients known to those skilled in the art, such as solvents (e.g., water), cosolvents, solubilizers (e.g., cyclodextrin), wetting agents, suspending agents, emulsifiers, thickeners, chelating agents, antioxidants, reducing agents, antimicrobial preservatives, swelling agents, and / or protective agents, and may be buffered to physiologically acceptable pH values ​​(e.g., pH from about 4.5 to about 9.5, such as from about 6 to about 9, such as from about 6.5 to about 8.5) using standard techniques, and / or may further contain tension modifiers (e.g., sodium chloride).

[0073] The compounds of the present invention can be further prepared and / or combined with suitable excipients in alternative embodiments: • Gel formulations (for which suitable gel matrix materials include cellulose derivatives, carbomer and alginate, tragacanth gum, gelatin, pectin, carrageenan, glucan gum, starch, xanthan gum, cationic guar gum, agar, non-cellulose polysaccharides, sugars such as glucose, glycerol, propylene glycol, vinyl polymers, acrylic resins, polyvinyl alcohol, carboxyvinyl polymers and especially hyaluronic acid); • Emulsions (for which suitable matrix materials include cellulose derivatives, glycerol, non-cellulose polysaccharides, polyethylene glycol and propylene glycol of different molecular weights); • Paste or ointment (for which, suitable paste base materials include glycerin, petrolatum, paraffin, polyethylene glycol with different molecular weights, etc.); • Creams or foams (for which suitable excipients (e.g., foaming agents) include hydroxypropyl methylcellulose, gelatin, polyethylene glycol with different molecular weights, sodium lauryl sulfate, sodium fatty alcohol polyoxyethylene ether sulfonate, corn gluten powder and acrylamide); • Powdered aerosols (for which suitable excipients include mannitol, glycine, dextrin, dextrose, sucrose, lactose, sorbitol, and polysorbate esters, such as dry powder inhalers); and / or • Liquids, such as water (aerosol) sprays for oral or inhalation (for which suitable excipients include viscosity modifiers such as hyaluronic acid, sugars such as glucose and lactose, emulsifiers, buffers, alcohols, water, preservatives, sweeteners, flavorings, etc.); • Injectable solutions or suspensions (which may be aqueous or otherwise, and for which suitable excipients include solvents and cosolvents, solubilizers, wetting agents, suspending agents, emulsifiers, thickeners, chelating agents, antioxidants, reducing agents, antibacterial preservatives, buffers and / or pH adjusters, swelling agents, protective agents and tension modifiers), particularly injectable solutions or suspensions that may be mentioned include dermal fillers (i.e., injectable fillers or soft tissue fillers), especially when the compounds of the present invention are combined with hyaluronic acid; • Oral tablets (for which suitable excipients include binders, such as syrup, gum arabic, gelatin, sorbitol, tragacanth gum, cellulose, or polyvinylpyrrolidone; fillers, such as lactose, sucrose, corn starch, calcium phosphate, sorbitol, or glycine; lubricants, such as magnesium stearate, talc, polyethylene glycol, or silica; and surfactants, such as sodium lauryl sulfate). • Effervescent products.

[0074] Depending on the circumstances, humectants (such as glycerin, glycerol, polyethylene glycol, trehalose, petrolatum, paraffin oil, silicone oil, hyaluronic acid and its salts (e.g., sodium and potassium salts), caprylic / capric glycerides, etc.); and / or antioxidants (such as vitamins and glutathione); and / or pH adjusters (such as acids, bases, and pH buffers) may also be included in such formulations. Additionally, the following substances may be included: surfactants / emulsifiers, such as cetyl alcohol (cetyl alcohol), fatty acids (e.g., stearic acid), sodium lauryl sulfate (sodium lauryl sulfate), sorbitan esters (e.g., sorbitan stearate, sorbitan oleate, etc.), monoacylglycerols (e.g., glyceryl monostearate), polyethoxylated alcohols, polyvinyl alcohol, polyol esters, polyoxyethylene alkyl esters (e.g., polyoxyethylene sorbitan monooleate), polyoxyethylene castor oil derivatives, ethoxylated fatty acid esters, polyoxyglycerol Esters, dodecyl dimethylamine oxide, bile salts (e.g., sodium deoxycholate, sodium cholate), lipids (e.g., fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, pentenol, glycolipids, polyketides), phospholipids, N,N-dimethyldodecylamine-N-oxide, hexadecyltrimethylammonium bromide, poloxamer, lecithin, sterols (e.g., cholesterol), glycolipids, polysorbates, etc.; preservatives, such as phenoxyethanol, ethylhexylglycerin, etc.; and thickeners, such as acryloyl dimethyl taurate / VP copolymer. In particular, stearic acid, glyceryl monostearate, hexadecyl alcohol, sorbitan stearate, cetyl alcohol, caprylic / capric glyceride, etc., may be included in cream formulations, especially.

[0075] According to other aspects of the invention, a method for preparing a pharmaceutical composition / formulation as defined in this application is provided, the method comprising mixing the compound of the invention as defined above with one or more pharmaceutically acceptable excipients as defined above.

[0076] According to other aspects of the invention, compositions (e.g., pharmaceuticals) are provided comprising the compounds of the invention and one or more pharmaceutically acceptable excipients, such as adjuvants, diluents, or carriers. Preferred formulations are suitable for topical application, for example, to mucous membranes (including vaginal mucosa), and therefore include locally acceptable adjuvants, diluents, or carriers.

[0077] Therefore, pharmaceutical compositions comprising the compounds of the present invention are further provided, which are suitable, adapted and / or packaged and presented for topical application (e.g. to mucous membranes, including vaginal mucous membranes), and the use of such formulations in treating VL or related disorders by means of direct topical application of the formulation (e.g. to mucous membranes, including vaginal mucous membranes).

[0078] Regarding this aspect of the invention, for the avoidance of doubt, topical formulations comprising the compounds of the invention may be used for any and all conditions described in this application, including treatment of the VL and related disorders mentioned, defined, or described above. Similarly, topical formulations comprising the compounds of the invention that may be mentioned include any and all those mentioned, defined, or described in this application. Any and all related disclosures of this application in connection with this aspect of the invention are incorporated herein by reference.

[0079] The compounds of this invention can be administered continuously or preferably intermittently, for example, according to a physician's prescription. The route of administration can also be determined by the timing and frequency of administration, but in the case of treating inflammation, it also depends on the severity of the symptoms.

[0080] Depending on the disease to be treated, the patient, and the route of administration, the compounds of the present invention can be administered to patients in need at different therapeutically effective doses.

[0081] Similarly, the amount of the compound of the present invention in the formulation will depend on the severity of the condition and the patient to be treated, but can be determined by a person skilled in the art.

[0082] In any case, a licensed physician or other technician will be able to routinely determine the most suitable actual dose for an individual patient based on the severity of the symptoms and the route of administration. The doses mentioned in this application are examples of average cases; of course, higher or lower dose ranges may be required in some cases, and these are all within the scope of this invention.

[0083] The compounds of this invention can be used daily. The dosage can be once or four times a day (e.g., three times a day).

[0084] The compounds of the present invention may be used occasionally and specifically over periods of days, weeks, and / or months, or as needed, such as before or during sexual intercourse. In alternative embodiments, the compounds of the present invention may be used regularly but not daily, for example, every other day over periods of weeks, months, or years.

