WO2016194855A1 - 環状ペプチド並びに該環状ペプチドを含む医薬、外用剤および化粧料 - Google Patents
環状ペプチド並びに該環状ペプチドを含む医薬、外用剤および化粧料 Download PDFInfo
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- WO2016194855A1 WO2016194855A1 PCT/JP2016/065839 JP2016065839W WO2016194855A1 WO 2016194855 A1 WO2016194855 A1 WO 2016194855A1 JP 2016065839 W JP2016065839 W JP 2016065839W WO 2016194855 A1 WO2016194855 A1 WO 2016194855A1
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- cyclic peptide
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- alopecia
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- skin
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Definitions
- the present invention relates to a cyclic peptide and a medicine, an external preparation and a cosmetic containing the cyclic peptide.
- BNP brain natriuretic peptide
- BNP is a hormone synthesized and secreted in the heart (mainly the ventricle). BNP has been isolated and identified from pig brain in 1988 and is known to be secreted from ventricular muscles such as humans. When the heart load increases or myocardial hypertrophy occurs, BNP is secreted and its blood concentration increases. In general, BNP is considered to be a hormone that acts to protect the heart muscle from damage caused by the burden on the heart, with diuretic action, vasodilatory action, renin / aldosterone secretion suppression, sympathetic nerve suppression, hypertrophy suppression, etc. It has been.
- BNP has slightly different amino acids constituting BNP depending on the individual species produced, but it has been found that the structure has a cyclic part and a tail part as a common structure (Non-Patent Documents 1 and 2).
- wild-type human BNP is known to consist of 32 amino acid residues, and fragments and derivatives thereof have also been proposed (Patent Documents 1 to 6).
- BNP is not a therapeutic drug in Japan but is widely used in clinical settings as a biochemical marker of heart failure. In the United States, BNP is also used as a drug for relieving symptoms of heart failure (trade name: natrecor (trademark)). in use. Recently, it has also been proposed to use an external preparation containing BNP as a treatment for dermatitis, rhinitis, alopecia, etc., or a skin quality improving agent (Patent Documents 7 to 9).
- BNP is considered to be a useful substance for the treatment of various diseases.
- it is necessary to develop a substance with higher drug efficacy and efficacy, and a substance with higher immediate effect and sustainability.
- the object of the present invention is to provide a novel peptide having a high medicinal effect and efficacy, a pharmaceutical or external preparation containing the peptide, particularly a preventive or therapeutic agent for dermatitis, rhinitis, alopecia, a hair growth agent, a hair restorer, an antipruritic agent, and a cosmetic.
- a pharmaceutical or external preparation containing the peptide particularly a preventive or therapeutic agent for dermatitis, rhinitis, alopecia, a hair growth agent, a hair restorer, an antipruritic agent, and a cosmetic.
- the tail in the peptide structure of BNP consisting of a cyclic part and a tail part was thought to play at least a certain important role. Is daring to pay attention to the ring part in the structure, and while conducting earnest research on the cyclic peptide obtained by deleting the tail part, the effect by the cyclic peptide, the high medicinal effect, the rapid expression of the effect, As a result of continuous research, it was possible to obtain completely new knowledge such as the sustainability of the effect, and the present invention was completed. That is, the present invention relates to the following.
- the amino acid sequence has the formula (Ia) to formula (Ie) In the formula, a line connecting two Cys represents a disulfide bond.
- An external preparation comprising at least one of the cyclic peptide and / or derivative thereof and / or a pharmaceutically acceptable salt thereof according to any one of [1] to [5].
- the external preparation according to [6] which is a material for a dermatitis therapeutic agent, dermatitis preventive agent, antipruritic agent, anti-inflammatory agent, epidermal regeneration promoter, wound epithelialization promoter or skin care product.
- [8] Skin care products for moisturizing and / or preventing and improving rough skin and / or sebum care / acne care and / or irritation mitigation / anti-inflammatory and / or whitening and / or anti-aging and / or UV injury prevention / relief The external preparation according to [7], which is for use and / or for slimming and / or for skin cleaning. [9] The external preparation according to [6], which is a bath agent, a body cleanser or a hair cleanser. [10] The external preparation according to [6], which is a therapeutic agent for alopecia, a preventive agent for alopecia, a hair restorer and / or a hair growth agent. [11] The external preparation according to [6], which is a rhinitis therapeutic agent and / or a rhinitis preventive agent.
- a method for using an external preparation which comprises applying the external preparation according to any one of [14] to the skin and / or mucous membrane of a subject.
- the method for using an external preparation according to [16] which is a method for treating and / or preventing dermatitis, a method for reducing or eliminating itching, erosion due to eczema, an ulcer treatment method, or a skin care method.
- BNP cyclic peptide here (hereinafter sometimes referred to as “BNP cyclic peptide”, “B ring” or “B ring compound”) is derived from wild type BNP as described above. Includes not only those derived from humans but also those derived from monkeys, pigs, birds and rats. Accordingly, the B-ring compounds include not only those derived from humans but also those derived from monkeys, pigs, birds and rats.
- a novel cyclic peptide and a composition containing the same can be provided.
- Such a composition is applied to an external preparation for preventing or treating dermatitis, rhinitis, and alopecia, and further to a hair growth agent, a hair restorer, an antipruritic agent, etc., all of which are pharmaceuticals, quasi drugs, skin care products, cosmetics.
- the term “external preparation” means an agent applied to the skin and mucous membrane, which is not limited to uses such as medicines, quasi drugs, skin care products, and cosmetics.
- the external preparation of the present invention is more markedly effective against dermatitis than conventional steroid external preparations, and has an excellent immediate effect such that symptoms generally begin to improve within 3 minutes. Large, durable and long remission period.
- the external preparation of the present invention when applied on the skin or mucous membrane of a subject suffering from dermatitis, is caused by or may cause dermatitis, pain (pain), heat feeling, tension feeling, infiltration, Dermatitis symptoms can be improved while rapidly relieving or eliminating various perceptible symptoms and conditions such as erythema.
- the external preparation of the present invention exerts a moisturizing effect at the application site, and when the stratum corneum is present at the application site, it exerts an effect of adjusting the texture of the application site.
- the texture is smooth and dry skin It can improve skin roughness, soft skin, moisturized, shallow wrinkles and inconspicuous, and can improve lip roughness.
- the external preparation of the present invention has an effect of preventing hair loss at the application site and promoting hair growth or hair growth when applied to a site such as a hair loss site or a hair growth site.
- a site such as a hair loss site or a hair growth site.
- the hair that grows tends to be hard and tends to be non-white hair.
- these effects are expressed relatively early compared to other active ingredients conventionally used in therapeutic agents for alopecia, such as BNP, and the obtained effects are also remarkable.
- the external preparation of the present invention has an immediate effect on rhinitis, has a large effect, is durable, and has a long remission period.
- the cyclic peptide of the present invention is a peptide having a common part in its structure with BNP, which is a hormone originally provided in the body, there is less concern about side effects, and as long as it is used in an appropriate amount or applied to the skin or the like. In some cases, the effect on hemodynamics is considered to be minor, and thus long-term administration is possible even for patients who need to be administered over a long period of time, for example, patients with chronic dermatitis. Furthermore, the external preparation of the present invention has no irritation when applied externally, and can be applied to children and women as well as to the face, neck and the like in addition to patients with sensitive skin.
- the cyclic peptide of the present invention has superior drug efficacy and efficacy compared to wild-type BNP.
- the cyclic peptide of the present invention is It is suggested that the NPR-A receptor (GC-A) binds more easily and strongly than the wild-type BNP. This suggests that the cyclic peptide has a medicinal effect and efficacy, particularly It is presumed that these quick effects are excellent.
- B-ring compounds include not only human-derived compounds but also B-rings derived from heterologous animals such as monkeys, pigs, birds, and rats, but these may have similar structures. As has been confirmed, it is strongly speculated that any of the B rings has the same effect as the human-derived B ring compound from the results of the structural analysis described later.
- X 1 represents Gly, Val, Ala, Ser or Thr
- X 2 represents Arg, Gln or His
- X 3 represents Lys or Arg
- X 4 represents Met, Leu or Ile
- X 5 represents Ile or Val
- X 6 represents Ser or Gly
- X 7 represents Ser or Ala
- X 8 represents Ser, Gln, Val, Ala, Thr, Leu, Ile or Met
- X 9 represents Ser, Val, Ala or Thr
- X 10 represents Gly or Arg
- X 11 represents Leu, Met, Ile, Val or Ala
- X 12 represents Gly, Ser or Ala
- the line connecting the two Cys represents a disulfide bond, Having an amino acid sequence represented by The amino acid sequence is a cyclic peptide having no peptide bond other than the amino acids constituting the amino acid sequence.
- Such a cyclic peptide binds to a receptor NPR-A (also known as GC-A) having a guanylate cyclase domain and binds to cyclic guanosine monophosphate (cGMP) in the same manner as conventionally known BNP. It is considered that it has actions such as diuretic action, vasodilatory action, renin / aldosterone secretion suppression, sympathetic nerve suppression, hypertrophy suppression, etc., but superior drug efficacy and efficacy compared to BNP Especially, it has an excellent immediate effect.
- a receptor NPR-A also known as GC-A
- cGMP cyclic guanosine monophosphate
- the cyclic peptide is used as a component of an external preparation such as a dermatitis treatment / prevention agent, rhinitis treatment / prevention agent, alopecia treatment / prevention agent, a hair restorer, a hair growth agent, an antipruritic agent, etc. It can be used as a material for skin care products, quasi drugs, and cosmetics. Further, in a medicine using the activity of BNP, for example, medicine for hypertension, unstable angina pectoris, acute myocardial infarction, edema disease, renal failure, heart failure, immune disease, obesity, metabolic syndrome, Alternatively, the above cyclic peptides can be used.
- the cyclic peptide of the present invention is the above-described formula (I), wherein X 1 to X 12 are the following (1) to (12): (1) X 1 represents Gly, Val, Ala, Ser or Thr. (2) X 2 represents Arg, Gln or His, (3) X 3 represents Lys or Arg, (4) X 4 represents Met, Leu or Ile, (5) X 5 represents Ile or Val. (6) X 6 represents Ser or Gly, (7) X 7 represents Ser or Ala, (8) X 8 represents Ser, Gln, Val, Ala, Thr, Leu, Ile or Met, (9) X 9 represents Ser, Val, Ala or Thr.
- X 10 represents Gly or Arg
- (11) X 11 represents Leu, Met, Ile, Val or Ala
- (12) X 12 represents Gly, Ser or Ala. 1 or 2 or more selected from the group consisting of In the cyclic peptide of the present invention, in the above formula (I), X 2 represents Arg, X 4 represents Met, X 6 represents Ser, X 7 represents Ser, and / or X 10 represents A cyclic peptide (SEQ ID NO: 2) showing Gly is preferred.
- the amino acid sequence represented by the formula (I) may be selected from SEQ ID NOs: 3 to 8 and SEQ ID NOs: 16 to 75.
- the cyclic peptide of the present invention has an amino acid sequence represented by the formula (I) having the formula (Ia) to the formula (Ie): (SEQ ID NO: 3) (SEQ ID NO: 4) (SEQ ID NO: 5) (SEQ ID NO: 6) (SEQ ID NO: 7)
- a line connecting two Cys represents a disulfide bond. It is preferably selected from the amino acid sequences represented by
- the amino acid sequences represented by these formulas (Ia) to (Ie) are human BNP (formula (Ia)), porcine BNP (formula (Ib)), rat BNP (formula (Ic)), the cyclic part of rabbit BNP (formula (Id)) and mouse BNP (formula (Ie)). Therefore, the cyclic peptide having such an amino acid sequence has the effect described above more reliably.
- porcine BNP cyclic peptide is a tri (SEQ ID NO: 8, Cys-Phe-Gly-Arg-Arg-Ile-Asp-Arg-Ile-Gly-Ser-Leu-Ser-Gly-Met-Gly-Cys, formula Among them, the first Cys and the 17th Cys have disulfide bonds), bovine (SEQ ID NO: 9, Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu- Ser-Gly-Leu-Gly-Cys, wherein the first Cys and the 17th Cys have disulfide bonds, cat (SEQ ID NO: 10, Cys-Phe-Gly-Arg-Arg-Leu-Asp -Arg-Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys, where the first Cys and number 17 In Cys of disulfide bond), dog (SEQ ID NO: 8,
- the amino acid sequence represented by the formula (I) is the amino acid sequence represented by the formula (Ia).
- it may be a cyclic peptide represented by SEQ ID NOs: 16 to 75.
- the cyclic peptide of the present invention includes a derivative of the above cyclic peptide.
- Such a derivative can be used as an active substance as it is or as a prodrug.
- the derivative of the present invention can add (modify) or substitute a known substituent to a specific group of an amino acid in a cyclic peptide, for example, a hydrogen atom, a hydroxyl group, a carboxy group, an amino group, an imino group, and the like. It can be obtained by substitution with a known substituent.
- a known substituent include, but are not limited to, chemical modifications such as sugar chain addition, acetylation, phosphorylation, and lipid addition to amino acids in the cyclic peptide.
- addition (modification) or substitution to an amino acid group in the cyclic peptide may occur simultaneously in one or more groups or more.
- a substituent if it can substitute with respect to said group, it will not specifically limit, A well-known substituent can be used, For example, it cannot be overemphasized that protective groups, such as BOC, are also contained naturally.
- the cyclic peptide of the present invention includes those obtained by mutating the cyclic peptide. That is, the mutant of the present invention can be obtained by deleting an amino acid in a cyclic peptide, or substituting or adding with another amino acid.
- the number of amino acids to be deleted or substituted or added with other amino acids is 4 or less, more preferably 3 or less, still more preferably 2 or less, and particularly preferably 1 or less. It goes without saying that deletion of amino acids in the cyclic peptide, substitution or addition with other amino acids may occur independently and simultaneously.
- amino acids that can be substituted with other amino acids can be exemplified as follows in terms of human BNP (formula (Ia)), but are not limited thereto.
- Gly which is the third amino acid from the left, may be substituted with any of Val, Ala, Ser, or Thr.
- Arg the fourth amino acid from the left, may be substituted with either Gln or His.
- Lys which is the fifth amino acid from the left, may be substituted with Arg.
- Met the sixth amino acid from the left, may be substituted with either Leu or Ile.
- Ile which is the ninth amino acid from the left, may be substituted with Val.
- Ser the 12th amino acid from the left, may be substituted with any of Gln, Val, Ala, Thr, Leu, Ile, and Met.
- Ser the 13th amino acid from the left, may be substituted with either Val, Ala, or Thr.
- Gly, which is the 14th amino acid from the left, may be substituted with any of Arg.
- Leu which is the 15th amino acid from the left, may be substituted with any of Met, Ile, Val, or Ala.
- Gly, which is the 16th amino acid from the left may be substituted with either Ser or Ala.
- Table 32 the example of the amino acid which can be substituted in the cyclic peptide of this invention was put together in Table 32, it is not limited to these.
- Examples of the cyclic peptide in which one amino acid is substituted include SEQ ID NOs: 16 to 44, but are not limited thereto.
- Examples of the cyclic peptide in which 2 amino acids are substituted include SEQ ID NOs: 45 to 58, but are not limited thereto.
- examples of the cyclic peptide in which 3 amino acids are substituted include SEQ ID NOs: 59 to 70, but are not limited thereto.
- examples of the cyclic peptide substituted with 4 amino acids include, but are not limited to, SEQ ID NOs: 71 to 75. It goes without saying that 5 or more amino acids can be substituted by appropriately combining the above-mentioned amino acids.
- amino acid from which one to several amino acids can be deleted can be performed in the same manner as the amino acids that can be substituted with other amino acids described above.
- the number of amino acids to be deleted or substituted or added with other amino acids may be 80% homologous to the cyclic peptide of the present invention, and preferably 90% homologous cyclic It may be a peptide.
- the present invention may be a mutant as described above and a derivative thereof. Any mutant or derivative thereof is included in the cyclic peptide according to the present invention as long as it has the effects of the present invention. In another aspect, it may have at least BNP activity.
- the amino acids constituting this can be modified as appropriate. For example, chemical modification of the cyclic peptide of the present invention to amino acids, etc., deletion of some amino acids constituting the cyclic peptide, substitution with other amino acids, and / or addition of new amino acids Can be made.
