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CA-2994091-C - A CNP CYCLIC PEPTIDE AND A MEDICAMENT, EXTERNAL PREPARATION AND COSMETIC COMPRISING THE CYCLIC PEPTIDE

CA2994091CCA 2994091 CCA2994091 CCA 2994091CCA-2994091-C

Abstract

The present invention is aimed at providing a novel peptide with quick expression of drug efficacy/effect and long duration of maintaining amelioration, a medicament or an external preparation comprising the same, in particular a prophylactic or therapeutic for dermatitis, skin roughness, rhinitis, alopecia or thinning hair, or a hair growth stimulant, hair growing agent, an antipruritic or a skin-care product, etc. The present invention has reached said object by providing a cyclic peptide having an amino acid sequence expressed by the formula I or a derivative thereof or a pharmaceutically acceptable salt thereof, wherein the amino acid sequence has no peptide bond other than those which are formed between the amino acids constituting the amino acid sequence.

Inventors

  • Kyoko Endo
  • Yori Endo

Assignees

  • IGISU CO., LTD.

Dates

Publication Date
20260505
Application Date
20160801
Priority Date
20150731

Claims (14)

  1. CLAIMS 1. An external preparation comprising one or more cyclic peptides having an amino acid sequence expressed by the formula I: - - wherein, xi denotes Gly or Ala, X2 denotes Leu, Ala or Met, X3 denotes Ile or Val, X4 denotes Ser, Thr, Ala, Val, Ile or Leu, X5 denotes Ser, Thr or Ala, X6 denotes Leu, Ala, Val, Ile, Met or Phe, the line that links two Cys represents a disulfide bond, and wherein the amino acid sequence has no peptide bond other than those which are formed between the amino acids constituting the amino acid sequence, or a pharmaceutically acceptable salt thereof, wherein the external preparation is: a) at least one of therapeutic for alopecia, a prophylactic for alopecia, a hair growing agent, a hair growth stimulant, a prophylactic/inhibitor for hair-falling and prophylactic cosmetic for hair-falling, b) at least one of a scalp care agent for preventing/improving dandruff or itch, a scalp care agent of improving/preventing hair/scalp dryness and a scalp care agent for improving/preventing seborrheic condition of scalp, or c) at least one of a therapeutic for rhinitis, a prophylactic for rhinitis, a therapeutic for rhinosinusitis and a prophylactic for rhinosinusitis.
  2. 2. The external preparation according to Claim 1, wherein xi denotes Gly.
  3. 3. The external preparation according to Claim 1, wherein the cyclic peptide has an amino acid sequence of SEQ ID NO: 61.
  4. 4. The external preparation according to Claim 1, wherein the cyclic peptide has an amino acid sequence selected from SEQ ID NOs: 30, 46 and 55. 124 Date Re9ue/Date Received 2024-02-16
  5. 5. The external preparation according to Claim 1, wherein the cyclic peptide has an amino acid sequence selected from SEQ ID NOs: 6, 8, 12 to 20, 32 to 41, 48 to 53 and 57 to 59.
  6. 6. The external preparation according to Claim 5, wherein 1 to 6 amino acid(s) in the cyclic peptide is deleted and has equal functions to the cyclic peptide expressed by each of said formulae.
  7. 7. The external preparation according to any one of Claims 1-6 being a bathing agent, body cleansing agent, hair cleansing agent, hair rinse/treatment, hair tonic, hair oil, hair lotion or scalp care agent.
  8. 8. The external preparation according to any one of Claims 1-6 being a cosmetic.
  9. 9. The external preparation according to any one of Claims 1-6, wherein the external preparation is a solid, semisolid, powder, liquid, spray, ointment, cream, emulsion, gel or patch.
  10. 10. The external preparation according to any one of Claim 1-6, comprising the cyclic peptide at a concentration from 0.0001 to 1000000 μg/mL.
  11. 11. A use of the external preparation according to any one of Claims 1-6 for applying to the skin and/or mucosa of a subject.
  12. 12. The use according to Claim 11, wherein the mucosa is a lip, oral cavity, nasal cavity, eye orvagma.
  13. 13. A use of an external preparation comprising one or more cyclic peptides having an amino acid sequence expressed by the formula I: Cys-Phe-X1-Leu-Lys-X2-Asp-Arg-X3-Gly-X4-Met-X5-Gly-X6-Gly-Cys (I) I I wherein, X1 denotes Gly or Ala, X2 denotes Leu, Ala or Met, X3 denotes Ile or Val, X4 denotes Ser, Thr, Ala, Val, Ile or Leu, X5 denotes Ser, Tor or Ala, X6 denotes Leu, Ala, Val, Ile, Met or Phe, the line that links two Cys represents a disulfide bond, and wherein the amino acid sequence has no peptide bond other than those which are formed between the amino acids constituting the amino acid sequence, or a pharmaceutically acceptable salt thereof, for: 125 Date Re9ue/Date Received 2024-02-16 a) at least one of treating dermatitis, preventing dermatitis, alleviating dermatitis, eliminating dermatitis, treating erosion/ulcer and skin-care, b) at least one of treating and preventing dermatitis, c) improving and preventing at least one of skin roughness, hypersensitivity of skin, dry skin, oily skin, photosensitivity, wrinkles, flabbiness, dullness, dandruffs and itches, d) at least one of treating thinning hair, preventing thinning hair, stimulating hair growth, growing hair, inhibiting hair falling and preventing hair falling, e) at least one of inhibiting dandruffs or itches, preventing dandruffs or itches, improving hair or scalp dryness preventing hair or scalp dryness, preventing seborrheic condition of scalp and improving seborrheic condition of scalp, or f) at least one of preventing rhinitis and preventing rhinosinusitis.
  14. 14. The use according to Claim 13, wherein the dermatitis selected from the group consisting of eczema, atopic dermatitis, contact dermatitis, photosensitivity, psoriasis, acne, cystic acne, seborrheic eczema and itches. 126 Date Re9ue/Date Received 2024-02-16