[0085] The appropriate concentration of the compound of the present invention in the aqueous solution product may be about 0.01 mg / mL (e.g., about 0.1 mg / mL, such as about 1 mg / mL) and up to about 30 mg / mL, including about 15.0 mg / mL, such as about 5 mg / mL, about 2 mg / mL or about 1 mg / mL, and these concentrations are all calculated as free (non-salt) compounds in all cases.

[0086] The suitable local dosage range of the compounds of the present invention is from about 0.05 to about 50 µg / cm. 2 Treatment area, from approximately 0.1 (e.g., approximately 0.5) to approximately 20 µg / cm². 2 Treatment area, including approximately 1 to approximately 10 µg / cm² 2 Treatment area, such as approximately 5 µg / cm² 2 The treatment area is calculated as free (non-salt) compound in all cases.

[0087] Preferably, the pH value of the formulation containing the compound of the present invention is in the range of about 1.0 to about 9.0 (e.g., about 3.0 to about 8.0, such as about 4.0 to about 6.0).

[0088] In any case, the dose administered to mammals (particularly humans) should, within the context of this invention, be sufficient to produce a therapeutic response in the mammal within a reasonable timeframe (as described above). Those skilled in the art will recognize that the selection of the exact dosage and composition, as well as the most suitable delivery method, will also be particularly influenced by factors such as the pharmacological properties of the formulation, the nature and severity of the condition to be treated, the recipient's physical condition and mental acuity, the age, status, weight, sex, and response of the patient to be treated, the stage / severity of the disease, and genetic differences between patients.

[0089] The compounds of this invention are intended for use in human and animal medicines. In this respect, and as described above, the compounds of this invention that possess appropriate levels of relevant pharmacological (or biological) activity can be used as human and / or animal medicines.

[0090] The compounds of this invention can be combined with a wide range of known pharmaceutical active ingredients, and can be combined in this way regardless of whether the compounds of this invention are used: • Used as a standalone active pharmaceutical ingredient in combination therapy; • As a medical device or as part of a medical device; or • As a drug-medical device combination or as the medical device component of a drug-medical device combination.

[0091] Such patients may also (and / or may have) received therapy based on administration of one or more of these other known pharmaceutical active ingredients, meaning receiving a prescribed dose of one or more active ingredients mentioned in this application before, in addition to and / or after treatment with the compounds of the present invention.

[0092] Pharmaceutical active agents that can be co-administered with the compounds of the present invention include any agent or drug capable of producing a physiological effect (whether therapeutic or preventative) on a living subject (including, in particular, mammals, especially human subjects (patients)).

[0093] Pharmaceutical active agents that can be used with the compounds of the present invention may, for example, be selected from: anti-inflammatory agents, antibiotics, antibacterial agents and / or antiprotozoal agents, antiviral agents (e.g., protease inhibitors).

[0094] Non-limiting examples of anti-inflammatory drugs that may be used also include those used to treat the following conditions: rheumatic diseases and / or arthritis (such as clotazone, betamethasone, naproxen, cyclosporine, chondroitin, celecoxib, etodoxacin, meclofenamic acid, disalicylic acid, methylprednisolone, and piroxicam); osteoarthritis (such as sulindac, meloxicam, fenoprofen, etodoxacin, and nabumetone); inflammation and its symptoms, such as... Fever, pain, itching, and / or swelling (such as mefenamic acid, indomethacin, aspirin, ketorolac, flumethrin, lorteprednisolone, hydrocortisone, flumethrin, bromfenac sodium, prednisolone acetate, indomethacin, and ibuprofen); allergies and their symptoms (such as pheniramine, diphenhydramine, naphazoline, antazoline, prednisolone, lodoxamide, pirimethasone, oxymetazoline, ketotifen, naphazoline, emestin fumarate). Olopatadine, azelastine, tranilastine, levocabastine, cortisone, ephedrine, cetirizine, levocetirizine, pseudoephedrine, fexofenadine, terfenadine, loratadine, and alexis); respiratory diseases, including asthma and / or COPD (such as budesonide, cizzonide, nedolometh, dexamethasone, ambroxol, and proxtromethorphan); skin diseases (such as mometasone, triamcinolone, desonide, sulfadiazine, and sulfadiazine). Aminoacetyl, tacrolimus, allantoin, and triamcinolone); mastocytosis (e.g., sodium cromoglycate); gout (e.g., diclofenac, febuxostat); conjunctivitis (e.g., hydroxybenzylazole, pranoprofen, and zinc sulfate); eye diseases (e.g., dextran 70, thyroxine / iodothyronine, and ocular extracts), any known or commercially available pharmaceutically acceptable salts of the foregoing substances, and any combination of the foregoing compounds and / or salts.

[0095] Anti-inflammatory drugs that may be mentioned include endogenous (and / or exogenous) lipid-based procatalytic, anti-inflammatory molecules or mediators, such as lipoxygenin, regressors, and protectants. Pro-inflammatory agents that may be mentioned include prostaglandins (e.g., latanoprost, prostaglandin E1, and prostaglandin E2) and leukotrienes (e.g., leukotriene B4).

[0096] Other anti-inflammatory agents that may be mentioned include one or more mussel adhesive proteins (MAPs), which include any adhesive protein that can be derived from mussel species, such as Mytilus edulis (Blue mussel), including full-length proteins (including all subtypes) that are or are derived from mussels, such as collagen pre-COL-P, pre-COL-D and pre-COL-NG, mussel byssal matrix proteins PTMP and DTMP, and more preferably mfps or mefps, such as mefp-2, mefp-3, mefp-4, mefp-5, mefp-6 and especially mefp-1, and including any mixtures or combinations of these proteins such as mefps. Naturally occurring MAPs can be prepared, for example, by mixed adsorption chromatography (see Chinese Patent ZL200710179491.0), by carboxymethyl ion exchange chromatography (see Chinese Patent ZL200710179492.5), and / or by salting out and dialysis (Chinese Patent ZL200910087567.6). Commercial sources of MAPs include USUN Bio Co. (China; sold as MAP Medical Device®), BD Biosciences (USA), Kollodis (South Korea), and Biopolymer (Sweden). MAPs can also be prepared using known recombinant DNA methods.

[0097] The hydrolyzed version can also be obtained using the MAPs mentioned above.

[0098] Anti-inflammatory compounds that may be specifically mentioned include those described in general and specific terms in the following documents: international patent applications WO 2017 / 028777, WO 2019 / 007355, WO 2019 / 228307, WO 2020 / 052677, WO 2021 / 047648, WO 2021 / 110061, WO 2021 / 110063, WO 2021 / 110064, WO 2022 / 194238, WO 2022 / 194239, WO 2024 / 169972 and WO 2024 / 260465, and the unpublished international patent application PCT / CN2024 / 126655, the disclosures of all of these documents are incorporated herein by reference in their entirety.