- the C-terminal group of one Cys of the cyclic peptide may be replaced with —COOR 1 , —CONHR 1 or —CONR 1 2 instead of —CONH, and / or the N-terminal group of the other Cys of the cyclic peptide with NH Instead of 2 , it can be —NHC (O) R 1 or —N (C (O) R 1 ) 2 .
- R 1 is independently a branched or straight chain hydrocarbon group having 1 to 20 carbon atoms, an alkylene glycol chain, or a sugar chain, each time it appears.
- the carbon number of R 1 is preferably 1 to 10, more preferably 1 to 5, and further preferably 1 to 2.
- the pharmaceutically acceptable salt is not particularly limited, and examples of the cyclic peptide or derivative of the present invention include a salt with an inorganic base, a salt with an organic base, a salt with an inorganic acid, and a salt with an organic acid. And salts with basic or acidic amino acids.
- the salt with inorganic base include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; and aluminum salt and ammonium salt.
- salts with organic bases include, for example, salts with alkylamines such as trimethylamine and triethylamine; salts with heterocyclic amines such as pyridine and picoline; alkanolamines such as ethanolamine, diethanolamine and triethanolamine And salts with cycloalkylamines such as cyclohexylamine and dicyclohexylamine; salts with alkylenediamine derivatives such as N, N′-dibenzylethylenediamine, and the like.
- salts with inorganic acid include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
- salts with organic acids include salts with monocarboxylic acids such as formic acid, acetic acid, trifluoroacetic acid and propionic acid; salts with polyvalent carboxylic acids such as fumaric acid, oxalic acid and maleic acid; And salts with oxycarboxylic acids such as tartaric acid, citric acid, succinic acid and malic acid; salts with sulfonic acids such as methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid; and salts with benzoic acid.
- monocarboxylic acids such as formic acid, acetic acid, trifluoroacetic acid and propionic acid
- salts with polyvalent carboxylic acids such as fumaric acid, oxalic acid and maleic acid
- oxycarboxylic acids such as tartaric acid, citric acid, succinic acid and malic acid
- salts with sulfonic acids such as methanes
- salts with neutral amino acids include, for example, salts with glycine, valine, leucine and the like
- salts with basic amino acids include, for example, arginine, lysine, ornithine and the like.
- Suitable salts with acidic amino acids include, for example, salts with aspartic acid, glutamic acid and the like.
- a cyclic peptide consisting of the amino acid sequence represented by the formula (I) or a pharmaceutically acceptable salt thereof is preferable. That is, the amino acid sequence represented by formula (I) is preferably not substituted.
- the production method of the cyclic peptide, derivative, and pharmaceutically acceptable salt thereof of the present invention is not particularly limited, and for example, a known chemical synthesis method or genetic engineering synthesis method can be used.
- the amino acid sequence When the amino acid sequence is synthesized by a chemical synthesis method, it may be synthesized by any chemical synthesis method, and can be synthesized by a known peptide synthesis method, for example, a solid phase synthesis method or a liquid phase synthesis method. . In the synthesis, a commercially available peptide synthesizer (eg, Shimadzu Corporation: PSSM-8) may be used.
- PSSM-8 a commercially available peptide synthesizer
- the disulfide bond in the amino acid sequence is not particularly limited, but can be formed, for example, by DMSO oxidation method, iodine oxidation method or the like.
- a free sulfhydryl group or a sulfhydryl group protected with a protecting group can be treated with DMSO or iodine (I 2 ) to form an intramolecular disulfide bond, resulting in a cyclic peptide. .
- protecting group examples include 4-methylbenzyl group (Bzl (4Me)), trityl group (Trt), tert-butyl group, N- (acetyl) aminomethyl group (Acm) and the like. Further, deprotection can be carried out by an appropriate treatment corresponding to these protecting groups, for example, by treating a 4-methylbenzyl group with a strong acid and an N- (acetyl) aminomethyl group with iodine. it can.
- derivatization of the cyclic peptide is performed as necessary to obtain a derivative.
- the derivatization can be performed by a known method.
- a pharmaceutically acceptable salt is produced by performing salt exchange of the cyclic peptide or derivative as necessary.
- Salt exchange can be performed, for example, by contacting the cyclic peptide or derivative with the desired acid or base.
- a DNA fragment encoding the amino acid sequence represented by formula (I) is prepared.
- a DNA fragment encoding the amino acid sequence represented by the formula (Ia) is prepared by synthesizing a predetermined DNA region using a vector containing a full-length human BNP gene as a template. It can be performed by amplifying a DNA fragment by the PCR method using the prepared primer. DNA fragments may be chemically synthesized.
- the amplified DNA fragment is ligated to an appropriate vector to obtain a recombinant vector for protein expression.
- the recombinant vector for protein expression is taken into the target cell, and the taken-in cell is selected.
- the protein produced from the cells protein consisting of the amino acid sequence represented by the formula (I)
- Disulfide bond formation, derivatization, and salt formation in the recovered protein can be performed as described above.
- confirmation that the compound, such as the target cyclic peptide, was obtained can be performed by well-known methods, such as reverse phase HPLC and mass spectrometry, for example.
- the presence or absence of the BNP activity of the obtained compound can be easily confirmed by known means, for example, it can be confirmed by testing cGMP production activity in NPR-A receptor-expressing cells. it can.
- the external preparation of the present invention comprises one or more cyclic peptides and / or derivatives thereof as described above and / or pharmaceutically acceptable salts thereof.
- the external preparation of the present invention comprises one or more cyclic peptides and / or derivatives thereof as described above and / or pharmaceutically acceptable salts thereof.
- cyclic peptides there is no particular upper limit to the kind of cyclic peptide to be mixed, but about 2 to 3 kinds are preferable from the viewpoint of preparation cost and simplicity. Examples thereof include SEQ ID NOs: 19, 29, 33, 36, 39, and 43, but are not limited to these as long as they do not impair the effects of the present invention. Can be combined.
- the external preparation of this invention is not specifically limited, For example, it can be used for the following uses, In each case, the outstanding effect which is not before is exhibited.
- the external preparation of the present invention is not particularly limited in any application, and can be used as a pharmaceutical, a quasi-drug and / or a cosmetic depending on its medicinal effect and efficacy.
- Dermatitis therapeutic agent dermatitis preventive agent
- the external preparation of the present invention can be a dermatitis therapeutic agent and / or a dermatitis preventive agent.
- the external preparation of the present invention When applied on the skin or mucous membrane of a subject suffering from dermatitis, the external preparation of the present invention causes or may cause itchiness, pain (pain), heat, tension, erythema, infiltration, papules. It is possible to improve symptoms of dermatitis while rapidly relieving or eliminating various perceptible symptoms and conditions such as lichenification, crusting, leaching and skin dryness. Moreover, the external preparation of this invention does not produce irritation in an application site
- the cyclic peptide of the present invention has a structure advantageous in binding to its receptor NPR-A receptor as compared with BNP. As a result, it is possible that the NPR-A receptor in the vicinity of the affected area can be bound more rapidly and the binding time is longer. In addition, by binding to the NPR-A receptor in the vicinity of the affected area relatively quickly, it is possible to prevent the cyclic peptide from diffusing outside the affected area due to blood flow or the like. It is thought that it can be stopped.
- the external preparation of the present invention not only suppresses or prevents inflammation of dermatitis but also has an action of restoring or maintaining the skin barrier function.
- the barrier function of the skin has a function to prevent irritation from the external environment and bacteria from entering the skin and a moisturizing function.
- the external preparation of the present invention has the effect of preparing the texture and moisturizing the skin. Therefore, the action of recovering and maintaining the barrier function of the skin of the external preparation is also apparent.
- the external preparation of the present invention is also effective for skin symptoms such as comedones commonly called acne, red papules, pustules, cysts and nodules.
- Such perceptible symptoms, amelioration of the state, and disappearance effect of the external preparation of the present invention generally develop within 10 minutes, preferably within 5 minutes, more preferably within 3 minutes after application.
- the external preparation of the present invention has a satisfactory therapeutic effect such as dermatitis causing steroid dermatosis or dermatitis that cannot be treated with other dermatitis drugs such as steroids and tacrolimus. It is also possible to treat dermatitis that is not possible, resistant to those formulations, unsuitable or undesirable.
- dermatitis that is not possible, resistant to those formulations, unsuitable or undesirable.
- steroid external preparations that have been widely used in the past, if the external application was stopped, there was a serious problem that it immediately returned to the severity before the external application or worsened before the external application due to a rebound phenomenon.
- the external preparation of the present invention does not have such a problem as the rebound phenomenon.
- Dermatitis is a disease that generally causes inflammation on the skin or mucous membranes. Dermatitis usually includes erythema, infiltrating erythema, papules, blisters, pustules, infiltration, ligation, desquamation and other chronic eczema symptoms, lichenification, pigmentation and other chronic eczema symptoms, scales, crusts (Scab) With one or more symptoms selected from the group consisting of adhesion, curettage, scratching scars, prurigo nodules, erosion, edema, tingling, and scaly.
- the dermatitis is not particularly limited as long as it is a disease accompanied by inflammation on the skin or mucous membrane.
- chronic eczema allergic eczema, eczema such as childhood dry eczema, atopic dermatitis
- allergic Contact dermatitis contact dermatitis such as primary irritant contact dermatitis
- seborrheic dermatitis sebum-deficient dermatitis
- stasis dermatitis allergic urticaria (eg food Urticaria such as physical urticaria, drug-induced urticaria), non-allergic urticaria (eg, physical urticaria, sunlight urticaria, choline urticaria); insect bites; drug eruption; psoriasis vulgaris, drops Psoriasis such as psoriasis, psoriatic erythroderma, pustular psoriasis
- the external preparation of the present invention is particularly effective against eczema, atopic dermatitis, contact dermatitis, seborrheic dermatitis, insect bite, allergic or non-allergic urticaria, psoriasis, preferably eczema, atopic dermatitis. It exhibits excellent effects against eczema and atopic dermatitis, more preferably against dermatitis, contact dermatitis and insect bites. Therefore, the external preparation of the present invention can be used for the purpose of treating or preventing at least one dermatitis selected from the above group.
- the external preparation of the present invention can be a material for cosmetic or skin care product.
- the external preparation of the present invention moisturizes the application site and exerts a moisturizing effect to prevent drying and rough skin.
- the stratum corneum is present at the application site, the effect of adjusting the texture of the application site is exhibited.
- moderate elasticity and flexibility are imparted to and maintained on the skin and mucous membranes, the skin becomes soft, and the skin and mucous membranes are crushed and tightened.
- wrinkles and sagging including fine lines and large wrinkles are improved at the application site, and dullness and spots become inconspicuous. Further, since dullness and blotches are not noticeable, a whitening effect is obtained as a result.
- the external preparation of the present invention is not particularly limited for the purpose of maintaining or improving the state of the skin and / or mucous membrane, but includes, for example, dry skin, rough skin, sensitive skin, rough lips, sagging, fine lines and fine lines.
- At least one effect selected from the above-mentioned effects for the purpose of at least one selected from the group consisting of prevention, improvement or prevention of the occurrence of, and maintenance of skin or mucous membrane state, anti-aging and whitening It can be used for the purpose of obtaining.
- rough skin includes a rash, a moistness, a crack, a redhead, an acne, a diaper rash, a sore, a crotch, and a razor.
- the specific use of the external preparation of the present invention as a material for cosmetics or skin care products is not particularly limited.
- the above-mentioned effects of the external preparation of the present invention are rapidly manifested, and generally vary within 10 minutes, preferably within 5 minutes, more preferably within 3 minutes after application, depending on the type of the effect.
- the above-described effects of the external preparation of the present invention last for a relatively long time, and vary depending on the type of the effect, but generally 4 hours or more after the effect is exerted, preferably 8 hours or more, more preferably 24 hours or more. continue.
- the external preparation of the present invention can be an antipruritic agent.
- the external preparation of the present invention is suitable as an antipruritic agent because it exhibits an excellent antipruritic effect at the application site when applied onto the skin or mucous membrane.
- the antipruritic effect of the external preparation of the present invention as described above generally develops within 10 minutes, preferably within 5 minutes, more preferably within 3 minutes after application.
- the external preparation of the present invention may be a hair loss treatment agent, hair loss prevention agent, hair growth agent and / or hair growth agent. it can.
- the external preparation of the present invention has an effect of preventing hair loss at the application site and promoting hair growth or hair growth when applied to a site such as a hair loss site or a hair growth site.
- effects such as hair restoration effect, hair growth promotion effect, thinning hair improvement / prevention.
- the hair that grows tends to be hard and tends to be non-white hair.
- these effects are expressed relatively early compared to other active ingredients conventionally used in therapeutic agents for alopecia, such as BNP, and the obtained effects are also remarkable.
- the external preparation of the present invention has an effect of improving and preventing dermatitis as described above. Therefore, the inflammation of the skin accompanying alopecia can be improved or prevented. Such an effect is particularly advantageous when alopecia is aggravated due to the skin condition of the application site such as the scalp.
- the external preparation of the present invention exhibits a moisturizing effect and an effect of adjusting the texture at the application site. It can remove dandruff and itching and suppress these occurrences, moisturize the hair and scalp, improve and prevent drying, and keep the scalp and hair healthy. Moreover, the seborrheic state can be improved
- the external preparation of the present invention has perceptible symptoms, amelioration of the state, and disappearance effect as described above. This reduces the burden on the subject (patient) and improves the patient's QOL. Furthermore, it is possible to prevent the patient from damaging the affected part, such as touching or scratching the affected part with concern about itching and pain, and as a result, it is possible to prevent the deterioration of the skin condition causing alopecia.
- alopecia therapeutic agent When the external preparation of the present invention is used as an alopecia therapeutic agent or an alopecia preventive agent, applicable alopecia is not particularly limited, and examples thereof include alopecia as described below. It can be used for the treatment or prevention of more than one species.
- Alopecia without scars or skin lesions Alopecia areata, male pattern alopecia, seborrheic alopecia, erosive alopecia, female pattern alopecia, gestational alopecia, malignant alopecia, senile Alopecia, frontal alopecia, multiple alopecia, serpentine alopecia, drug-induced alopecia, cancer chemotherapeutic alopecia and alopecia due to radiation exposure, traumatic / mechanical alopecia, nutritional disorders / metabolic disorders Alopecia associated with, alopecia associated with endocrine abnormalities, resting alopecia (postpartum alopecia, alopecia after high fever))
- Congenital alopecia Diffuse hair loss, congenital alopecia, hair loss in hereditary syndrome, localized hair loss, nevus, aplasia cutis, congenital triangular hair loss
- the external preparation of the present invention is particularly suitable for acquired alopecia, preferably for alopecia without scars or skin lesions, more preferably alopecia areata, androgenetic alopecia, fat.
- Alopecia areata, fertility alopecia, female pattern alopecia, gestational alopecia, malignant alopecia, senile alopecia, frontal alopecia, multiple alopecia, serpentine alopecia, drug alopecia, cancer
- Rhinitis therapeutic agent and / or rhinitis preventive agent The external preparation of the present invention can be a rhinitis therapeutic agent and / or a rhinitis preventive agent.
- Rhinitis is a disease caused by inflammation of the mucous membrane of the nasal cavity and / or sinuses, and causes symptoms such as pruritus as well as main symptoms such as nasal congestion, rhinorrhea, and sudden sneezing.
- rhinitis includes not only rhinitis accompanied by inflammation of the nasal mucosa in a narrow sense but also sinusitis accompanied by inflammation of the sinus mucosa.
- the external preparation of the present invention can improve or prevent various symptoms associated with rhinitis such as nasal congestion, rhinorrhea, sneezing and pruritus when applied to the nasal mucosa and / or sinus mucosa.
- these effects appear rapidly and have a long duration as compared with a rhinitis therapeutic agent containing BNP having a tail.
- Such an effect of the external preparation of the present invention on rhinitis generally develops within 8 minutes after application, preferably within 5 minutes, more preferably within 3 minutes.
- the effect with respect to rhinitis of the external preparation of the present invention as described above generally lasts for 4 hours or more, preferably 8 hours or more, more preferably 24 hours or more after the onset of the effect.
- rhinitis is not particularly limited.