Description

[Specification] [Title of Invention] A CNP cyclic peptide and a medicament, external preparation and cosmetic comprising the cyclic peptide [Technical Field] [0001] The present invention relates to a CNP cyclic peptide, and a medicament, external preparation and cosmetic comprising the cyclic peptide. [Background Arts] [0002] CNP (C-type natriuretic peptide), which belongs to human NP family, have been known to be specifically expressed in brain, unlike ANP and BNP which are classified to the same family. It has ben also known that CNP has a weaker natriuresis utilization and antihypertensive activity as compared to ANP and BNP, but has a stronger effect of increasing intracellular cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells, etc. (Non-patent Reference 1 ). Thus, it has been considered that CNP takes other physiological roles than those in maintaining homeostasis in body fluid volume and blood pressure. [0003] It has been known that CNP is highly conserved in its amino acid sequence consitution with little differences between species, and its structure possesses a cyclic moiety and tail part as common structures. In this context, it has been shown that the smallest active structure for increasing intracellular cGMP in vascular smooth muscle cells is the cyclic moiety (hereinbelow may also simply referred to as C-ring) of CNP, and various CNP mutants and derivatives have been reported (Patent References 1 and 6). Recently, several therapeutic drugs and treatment method utilizing such CNPs have just become known (Patent References 1 to 5), among which there is a report that CNP cyclic peptide is effective for arthritis (Patent Reference 6). [0004] Nevertheless, for treating dermatitis, steroids, tacrolimus, etc. are still used now as main stream. Although the use of these drugs is hesitated in children and particular subjects because of their strong side effects such as developing skin atrophy by long-term topical application, increasing likelihood of causing adrenal insufficiency in cases of an extensive skin rash, and increasing risk of infections due to it immunosuppressing effect, the actual circumstances are that there is no other choice but to use these drugs in order to suppress the conditions of diseases while enduring such strong side effects. In this context, it has been reported that therapeutics for dermatitis comprising CNP have no such side effect and dramatically suppresses the symptoms of dermatitis (Patent References 2 to 4). Besides, steroids are also often used in rhinitis though their therapeutic effect is short for their side effecr and cases are found now and then in which the obtained effect is not as much as expected. On the other hand, therapeutics for rhinitis comprising CNP have been reported to have a long effective duration with no side effects (Patent Reference 2 to 4). Furthermore, in alopecia, for which none of the various drugs that have been used exhibited an effect that was equal to or more than expected, it has been demonstrated that therapeutics for alopecia comprising CNP exhibit significant hair stimulating or hair growing effect (Patent Reference 2 to 4). [Prior Art References] [Patent References] [0005] [Patent Reference 1] [Patent Reference 2] [Patent Reference 3] [Patent Reference 4] [Patent Reference 5] [Patent Reference 6] [Non-patent References] [0006] JP B 2809533 WO 2010/062459 WO 2011 /064644 WO 2011/024973 US Patent No. 7276481 Specification Published US Patent Application No. 2007 /0197434 Specification [Non-Patent Reference 1] Furuya M, Takehisa M, Minamitake Y, Kitajima Y, Hayashi Y, Ohnuma N, Ishihara T, Minamino N, Kangawa K, Matsuo H Biochem Biophys Res Commun. 1990 Jul 16; 170(1 ):201-8. [Summary of the Invention] [Problems to be Solved by the Invention] [0007] As mentioned above, CNP and CNP cyclic peptide are considered to be a substance that is useful for treating various diseases such as arthritis. However, it is desired to develop substances having more potent drug efficacy/ effect and substances that acts quicker and for longer dutation in order to obtain higher therapeutic/treatment effect as compared to conventional drugs. Also, a less expensive formulation as compared to conventional ones are desired. [0008] It is quite meaningful to further increasing sustainability and immediate effectiveness of drug efficacy/ effect from the viewpoint of reducing required number/frequency of treatment, palliating pain of patient or user, increasing quality of life and improving daily spiritual/physical/social satisfaction (QOL:quality of life). For example, in dermatitis, in cases where the affected site is accompanied by an itches, erythema or a hot flash, or in diseases where a systemic erythema with thich scales like psoriasis is observed, flaking scales often severely impair QOL with problem of appearance. Quickly reliefing these symtoms will reduce pain of the patient. In rhinitis, which is often accompanied by symptoms of nasa