[0099] Specific compounds disclosed in the aforementioned international patent applications that may be mentioned in connection with potential combinations of the compounds of the present invention include isolated peptide compounds having the following sequences: Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys (SEQ ID No: 111); Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys (SEQ ID No: 112); DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys (SEQ ID No: 113); DOPA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys (SEQ ID No: 114); HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys (SEQ ID No: 115); HCA-Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys (SEQ ID No: 116); Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys-Dopamine (SEQ ID No: 117); Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Hyp-Lys-Dopamine (SEQ ID No: 118); Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Hyp-Lys (SEQ ID No: 119); Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Hyp-Lys (SEQ ID No: 120); Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys (SEQ ID No: 121); Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys (SEQ ID No: 122); Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys (SEQ ID No: 123); Ala-Lys-Pro-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys (SEQ ID No: 124); Ala-Lys-Hyp-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys (SEQ ID No: 125); Ala-Lys-Hyp-Ser-Tyr-Hyp-Hyp-Thr-DOPA-Lys (SEQ ID No: 126); Ala-Lys-Hyp-Ser-Tyr-Hyp-Thr-Tyr-Hyp-Lys (SEQ ID No: 127); Ala-Lys-Hyp-Ser-Tyr-Hyp-Thr-DOPA-Hyp-Lys (SEQ ID No: 128); Lys-Pro-Ser-Tyr-Hyp-Tyr-Lys (SEQ ID No: 129); and Lys-Pro-Ser-Tyr-Hyp-DOPA-Lys (SEQ ID No: 130), And possible linear repeating sequences of these peptides, Lys-branched repeating sequences of these peptide sequences, such as those described in International Patent Application WO 2021 / 110064, and / or PEG-branched repeating sequences of these peptide sequences, such as those described in International Patent Application WO 2024 / 169972.

[0100] Non-limiting examples of antibiotics that may be used also include chloramphenicol, ofloxacin, levofloxacin, tobramycin, norfloxacin, ciprofloxacin, lomefloxacin, lincomycin, fluconazole, enoxacin, furazolidone, nitrofurazone, rifampin, fenofibrate, gentamicin, cetylpyridinium chloride, neomycin, roxithromycin, silver sulfadiazine, clarithromycin, clindamycin, metronidazole, azithromycin, sulfamidone, sulfamethoxazole, acetaminophen, chloramphenicol, pseudoephedrine, mupirocin, amoxicillin, amoxicillin / clavulanic acid, trimethoprim / sulfamethoxazole, cephalexin, moxifloxacin, any known or commercially available pharmaceutically acceptable salts of the foregoing substances, and any combination of the foregoing compounds and / or salts.

[0101] Non-limiting examples of antiviral drugs that may be used also include tobramycin, ribavirin, acyclovir, moroxydine, foscarnet, ganciclovir, idoxuridine, trifluorouridine, brivudine, vidarabine, entecavir, telbivudine, foscarnet, zidovudine, doxorinosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine, nevirapine, deraviridine, efavirenz, etravirine, rilpivirine, saquinavir, ritonavir, indinavir, nelfinavir, lorpinavir, ritonavir, atazanavir, fosanavir, telanavir, darunavir, terapyrvir, boprevir, cimetidine. Piper, asunaprevir, raltegravir, ereltegravir, dolutegravir, respiratory syncytial virus immunoglobulin (RSV-igiV), palilizumab, dicofol, enfuvirtide, malaviro, varicella-zoster immunoglobulin (VZIG), varicella-zoster immunoglobulin (VZIG), acyclovir, ganciclovir, famciclovir, valacyclovir, penciclovir, valganciclovir, cidofovir, tenofovir disoproxil fumarate, adefovir dipivoxil, fomivirex, podophyllotoxin, imiquimod, sinecatechins, interferon-alpha 2b (recombinant, human), any known or commercially available pharmaceutically acceptable salts of the foregoing substances, and any combination of the foregoing compounds and / or salts.

[0102] Such active pharmaceutical ingredients include those that can be administered topically, for example, to mucosal surfaces, together with the compounds of the present invention. In this respect, preferred active ingredients from the above list include cyclosporine, chondroitin, clotipreno, flumethonone, bromofenac sodium, prednisolone acetate, indomethacin, oxymetazoline, ketotifen, naphazoline, emestin fumarate, olopatadine, azelastine, tranilastine, levocabastine, cortisone, ephedrine, cetirizine, pseudoephedrine, levocetirizine, fexofenadine, terfenadine, loratadine, alexis, dexamethasone, ambroxol, sulfacetamide, tacrolimus, allantoin, triamcinolone, sodium cromoglycate, nedolometabolite, diclofenac, hydroxybenzylazole, pranoprofen, zinc sulfate, dextran 70, thyroxine / iodothyronine, and ocular extracts. Pro-inflammatory agents that may be mentioned include prostaglandins (e.g., latanoprost, prostaglandin E1, and prostaglandin E2), and leukotrienes (e.g., leukotriene B4), chloramphenicol, ofloxacin, levofloxacin, tobramycin, norfloxacin, ciprofloxacin, lomefloxacin, lincomycin, fluconazole, enoxacin, furazolidone, nitrofurazone, rifampin, fenofibrate, gentamicin, cetylpyridinium chloride, neomycin, roxithromycin, silver sulfadiazine, zinc sulfadiazine, clarithromycin, sulfamethoxazole, chloramphenicol, tobramycin, ribavirin, acyclovir, moroxydine, phosphonoformic acid, ganciclovir, interferon-α2b (recombinant, human), and any known or commercially available pharmaceutically acceptable salts of the foregoing substances, and any combination of the foregoing compounds and / or salts.

[0103] More preferred pharmaceutically active ingredients that can be co-administered with the compositions of the present invention include prostaglandins (especially latanoprost) and anti-inflammatory agents (especially aspirin, montelukast, one or more of the above-listed MAPs (including their hydrolyzed versions) and / or one or more of the specifically listed anti-inflammatory peptides having SEQ ID Nos: 111 to 130 (including the endpoints), or antibacterial agents (especially metronidazole, clindamycin and povidone-iodine) and / or antiviral agents (especially salicylic acid, imiquimod, pudafilo and trichloroacetic acid).

[0104] Other known active pharmaceutical ingredients can also be administered in combination with the compounds of the present invention in numerous ways.

[0105] For example, the compounds of the present invention can be 'combined' with the (or other) pharmaceutical active ingredient (or 'therapeutic agent') for administration with the same (e.g., pharmaceutical) formulation, or administered alone (simultaneously or sequentially) in different (e.g., pharmaceutical) formulations.

[0106] Therefore, such combination products provide combined administration of the compound of the present invention with the (or other) therapeutic agent, and can thus be presented as a single formulation, wherein at least one of those formulations contains the compound of the present invention and at least one contains the (or other) therapeutic agent, or can be presented (i.e., formulated) as a combination formulation (i.e., presented as a single formulation comprising the compound of the present invention and the (or other) therapeutic agent).

[0107] Therefore, the following further information is provided: (1) (e.g., a pharmaceutical) formulation comprising the compound of the present invention; another pharmaceutically active ingredient (e.g., one or more of those described above); and optionally, a pharmaceutically acceptable inactive excipient (e.g., an adjuvant, diluent, or carrier), the formulation hereinafter referred to as a 'combination formulation'; and (2) A kit comprising the following components: (A) The compounds of the present invention are optionally in the form of a mixture of a (e.g., a pharmaceutical) formulation and a pharmaceutically acceptable inactive excipient (e.g., an adjuvant, diluent, or carrier); and (B) Another pharmaceutically active ingredient (e.g., one or more of those described above), optionally in the form of a mixture of a (e.g., a pharmaceutical) formulation with a pharmaceutically acceptable adjuvant, diluent, or carrier. Components (A) and (B) are each provided in a form suitable for administration in combination with another.