- infectious rhinitis including acute rhinitis and chronic rhinitis; complex type (flower Hypersensitivity) Rhinitis, rhinorrhea, congestive rhinitis, hypersensitivity noninfectious rhinitis including edema and dry rhinitis; physical rhinitis, irritant rhinitis including chemical rhinitis and radiation rhinitis; and atrophic Rhinitis and characteristic granulomatous rhinitis; including sinusitis such as acute sinusitis, chronic sinusitis (pyremic), eosinophilic sinusitis, sinus mycosis, etc. It can be used for treatment or prevention purposes.
- rhinitis examples include allergic rhinitis including perennial allergic rhinitis and seasonal allergic rhinitis, and non-allergic rhinitis including vasomotor (essential) rhinitis and eosinophilia rhinitis. And so on.
- allergic rhinitis examples include perennial allergic rhinitis and seasonal allergic rhinitis, and non-allergic rhinitis including vasomotor (essential) rhinitis and eosinophilia rhinitis. And so on.
- rhinorrhea examples include rhinitis, cold inhalation rhinitis, and senile rhinitis.
- congestive rhinitis examples include drug-induced rhinitis, psychogenic rhinitis, gestational rhinitis, endocrine rhinitis and cold rhinitis.
- edema type rhinitis examples include aspirin hypersensitivity rhinitis.
- the external preparation of the present invention is particularly preferable for hypersensitivity non-infectious rhinitis, irritant rhinitis and sinusitis, preferably for hypersensitivity non-infectious rhinitis and chronic sinusitis.
- the external preparation of the present invention can be used for the purpose of treating or preventing at least one rhinitis selected from the above group.
- the external preparation of the present invention has the effects as described above, and therefore, it can be used for any of sneezing / nasal rhinitis, nasal rhinitis and full rhinitis. it can. Furthermore, the external preparation of the present invention exhibits an effect of improving symptoms even for rhinitis that is difficult to treat with conventionally used rhinitis therapeutic agents such as steroid drugs.
- the external preparations of the present invention can also be used for uses other than those described above for the purpose of the effect of the cyclic peptide.
- the external preparation of the present invention may mainly have effects other than the effects of the cyclic peptide.
- the cyclic peptide of the present invention, its derivative and / or pharmaceutically acceptable salt is used for the purpose of assisting the main effect of the external preparation or adding an effect other than the main effect.
- Examples of such applications include, but are not limited to, body powder, deodorant, hair removal agent, soap, body shampoo, bathing agent, hand soap, perfume, sunscreen agent, anti-inflammatory analgesic agent, antifungal agent and the like. .
- the topical preparation of the present invention is locally administered to a target site (for example, an affected area) of the skin or mucous membrane, whereby a cyclic peptide as an active ingredient, its derivative and / or pharmaceutically acceptable.
- a target site for example, an affected area
- a cyclic peptide as an active ingredient, its derivative and / or pharmaceutically acceptable.
- the effect of a simple salt can be more reliably and rapidly expressed in the vicinity of the application site.
- Such an external preparation is not particularly limited, and can be, for example, an external preparation, eye drops, ear drops, nasal drops, oral preparations, or suppositories.
- the external preparation of the present invention is a dermatitis therapeutic agent, dermatitis preventive agent, antipruritic agent, skin care product, alopecia therapeutic agent, alopecia preventive agent, hair restorer or hair growth agent, An agent is preferred.
- the external preparation of the present invention is a rhinitis therapeutic agent and / or a rhinitis preventive agent, it is preferably a nasal drop.
- an eye drop is preferable.
- the external preparation of the present invention is not particularly limited when it is an external preparation, but it can be, for example, an external solid preparation, external preparation, spray, ointment, emulsion, cream, gel, or patch.
- An external solid preparation is a solid preparation for application or application to the skin or the like.
- Examples of such external solid preparations include powdery external powders.
- the external liquid preparation is a liquid preparation for application to the skin and the like. Examples of such external liquid preparations include lotions and liniments.
- a spray is a preparation in which an active ingredient is sprayed onto the skin in the form of a mist, powder, foam, paste, or the like. Examples of such sprays include external aerosols and pump sprays.
- An ointment is a semisolid preparation that is applied to the skin and in which an active ingredient is dissolved or dispersed in a base. Further, the ointment may be a lip balm for applying to the local area such as lips.
- a cream is a semi-solid preparation emulsified in an oil-in-water or water-in-oil type that is applied to the skin.
- a gel is a gel-like preparation applied to the skin.
- the gel agent include an aqueous gel agent and an oily gel agent.
- a patch is a preparation to be applied to the skin. Examples of the patch include a tape and a poultice.
- Nasal drops are formulations that are administered to the nasal cavity or nasal mucosa. Examples of the nasal drops include nasal powders and nasal drops. Of these, nasal drops are preferred.
- the external preparation of the present invention contains at least the cyclic peptide of the present invention and / or a derivative thereof and / or a pharmaceutically acceptable salt thereof as described above.
- the external preparation of the present invention contains a cyclic peptide and / or a derivative thereof and / or a pharmaceutically acceptable salt thereof, for example. 0.0001 to 1000000 ⁇ g / g, preferably 0.001 to 10,000 ⁇ g / g, more preferably 0.01 to 1000 ⁇ g / g, and still more preferably 0.1 to 100 ⁇ g / g. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / g or 3 to 500 ⁇ g / g.
- the external preparation of the present invention contains, for example, a cyclic peptide and / or a derivative thereof and / or a pharmaceutically acceptable salt thereof in the stock solution of the spray. , 0.0001 to 1000000 ⁇ g / mL, preferably 0.001 to 10,000 ⁇ g / mL, 0.01 to 1000 ⁇ g / mL, more preferably 0.1 to 100 ⁇ g / mL, even more preferably 1 to 100 ⁇ g / mL . In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the external preparation of the present invention contains a cyclic peptide and / or a derivative thereof and / or a pharmaceutically acceptable salt thereof, for example, 0.0001 to 1000000 ⁇ g / mL, Preferably, it is contained at a concentration of 0.001 to 10,000 ⁇ g / mL, more preferably 0.01 to 1000 ⁇ g / mL, still more preferably 0.1 to 100 ⁇ g / mL, and particularly preferably 1 to 100 ⁇ g / mL. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the external preparation of the present invention is a cyclic peptide and / or a derivative thereof and / or a nasal drop liquid (nasal drop).
- These pharmaceutically acceptable salts are, for example, 0.0001 to 1000000 ⁇ g / mL, preferably 0.001 to 10,000 ⁇ g / mL, more preferably 0.01 to 1000 ⁇ g / mL, and further preferably 0.1 to 100 ⁇ g. / ML, particularly preferably at a concentration of 1 to 100 ⁇ g / mL. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the external preparation of the present invention can be formulated using methods and constituent materials known to those skilled in the art regardless of the dosage form as described above.
- examples of usable constituent materials include, but are not limited to, gelling agents, oily components, higher alcohols, fatty acids, UV absorbers, UV scattering agents, powders, pigments, surfactants, polyhydric alcohols / sugars, Polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives and the like can be mentioned.
- gelling agent various gelling agents of organic and inorganic compounds can be used.
- examples of the gelling agent for inorganic compounds include hydrated or water-absorbing silicates such as aluminum silicate (eg bentonite), magnesium silicate-aluminum, colloidal silica, and the like.
- As the gelling agent for organic compounds natural, semi-synthetic or synthetic polymers can be used.
- Natural and semi-synthetic polymers include, for example, polysaccharides such as cellulose, starch, tragacanth, gum arabic, xanthan gum, agar, gelatin, alginic acid and its salts (such as sodium alginate and its derivatives), lower alkyl cellulose (such as methylcellulose or ethylcellulose) ), Carboxy- or hydroxy-lower-alkyl cellulose (for example, carboxymethyl cellulose or hydroxypropyl cellulose) and the like.
- polysaccharides such as cellulose, starch, tragacanth, gum arabic, xanthan gum, agar, gelatin, alginic acid and its salts (such as sodium alginate and its derivatives), lower alkyl cellulose (such as methylcellulose or ethylcellulose) ), Carboxy- or hydroxy-lower-alkyl cellulose (for example, carboxymethyl cellulose or hydroxypropyl cellulose) and the like.
- Examples of the synthetic polymer include carboxyl vinyl polymer, sodium polyacrylate, (vinyl methyl ether / ethyl maleate) copolymer, polymethacrylate, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acid or polymethacrylic acid.
- commercially available gelling agents such as Lubragel NP, Lubragel CG, Lubragel DV, Lubragel MS, Lubragel OIL, Lubragel TW, Lubragel DS, etc. (Ashland) may be used as the gel agent.
- ester-based oil phase component examples include glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, Butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate
- hydrocarbon oil phase component examples include squalane, liquid paraffin, ⁇ -olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, solid paraffin, polybutene, microcrystalline wax, petrolatum and the like.
- silicone-based oil phase components include dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organo Polysiloxane, dimethylsiloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, Examples thereof include silicone gel, acrylic silicone, trimethylsiloxysilicic acid, silicone RTV rubber and the like.
- fluorinated oil phase component examples include perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, and fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane.
- Animal and vegetable oils and their hardened oils, and naturally occurring waxes include, for example, beef tallow, hardened beef tallow, pork tallow, hardened tallow, horse oil, hardened horse oil, mink oil, orange luffy oil, fish oil, hardened fish oil, egg yolk, Animal and plant oils such as jojoba oil and its hardened oils, avocado oil, almond oil, olive oil, cacao butter, apricot oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, large Bean oil, evening primrose oil, camellia oil, corn oil, rapeseed oil, hardened rapeseed oil, palm kernel oil, hardened palm kernel oil, palm oil, hardened palm oil, peanut oil, hardened peanut oil, castor oil, hardened castor oil, sunflower oil , Grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed
- higher alcohols examples include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like.
- fatty acids examples include caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid Erucic acid, 2-ethylhexanoic acid and the like.
- Examples of the ultraviolet absorber include paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, and salicylic acid.
- Octyl triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono-2-diparamethoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamic acid, diisopropyl diiso Lopylcinnamic acid ester mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and its salt, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydime
- transdermal absorption aid examples include acetic acid, sodium acetate, limonene, menthol, salicylic acid, hyaluronic acid, oleic acid, N, N-diethyl-m-toluamide (N, N-diethyl-3-methylbenzamide), stearin Examples include n-butyl acid, benzyl alcohol, isopropyl myristate, isopropyl palmitate, polypropylene glycol, crotamiton, diethyl sebacate, N-methylpyrrolidone, N-ethylpyrrolidone, lauryl alcohol, and the like.
- powders and pigments examples include red No. 104, red No. 201, yellow No. 4, blue No. 1, black No. 401, pigments such as basic dyes, HC colors, disperse dyes and direct dyes, yellow No. 4 AL lake , Yellow 203 BA lake and other lake pigments, nylon powder, silk powder, urethane powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder, etc., yellow iron oxide , Red iron oxide, black iron oxide, chromium oxide, carbon black, colored pigments such as ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide, cerium oxide, talc, mica, sericite, kaolin, plate-like barium sulfate, etc.
- pigments such as basic dyes, HC colors, disperse dyes and direct dyes
- yellow No. 4 AL lake Yellow 203 BA lake and other lake pigments
- nylon powder silk powder, urethane powder
- Extender pigments pearl pigments such as titanium mica, barium sulfate, calcium carbonate, magnesium carbonate ,
- Metal salts such as aluminum silicate, magnesium silicate, inorganic powder such as silica, alumina, metals such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate
- Examples include soap, bentonite, smectite, and boron nitride.
- shape of these powders spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.
- These powders and pigments are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine.
- Surface treatment may be performed in advance by treatment, polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment, or the like.
- any of an anionic surfactant, a cationic surfactant, an amphoteric surfactant and a nonionic surfactant can be used as appropriate.
- the anionic surfactant include fatty acid soap, ⁇ -acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkyl amide sulfate.
- alkyl phosphate POE alkyl phosphate, alkyl amide phosphate, alkyloyl alkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, sodium alkyl sulfoacetate, acyl isethionic acid
- Examples include salts, acylated hydrolyzed collagen peptide salts, and perfluoroalkyl phosphate esters.
- cationic surfactant examples include alkyl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, cetostearyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, behenyl trimethyl ammonium bromide, Benzalkonium chloride, behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, and the like.
- tertiary amines such as fatty acid amide dialkylamine, and its salt are also mentioned.
- amphoteric surfactants include carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, and amidoamine type amphoteric types.
- a system surfactant is mentioned.
- Nonionic surfactants include, for example, propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE sorbitol fatty acid esters, POE glycerin fatty acid esters, POE alkyl ethers, POE fatty acid esters.
- POE hydrogenated castor oil POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, hydroxylated soybean phospholipid, polymer System surfactants, biosurfactants and the like.
- Natural surfactants can also be used, and examples of such surfactants include lecithin, saponin, and sugar surfactants.
- polyhydric alcohol and sugar examples include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3 -Butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. These chemically modified compounds can also be used.
- polymer examples include acrylic acid ester / methacrylic acid ester copolymer, vinyl acetate / crotonic acid copolymer, vinyl acetate / crotonic acid / vinyl neodecanate copolymer, methyl vinyl ether maleic acid half ester, T- Butyl acrylate / ethyl acrylate / methacrylic acid copolymer, vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer, vinyl acetate / crotonic acid copolymer (Rubiset CA: manufactured by BASF), vinyl acetate / crotonic acid / Vinylpyrrolidone copolymer, vinylpyrrolidone / acrylate copolymer, acrylate / acrylamide copolymer, vinyl acetate / butyl maleate / isobornyl acrylate copolymer, carboxyvinyl polymer, acrylic acid / methacrylic acid An
- Naturally derived polymer compounds such as galactan, gum karaya, gum tragacanth, alginic acid, albumin, casein, curdlan, gellan gum, dextran, glucooligosaccharides, fucose-containing polys
- Physiologically active ingredients include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening, anti-inflammation, anti-aging, UV protection, slimming, squeezing, antioxidant, hair growth / hair growth, hair retention, moisturizing, blood circulation promotion, antibacterial / sterilization, cooling / warming, promotion of wound healing, stimulation relief, Ingredients having effects such as analgesia, cell activation, plant extracts, seaweed extracts, vitamins and derivatives thereof, amino acids, various peptides other than cyclic peptides, biopolymers such as sodium hyaluronate, mucopolysaccharide, ceramide, phytosphingosine, Examples include intercellular lipid components such as cholesterol and phytosterol, or similar components, enzyme components, and the like.
- suitable ingredients include, for example, Ashitaba extract, avocado extract, amateur extract,retea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, isoflavone, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract.
- Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Betaine, whey, trimethylglycine, lysine / arginine condensate and other moisturizing ingredients, sphingolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, phytosterol derivatives, phospholipids and other intracellular lipid components or similar , ⁇ -aminocaproic acid, glycyrrhizic acid, ⁇ -glycyrrhetinic acid, lysozyme chloride, guaiazulene, hydrocortisone, tea tree oil, etc., vitamin A and
- antioxidants examples include sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxyl
- plant extracts having an antioxidant effect such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoid, flavonoid, tannin, lignan, saponin, apple extract and clove extract.
- solvent examples include physiological saline, purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, and next-generation fluorocarbon.
- the present invention also includes the present invention. It also relates to the use of the inventive cyclic peptides and / or derivatives thereof and / or their pharmaceutically acceptable salts for the preparation of external preparations.
- the method for using the external preparation of the present invention includes applying the above-described external preparation of the present invention to the skin and / or mucous membrane of the subject.
- the target is not limited to humans, and examples thereof include vertebrates such as birds and mammals.
- mammals include, for example, laboratory animals such as rodents and rabbits such as mice, rats, gerbils, hamsters and guinea pigs, domestic animals such as pigs, cows, goats, horses, sheep and minks, and pets such as dogs and cats.
- Primates such as humans, monkeys, cynomolgus monkeys, rhesus monkeys, marmosets, orangutans and chimpanzees.
- humans can also be excluded from subjects.
- the skin and / or mucous membrane of the subject to which the external preparation is applied may be the skin or mucous membrane of any part of the subject, for example, the head (scalp), face, neck, arm, trunk, arm, hand. It can be applied to skin or mucous membranes such as feet.
- the more specific usage method of the external preparation of this invention is as follows.
- the target skin and / or mucosal site (for example, dermatitis has developed) It can be applied directly to the affected area).
- the frequency of application is not particularly limited, but is, for example, 1 to 10 times / day, preferably 1 to 5 times / day, and more preferably 1 to 3 times / day.
- the external preparation of this invention has the long duration of the effect, even if it is a case where it applies at a comparatively little frequency, for example, once / day, sufficient effect is exhibited.
- the dose is not particularly limited.
- the total amount of the cyclic peptide of the present invention and derivatives thereof and pharmaceutically acceptable salts thereof is 0.0001 to 1000000 ⁇ g / mL, preferably 0. 0.001 to 10,000 ⁇ g / mL, more preferably 0.01 to 1000 ⁇ g / mL, still more preferably 0.1 to 100 ⁇ g / mL, and particularly preferably 1 to 100 ⁇ g / mL. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the external preparation of the present invention When the external preparation of the present invention is used as an antipruritic agent, it can be directly applied to the intended skin and / or mucosal site.
- the frequency of application is not particularly limited, but is, for example, 1 to 10 times / day, preferably 1 to 5 times / day, and more preferably 1 to 3 times / day.
- the dose is not particularly limited.
- the total amount of the cyclic peptide of the present invention and derivatives thereof and pharmaceutically acceptable salts thereof is 0.0001 to 1000000 ⁇ g / mL, preferably 0.
- 0.001 to 10,000 ⁇ g / mL more preferably 0.01 to 1000 ⁇ g / mL, still more preferably 0.1 to 100 ⁇ g / mL, and particularly preferably 1 to 100 ⁇ g / mL. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the external preparation of the present invention When the external preparation of the present invention is used as a cosmetic, it can be directly applied to the skin and / or mucosal site for which the external preparation is intended.
- the frequency of application is not particularly limited, but is, for example, 1 to 10 times / day, preferably 1 to 5 times / day, and more preferably 1 to 3 times / day.
- the dose is not particularly limited.
- the total amount of the cyclic peptide of the present invention and derivatives thereof and pharmaceutically acceptable salts thereof is 0.0001 to 1000000 ⁇ g / mL, preferably 0.
- 0.001 to 10,000 ⁇ g / mL more preferably 0.01 to 1000 ⁇ g / mL, still more preferably 0.1 to 100 ⁇ g / mL, and particularly preferably 1 to 100 ⁇ g / mL. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the external preparation of the present invention is used as a hair loss treatment agent, alopecia prevention agent, hair growth agent or hair growth agent
- the external preparation is intended. It can be applied directly to the part to be performed (for example, the scalp, the hair loss part of the skin).
- the frequency of application is not particularly limited, but is, for example, 1 to 10 times / day, preferably 1 to 5 times / day, and more preferably 1 to 3 times / day.
- the dose is not particularly limited.
- the total amount of the cyclic peptide of the present invention and derivatives thereof and pharmaceutically acceptable salts thereof is 0.0001 to 1000000 ⁇ g / mL, preferably 0.
- 0.001 to 10,000 ⁇ g / mL more preferably 0.01 to 1000 ⁇ g / mL, still more preferably 0.1 to 100 ⁇ g / mL, and particularly preferably 1 to 100 ⁇ g / mL. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the external preparation of the present invention can be directly applied to a target site (for example, nasal mucosa).
- a target site for example, nasal mucosa.
- the frequency of application is not particularly limited, but is, for example, 1 to 10 times / day, preferably 1 to 5 times / day, and more preferably 1 to 3 times / day.
- the dose is not particularly limited.
- the total amount of the cyclic peptide of the present invention and derivatives thereof and their pharmaceutically acceptable salts is preferably 0.0001 to 1000000 ⁇ g / mL, preferably Can be 0.001 to 10,000 ⁇ g / mL, more preferably 0.01 to 1000 ⁇ g / mL, still more preferably 0.1 to 100 ⁇ g / mL, and particularly preferably 1 to 100 ⁇ g / mL. In another embodiment, it may be contained at a concentration of 1 to 800 ⁇ g / mL and 3 to 500 ⁇ g / mL.
- the medicament of the present invention includes one or more cyclic peptides of the present invention or derivatives thereof, or pharmaceutically acceptable salts thereof.
- the cyclic peptide of the present invention or a derivative thereof or a pharmaceutically acceptable salt thereof binds to the receptor NPR-A (also known as GC-A) having a guanylate cyclase domain, like BNP. It promotes the production of cyclic guanosine monophosphate (cGMP) and is considered to have actions such as diuretic action, vasodilatory action, renin-aldosterone secretion inhibition, sympathetic nerve inhibition, and hypertrophy inhibition. .
- these compounds of the present invention are considered to have excellent drug efficacy and efficacy, particularly excellent immediate effect, as compared with BNP.
- the medicament of the present invention can be used for the same purpose as a medicament conventionally containing BNP as an active ingredient.
- the disease to which the medicament of the present invention can be applied is not particularly limited.
- various diseases hypertension, unstable angina, acute myocardial infarction, edematous disease, renal failure, heart failure, immune disease , Obesity, metabolic syndrome and the like.
- the pharmaceutical dosage form of the present invention is not particularly limited.
- oral administration such as tablets, capsules, granules, powders, oral solutions, syrups, oral jellys, etc.
- a cyclic peptide consisting of the amino acid sequence represented by the formula Ia was synthesized. Specifically, using a peptide synthesizer, amino acids were sequentially linked by a peptide solid phase synthesis method to form a linear peptide consisting of 17 amino acids. Thereafter, after protecting groups in Cys1 and Cys17 were removed, iodine (I 2 ) treatment was performed to form a cysteine bond between the amino acid residues oxidatively to form a cyclic peptide. The obtained composition containing a cyclic peptide was purified by reverse phase liquid high-performance chromatography (reverse phase HPLC) and then freeze-dried to obtain a purified product of the cyclic peptide as a white powder.
- reverse phase HPLC reverse phase liquid high-performance chromatography
- a gel base preparation (B ring gel preparation) having a B ring concentration of about 1 ⁇ M (about 1.8 ⁇ g / g) was prepared by uniformly stirring and mixing with 10 g of the gel base.
- gel-based preparations having B-ring concentrations of about 0.3 ⁇ M (about 0.54 ⁇ g / g), about 0.5 ⁇ M (about 0.9 ⁇ g / g), and about 2.0 ⁇ M (about 3.6 ⁇ g / g) Manufactured.
- a “B-ring gel preparation” having a B-ring concentration of about 1 ⁇ M was used unless otherwise specified.
- 0.2 mL of BNP solution obtained by dissolving 20.5 mg of human BNP-32 (American Peptide Company) in 118 mL of physiological saline was uniformly stirred and mixed with 10 g of the gel base obtained above.
- a gel base preparation (BNP gel preparation) having a BNP-32 concentration of about 1 ⁇ M was produced.
- gel-based preparations having BNP-32 concentrations of about 0.5 ⁇ M and 2.0 ⁇ M were produced.
- a “BNP gel preparation” having a BNP concentration of about 1 ⁇ M was used unless otherwise specified.
- Nasal drops containing a cyclic peptide (B ring) consisting of the amino acid sequence represented by Formula Ia (B ring nasal drops, Examples) and nasal drops containing human BNP ( BNP nasal drops, comparative example) were prepared as follows.
- a cyclic peptide (ring B) consisting of the amino acid sequence represented by formula Ia is dissolved in physiological saline, and the concentration is adjusted to give about 1 ⁇ mol / l (about 1.8 ⁇ g / g) of B ring.
- Concentration B ring nasal solution was obtained.
- the B ring nasal solution is filled into a quantitative nasal spray container (manufactured by ASONE Co., Ltd.), and the spray amount per time is adjusted to 100 ⁇ l (0.1 ml), B ring nose was obtained.
- BNP nasal solution having a BNP concentration of 1 ⁇ mol / l was obtained, and this was filled into a quantitative nasal spray container (manufactured by ASONE), and further 1 The spray amount per time was adjusted to 100 ⁇ l (0.1 ml) to obtain a BNP nasal drop.
- B-ring gel preparation and gel base were applied to the affected area, and changes in symptoms before and after application were observed (Table below).
- the ring B of the present invention has a moisturizing effect on the skin and can adjust the texture, and is effective for improving skin quality such as whitening (stain, dullness) and anti-aging (sagging, beam, large wrinkles). At the same time, it was shown to be effective in improving mucosal conditions such as rough lips.
- the site where the B-ring gel formulation was applied showed a marked improvement in skin quality and its maintenance. Specifically, the skin is smoothed, the skin is moisturized, the skin texture is smoothed, the skin is softened and softened, the skin becomes soft, the drying of the skin is suppressed, the fine lines are inconspicuous, the moisture of the skin, The oil is supplemented and kept, the wrinkles of the eyes are shallow, not noticeable, the skin feels irritated, itching and relieving, the skin is softened, the skin is kept healthy, etc. The effect was significantly recognized at the site where the B-ring gel formulation was applied compared to the site where the BNP gel formulation was applied.
- FIG. 1 shows a photograph of the right facial face of a 60-year-old subject after applying the B-ring gel preparation.
- 20 minutes after application of the B-ring gel preparation moisturizes and moisturizes the skin, gives gloss and flexibility, tightens the skin, prepares the texture, gives a beam, and notices skin wrinkles. The effect to lose was recognized.
- this result shows that the cyclic peptide of the present invention is effective not only for fine lines but also for wrinkles and sagging, and also has an effect of making the spots and dullness inconspicuous.
- the cyclic peptide of the present invention has an action of improving the state of the mucosa and further has an immediate effect with respect to such action.
- the BNP cyclic peptide of the present invention moisturizes and maintains the scalp and hair, supplements and maintains moderate moisture and oil, improves and prevents drying, and cleans the scalp and hair.
- it is effective for suppressing itching and dandruff of the scalp, and also for hair, prevention of thinning and hair loss, hair growth, hair growth promotion, hair growth, and hair promotion. It has been shown to be effective in improving hair removal and hair restoration.
- the bathing agent containing the ring B of the present invention not only relieves the skin cracks and tingling of the skin, but also improves the effects of eczema. Furthermore, improvement of skin dryness and skin pain was observed, which was shown to be effective in improving the skin condition.
- a shampoo containing a B ring was blended and manufactured with the following composition. After A and B were dissolved by heating at 70 ° C., B was added to A and stirred and mixed. Further, C was added at 40 to 35 ° C. with stirring, and the mixture was cooled to room temperature while stirring.
- a treatment containing a B ring was formulated and manufactured with the following composition. After A and B were heated and dissolved at 80 ° C., B was gradually added to A and emulsified while A and B were kept at 80 ° C. while stirring A with a homomixer. Further C was added and cooled to 35 ° C. with stirring.
- a body soap containing a 4.5.3 B ring was blended and manufactured with the following composition. After A and B are heated and dissolved at 80 ° C., B is gradually added to A while stirring. Further, C was added at 40 to 35 ° C. with stirring, and the mixture was cooled to room temperature while stirring.
- the B-ring gel preparation was able to improve seborrhea, clean the scalp and suppress dandruff. It also prevented gray hair, grew black hair, and improved thinning hair. Furthermore, it was found that the effect of suppressing itching can be suppressed after 10 minutes, and the effect of immediate effect is high. In some cases, itching could be suppressed within 3 minutes after application.
- a template structure for examining the binding state between human BNP and the A-type receptor was selected.
- a three-dimensional structure of a complex of rat NPR-A and rat ANP peptide (PDB ID: 1T34) was used.
- Rat NPR-A is a homodimer consisting of A and B chains.
- Such a rat NPR-A has a three-dimensional structure determined by X-ray crystal structure analysis in a state where 21 residues of Cys7 to Arg27 of rat ANP are bound.
- the three-dimensional structure of rat NPR-A was obtained from Protein Data Bank, which is a protein three-dimensional structure database.
- the amino acid identity between human NPR-A and rat NPR-A is 85%.
- BNP Peptide Model As a peptide model of BNP, human BNP (BNP-32, SEQ ID NO: 13, Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Gly-Cys-Phe shown below is shown below.
- the amino acid sequence of the B ring of the present invention corresponds to Cys10 to Cys26 in the human BNP, that is, Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser -Ser-Ser-Ser-Gly-Leu-Gly-Cys (SEQ ID NO: 15) region.
- a complex model in which a BNP peptide was bound to human NPR-A was constructed by homology modeling. Specifically, a human BNP peptide model was modeled based on a rat ANP peptide having a template structure and a model structure of human NPR-A was modeled based on a rat NPR-A having a template structure by homology modeling. Next, residues directly involved in the interaction were deduced from the amino acid residues detected between the human BNP peptide model and human NPR-A.
- the amino acid sequence used in the model (SEQ ID NO: 14, Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys-Lys-Val Amino acids in amino acid sequences such as -Leu-Arg) are expressed as amino acids (numbers). That is, the number in parenthesis represents the number counted from the N-terminus of the amino acid sequence, and for example, Phe2 refers to the second amino acid that is the second Phe counted from the N-terminus of the peptide model.
- human BNP is a residue in which the amino acid residue present in the cyclic part contributes to the activation of NPR-A, while in the tail It was speculated that the amino acid residues present were residues that did not contribute. In addition, it was suggested that the BNP cyclic structure is smaller than BNP-32 and can be easily and rapidly bound. Actually, when a peptide having a BNP cyclic structure was clinically applied, it was actually confirmed that the BNP cyclic structure can provide a therapeutic effect more rapidly than BNP-32.
- the BNP cyclic structure contributes to the activation of NPR-A and can be more easily and rapidly bound by BNP-32. Therefore, the BNP cyclic structure is considered to be a different substance having a therapeutic effect superior to that of a general BNP peptide.
- BNP cyclic structure (B-ring) derived from non-human species on human type A receptor
- B-ring BNP cyclic structure
- porcine, avian, and rat-derived BNP rings was created. I guessed about the interaction.
- the effects of the present invention can be sufficiently expected as long as they have affinity for human NPR-A even if BNP rings other than human species such as pigs, birds and rats are used. It was suggested that it can be done.
- intramolecular energy was calculated by the Swiss-Pdb viewer's Compute Energy command.
- the intramolecular energy was calculated in units of kilojoule / mol (Kj / mol) based on the total of the bond length between atoms, bond angle, twist, bond energy, and the like.
- the hair loss at the application site is prevented and the effect of promoting hair growth or hair growth is given, the hair is firm and firm, the volume is increased, and hair loss is played.
- the application site has effects such as a hair nourishing effect, hair growth promoting effect, and thinning hair improvement / prevention.
- the hair that grows tends to be hard and tends to be non-white hair.
- these effects are compared with other active ingredients conventionally used in therapeutic agents for alopecia, such as BNP, for example, intractable multiple alopecia and serpentine alopecia.
- the hair growth can be confirmed on the next day only by application, and it is expressed very early, and the obtained effect is remarkably sustained, for example, the hair growth continues even after the application is stopped.
- the next day gives the hair a firmness and firmness, increases its volume, and has an immediate effect of dramatically reducing hair loss, and this effect persists even after the application is stopped. It also has the effect of improving and preventing dermatitis. Therefore, the inflammation of the skin accompanying alopecia can be improved or prevented. Such an effect is advantageous when alopecia is aggravated due to the skin condition of the application site such as the scalp.
- the external preparation of the present invention when applied to the skin as described above, it exerts a moisturizing effect and an effect of adjusting the texture at the application site. It can remove dandruff and itching and suppress these occurrences, moisturize the hair and scalp, improve and prevent drying, and keep the scalp and hair healthy. Moreover, a seborrheic state can be improved.
- applicable alopecia when used as an alopecia therapeutic agent or an alopecia preventive agent, applicable alopecia is not particularly limited, and examples thereof include alopecia as follows, and one or more of these treatments or Can be used for prevention purposes.