[0108] In other aspects of the invention, a method for preparing the combination formulation (1) as defined above is provided, the method comprising mixing the compound of the invention, other pharmaceutically active ingredients, and at least one (e.g., pharmaceutically acceptable) excipient.

[0109] In other aspects of the invention, a method for preparing the kit (2) as defined above is provided, the method comprising mixing components (A) and (B). As used herein, reference to mixing indicates that the two components are adapted to be administered in combination with each other.

[0110] Therefore, regarding the method for preparing the kit as defined above, by 'combining' the two components with each other, this application intends to include the following: the two components of the kit can be: (i) provided separately (i.e., independently of each other), and then the two components are put together for use in combination therapy; or (ii) Packaged as individual components in a 'combination package' and presented together for use in combination therapy.

[0111] Therefore, a kit is further provided, which includes: (I) One of components (A) and (B) as defined in this application; together with (II) Instructions for use of this component in combination with another of the two components.

[0112] Regarding the above-described kit, although the compounds of the present invention may be provided as a mixture of a pharmaceutical formulation and one or more other pharmaceutically acceptable excipients (e.g., adjuvants, diluents, or carriers), it is preferred in any case that the (other) pharmaceutical active ingredient of the kit is provided as a mixture of a pharmaceutical formulation and a pharmaceutically acceptable adjuvant, diluent, or carrier.

[0113] The kit described in this application may include formulations of more than one (e.g., including one) appropriate amount / dosage of the compound of the present invention, and / or formulations of more than one (e.g., including one) appropriate amount / dosage of other pharmaceutically active ingredients, in order to provide repeated dosing. If there are more than one formulation containing a certain amount / dosage of any of the aforementioned substances, these formulations may be the same or different in terms of the dosage, chemical composition and / or physical form of any compound.

[0114] Regarding the kit described in this application, by means of 'combined administration', this application is intended to include the sequential, individual and / or simultaneous administration of the corresponding components during the treatment of related symptoms.

[0115] Therefore, regarding the combination products according to the invention, the term 'combined administration' includes administering two components of the combination product (the compound of the invention and other pharmaceutically active ingredients) simultaneously or in sufficiently close proximity (optionally repeatedly) such that the beneficial effect on the patient during treatment of the relevant symptom is greater than the beneficial effect on the patient if the compound of the invention, or an formulation containing (e.g., other agents), were administered alone (optionally repeatedly) in the absence of the other component during the same treatment. Determining whether a combination provides a greater beneficial effect during treatment of a particular symptom will depend on the symptom to be treated or prevented, but this can be conventionally accomplished by those skilled in the art.

[0116] Furthermore, in the context of the kit according to the invention, the term 'combination' includes the possibility of administering one or more of the two components before, after, and / or simultaneously (optionally repeatedly) the administration of other components. When used in this context, the terms 'simultaneous administration' and 'administering at the same time as...' include administering individual amounts / doses of the relevant compound of the invention and other active pharmaceutical ingredients within 48 hours (e.g., 24 hours) of each other's administration.

[0117] Regarding the combination formulations and kits described above, it is preferred that the other active pharmaceutical ingredients are the anti-inflammatory agents described above.

[0118] Where the word 'about' is used in this application, for example in the context of the amount of active ingredient and / or compounds of the invention, such as concentration and / or dosage, molecular weight, or pH value, it should be understood that such variables are approximate values ​​and may therefore differ from the figures specified in this application by ±10%, for example ±5%, preferably ±2% (e.g., ±1%). In this respect, the term 'about 10%' means, for example, ±10% around the number 10, i.e., between 9% and 11%.

[0119] The advantage of the compounds of this invention is that they are useful in treating VL and related disorders.

[0120] The compounds, uses, and methods described in this application may also have the advantages of being more convenient, more effective, less toxic, having a wider range of activities, greater potency, and fewer side effects for physicians and / or patients in the treatments mentioned above, or they may have other useful pharmacological properties, whether for the treatment of any of the above-mentioned conditions (including VL and related conditions, other conditions mentioned above), or other conditions.

[0121] The present invention will be described with reference to the accompanying drawings and through the following embodiments, but is not intended to limit its application. Figure 1 and Figure 2 This shows the results of vaginal smooth muscle contraction induced by the various test compounds of the present invention in in vitro studies conducted in rabbits. Figure 3 This section presents a summary of feedback regarding the effectiveness of gels containing the test compounds of this invention, which was obtained during clinical studies.

[0122] Example Example 1 His-Ser-Asp (SEQ ID No: 19) Fmoc-Asp(O t Bu-Wang resin (9.87 g, 3 mmol; GL Biochem, Shanghai, China) was loaded into a glass reaction column.

[0123] Dichloromethane (DCM, 200 mL; Shandong Jinling Chemical Co., Ltd., Shandong, China) was added to the column, and the resin was soaked for about half an hour. The DCM was then removed by vacuum filtration.

[0124] The resin was then washed three times with N,N-dimethylformamide (DMF, 200 mL; Shandong Shifeng Fertilizer Co., Ltd., Shandong, China). A 20% piperidine solution (Shandong Shifeng Fertilizer Co., Ltd., Shandong, China) in DMF (DBLK, 200 mL) was then added as a deprotection solution, and the reaction was allowed to proceed for 20 minutes. The solution was then removed by vacuum filtration, and the gel was washed six times with DMF.

[0125] Fmoc-Ser(tBu)-OH (3.45 g, 9 mmol; GL Biochem, Shanghai, China) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyltetrafluoroborate ammonium (TBTU, 2.89 g, 9 mmol; GL Biochem, Shanghai, China) were added to the resin. DMF (150 mL) was added to the reaction column, followed by N,N-diisopropylethylamine (DIPEA, 2.33 g, 9 mmol; Suzhou Haofan Biotechnology Co., Ltd., Jiangsu, China). After a reaction time of 30 minutes, a Kaiser test was performed on a portion of the resin, indicating that the reaction was complete. The solvent was removed by vacuum filtration.

[0126] Repeat the above coupling steps to couple the remaining amino acids (using: Boc-His(Trt)-OH) in the same molar amount.

[0127] Following Boc-His(Trt)-OH coupling, the resin was washed three times with each of the following solvents: DMF (200 mL each time), DCM (200 mL each time), and methanol (200 mL each time; Xilong Scientific Co., Ltd., Guangdong, China). The resin was then dried under vacuum for approximately 2 hours.

[0128] 100.0 mL (i.e., 10 mL / g dry resin) of the lysate containing 95% trifluoroacetic acid (TFA, Macklin, Shanghai, China), 2.5% water, and 2.5% triisopropylsilane (Tis, Macklin, Shanghai, China) was added to submerge the peptide-containing compound bound to the resin. After the lysis reaction had proceeded for approximately 2 hours, the solid support was removed by filtration, and the filtrate was collected under reduced pressure.

[0129] The filtrate was precipitated with 1000 mL (i.e., 10 mL / ml filtrate) of diethyl ether (Xilong Scientific Co., Ltd., Guangdong, China), and the precipitate was collected by filtration. The precipitate was dried under vacuum for about 2 hours to give 1.12 g of crude title compound.