- Alopecia without scars or skin lesions (alopecia areata, male pattern alopecia, seborrheic alopecia, dwarf alopecia, female pattern alopecia, gestational alopecia, malignant alopecia, senile Alopecia, frontal alopecia, multiple alopecia, serpentine alopecia, drug-induced alopecia, cancer chemotherapeutic alopecia and alopecia due to radiation exposure, traumatic / mechanical alopecia, nutritional disorders / metabolic disorders Alopecia associated with, alopecia associated with endocrine abnormalities, resting alopecia (postpartum alopecia, alopecia after high fever)) (Ii) Alopecia found in skin lesions or pathological skin (hair loss due to infection, hair loss due to tumor, hair loss due to inflammation) (Iii) Scarring alopecia (hair loss due to skin infection, hair loss due to inflammatory cell infiltration)
- alopecia areata, androgenetic alopecia, seborrheic alopecia, erosion alopecia, Female pattern alopecia, gestational alopecia, malignant alopecia, senile alopecia, frontal alopecia, multiple alopecia, serpentine alopecia, drug-induced alopecia, cancer chemotherapeutic alopecia and radiation-induced alopecia It exhibits excellent effects on alopecia, traumatic / mechanical alopecia, alopecia associated with nutritional disorders and metabolic disorders, alopecia associated with endocrine abnormalities, and resting hair loss.
- the external preparation of the present invention can be used for the purpose of treating or preventing at least one alopecia selected from the above-mentioned group.
- the simple application of 3 ⁇ g / ml to 500 ⁇ g / ml to the affected area immediately after it is applied to the affected area, it can improve and eliminate dandruff, redness of the scalp, inflammation, etc.
- hair growth, hair growth, elasticity and stiffness of the hair increased, the volume increased, hair loss dramatically decreased, and the effect continued for more than a week.
- those effects are further improved. Even after the application is interrupted, the hair growth and the hair growth continue for one to two weeks, and the state where there is almost no hair loss continues. The effect was seen.
- rhinitis when applied to the nasal mucosa and / or sinus mucosa, various symptoms associated with rhinitis such as nasal congestion, rhinorrhea, sneezing and pruritus can be improved or prevented.
- the rhinitis is not particularly limited and includes, for example, acute rhinitis, infectious rhinitis including chronic rhinitis; complex (flower hypersensitivity) rhinitis, rhinorrhea rhinitis, congestive rhinitis, edema rhinitis and dry rhinitis Irritable non-infectious rhinitis; irritating rhinitis including physical rhinitis, chemical rhinitis and radiation rhinitis; and atrophic rhinitis and characteristic granulomatous rhinitis; acute sinusitis, chronic sinusitis (pyremic) Examples thereof include sinusitis such as bulbar sinusitis and sinus mycosis, and can be used for
- Examples of complex rhinitis include allergic rhinitis including perennial allergic rhinitis and seasonal allergic rhinitis, and non-allergic rhinitis including vasomotor (essential) rhinitis and eosinophilia. And so on.
- Examples of rhinorrhea include rhinitis, cold inhalation rhinitis, and senile rhinitis.
- Examples of congestive rhinitis include drug-induced rhinitis, psychogenic rhinitis, gestational rhinitis, endocrine rhinitis and cold rhinitis.
- Examples of edema type rhinitis include aspirin hypersensitivity rhinitis.
- the external preparation of the present invention can be used for the purpose of treating or preventing at least one rhinitis selected from the above group.
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Abstract
Description
したがって、本発明の目的は、薬効、効能の強い新規ペプチド、これを含む医薬や外用剤、特に皮膚炎、鼻炎、脱毛症に対する予防または治療剤や発毛剤、育毛剤、鎮痒剤、化粧料、スキンケア用品などを提供することにある。
すなわち、本発明は以下に関する。
式I:
X1は、Gly、Val、Ala、SerまたはThrを示し、
X2は、Arg、GlnまたはHisを示し、
X3は、LysまたはArgを示し、
X4は、Met、LeuまたはIleを示し、
X5は、IleまたはValを示し、
X6は、SerまたはGlyを示し、
X7は、SerまたはAlaを示し、
X8は、Ser、Gln、Val、Ala、Thr、Leu、IleまたはMetを示し、
X9は、Ser、Val、AlaまたはThrを示し、
X10は、GlyまたはArgを示し、
X11は、Leu、Met、Ile、ValまたはAlaを示し、
X12は、Gly、SerまたはAlaを示し、
2つのCysを結ぶ線は、ジスルフィド結合を表す、
で表されるアミノ酸配列を有し、
当該アミノ酸配列が、当該アミノ酸配列を構成するアミノ酸同士以外のペプチド結合を有さない、
環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。
X2が、Argを示し、
X4が、Metを示し、
X6が、Serを示し、
X7が、Serを示し、かつ、
X10が、Glyを示す、[1]に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。
[3]
前記アミノ酸配列が、式(I-a)~式(I-e)
で表されるアミノ酸配列から選択される、[1]に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。
誘導体が環状ペプチド中の水素原子、水酸基、カルボキシ基、アミノ基、イミノ基に対して置換可能な置換基で置換されたものである、[1]~[3]のいずれか一項に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。
[5]
[3]に記載の式(I-a)~(I-e)のいずれかで表される環状ペプチド中のアミノ酸の1以上4以下を欠失させるか、他のアミノ酸で置換または付加することにより形成され、かつ前記各式で表される環状ペプチドと同等の機能を有する環状ペプチドもしくはその誘導体またはその薬学的に許容可能な塩。
[6]
[1]~[5]のいずれか一項に記載の環状ペプチドおよび/もしくはその誘導体ならびに/またはこれらの薬学的に許容可能な塩を1種以上含む、外用剤。
[7]
皮膚炎治療剤、皮膚炎予防剤、鎮痒剤、消炎剤、表皮再生促進剤、傷上皮化促進剤またはスキンケア用品の材料である、[6]に記載の外用剤。
スキンケア用品が、保湿用および/または肌荒れ防止・改善用および/または皮脂ケア・ニキビケア用および/または刺激緩和・抗炎症用および/または美白用および/または老化防止用および/または紫外線傷害予防・緩和用および/またはスリミング用および/または皮膚清浄用である、[7]に記載の外用剤。
[9]
入浴剤、身体洗浄剤または頭髪用洗浄剤である、[6]に記載の外用剤。
[10]
脱毛症治療剤、脱毛症予防剤、育毛剤および/または発毛剤である、[6]に記載の外用剤。
[11]
鼻炎治療剤および/または鼻炎予防剤である、[6]に記載の外用剤。
化粧料である、[6]に記載の外用剤。
[13]
剤形が、固形剤、半固形剤、粉末剤、液剤、スプレー剤、軟膏剤、クリーム剤、乳液剤、ゲル剤または貼付剤である、[6]~[12]のいずれか一項に記載の外用剤。
[14]
医薬品、医薬部外品または化粧品として用いられる、[6]~[13]のいずれか一項に記載の外用剤。
[15]
[1]~[4]のいずれか一項に記載の環状ペプチドおよび/もしくはその誘導体ならびに/またはこれらの薬学的に許容可能な塩の外用剤の製造のための使用。
[6]~[14]のいずれか一項に記載の外用剤を、対象の皮膚および/または粘膜に適用することを含む、外用剤の使用方法。
[17]
粘膜が口唇、口腔、鼻腔、眼または膣である、[16]に記載の外用剤の使用方法。
[18]
皮膚炎の治療および/もしくは予防方法、痒みの軽減もしくは消失方法、湿疹等によるびらん、潰瘍の治療方法またはスキンケア方法である、[16]に記載の外用剤の使用方法。
脱毛症の治療および/もしくは予防方法ならびに/または発毛方法ならびに/または育毛方法である、[16]に記載の外用剤の使用方法。
[20]
鼻炎の治療および/または予防方法である、[16]に記載の外用剤の使用方法。
[21]
[1]~[5]のいずれか一項に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩を1種以上含む、医薬。
[22]
高血圧症、不安定狭心症、急性心筋梗塞、浮腫性疾患、腎不全、心不全、免疫疾患、肥満、メタボリックシンドロームの治療薬である、[21]に記載の医薬。
ここでいう環状ペプチド(以下、「BNP環状ペプチド」、「B環」または「B環化合物」ということがある)は、前記のとおり野生型BNPから誘導されるものであるが、野生型BNPとしては、ヒト由来のそればかりでなく、サル、ブタ、トリ、ラット由来のものが包含される。したがって、B環化合物としても、ヒト由来のそればかりでなく、サル、ブタ、トリ、ラット由来のものが包含される。
また、本発明の外用剤は、皮膚炎に罹患した対象の皮膚または粘膜上に適用した場合において、皮膚炎によって生じるまたは生じ得る什痒感、痛み(疼痛)、熱感、突っ張り感、浸潤、紅斑等の知覚可能な各種症状、状態を迅速に軽快もしくは消失させつつ、皮膚炎の症状を改善することができる。
まず、本発明の環状ペプチド、その誘導体およびこれらの薬学的に許容可能な塩について説明する。
本発明の環状ペプチドは、式I:
X1は、Gly、Val、Ala、SerまたはThrを示し、
X2は、Arg、GlnまたはHisを示し、
X3は、LysまたはArgを示し、
X4は、Met、LeuまたはIleを示し、
X5は、IleまたはValを示し、
X6は、SerまたはGlyを示し、
X7は、SerまたはAlaを示し、
X8は、Ser、Gln、Val、Ala、Thr、Leu、IleまたはMetを示し、
X9は、Ser、Val、AlaまたはThrを示し、
X10は、GlyまたはArgを示し、
X11は、Leu、Met、Ile、ValまたはAlaを示し、
X12は、Gly、SerまたはAlaを示し、
2つのCysを結ぶ線は、ジスルフィド結合を表す、
で表されるアミノ酸配列を有し、
当該アミノ酸配列が、当該アミノ酸配列を構成するアミノ酸同士以外のペプチド結合を有さない、環状ペプチドである。
このような環状ペプチドは、従来知られているBNPと同様に、グアニル酸シクラーゼドメインを有する受容体NPR-A(別名GC-A)と結合して環状グアノシン一リン酸(Cyclic guanosine monophosphate、cGMP)の産生を促進し、例えば、利尿作用、血管拡張作用、レニン・アルドステロン分泌抑制、交感神経抑制、肥大の抑制などの作用を有するものと考えられるが、BNPと比較して、優れた薬効、効能、特に優れた即効性を有する。
(1)X1が、Gly、Val、Ala、SerまたはThrを示す、
(2)X2が、Arg、GlnまたはHisを示す、
(3)X3が、LysまたはArgを示す、
(4)X4が、Met、LeuまたはIleを示す、
(5)X5が、IleまたはValを示す、
(6)X6が、SerまたはGlyを示す、
(7)X7が、SerまたはAlaを示す、
(8)X8が、Ser、Gln、Val、Ala、Thr、Leu、IleまたはMetを示す、
(9)X9が、Ser、Val、AlaまたはThrを示す、
(10)X10が、GlyまたはArgを示す、
(11)X11が、Leu、Met、Ile、ValまたはAlaを示す、および
(12)X12が、Gly、SerまたはAlaを示す、
からなる群か選択される1または2以上であってもよい。
また、本発明の環状ペプチドは、上記式(I)において、X2がArgを示し、X4がMetを示し、X6がSerを示し、X7がSerを示し、および/またはX10がGlyを示す環状ペプチド(配列番号2)が好ましい。
式中、2つのCysを結ぶ線は、ジスルフィド結合を表す、
で表されるアミノ酸配列から選択される、ことが好ましい。
回収されたタンパク質におけるジスルフィド結合の形成、誘導体化、塩の形成は、上述したように行うことができる。
また、得られた化合物のBNP活性の有無については、公知の手段によって容易に確認することが可能であり、例えばNPR-A受容体発現細胞におけるcGMP産生活性を試験することにより確認することができる。
次に、本発明の外用剤について説明する。
本発明の外用剤は、1種以上の上述したような環状ペプチドおよび/もしくはその誘導体ならびに/またはこれらの薬学的に許容可能な塩を含む。なお、2種以上の環状ペプチドを用いる場合、混合する環状ペプチドの種類に特に上限はないが、調製コストや簡便性の点から、2~3種程度が好ましい。例えば、配列番号19、29、33、36、39および43等が挙げられるが、本発明の効果を害するものでなければ、これらに限定されず、適用対象等に合わせて、適宜これらの環状ペプチドを組み合わせることができる。
本発明の外用剤は、特に限定されないが、例えば、以下のような用途に用いることができ、それぞれの場合において、従来にない顕著な効果を発揮する。なお、本発明の外用剤は、いずれの用途においても、特に限定されず、その薬効、効能に応じて、医薬品、医薬部外品および/または化粧品として使用することができる。
(1)皮膚炎治療剤、皮膚炎予防剤
本発明の外用剤は、皮膚炎治療剤および/または皮膚炎予防剤であることができる。
本発明の外用剤は、化粧料またはスキンケア用品の材料であることができる。
本発明の外用剤は、皮膚および/または粘膜に適用した場合に、適用部位において潤を与え、保湿効果を発揮して乾燥を防ぐとともに、肌荒れを防ぐ。適用部位に角質層が存在する場合には適用部位の肌理を整える効果を発揮する。また、皮膚および粘膜に適度な弾力性と柔軟性が付与・保持され、肌が柔らかくなり、皮膚、粘膜にハリが生じ、ひきしまる。また、適用部位において小じわ、大じわを含むしわやたるみが改善され、さらにくすみ、しみが目立たないものとなる。また、くすみ、しみが目立たなくなることから、結果的に美白効果が得られる。
なお、本明細書中において、肌荒れは、あせも、しもやけ、ひび、あかぎれ、にきび、おしめ(おむつ)かぶれ、ただれ、股ずれおよび剃刀まけを含む。
また、本発明の外用剤の上記効果は、比較的長く持続するものであり、その効果の種類によって異なるが、一般に効果発現後4時間以上、好ましくは、8時間以上、より好ましくは24時間以上持続する。