[0130] First, the crude product of the sample as 1 mg / mL in pure water was analyzed using a Shimadzu LCMS-8050 system (Shimadzu, Japan). The analytical column was an Agilent ZORBAX Eclipse SB-C18 (4.6 × 250 mm, 5 µm column; detection: UV, at 220 nm; solvent A: 0.1% TFA in MeCN, solvent B: 0.1% TFA in water, linear gradient from 5% to 90% of solvent A concentration over 50 min; flow rate 1.0 mL / min; sample volume: 10 µL).

[0131] The target peak was eluted at 8.291 minutes and had the expected molecular weight, with a purity of 86.992%.

[0132] MS: m / z 357.32 Then, 1.1 g of the crude product was dissolved in 30 mL of pure water and purified using an NP7010C semi-preparative apparatus (Hanbang Technology Co., Ltd., Jiangsu, China). The preparative column was a Dubhe-C18 model (Hanbang Technology Co., Ltd., Jiangsu, China) (50...). 250 mm, 100 Å column; detection: UV at 220 nm). The appropriate gradient for elution was calculated using the LCMS detection procedure (solvent A: 0.1% TFA in MeCN, solvent B: 0.1% TFA in water, with a linear gradient from 5% to 20% solvent A concentration over 30 minutes; flow rate 60.0 mL / min). Fractions were collected and analyzed using a Shimadzu LC-20 HPLC system (Shimadzu, Japan) (column as above, except the linear gradient was from 5% to 20% solvent A concentration over 25 minutes).

[0133] Fractions with a purity higher than 90% were then mixed together for the anion exchange step. This was achieved using an NP7010C semi-preparative apparatus with a Dubhe-C18 column (as above). The fractions were diluted once with pure water and loaded directly onto the column, which was then washed with 3.2% ammonium acetate in pure water for approximately 20 minutes at a flow rate of 60 mL / min, followed by a further wash with pure water for 10 minutes. Elution was then performed using the following gradient (solvent A: 0.1% HAc in MeCN, solvent B: 0.1% HAc in water, where the linear gradient was from 5% to 20% of solvent A concentration over 30 minutes; flow rate 60.0 mL / min).

[0134] Fractions were collected and analyzed using a Shimadzu LC-20 HPLC system (column and conditions as described above). Fractions with a purity higher than 95% were mixed and lyophilized to give 0.78 g of purified title compound.

[0135] Example 2 His-Ser-Asp-Gly-Ile-Phe (SEQ ID No: 105) The title compound was prepared using essentially the same synthetic process as described in Example 1 above, except that Fmoc-Phe-Wang resin was used instead of Fmoc-Asp(OtBu)-Wang resin (in the same molar amount), and subsequently, where appropriate, suitable protected amino acids were used in the relevant peptide coupling sequences (i.e., Fmoc-Ile-OH, Fmoc-Gly-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Ser(tBu)-OH, and Boc-His(Trt)-OH) in the same molar amounts.

[0136] This yielded a batch of crude title compound (yield 2.19 g). Analysis showed a target peak at elution at 25.839 min, with the expected molecular weight and a purity of 71.827%.

[0137] MS: m / z 674.71 The crude product was then purified using essentially the same purification process as described in Example 1, except that a gradient of 25%–40% was used instead of a gradient of 5%–20%, and lyophilized to obtain 1.39 g of pure title compound.

[0138] Example 3 His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg (Compound I; SEQ ID No: 106) The title compound was prepared using essentially the same synthetic process as described in Example 1 above, except that Fmoc-Arg(Pbf)-Wang resin was used at the beginning in the same amount (molar number) instead of Fmoc-Asp(OtBu)-Wang resin, and subsequently, where appropriate, suitable amino acids were used in the same molar amounts in the relevant peptide coupling sequences (i.e., Fmoc-Thr(tBu)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Phe-OH, Fmoc-Val-OH, Fmoc-Ala-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Ser(tBu)-OH, and Boc-His(Trt)-OH).

[0139] The process was repeated substantially the same as described in Example 1 above to obtain a batch of crude title compound (yield 4.35 g). Analysis showed a target peak eluted at 20.182 min, which had the expected molecular weight and a purity of 62.381%.

[0140] MS: m / z 1425.48 The crude product was then purified using essentially the same purification process as described in Example 1, except that a 20%–35% gradient was used instead of a 5%–20% gradient. After lyophilization, 2.06 g of the pure title compound was obtained.

[0141] Example 4 His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (Compound II; SEQ ID No: 107) The title compound was prepared using essentially the same synthetic process as described in Example 1 above, except that Fmoc-Lys(Boc)-Wang resin was used instead of Fmoc-Asp(OtBu)-Wang resin in the same molar amount, and subsequently, where appropriate, suitable amino acids were used in the relevant peptide coupling sequences (i.e., Fmoc-Arg(Pbf)-OH, Fmoc-Leu-OH, Fmoc-Thr(tBu)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Phe-OH, Fmoc-Val-OH, Fmoc-Ala-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Ser(tBu)-OH, and Boc-His(Trt)-OH) in the same molar amount.

[0142] A batch of crude title compound (yield 5.59 g) was obtained using essentially the same process as described in Example 1 above. Analysis showed a target peak at elution at 23.827 min, with the expected molecular weight. The purity was 58.938%.

[0143] MS: m / z 1823.00 The crude product was then purified using essentially the same purification process as described in Example 1, except that a gradient of 25%–40% was used instead of a gradient of 5%–20%, and lyophilized to obtain 2.19 g of pure title compound.

[0144] Example 5 Palm-His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (SEQ ID No: 108) The title compound was prepared using essentially the same synthetic process as described in Example 4 above, except that Fmoc-His(Trt)-OH was used instead of Boc-His(Trt)-OH. Subsequently, a separate coupling step was performed to couple palmitic acid (2.31 g, 9 mmol; Merck KGaA, Darmstadt, Germany) in the same molar amount.

[0145] The same process as described in Example 1 above yielded a batch of crude title compound (yield 6.21 g). Analysis showed a target peak eluted at 40.278 min, with the expected molecular weight and a purity of 56.811%.

[0146] MS: m / z 2061.42 The crude product was then purified using essentially the same purification process as described in Example 1, except that a gradient of 55%–70% was used instead of a gradient of 5%–20%, and after lyophilization, 2.79 g of the pure title compound was obtained.

[0147] Example 6 His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys(Palm) (SEQ ID No: 109) The title compound was prepared using essentially the same synthetic process as described in Example 4 above.

[0148] Initially, Fmoc-Lys(Dde)-Wang resin was used instead of Fmoc-Lys(Boc)-Wang resin in the same molar amount. After resin swelling, a side-chain coupling step was performed first. This step began by washing the resin three times with DMF (200 mL), followed by adding a 5% hydrazine monohydrate (Merck KGaA, Darmstadt, Germany) solution in DMF (200 mL) as a deprotection solution. This side-chain coupling step was carried out for 20 minutes. The solution was then removed by vacuum filtration, and the column was washed six times with DMF.

[0149] Palmitic acid (2.31 g, 9 mmol) and TBTU (2.89 g, 9 mmol) were added to the resin. DMF (150 mL) was added to the reaction column, followed by DIPEA (2.33 g, 9 mmol). After 30 minutes of reaction, a Kaiser test was performed with minimal resin use, indicating completion of the reaction. The solvent was removed by vacuum filtration.

[0150] After palmitic acid coupling, other amino acids are then coupled to the resin. The same synthetic process as described in Example 3 above is repeated to obtain the title compound.

[0151] The process was repeated in essentially the same manner as described in Example 1 above to obtain a batch of crude title compound (yield 6.15 g). Analysis showed the target peak at elution at 39.928 min, with the expected molecular weight and purity of 55.298%.

[0152] MS: m / z 2061.42 The crude product was then purified using essentially the same purification process as described in Example 1, except that a gradient of 55%–70% was used instead of a gradient of 5%–20%, and 2.66 g of pure title compound was obtained after lyophilization.

[0153] Example 7 (contrast) His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met- Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-NH2 (VIP; Compound III; SEQ ID No: 110) The title compound was prepared using essentially the same synthetic process as described in Example 1 above, except that Fmoc-Asn(Trt)-Rink amide resin was used at the beginning in the same molar amount instead of Fmoc-Asp(OtBu)-Wang resin, and subsequently, where appropriate, in the relevant peptide coupling sequences (i.e., Fmoc-Leu-OH, Fmoc-Ile-OH, Fmoc-Ser(tBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Leu-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Val-OH). Among Fmoc-Met-OH, Fmoc-Gln(Trt)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Leu-OH, Fmoc-Thr(tBu)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Phe-OH, Fmoc-Val-OH, Fmoc-Ala-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Ser(tBu)-OH, and Boc-His(Trt)-OH, the appropriate amino acid is used in the same molar amount.

[0154] The process was repeated in essentially the same manner as described in Example 1 above to obtain a batch of crude title compound (yield 10.21 g). Analysis showed the target peak eluted at 43.272 min, with the expected molecular weight and a purity of 47.828%.

[0155] MS: m / z 3325.85 The crude product was then purified using essentially the same purification process as described in Example 1, except that a gradient of 65%–80% was used instead of a gradient of 5%–20%, and lyophilized to obtain 3.25 g of pure title compound.

[0156] Example 8 Gynecological gel Various gels were prepared according to the compositions shown in Table 1 below.

[0157] First, the components of the corresponding components 'A' (i.e., components A1 to A4) prepared with or without optional component 'B' are mixed and stirred for 5 minutes to obtain a clear solution. Then, the corresponding components 'C' (i.e., C1 to C3) are added and stirred for 30 minutes to obtain six different gels containing different gelling agents (hyaluronic acid (HA) gel, carbomer gel, and methylcellulose (MC) gel, each with or without mussel adhesive protein (MAP)). Each mixture is allowed to swell for approximately 4 hours to homogenize the system.

[0158] Table 1

[0159] The concentration of compound II in the above gels was 0.1% (i.e., 1 mg / mL). Similar gels were prepared using 1.5 mg / mL and 2 mg / mL of compound II (thereby reducing the amount of aqueous medium from the values ​​listed above by 0.05% and 0.1%, respectively). More specifically, 1.5 mg / mL carbomer gels and 2 mg / mL HA and cellulose gels were prepared.

[0160] The above process was used to provide 12 additional gynecological gels, the difference being that compounds I and III were used instead of compound II.

[0161] Example 9 Clinical research (A) Using a commercial vaginal applicator, 2 mL of compound II-HA gel (1 mg / g; see Example 8 above) was applied to the vagina of a woman nearly 60 years of age. After 5 minutes, spasmodic contractions of the subject's vagina were observed. The response became stronger over the next 30 minutes and then gradually diminished.

[0162] (B) Using a commercial vaginal applicator, 2 mL of compound II-cellulose gel (2 mg / g; see Example 8 above) was applied to the vagina of a woman nearly 60 years of age. After 10 minutes, the subject's vagina became very sensitive and she reported mild pain. A large amount of mucus discharge was also observed from the subject's vagina. After 20 minutes, the subject's vagina became very narrow. After 40 minutes, the woman experienced uterine contractions.

[0163] (C) Fifteen minutes before intercourse, 2 mL of compound II-HA gel (2 mg / g; see Example 8 above) was applied to the vagina of a woman nearly 60 years of age using a commercial vaginal applicator. The subject reported that: (1) her vagina felt very sensitive and wet from the beginning; (2) she reached orgasm faster than usual; and (3) she experienced a more intense orgasm than normal.

[0164] (D) Using a commercial vaginal applicator, 2 mL of compound I-HA gel (1 mg / g; see Example 8 above) was applied to the vagina of a woman nearly 60 years of age. The subject reported that her vagina became slightly more sensitive, but no other adverse reactions were reported.

[0165] (E) For two weeks, 2 mL of compound II-carbomer gel (1.5 mg / g; see Example 8 above) was applied to the vagina of a woman nearing 60 years of age every other day using a commercial vaginal applicator. Fifteen minutes after administration, the subject noticed spasmodic contractions of her vagina and increased vaginal lubrication. After two weeks of treatment, her vagina became significantly tighter and more lubricated than usual.

[0166] Example 10 In vitro study on vaginal smooth muscle contraction I Eighteen healthy female New Zealand White rabbits (Shanghai Songjiang District Chedun Experimental Animal Breeding Farm Co., Ltd.), at least 10 weeks old and with an average weight of 2 to 3 kg, were kept in individual cages in a room equipped with a high-efficiency air filter at the Novopathway animal facility. Ventilation was maintained at 15-25 air changes per hour. The temperature was kept at 20-26°C, and the relative humidity at 40-70%. Lighting was provided for 12 hours daily (08:00-20:00). The rabbits had free access to food and water.

[0167] After 7 days of acclimatization, the rabbits were anesthetized and euthanized. The vaginas were separated, and each vaginal opening was cut into four muscle strips, each 1.5 cm long and 0.3 cm wide. These muscle strips were assigned to the positive control group (G1; estradiol benzoate (Shanghai Yuanye Biotechnology Co., Ltd.)), the low-dose test substance (His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys; SEQ ID No: 107; see Example 4 above; hereinafter referred to as "Compound II") group (G2), the medium-dose test substance (His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys; SEQ ID No: 107; see Example 4 above; hereinafter referred to as "Compound II") group (G3), and the high-dose test substance (His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys; SEQ ID No: 107; see Example 4 above; hereinafter referred to as "Compound II") group (G3), and the high-dose test substance (His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys; SEQ ID No: 107). 107; see Example 4 above; hereinafter referred to as "Compound II") group (G4), 18 muscle strips per group. The experimental groups are shown in Table 2 below.

[0168] Table 2

[0169] The muscle strips were placed in 30 mL of Tyrode's solution, oxygenated, and equilibrated. Baseline tension was measured. 3 mg of estradiol, and 3 mg, 15 mg, and 60 mg of compound II, respectively, were added to obtain the concentrations described in Table 2 above. Tension was measured after administration for all 18 muscle strips in each group.

[0170] Contraction intensity was recorded before and after drug administration using a multi-channel physiological signal acquisition and processing system. Data are expressed as mean ± standard error. Statistical analysis was performed using GraphPad Prism software. A p-value <0.05 was considered statistically significant. Experimental results are shown in Table 3 below and in [the table is missing from the original text]. Figure 1 .

[0171] Table 3

[0172] Compared with the positive control group, p < 0.01; p < 0.001; p < 0.0001 In vitro vaginal smooth muscle contraction assays showed that compound II induced contraction at a minimum concentration of 0.1 mg / mL. Significant contraction was observed at 0.5 mg / mL, while the contractile effect decreased slightly at 2.0 mg / mL. The contraction intensity induced by medium and high doses of compound II was higher than that induced by the positive control estradiol.