本発明の外用剤は、鎮痒剤であることができる。
上述したように、本発明の外用剤は、皮膚または粘膜上に適用した際に、適用部位において優れた鎮痒効果を迅速に発揮するため、鎮痒剤として適している。
また、上述したような本発明の外用剤の鎮痒効果は、一般に適用後10分以内、好ましくは、5分以内、より好ましくは3分以内に発現する。
また、本発明の外用剤は、脱毛症治療剤、脱毛症予防剤、育毛剤および/または発毛剤であることができる。
本発明の外用剤は、脱毛部位または発毛部位等の部位に適用した場合において、適用部位における脱毛を防止するとともに、発毛または育毛を促進させる効果を有する。また適用部位においては、養毛効果、毛生促進効果、薄毛改善・予防などの効果がある。この場合において、発毛する毛髪は硬毛となりやすく、白髪ではない髪となりやすい傾向にある。また、これらの効果は、従来脱毛症治療剤において用いられた他の活性成分、例えばBNPと比較して比較的早期に発現し、得られる効果も顕著である。
(i) 瘢痕または皮膚病変を伴わない脱毛症(円形脱毛症、男性型脱毛症、脂漏性脱毛症、粃糠性脱毛症、女性型脱毛症、妊娠性脱毛症、悪性脱毛症、老人性脱毛症、前頭脱毛症、多発性脱毛症、蛇行性脱毛症、薬物による脱毛症、癌化学療法剤性脱毛症及び放射線被爆による脱毛症、外傷性・機械的脱毛症、栄養障害・代謝障害に伴う脱毛症、内分泌異常に伴う脱毛症、休止期脱毛(分娩後脱毛症、高熱後脱毛症))
(iii)瘢痕性脱毛症(皮膚感染症による脱毛、炎症性細胞浸潤による脱毛)
瀰漫性脱毛、先天性無毛症、遺伝性の症候群における脱毛、限局性脱毛、母斑性、aplasia cutis、先天性三角形脱毛
また、本発明の外用剤は、鼻炎治療剤および/または鼻炎予防剤であることができる。
鼻炎は、鼻腔および/または副鼻腔の粘膜の炎症に起因する疾患であり、鼻閉、鼻漏、突発反復性のくしゃみといった主症状の他、掻痒感等の症状を引き起こす。なお、本発明において、「鼻炎」は、狭義の意味での鼻腔粘膜の炎症を伴う鼻炎のみならず、副鼻腔粘膜の炎症を伴う副鼻腔炎も含むものとする。
また、上述したような本発明の外用剤の鼻炎に対する効果は、一般に効果発現後4時間以上、好ましくは、8時間以上、より好ましくは24時間以上持続する。
鼻漏型鼻炎としては、例えば、味覚性鼻炎、冷気吸入性鼻炎および老人性鼻炎が挙げられる。
浮腫型鼻炎としては、例えば、アスピリン過敏性鼻炎が挙げられる。
さらに、本発明の外用剤は、ステロイド薬といった従来用いられてきた鼻炎治療剤によって治療困難な鼻炎に対しても症状の改善効果を示す。
また、本発明の外用剤は、上記環状ペプチドの効果を目的として、上述した以外の用途にも用いることができる。この場合において、本発明の外用剤は、上記環状ペプチドの効果以外の効果を主目的としてもよい。この場合、本発明の環状ペプチド、その誘導体および/または薬学的に許容可能な塩は、外用剤の主たる効果を補助するまたは主たる効果以外の効果を追加する目的で用いられる。
本発明の外用剤は、皮膚または粘膜の目的とする部位(例えば患部)に局所的に投与されることにより、有効成分たる環状ペプチド、その誘導体および/または薬学的に許容可能な塩の効果を適用部位付近においてより確実かつ迅速に発現させることができる。
このような外用剤は、特に限定されないが、例えば、外皮用剤、点眼剤、点耳剤、点鼻剤、口腔剤、または坐剤であることができる。これらのうち、本発明の外用剤が、皮膚炎治療剤、皮膚炎予防剤、鎮痒剤、スキンケア用品、脱毛症治療剤、脱毛症予防剤、育毛剤または発毛剤である場合には、外皮用剤であることが好ましい。一方で、本発明の外用剤が鼻炎治療剤および/または鼻炎予防剤である場合、点鼻剤であることが好ましい。さらに角膜疾患治療および/予防剤である場合、点眼剤であることが好ましい。
外用液剤は、皮膚等に対し塗布するための液状の製剤である。このような外用液剤としては、例えばローション剤およびリニメント剤が挙げられる。
軟膏剤は、皮膚に塗布する、有効成分を基剤に溶解または分散させた半固形の製剤である。また、軟膏剤は、唇等の局所に塗布するためのリップクリームであってもよい。
クリーム剤は、皮膚に塗布する、水中油型または油中水型に乳化した半固形の製剤である。
貼付剤は、皮膚に貼付する製剤である。貼付剤としては、例えばテープ剤およびパップ剤が挙げられる。
点鼻剤は、鼻腔または鼻粘膜に投与する製剤である。点鼻剤としては、例えば、点鼻粉末剤および点鼻液剤が挙げられる。このうち、点鼻液剤が好ましい。
また、剤形が、スプレー剤である場合には、本発明の外用剤は、スプレー剤の原液中に、環状ペプチドおよび/もしくはその誘導体ならびに/またはこれらの薬学的に許容可能な塩を、例えば、0.0001~1000000μg/mL、好ましくは0.001~10000μg/mL、0.01~1000μg/mL、より好ましくは0.1~100μg/mL、さらに好ましくは1~100μg/mLの濃度で含む。また、別の態様において、1~800μg/mL、3~500μg/mLの濃度で含んでもよい。
また、剤形が点鼻剤、特に液体点鼻剤である場合には、本発明の外用剤は、点鼻剤の液体(点鼻液)中において、環状ペプチドおよび/もしくはその誘導体ならびに/またはこれらの薬学的に許容可能な塩を、例えば、0.0001~1000000μg/mL、好ましくは0.001~10000μg/mL、より好ましくは0.01~1000μg/mL、さらに好ましくは0.1~100μg/mL、特に好ましくは1~100μg/mLの濃度で含む。また、別の態様において、1~800μg/mL、3~500μg/mLの濃度で含んでもよい。
利用可能な構成材料としては、特に限定されないが、例えば、ゲル化剤、油性成分、高級アルコール、脂肪酸、紫外線吸収剤、紫外線散乱剤、粉体、顔料、界面活性剤、多価アルコール・糖、高分子、生理活性成分、溶媒、酸化防止剤、香料、防腐剤等が挙げられる。
無機化合物のゲル化剤としては、例えば、含水性又は吸水性のケイ酸塩、例えばケイ酸アルミニウム(例えばベントナイト)、ケイ酸マグネシウム-アルミニウム、コロイドシリカ等が挙げられる。
有機化合物のゲル化剤としては、天然、半合成又は合成のポリマーの使用が可能である。天然および半合成ポリマーとしては、例えば、セルロース等の多糖類、デンプン、トラガカント、アラビアゴム、キサンタンガム、寒天、ゼラチン、アルギン酸及びその塩(例えばアルギン酸ナトリウム及びその誘導体)、低級アルキルセルロース(例えばメチルセルロース又はエチルセルロース)、カルボキシ-又はヒドロキシ-低級-アルキルセルロース(例えばカルボキシメチルセルロース又はヒドロキシプロピルセルロース)等が挙げられる。合成ポリマーとしては、例えば、カルボキシルビニルポリマー、ポリアクリル酸ナトリウム、(ビニルメチルエーテル/マレイン酸エチル)コポリマー、ポリメタクリレート、ポリビニルアルコール、ポリビニルピロリドン、ポリアクリル酸又はポリメタクリル酸等が挙げられる。なお、ゲル剤として、例えば、ルブラジェルNP、ルブラジェルCG、ルブラジェルDV、ルブラジェルMS、ルブラジェルOIL、ルブラジェルTW、ルブラジェルDS等(アシュランド社)等の市販のゲル化剤を用いることもできる。
エステル系の油相成分としては、例えば、トリ2-エチルヘキサン酸グリセリル、2-エチルヘキサン酸セチル、ミリスチン酸イソプロピル、ミリスチン酸ブチル、パルミチン酸イソプロピル、ステアリン酸エチル、パルミチン酸オクチル、イソステアリン酸イソセチル、ステアリン酸ブチル、ミリスチン酸ブチル、リノール酸エチル、リノール酸イソプロピル、オレイン酸エチル、ミリスチン酸イソセチル、ミリスチン酸イソステアリル、パルミチン酸イソステアリル、ミリスチン酸オクチルドデシル、イソステアリン酸イソセチル、セバシン酸ジエチル、アジピン酸ジイソプロピル、ネオペンタン酸イソアラキル、トリ(カプリル・カプリン酸)グリセリル、トリ2-エチルヘキサン酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、テトラ2-エチルヘキサン酸ペンタエリスリトール、カプリル酸セチル、ラウリン酸デシル、ラウリン酸ヘキシル、ミリスチン酸デシル、ミリスチン酸ミリスチル、ミリスチン酸セチル、ステアリン酸ステアリル、オレイン酸デシル、リシノレイン酸セチル、ラウリン酸イソステアリル、ミリスチン酸イソトリデシル、ミリスチン酸イソセチル、ミリスチン酸イソステアリル、パルミチン酸イソセチル、パルミチン酸イソステアリル、ステアリン酸オクチル、ステアリン酸イソセチル、オレイン酸イソデシル、オレイン酸オクチルドデシル、リノール酸オクチルドデシル、イソステアリン酸イソプロピル、2-エチルヘキサン酸セトステアリル、2-エチルヘキサン酸ステアリル、イソステアリン酸ヘキシル、ジオクタン酸エチレングリコール、ジオレイン酸エチレングリコール、ジカプリン酸プロピレングリコール、ジ(カプリル・カプリン酸)プロピレングリコール、ジカプリル酸プロピレングリコール、ジカプリン酸ネオペンチルグリコール、ジオクタン酸ネオペンチルグリコール、トリカプリル酸グリセリル、トリウンデシル酸グリセリル、トリイソパルミチン酸グリセリル、トリイソステアリン酸グリセリル、ネオペンタン酸オクチルドデシル、オクタン酸イソステアリル、イソノナン酸オクチル、ネオデカン酸ヘキシルデシル、ネオデカン酸オクチルドデシル、イソステアリン酸イソセチル、イソステアリン酸イソステアリル、イソステアリン酸オクチルデシル、ポリグリセリンオレイン酸エステル、ポリグリセリンイソステアリン酸エステル、炭酸ジプロピル、炭酸ジアルキル(C12-18)、クエン酸トリイソセチル、クエン酸トリイソアラキル、クエン酸トリイソオクチル、乳酸ラウリル、乳酸ミリスチル、乳酸セチル、乳酸オクチルデシル、クエン酸トリエチル、クエン酸アセチルトリエチル、クエン酸アセチルトリブチル、クエン酸トリオクチル、リンゴ酸ジイソステアリル、ヒドロキシステアリン酸2-エチルヘキシル、コハク酸ジ2-エチルヘキシル、アジピン酸ジイソブチル、セバシン酸ジイソプロピル、セバシン酸ジオクチル、ステアリン酸コレステリル、イソステアリン酸コレステリル、ヒドロキシステアリン酸コレステリル、オレイン酸コレステリル、オレイン酸ジヒドロコレステリル、イソステアリン酸フィトステリル、オレイン酸フィトステリル、12-ステアロイルヒドロキシステアリン酸イソセチル、12-ステアロイルヒドロキシステアリン酸ステアリル、12-ステアロイルヒドロキシステアリン酸イソステアリル等が挙げられる。
フッ素系の油相成分としては、例えば、パーフルオロポリエーテル、フッ素変性オルガノポリシロキサン、フッ化ピッチ、フルオロカーボン、フルオロアルコール、フルオロアルキル・ポリオキシアルキレン共変性オルガノポリシロキサン等が挙げられる。
アニオン性界面活性剤としては、例えば、脂肪酸セッケン、α-アシルスルホン酸塩、アルキルスルホン酸塩、アルキルアリルスルホン酸塩、アルキルナフタレンスルホン酸塩、アルキル硫酸塩、POEアルキルエーテル硫酸塩、アルキルアミド硫酸塩、アルキルリン酸塩、POEアルキルリン酸塩、アルキルアミドリン酸塩、アルキロイルアルキルタウリン塩、N-アシルアミノ酸塩、POEアルキルエーテルカルボン酸塩、アルキルスルホコハク酸塩、アルキルスルホ酢酸ナトリウム、アシルイセチオン酸塩、アシル化加水分解コラーゲンペプチド塩、パーフルオロアルキルリン酸エステル等が挙げられる。
ノニオン性界面活性剤としては、例えば、プロピレングリコール脂肪酸エステル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、POEソルビタン脂肪酸エステル、POEソルビット脂肪酸エステル、POEグリセリン脂肪酸エステル、POEアルキルエーテル、POE脂肪酸エステル、POE硬化ヒマシ油、POEヒマシ油、POE・POP共重合体、POE・POPアルキルエーテル、ポリエーテル変性シリコーンラウリン酸アルカノールアミド、アルキルアミンオキシド、水素添加大豆リン脂質、水酸化大豆リン脂質、高分子系界面活性剤、バイオサーファクタント等が挙げられる。
なお、天然系界面活性剤も用いることができ、このような界面活性剤としては、例えば、レシチン、サポニン、糖系界面活性剤等が挙げられる。
次に、本発明の外用剤の使用方法について説明する。
本発明の外用剤の使用方法は、上述した本発明の外用剤を、対象の皮膚および/または粘膜に適用することを含む。
本発明の外用剤のより具体的な使用方法は、以下のとおりである。
本発明の外用剤を、皮膚炎治療剤または皮膚炎予防剤として用いる場合、当該外用剤を目的とする皮膚および/または粘膜部位(例えば皮膚炎が発症した患部)に対し直接適用することができる。
適用頻度としては、特に限定されないが、例えば、1~10回/日、好ましくは1~5回/日、さらに好ましくは1~3回/日である。なお、本発明の外用剤は、その効果の持続時間が長いため、比較的少ない頻度、例えば、1回/日で適用した場合であっても、十分な効果を発揮する。
また、用量としては特に限定されないが、例えば、適用1回につき、本発明の環状ペプチドおよびその誘導体ならびにこれらの薬学的に許容可能な塩の合計量を0.0001~1000000μg/mL、好ましくは0.001~10000μg/mL、より好ましくは0.01~1000μg/mL、さらに好ましくは0.1~100μg/mL、特に好ましくは1~100μg/mLとすることができる。また、別の態様において、1~800μg/mL、3~500μg/mLの濃度で含んでもよい。
本発明の外用剤を、鎮痒剤として用いる場合、当該外用剤を目的とする皮膚および/または粘膜部位に対し直接適用することができる。
適用頻度としては、特に限定されないが、例えば、1~10回/日、好ましくは1~5回/日、さらに好ましくは1~3回/日である。
また、用量としては特に限定されないが、例えば、適用1回につき、本発明の環状ペプチドおよびその誘導体ならびにこれらの薬学的に許容可能な塩の合計量を0.0001~1000000μg/mL、好ましくは0.001~10000μg/mL、より好ましくは0.01~1000μg/mL、さらに好ましくは0.1~100μg/mL、特に好ましくは1~100μg/mLとすることができる。また、別の態様において、1~800μg/mL、3~500μg/mLの濃度で含んでもよい。
本発明の外用剤を、化粧料として用いる場合、当該外用剤を目的とする皮膚および/または粘膜部位に対し直接適用することができる。
適用頻度としては、特に限定されないが、例えば、1~10回/日、好ましくは1~5回/日、さらに好ましくは1~3回/日である。
また、用量としては特に限定されないが、例えば、適用1回につき、本発明の環状ペプチドおよびその誘導体ならびにこれらの薬学的に許容可能な塩の合計量を0.0001~1000000μg/mL、好ましくは0.001~10000μg/mL、より好ましくは0.01~1000μg/mL、さらに好ましくは0.1~100μg/mL、特に好ましくは1~100μg/mLとすることができる。また、別の態様において、1~800μg/mL、3~500μg/mLの濃度で含んでもよい。
本発明の外用剤を、脱毛症治療剤、脱毛症予防剤、発毛剤または育毛剤として用いる場合、当該外用剤を目的とする部位(例えば、頭皮、皮膚の脱毛部位)に対し直接適用することができる。
適用頻度としては、特に限定されないが、例えば、1~10回/日、好ましくは1~5回/日、さらに好ましくは1~3回/日である。
また、用量としては特に限定されないが、例えば、適用1回につき、本発明の環状ペプチドおよびその誘導体ならびにこれらの薬学的に許容可能な塩の合計量を0.0001~1000000μg/mL、好ましくは0.001~10000μg/mL、より好ましくは0.01~1000μg/mL、さらに好ましくは0.1~100μg/mL、特に好ましくは1~100μg/mLとすることができる。また、別の態様において、1~800μg/mL、3~500μg/mLの濃度で含んでもよい。
本発明の外用剤を、鼻炎治療剤または鼻炎予防剤として用いる場合、当該外用剤を目的とする部位(例えば、鼻腔粘膜)に対し直接適用することができる。
適用頻度としては、特に限定されないが、例えば、1~10回/日、好ましくは1~5回/日、さらに好ましくは1~3回/日である。
また、用量としては特に限定されないが、例えば、適用1回各鼻腔につき、本発明の環状ペプチドおよびその誘導体ならびにこれらの薬学的に許容可能な塩の合計量を0.0001~1000000μg/mL、好ましくは0.001~10000μg/mL、より好ましくは0.01~1000μg/mL、さらに好ましくは0.1~100μg/mL、特に好ましくは1~100μg/mLとすることができる。また、別の態様において、1~800μg/mL、3~500μg/mLの濃度で含んでもよい。
次に、本発明の医薬について説明する。
本発明の医薬は、1種以上の本発明の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩を含む。
本発明の医薬が適用可能な疾患としては、特に限定されないが、例えば、上述した各種疾患の他、高血圧症、不安定狭心症、急性心筋梗塞、浮腫性疾患、腎不全、心不全、免疫疾患、肥満、メタボリックシンドローム等が挙げられる。
まず、式I-aで表されるアミノ酸配列からなる環状ペプチドを合成した。
具体的には、ペプチド合成機を用いて、ペプチド固相合成法により、アミノ酸を順次結合して17個のアミノ酸からなる直鎖状のペプチドを形成した。その後、Cys1、Cys17にある保護基を脱離させた後にヨウ素(I2)処理を行って、酸化的に同アミノ酸残基間のシステイン結合を形成し、環状ペプチドを形成した。
得られ環状ペプチドを含む組成物について、逆相液体高速クロマトグラフィー(逆相HPLC)による精製を行い、その後凍結乾燥を行って、白色粉末としての環状ペプチドの精製物を得た。
HPLCの条件を以下に示す。
装置:Agilent 1100
流速:1.0ml/min
溶離液A:0.1%トリフルオロ酢酸/水
溶離液B:0.1%トリフルオロ酢酸/アセトニトリル
勾配:80%溶離液B アイソクラティック
質量分析(MS)の条件を以下に示す。
装置:Thermo Finnigan LCQ Advantage
イオン化法:エレクトロスプレーイオン化
分析法:イオントラップ法
カラム:Discovery C18、4.6mm×250mm、粒径5ミクロン
カラム温度:室温
溶離液A:0.1%トリフルオロ酢酸/水
溶離液B:0.1%トリフルオロ酢酸/アセトニトリル
勾配:10~30%溶離液B/20分
流量:1.2ml/分
温度:室温
注入量:20μl
検出器:UV検出器(検出波長215nm)
測定の結果、得られたタンパク質の純度は、99.2%であることが確認された。
2.1 ゲル製剤の製造
式I-aで表されるアミノ酸配列からなる環状ペプチド(以下の実施例において「B環」という場合、かかる式I-aで表される環状ペプチドを意味する)を含むゲルベース製剤(B環ゲル製剤、実施例)およびヒトBNPを含むゲルベース製剤(BNPゲル製剤、比較例)を以下のようにして製造した。
パラオキシ安息香酸メチルエステル(商品名:メッキンスM、上野製薬製)0.1g、フェノキシエタノール0.2g、1,2-ペンタンジオール3.0gを同一容器中に秤量し、60~70℃に加熱して均一な溶液とし、混合釜に投入した。