[0173] Example 11 In vitro study on vaginal smooth muscle contraction II The following two test compounds were tested according to essentially the same procedure as described in Example 10 above: • Palm-His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (SEQ ID No: 108; see Example 5 above; hereinafter referred to as "Compound IV"); and His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys(Palm) (SEQ ID No: 109; see Example 6 above; hereinafter referred to as "Compound V") The research groups are shown in Table 4 below.

[0174] Table 4

[0175] The results are shown in Table 5 below and Figure 2 .

[0176] Table 5

[0177] Compared with the positive control group, p < 0.01; p < 0.001; p < 0.0001 The results showed that compounds II, IV, and V at a concentration of 0.5 mg / mL all induced significant contractions, which was the largest effective contraction observed with compound II in Example 10 above. All three tested compounds demonstrated higher vaginal contractions than the positive control estradiol.

[0178] Example 12 Clinical research Thirty-six women aged 31 to 57 (median age 43.5 years) participated in the clinical study.

[0179] Eleven subjects had entered menopause. All subjects received one to three doses of the gynecological gel prepared according to Example 8 above, wherein the concentration of compound II, as the active ingredient, was 1 mg / mL.

[0180] 2 mL of gel was pre-packaged in a commercial vaginal applicator for immediate use. 29 volunteers received one dose of gel, 4 volunteers received two doses (one applicator per application), and 3 subjects received three doses (one applicator per application).

[0181] All participants were asked to complete a feedback form, which included their name, age, whether they were menopausal, date of their last menstrual period, and their own and their partners' subjective feelings about moisturizing sensations, vaginal tightness, and other sensations, including sexual arousal. The results showed an overall effective rate of 94% (34 / 36).

[0182] Of the participants, 24 out of 36 reported significant improvements in hydration, and 20 out of 36 reported vaginal tightening. Additionally, four participants reported pelvic floor muscle relaxation due to urinary incontinence. All four reported improvement in this issue after using the gel.

[0183] The summary of the feedback form is shown in Figure 3 .

Claims

1. A compound or a regioisomer, stereoisomer, or pharmaceutically or cosmetically acceptable salt thereof, for the treatment of vaginal laxity or related disorders, said compound comprising essentially 3 to 21 N-terminal amino acids having the following peptide sequence: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 1) in: X 4 X 5 X 9 X 11 and / or X 13 Each of the following amino acids is independently selected: Ala, Val, Ile, Gly, Asn, Ser, Thr, Tyr, and Leu; The peptide sequence is optionally coupled to the group Y, or when the C-terminal amino acid is not Lys, the peptide sequence is optionally coupled to the group -Lys-Y; and Y represents one or more latanoprost molecules and / or one or more lipids selected from: vitamin A, vitamin E, cholesterol, and fatty acids containing one or more carboxylic acid groups, 1 to 50 carbons, and / or one or more rings, or derivatives of any of these lipids, said lipids being linear or branched, saturated or unsaturated with 1 to 10 carbon-carbon double bonds and / or substituted with 1 to 10 -OH groups.

2. The compound for the stated purpose according to claim 1, wherein Y or -Lys-Y is absent.

3. The compound of claim 2 for the said use, wherein the peptide sequence is selected from: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(SEQ ID No: 2); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val(SEQ ID No: 3); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala (SEQ IDNo: 4); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met (SEQ ID No:5); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln (SEQ ID No: 6); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ ID No: 7); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No: 8); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 9); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg (SEQ ID No: 10); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 (SEQ ID No: 11); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr (SEQ ID No: 12); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 (SEQ ID No: 13); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp (SEQ ID No: 14); His-Ser-Asp-X 4 -X 5 -Phe-Thr (SEQ ID No: 15); His-Ser-Asp-X 4 -X 5 -Phe (SEQ ID No: 16); His-Ser-Asp-X 4 -X 5 (SEQ ID No: 17); His-Ser-Asp-X 4 (SEQ ID No: 18); and His-Ser-Asp (SEQ ID No: 19).

4. The compound for the said use according to claim 1, wherein Y represents at least one lipid as defined in claim 1.

5. The compound for the said use according to claim 1 or claim 4, wherein Y represents a lipid selected from fatty acid derivatives as defined in claim 1.

6. The compound according to claim 5, wherein the lipid is selected from: palmitic acid, stearic acid, oleic acid, octadecanoic acid, docosahexaenoic acid and leukotriene B4 (LTB4), or any derivative of these lipids.

7. The compound according to any one of claims 1 to 6, wherein the lipid is palmitic acid or a derivative thereof.

8. The compound for the said use according to claim 7, wherein the peptide sequence is selected from: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 20); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 21); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 22); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm)(SEQ ID No: 23); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Lys(Palm) (SEQID No: 24); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm) (SEQ ID No:25); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ ID No: 26); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No: 27); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Lys(Palm) (SEQ ID No: 28); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-Lys(Palm) (SEQ ID No: 29); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Lys(Palm) (SEQ ID No: 30); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-Lys(Palm) (SEQ ID No: 31); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Lys(Palm) (SEQ ID No: 32); His-Ser-Asp-X 4 -X 5 -Phe-Lys(Palm) (SEQ ID No: 33); His-Ser-Asp-X 4 -X 5 -Lys(Palm) (SEQ ID No: 34); His-Ser-Asp-X 4 -Lys(Palm) (SEQ ID No: 35); His-Ser-Asp-Lys(Palm) (SEQ ID No: 36); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 37); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 38); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 39); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 40); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 41); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 42); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys (SEQ ID No: 43); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 44); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val (SEQ ID No: 45); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala(SEQ ID No: 46); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 47); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met (SEQID No: 48); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Lys(Palm) (SEQ ID No: 49); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln (SEQ IDNo: 50); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Lys(Palm)(SEQ ID No: 51); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 52); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys (SEQ ID No: 53); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val (SEQ ID No: 54); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala(SEQ ID No: 55); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met (SEQID No: 56); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln (SEQ IDNo: 57); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ ID No:58); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No: 59); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 60); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg (SEQ ID No: 61); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 (SEQ ID No: 62); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr (SEQ ID No: 63); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 (SEQ ID No: 64); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp (SEQ ID No: 65); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr (SEQ ID No: 66); Palm-His-Ser-Asp-X 4 -X 5 -Phe (SEQ ID No: 67); Palm-His-Ser-Asp-X 4 -X 5 (SEQ ID No: 68); Palm-His-Ser-Asp-X 4 (SEQ ID No: 69); Palm-His-Ser-Asp (SEQ ID No: 70); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys (SEQ ID No: 71); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 72); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 73); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys (SEQ ID No: 74); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys-Lys(Palm) (SEQ ID No: 75); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 76); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm)-Lys(Palm) (SEQ ID No: 77); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys (SEQ ID No: 78); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 79); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 80); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val (SEQ ID No: 81); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 82); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Val-Lys(Palm) (SEQ ID No: 83); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala (SEQ ID No: 84); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 85); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Ala-Lys(Palm) (SEQ ID No: 86); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met(SEQ ID No: 87); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm) (SEQ ID No: 88); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Lys(Palm) (SEQ ID No: 89); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln (SEQID No: 90); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Lys(Palm)(SEQ ID No: 91); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Lys(Palm) (SEQ ID No: 92); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm) (SEQ IDNo: 93); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ ID No:94); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No:95); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Lys(Palm) (SEQ ID No: 96); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-Lys(Palm) (SEQ ID No: 97); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Lys(Palm) (SEQ ID No: 98); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-Lys(Palm) (SEQ ID No: 99); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Lys(Palm) (SEQ ID No: 100); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Lys(Palm) (SEQ ID No: 101); Palm-His-Ser-Asp-X 4 -X 5 -Lys(Palm) (SEQ ID No: 102); Palm-His-Ser-Asp-X 4 -Lys(Palm) (SEQ ID No: 103); and Palm-His-Ser-Asp-Lys(Palm) (SEQ ID No: 104).