次に、混合釜に、濃グリセリン6.0gを投入し、その後、カルボキシビニルポリマー(商品名:カーボポール940、ルーブリゾール・アドバンスト・マテリアルズ社製)0.44gとキサンタンガム(商品名:ケルトロールT、CP KELCO社製)0.08gの混合物を加えてパドルで撹拌し、これらを十分に分散させた。
次に、ヒトBNP-32:20.5mg(American Peptide Company社)を、118mLの生理食塩水に溶解して得られたBNP溶液0.2mLを上記で得られたゲルベース10gに均一に撹拌混合してBNP-32の濃度が約1μMのゲルベース製剤(BNPゲル製剤)を製造した。同様にして、BNP-32の濃度が約0.5μM、2.0μMのゲルベース製剤を製造した。なお、以下の実施例において、特に記載しない限り、「BNPゲル製剤」は、約1μMのBNP濃度のものを使用した。
次に、B環点鼻液を、定量式の点鼻用噴霧容器(アズワン株式会社製)に充填し、さらに1回あたりの噴霧量を100μl(0.1ml)となるように調節して、B環点鼻剤を得た。
3.1 B環ゲル製剤の効果確認
種々の皮膚炎に罹患した被験者について、前記のB環ゲル製剤を患部に塗布し、塗布前後の症状の変化を観察した。なお、可能な場合、比較例として同一の被験者に対し、B環ゲル製剤を塗布していない患部に前記のBNPゲル製剤を塗布し、塗布前後の症状の変化を観察した。なお、掻痒感については、患部毎にVAS(Visual analogue scale)を用いて10段階で評価した。
試験結果を、被験者の年齢、性別、症状および被験者に対する処方とともに表1~7に示す。
特に、B環ゲル製剤を適用した場合には、適用直後から掻痒感の軽快、消失が観察された。皮膚炎においては、一般に、患者は掻痒感を覚えると、掻痒感を覚えた部位を掻きむしる傾向にあり、これが皮膚炎の重症化の一因となり得る。しかしながら、このように掻痒感が顕著に軽快、消失することにより、結果的に皮膚炎の重症化を防止することが可能となる。
また、B環ゲル製剤の効果は、いずれの症例においても、BNPゲル製剤を適用した場合の効果と比較して優れていた。特に、B環ゲル製剤は、BNPゲル製剤と比較して、即効性と持続性に優れ、より強力な鎮痒効果を有していた。なお、これらの効果はゲルベースでは得られない事が確認された。
B環を含む化粧料による効果は、B環を含んだゲル剤、入浴剤および頭髪化粧品(シャンプー、リンス)またはボディーソープとして使用した結果を評価し、その効果を確認した。
4.1.1 肌質改善効果の確認(B環ゲル製剤とBNPゲル製剤との比較)
被験者に対し、上記のB環ゲル製剤、BNPゲル製剤を処方した。そして、各被験者の頬や目元に、B環ゲル製剤を右側に、BNPゲル製剤を左側に塗布して、肌状態の変化を観察し比較した(下表)。なお、肌状態の変化は、被験者の体感的な評価と、医師としての本発明者による客観的な観察とに基づいて判定した。
さらに、特に40歳代~50歳代の被験者では、B環ゲル製剤塗布後迅速に、たるみ、大シワ、乾燥が改善され、肌が引きしまり、くすみ、シミが目立たなくなるなどという効果が顕著に見られ、その効果はBNPゲル剤塗布した際の効果より大きかった。
B環ゲル製剤とBNPゲル製剤の効果におけるゲルベースの寄与の有無を検討するために、3名の被験者の右顔面にB環ゲル製剤を、左顔面にゲルベースを塗布し、被験者の顔面の肌状態の変化について観察した(下表)。
唇荒れの症状を有する正常被験者に対し、B環ゲル製剤を塗布し、唇の粘膜の状態の変化を観察した(下表)なお、粘膜の状態の変化は、被験者の体感的な評価と、医師としての本発明者による客観的な観察とに基づいて判定した。
頭皮・毛髪の症状を有する正常被験者に対し、B環ゲル製剤を塗布し、頭皮および毛髪の状態の変化を観察した(下表)なお、粘膜の状態の変化は、被験者の体感的な評価と、医師としての本発明者による客観的な観察とに基づいて判定した。
B環を0.01μMになるように溶解した37~41℃のお湯(お湯200Lに対してB環20μM溶液を100ml溶解)に、1回/日、14日間、被験者を入浴させ、被験者の皮膚状態をさら湯(お湯のみ)のときと比較した(表14)。なお、皮膚状態の変化は、被験者の体感的な評価と、医師としての本発明者による客観的な観察とに基づいて判定した。
B環ゲル製剤、BNPゲル製剤を塗布し、種々の脱毛に関する症状に対する効果を観察した(下表)。なお、症状の変化は、被験者の体感的な評価と、医師としての本発明者による客観的な観察とに基づいて判定した。
上記の女性型脱毛症、男性型脱毛症、汎発性脱毛症、蛇行状脱毛症、多発性脱毛症を有する被験者の症例においても、比較対照としてBNPゲル製剤と比べ、実施例に係るB環ゲル製剤を適用した場合、抜け毛が顕著に減少し、硬毛の発毛範囲が拡大し、その成長も早かった(図2を参照)。さらに、既存の毛髪のハリが生じ、そのコシが強くなった。いずれも比較例にかかるBNPゲル製剤を適用した場合と比較して、その症状の改善が顕著に表れた。すなわち、B環ゲル製剤は、BNPゲル製剤と比較して、上記症状に対する効能が優れていた。
さらに、B環ゲル製剤は、脂漏性を改善し、頭皮を清浄にし、フケを抑えることができた。また、白髪を予防し、黒い毛を生やし、薄毛の改善をもたらすものであった。さらには、かゆみを抑える効果は10分後には抑えることができ、その即効性の効果が高いことがわかった。また症例によっては、塗布後3分以内にかゆみを抑えることができた。
6.1 症例
B環点鼻剤、BNPゲル点鼻剤を噴霧し、被験者の鼻炎等に対する効果を観察した(表17)。なお、症状の変化は、被験者の体感的な評価と、医師としての本発明者による客観的な観察とに基づいて判定した。
上記いずれの症例においても、実施例に係るB環点鼻剤を適用した場合、鼻漏、鼻閉ともに比較例にかかるBNP点鼻剤を適用した場合と比較して、その改善、解消が迅速に行われていた。すなわち、B環点鼻剤は、BNP点鼻剤と比較して即効性に優れていた。また、B環点鼻剤の効能はBNP点鼻点鼻剤の効能と比較して同等以上であり、また、その効能の持続時間が長く、症状の再発を抑える事ができるものであった。
本発明のB環化合物が従来のBNPに比べて各疾病等に対する薬理効果に優れることについては、以上のとおり、各臨床例に基づきデータをもって説明したが、かかる薬理効果は発明者らが行った、化合物の立体構造解析の結果からも裏付けられるものであることについて参考のため以下の実験レポートをもって説明する。
ヒトBNP(BNP-32)と、同BNPの受容体であるA型受容体(NPR-A)との結合状態を検討するため、立体構造を用いた、ホモロジーモデリングによるin silico解析を行った。モデリングには、Swiss-Pdb viewerおよびSWISS-MODELを使用した。
まず、上記解析に先立ち、ヒトBNPとA型受容体との間の結合状態の検討のためのテンプレート構造を選定した。このテンプレート構造として、ラットNPR-AとラットANPペプチドとの複合体の立体構造(PDB ID:1T34)を使用した。ラットNPR-Aは、A鎖、B鎖からなるホモ二量体である。そして、このようなラットNPR-Aは、ラットANPのCys7~Arg27の21残基が結合した状態でX線結晶構造解析により立体構造が決定されている。また、ラットNPR-Aの立体構造は、タンパク質立体構造データベースであるProtein Data Bankから入手した。また、ヒトNPR-AとラットNPR-Aのアミノ酸一致度は85%である。
今回、BNPのペプチドモデルとして、以下に示す、ヒトBNP(BNP-32、配列番号13、Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Gly-Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys-Lys-Val-Leu-Arg-Arg-His)中のCys10~Arg30の領域のアミノ酸配列(配列番号14、Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys-Lys-Val-Leu-Arg)を使用した。なお、上記ペプチドモデルにおいて、本願発明のB環のアミノ酸配列は、上記ヒトBNP中のCys10~Cys26に相当し、すなわち、Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys(配列番号15)の領域である。
ヒトNPR-AのヒトBNP結合に関与するアミノ酸残基を推察するため、BNPペプチドがヒトNPR-Aに結合した複合体モデルをホモロジーモデリングにより構築した。具体的には、ホモロジーモデリングにより、テンプレート構造のラットANPペプチドに基づいてヒトBNPペプチドモデルを、テンプレート構造のラットNPR-Aに基づいてヒトNPR-Aのモデル構造をモデリングした。
次に、ヒトBNPペプチドモデルとヒトNPR-Aとの間で検出されたアミノ酸残基から、相互作用に直接関与する残基を推測した。
以上より、in silico解析による立体構造解析から、ヒトBNPは、その環状部分に存在するアミノ酸残基が、NPR-Aの活性化に寄与する残基であり、一方で、尾部に存在するアミノ酸残基は寄与しない残基であることが推測された。また、BNP環状構造は、BNP-32よりも低分子であり、容易にかつ迅速に結合できることが示唆された。実際にBNP環状構造のペプチドを臨床的に適用したところ、BNP環状構造の方がBNP-32よりも治療効果が速やかに得られることが現に確認された。この臨床結果は、BNP環状構造がNPR-Aの活性化に寄与し、さらにBNP-32によりも容易にかつ迅速に結合できるという、in silico解析と合致するものである。よって、BNP環状構造は一般的なBNPペプチドよりも優れた治療効果を持つ異なる物質と考えられる。
構築した複合体のモデル構造を使用して、相互作用が推察されたアミノ酸残基以外のアミノ酸残基の置換可能性について検討を行った。
具体的には、相互作用が推察されたアミノ酸残基以外のアミノ酸残基を他のアミノ酸に置換した際に、置換ペプチドが、NPR-Aに対して結合可能か否かを検討するために、BNPの変異体モデルを作製し、相互作用について解析した。モデリングには、Swiss-Pdb viewerを使用した。
・NPR-Aに結合する際に立体障害を起こさない。NPR-AとBNP変異体モデル構造において、原子間の衝突が見られない。
・表面の静電ポテンシャルに影響を与えない。
・分子内エネルギーの値が大きく増加しない(原子間の結合に無理な角度やねじれを生じない)。
・NPR-AとBNPとの鎖間およびBNPの鎖内で本来見られない水素結合を形成しない。
・Cavity(空洞、すき間)を生じない。
次に、一部のアミノ酸を置換した環状ペプチドについて、その効果を確認すべく以下の試験に供した。なお、上記環状ペプチドの製造方法および製造されたペプチドのアミノ酸配列の確認方法は、上記した環状ペプチドの製造方法および質量分析方法と同様であった。
得られた環状ペプチドを、精製水で、3、15、30、100、500μg/mlに配合し患部に塗布した。なお、表中の処方A~Eは、それぞれ3、15、30、100、500μg/mlの環状ペプチド濃度を指す。精製水で処置した場合は、効果がないことから、プラセボ効果ではないことが確認された。
(i)瘢痕または皮膚病変を伴わない脱毛症(円形脱毛症、男性型脱毛症、脂漏性脱毛症、粃糠性脱毛症、女性型脱毛症、妊娠性脱毛症、悪性脱毛症、老人性脱毛症、前頭脱毛症、多発性脱毛症、蛇行性脱毛症、薬物による脱毛症、癌化学療法剤性脱毛症及び放射線被爆による脱毛症、外傷性・機械的脱毛症、栄養障害・代謝障害に伴う脱毛症、内分泌異常に伴う脱毛症、休止期脱毛(分娩後脱毛症、高熱後脱毛症))
(ii)皮膚病変ないし病的皮膚にみられる脱毛症(感染による脱毛、腫瘍による脱毛、炎症による脱毛)
(iii)瘢痕性脱毛症(皮膚感染症による脱毛、炎症性細胞浸潤による脱毛)
(先天性脱毛症)
瀰漫性脱毛、先天性無毛症、遺伝性の症候群における脱毛、限局性脱毛、母斑性、aplasia cutis、先天性三角形脱毛
前述の適用箇所に、3μg/ml~500μg/mlを、患部に1回単純塗布した直後からから痒み、フケ、頭皮の赤み、炎症等の改善,消失させる即効性と、わずか1回の塗布で、翌日から発毛、育毛、髪のハリやコシが出てボリュームが増し、抜け毛が劇的に減少し、1週間以上その効果が続く持続性がみられた。また、一週間程度、塗布を継続すると、さらにそれらの効果が向上し、塗布中断後も、1週間から2週間にわたって、発毛、増毛が持続し続け、抜け毛もほとんどない状態が続く持続性の効果がみられた。
得られた環状ペプチドを、精製水で、3、15、30、100、500μg/mlに配合し患部に塗布した。なお、表中の処方A~Eは、それぞれ3、15、30、100、500μg/mlの環状ペプチド濃度を指す。なお、ペプチドを配合しない、精製水で処置した場合は、効果がないことから、プラセボ効果ではないことが確認された。
なお、健常肌や肌荒れに適用した場合、塗布直後から数分以内に保湿効果を発揮して乾燥を改善し、皮膚および粘膜に適度な弾力性と柔軟性が付与・保持され、肌が柔らかくなり、皮膚、粘膜にハリが生じ、ひきしまる。また、適用部位において小じわややたるみが改善され、さらにくすみ、しみが目立たないものとなる。これらは、1回の塗布で1週間以上の効果の持続性がみられた。
得られた環状ペプチドを、生理食塩水で、3、15、30、100、500μg/mlに配合し、およそ0.1mlを鼻腔に点鼻した。なお、表中の処方A~Eは、それぞれ3、15、30、100、500μg/mlの環状ペプチド濃度を指す。なお、ペプチドを配合しない、生理食塩水で処置した場合は、効果がないことから、プラセボ効果ではないことが確認された。
そして、複合型鼻炎としては、例えば、通年性アレルギー性鼻炎および季節性アレルギー性鼻炎を含むアレルギー性鼻炎と、血管運動性(本態性)鼻炎および好酸球増多性鼻炎を含む非アレルギー性鼻炎とが挙げられる。鼻漏型鼻炎としては、例えば、味覚性鼻炎、冷気吸入性鼻炎および老人性鼻炎が挙げられる。
うっ血型鼻炎としては、例えば、薬物性鼻炎、心因性鼻炎、妊娠性鼻炎、内分泌性鼻炎および寒冷性鼻炎が挙げられる。
浮腫型鼻炎としては、例えば、アスピリン過敏性鼻炎が挙げられる。
また、症状の観点からは、上述したような効果を有することから、くしゃみ・鼻漏型鼻炎、鼻閉型鼻炎および充全型鼻炎のいずれに対しても用いることができる。
3μg/ml~500μg/ml、0.1mlを各鼻腔、患部に1回点鼻した直後から鼻汁を止め、鼻閉を改善し、鼻腔粘膜の痒みやくしゃみを止める即効性と、わずか1回の点鼻塗布で、1日持続し、症例によっては1週間以上その効果が続く持続性がみられた。その他に従来のステロイド薬といった従来用いられてきた鼻炎治療剤によって、局所刺激が強く、点鼻薬使用を希望されない被験者でも、全く局所刺激がないので、安心して使える。
Claims (22)
- 式I:
X1は、Gly、Val、Ala、SerまたはThrを示し、
X2は、Arg、GlnまたはHisを示し、
X3は、LysまたはArgを示し、
X4は、Met、LeuまたはIleを示し、
X5は、IleまたはValを示し、
X6は、SerまたはGlyを示し、
X7は、SerまたはAlaを示し、
X8は、Ser、Gln、Val、Ala、Thr、Leu、IleまたはMetを示し、
X9は、Ser、Val、AlaまたはThrを示し、
X10は、GlyまたはArgを示し、
X11は、Leu、Met、Ile、ValまたはAlaを示し、
X12は、Gly、SerまたはAlaを示し、
2つのCysを結ぶ線は、ジスルフィド結合を表す、
で表されるアミノ酸配列を有し、
当該アミノ酸配列が、当該アミノ酸配列を構成するアミノ酸同士以外のペプチド結合を有さない、
環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。 - X1~X12が、以下の(1)~(12):
(1)X1が、Gly、Val、Ala、SerまたはThrを示す、
(2)X2が、Arg、GlnまたはHisを示す、
(3)X3が、LysまたはArgを示す、
(4)X4が、Met、LeuまたはIleを示す、
(5)X5が、IleまたはValを示す、
(6)X6が、SerまたはGlyを示す、
(7)X7が、SerまたはAlaを示す、
(8)X8が、Ser、Gln、Val、Ala、Thr、Leu、IleまたはMetを示す、
(9)X9が、Ser、Val、AlaまたはThrを示す、
(10)X10が、GlyまたはArgを示す、
(11)X11が、Leu、Met、Ile、ValまたはAlaを示す、および
(12)X12が、Gly、SerまたはAlaを示す、
からなる群か選択される1または2以上である、
請求項1に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。 - 配列番号3~8および配列番号16~75の環状ペプチドから選択される、請求項1に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。
- 誘導体が環状ペプチド中の水素原子、水酸基、カルボキシ基、アミノ基、イミノ基に対して置換可能な置換基で置換されたものである、請求項1~3のいずれか一項に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩。
- 請求項3に記載の式(I-a)~(I-e)のいずれかで表される環状ペプチド中のアミノ酸の1以上4以下を欠失させるか、他のアミノ酸で置換または付加することにより形成され、かつ前記各式で表される環状ペプチドと同等の機能を有する環状ペプチドもしくはその誘導体またはその薬学的に許容可能な塩。
- 請求項1~5のいずれか一項に記載の環状ペプチドおよび/もしくはその誘導体ならびに/またはこれらの薬学的に許容可能な塩を1種以上含む、外用剤。
- 皮膚炎治療剤、皮膚炎予防剤、鎮痒剤、消炎剤、傷上皮化促進剤またはスキンケア用品の材料である、請求項6に記載の外用剤。
- スキンケア用品が、保湿用および/または肌荒れ防止・改善用および/または皮脂ケア・ニキビケア用および/または刺激緩和・抗炎症用および/または美白用および/または老化防止用および/または紫外線傷害予防・緩和用および/またはスリミング用および/または皮膚清浄用である、請求項7に記載の外用剤。
- 入浴剤、身体洗浄剤または頭髪用洗浄剤である、請求項6に記載の外用剤。
- 脱毛症治療剤、脱毛症予防剤、育毛剤および/または発毛剤である、請求項6に記載の外用剤。
- 鼻炎治療剤および/または鼻炎予防剤である、請求項6に記載の外用剤。
- 化粧料である、請求項6に記載の外用剤。
- 剤形が、固形剤、半固形剤、粉末剤、液剤、スプレー剤、軟膏剤、クリーム剤、乳液剤、ゲル剤または貼付剤である、請求項6~12のいずれか一項に記載の外用剤。
- 医薬品、医薬部外品または化粧品として用いられる、請求項6~13のいずれか一項に記載の外用剤。
- 請求項1~4のいずれか一項に記載の環状ペプチドおよび/もしくはその誘導体ならびに/またはこれらの薬学的に許容可能な塩の外用剤の製造のための使用。