9. The compound for the said use according to claim 3 or claim 8, wherein the peptide sequence is selected from: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met (SEQ ID No:5); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln (SEQ ID No: 6); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ ID No: 7); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No: 8); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 9); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm)(SEQ ID No: 23); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Lys(Palm) (SEQID No: 24); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm) (SEQ ID No:25); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ ID No: 26); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No: 27); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met (SEQID No: 56); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln (SEQ IDNo: 57); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ ID No:58); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No: 59); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 60); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met(SEQ ID No: 87); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Met-Lys(Palm) (SEQ ID No: 88); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Met-Lys(Palm) (SEQ ID No: 89); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln (SEQID No: 90); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys-Gln-Lys(Palm)(SEQ ID No: 91); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm)-Gln-Lys(Palm) (SEQ ID No: 92); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys(Palm) (SEQ IDNo: 93); Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Lys(Palm) (SEQ ID No:94); and Palm-His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-Lys(Palm) (SEQ ID No:95)。 10. A compound for the said use according to any one of the preceding claims, wherein X 4 It represents Gly or Ala.

11. A compound for the said use according to any one of the preceding claims, wherein X 5 It represents Ile or Val.

12. The compound for the said use according to any one of the preceding claims, wherein X 9 It represents Ser or Asn.

13. A compound for the said use according to any one of the preceding claims, wherein X 11 It represents Ser or Thr.

14. A compound for the said use according to any one of the preceding claims, wherein X 13 This indicates Tyr or Leu.

15. The compound for the said use according to any one of claims 10 to 14, wherein the peptide sequence is selected from: His-Ser-Asp-Gly-Ile-Phe (SEQ ID No: 105); His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (SEQ ID No: 107); Palm-His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (SEQ IDNo: 108); and His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys (Palm) (SEQ ID No: 109).

16. The compound for the use according to any one of the preceding claims, wherein the vaginal laxity is characterized by a measurable loss of elasticity and strength of the vagina and / or surrounding tissues, and / or a perception by the patient or their sexual partner.

17. The compound for the use according to any one of the preceding claims, wherein the vaginal laxity is caused by childbirth, menopause, aging, genetics, and / or pelvic surgery, etc.

18. The compound for the use according to any one of the preceding claims, wherein the treatment is or is part of a vaginal restoration procedure.

19. The compound of claim 18 for the stated purpose, wherein the vaginal restoration is intended to restore the aesthetic appearance and / or function of the vagina.

20. The compound for the said use according to claim 18 or claim 19, wherein the vaginal restoration also includes surgery, vaginoplasty, and / or energy-based devices to promote tissue remodeling.

21. The compound for the use according to any one of claims 1 to 16, wherein the treatment is generally for treating frigidity.

22. The compound for the use according to any one of the preceding claims, wherein the treatment is administered just before sexual intimacy and / or intercourse.

23. The compound for the use according to any one of the preceding claims, wherein the treatment improves vaginal function during sexual intimacy and / or intercourse, increases the sensitivity of female reproductive organs, and / or enhances sexual arousal.

24. An isolated compound or a regioisomer, stereoisomer, or pharmaceutically or cosmetically acceptable salt thereof, said isolated compound being substantially composed of any of the following peptide sequences: His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg-Lys (SEQ ID No: 7); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 -Arg (SEQ ID No: 8); His-Ser-Asp-X 4 -X 5 -Phe-Thr-Asp-X 9 -Tyr-X 11 -Arg-X 13 (SEQ ID No: 9); or The peptide sequence having any one of SEQ ID Nos: 4 to 105, 107, 108 or 109 as defined in any one of claims 3, 8, 9 or 15 (as the case may be).

25. The isolated compound according to claim 24, wherein the peptide sequence is as defined in claim 9 or claim 15, or a regioisomer, stereoisomer, or pharmaceutically or cosmetically acceptable salt thereof.

26. The isolated compound according to claim 24, and regioisomers, stereoisomers, and pharmaceutically or cosmetically acceptable salts thereof, wherein the compound is substantially composed of any one of the peptide sequences having SEQ IDs Nos: 7, 8, 9, 23 to 25, 56 to 60, 87-95, 105, or 107 to 109.

27. The compound according to any one of claims 24 to 26, for use in human or animal medicine.

28. The compound according to any one of claims 24 to 26, used as a medicine.

29. A pharmaceutical preparation comprising the compound according to any one of claims 24 to 26.

30. The pharmaceutical formulation of claim 29, further comprising a pharmaceutically or cosmetically acceptable adjuvant, diluent, or carrier.

31. The pharmaceutical formulation of claim 29 or claim 30, suitable for, adapted to, and / or packaged and presented for topical application, wherein the pharmaceutically or cosmetically acceptable adjuvant, diluent, or carrier is a topical adjuvant, diluent, or carrier.

32. The pharmaceutical preparation according to any one of claims 29 to 31, wherein it is in the form of a liquid, gel, cream, emulsion, essential oil, powder, foam, effervescent composition, or suppository.

33. The pharmaceutical preparation according to any one of claims 29 to 32, further comprising other pharmaceutically active ingredients.

34. A kit comprising the following components: (A) a compound according to any one of claims 1 to 15 or 24 to 26, or a pharmaceutical preparation according to any one of claims 29 to 33; and (B) Pharmaceutical formulations, which include other pharmaceutically active ingredients that are mixed with pharmaceutically acceptable adjuvants, diluents, or carriers. The components (A) and (B) are each provided in a form suitable for combined application with each other.

35. The pharmaceutical preparation of claim 33, or the kit of claim 34, wherein the active pharmaceutical ingredient is an anti-inflammatory agent, a pro-inflammatory agent, an antibiotic, an antibacterial agent, an antiprotozoal agent, or an antiviral agent.

36. The pharmaceutical formulation or kit according to claim 35, wherein the active pharmaceutical ingredient is an anti-inflammatory agent.

37. The compound according to any one of claims 1 to 15 or 24 to 26, the formulation according to any one of claims 29 to 33, 35 or 36, or the kit according to any one of claims 34 to 36, for the treatment of vaginal laxity or related disorders as defined in any one of claims 1 or 16 to 23.

38. Use of the compound of any one of claims 1 to 15 or 24 to 26, the formulation of any one of claims 29 to 33, 35 or 36, or the kit of any one of claims 34 to 36 in the preparation of a medicament for treating vaginal laxity or related disorders as defined in any one of claims 1 or 16 to 23.

39. A method of treating vaginal laxity or related disorders as defined in any one of claims 1 to 23, the method comprising administering a compound according to any one of claims 1 to 15 or 24 to 26, an agent according to any one of claims 29 to 33, 35 or 36, or a kit according to any one of claims 34 to 36 to a patient in need of such treatment.

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