- 請求項6~14のいずれか一項に記載の外用剤を、対象の皮膚および/または粘膜に適用することを含む、外用剤の使用方法。
- 粘膜が口唇、口腔、鼻腔、眼または膣である、請求項16に記載の外用剤の使用方法。
- 皮膚炎の治療および/もしくは予防方法、痒みの軽減もしくは消失方法、湿疹等によるびらん、潰瘍の治療方法またはスキンケア方法である、請求項16に記載の外用剤の使用方法。
- 脱毛症の治療および/もしくは予防方法ならびに/または発毛方法ならびに/または育毛方法である、請求項16に記載の外用剤の使用方法。
- 鼻炎の治療および/または予防方法である、請求項16に記載の外用剤の使用方法。
- 請求項1~5のいずれか一項に記載の環状ペプチドもしくはその誘導体またはこれらの薬学的に許容可能な塩を1種以上含む、医薬。
- 高血圧症、不安定狭心症、急性心筋梗塞、浮腫性疾患、腎不全、心不全、免疫疾患、肥満、メタボリックシンドロームの治療薬である、請求項21に記載の医薬。
Priority Applications (10)
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KR1020177037404A KR20180010267A (ko) | 2015-05-29 | 2016-05-27 | 환상 펩티드 및 그 환상 펩티드를 포함한 의약, 외용제 및 화장료 |
AU2016272282A AU2016272282A1 (en) | 2015-05-29 | 2016-05-27 | Cyclic peptide, and medicine, external preparation and cosmetic each containing said cyclic peptide |
EP21196424.2A EP4014987A3 (en) | 2015-05-29 | 2016-05-27 | Cyclic peptide, and medicine, external preparation and cosmetic each containing said cyclic peptide |
JP2017521929A JPWO2016194855A1 (ja) | 2015-05-29 | 2016-05-27 | 環状ペプチド並びに該環状ペプチドを含む医薬、外用剤および化粧料 |
EP16803290.2A EP3305804A4 (en) | 2015-05-29 | 2016-05-27 | Cyclic peptide, and medicine, external preparation and cosmetic each containing said cyclic peptide |
CA2986086A CA2986086A1 (en) | 2015-05-29 | 2016-05-27 | Cyclyc peptide, and medicine, external preparation and cosmetic each containing said cyclic peptide |
US15/122,753 US20180066020A1 (en) | 2015-05-29 | 2016-05-27 | A cyclic peptide and a medicament, external preparation and cosmetic comprising said cyclic peptide |
CN201680031367.7A CN107709352A (zh) | 2015-05-29 | 2016-05-27 | 环肽以及含有该环肽的药物、外用剂和化妆品 |
US16/745,520 US12065512B2 (en) | 2015-05-29 | 2020-01-17 | Cyclic peptide and a medicament, external preparation and cosmetic comprising said cyclic peptide |
AU2021202995A AU2021202995A1 (en) | 2015-05-29 | 2021-05-11 | Cyclic peptide, and medicine, external preparation and cosmetic each containing said cyclic peptide |
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JP2015110622 | 2015-05-29 | ||
JP2015-110622 | 2015-05-29 |
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US15/122,753 A-371-Of-International US20180066020A1 (en) | 2015-05-29 | 2016-05-27 | A cyclic peptide and a medicament, external preparation and cosmetic comprising said cyclic peptide |
US16/745,520 Division US12065512B2 (en) | 2015-05-29 | 2020-01-17 | Cyclic peptide and a medicament, external preparation and cosmetic comprising said cyclic peptide |
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WO2016194855A1 true WO2016194855A1 (ja) | 2016-12-08 |
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PCT/JP2016/065839 WO2016194855A1 (ja) | 2015-05-29 | 2016-05-27 | 環状ペプチド並びに該環状ペプチドを含む医薬、外用剤および化粧料 |
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US (2) | US20180066020A1 (ja) |
EP (2) | EP4014987A3 (ja) |
JP (3) | JPWO2016194855A1 (ja) |
KR (1) | KR20180010267A (ja) |
CN (1) | CN107709352A (ja) |
AU (2) | AU2016272282A1 (ja) |
CA (1) | CA2986086A1 (ja) |
TW (1) | TW201708247A (ja) |
WO (1) | WO2016194855A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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EP4014987A3 (en) | 2015-05-29 | 2022-07-06 | Igisu Co., Ltd. | Cyclic peptide, and medicine, external preparation and cosmetic each containing said cyclic peptide |
CN111557867B (zh) * | 2020-04-21 | 2022-12-06 | 昌正医疗(苏州)有限公司 | 一种婴幼儿舒缓膏及其制备方法 |
JP2023535057A (ja) | 2020-07-21 | 2023-08-15 | ケムボー・エルエルシー | ジエステル化粧用配合物及びその使用 |
TWI803993B (zh) * | 2021-09-28 | 2023-06-01 | 廖嘉鴻 | 環胜肽自組裝3d微粒裝置及其製造方法 |
CN115010949B (zh) * | 2022-07-12 | 2024-02-13 | 华熙生物科技股份有限公司 | 促渗物、护肤品组合物以及化妆品 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006515579A (ja) * | 2002-11-26 | 2006-06-01 | ノベックス コーポレーション | ナトリウム排泄増加性化合物、結合体、およびその使用 |
WO2008140125A1 (ja) * | 2007-05-10 | 2008-11-20 | National University Corporation Nagoya University | 腹膜線維化抑制用医薬組成物 |
WO2010002583A2 (en) * | 2008-07-02 | 2010-01-07 | Mayo Foundation For Medical Education And Research | Natriuretic polypeptides with unique pharmacologic profiles |
WO2011010732A1 (ja) * | 2009-07-23 | 2011-01-27 | 株式会社 イギス | 皮膚外用剤組成物 |
WO2011024973A1 (ja) * | 2009-08-27 | 2011-03-03 | 株式会社 イギス | 鼻炎治療剤 |
WO2012099258A1 (ja) * | 2011-01-21 | 2012-07-26 | 株式会社 イギス | 脱毛症治療剤 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5114923A (en) | 1988-05-31 | 1992-05-19 | California Biotechnology Inc. | Recombinant techniques for production of novel natriuretic and vasodilator peptides |
CA1339210C (en) * | 1988-05-31 | 1997-08-05 | John Lewicki | Recombinant techniques for production of novel natriuretic and vasodilator peptides |
US6028055A (en) | 1996-10-22 | 2000-02-22 | Genetech, Inc. | Receptor selective BNP |
US6407211B1 (en) | 1999-12-17 | 2002-06-18 | Mayo Foundation For Medical Education And Research | Chimeric natriuretic peptides |
IL142118A0 (en) * | 2001-03-20 | 2002-03-10 | Prochon Biotech Ltd | Method and composition for treatment of skeletal dysplasias |
DE60239763D1 (de) | 2001-12-20 | 2011-05-26 | Enobia Pharma Inc | Knochenpolypeptid-1 |
JP2006514607A (ja) * | 2002-07-31 | 2006-05-11 | コンジュケム,インコーポレーテッド | 長時間持続性ナトリウム排泄増加性ペプチド誘導体 |
US7648962B2 (en) * | 2002-11-26 | 2010-01-19 | Biocon Limited | Natriuretic compounds, conjugates, and uses thereof |
EP1730181A2 (en) | 2004-01-27 | 2006-12-13 | Compugen USA, Inc. | Novel brain natriuretic peptide variants and methods of use thereof |
JP2007525213A (ja) | 2004-01-27 | 2007-09-06 | コンピュゲン ユーエスエイ,インク. | 新規の脳性ナトリウム利尿ペプチドの変異体及びその利用方法 |
MX2007001667A (es) | 2004-08-11 | 2007-10-02 | Johnson & Johnson | Aparato y metodo para el suministro transdermico de peptidos natriureticos. |
US20080207505A1 (en) | 2005-01-12 | 2008-08-28 | James Kenneth D | Bna Conjugates and Methods of Use |
US7731965B2 (en) * | 2005-02-17 | 2010-06-08 | Abbott Lab | Human ring specific BNP antibodies |
WO2008032450A1 (fr) | 2006-09-15 | 2008-03-20 | Kyoto University | Agent prophylactique et/ou thérapeutique pour une stéatose hépatique |
JP5010913B2 (ja) * | 2006-12-31 | 2012-08-29 | 寿子 小出 | 心房利尿ホルモンファミリー分子を活性物質として含有する組織再生製剤また該製剤をもちいる組織再生方法、および心房利尿ホルモンファミリー分子を活性物質として含有する発毛、増毛、育毛剤および皮膚組織修復改善剤また該製剤を用いる発毛、増毛、育毛促進方法および皮膚組織修復改善方法 |
EP4014987A3 (en) | 2015-05-29 | 2022-07-06 | Igisu Co., Ltd. | Cyclic peptide, and medicine, external preparation and cosmetic each containing said cyclic peptide |
-
2016
- 2016-05-27 EP EP21196424.2A patent/EP4014987A3/en active Pending
- 2016-05-27 KR KR1020177037404A patent/KR20180010267A/ko not_active Application Discontinuation
- 2016-05-27 WO PCT/JP2016/065839 patent/WO2016194855A1/ja active Application Filing
- 2016-05-27 JP JP2017521929A patent/JPWO2016194855A1/ja active Pending
- 2016-05-27 US US15/122,753 patent/US20180066020A1/en active Pending
- 2016-05-27 TW TW105116780A patent/TW201708247A/zh unknown
- 2016-05-27 AU AU2016272282A patent/AU2016272282A1/en not_active Abandoned
- 2016-05-27 EP EP16803290.2A patent/EP3305804A4/en not_active Ceased
- 2016-05-27 CA CA2986086A patent/CA2986086A1/en active Pending
- 2016-05-27 CN CN201680031367.7A patent/CN107709352A/zh active Pending
-
2020
- 2020-01-17 US US16/745,520 patent/US12065512B2/en active Active
-
2021
- 2021-01-20 JP JP2021007638A patent/JP2021073234A/ja active Pending
- 2021-05-11 AU AU2021202995A patent/AU2021202995A1/en not_active Abandoned
-
2023
- 2023-05-19 JP JP2023082711A patent/JP2023096139A/ja active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006515579A (ja) * | 2002-11-26 | 2006-06-01 | ノベックス コーポレーション | ナトリウム排泄増加性化合物、結合体、およびその使用 |
WO2008140125A1 (ja) * | 2007-05-10 | 2008-11-20 | National University Corporation Nagoya University | 腹膜線維化抑制用医薬組成物 |
WO2010002583A2 (en) * | 2008-07-02 | 2010-01-07 | Mayo Foundation For Medical Education And Research | Natriuretic polypeptides with unique pharmacologic profiles |
WO2011010732A1 (ja) * | 2009-07-23 | 2011-01-27 | 株式会社 イギス | 皮膚外用剤組成物 |
WO2011024973A1 (ja) * | 2009-08-27 | 2011-03-03 | 株式会社 イギス | 鼻炎治療剤 |
WO2012099258A1 (ja) * | 2011-01-21 | 2012-07-26 | 株式会社 イギス | 脱毛症治療剤 |
Non-Patent Citations (1)
Title |
---|
See also references of EP3305804A4 * |
Also Published As
Publication number | Publication date |
---|---|
AU2016272282A1 (en) | 2018-01-25 |
US20200347096A1 (en) | 2020-11-05 |
EP3305804A4 (en) | 2018-11-21 |
JPWO2016194855A1 (ja) | 2018-06-07 |
US12065512B2 (en) | 2024-08-20 |
EP3305804A1 (en) | 2018-04-11 |
CN107709352A (zh) | 2018-02-16 |
CA2986086A1 (en) | 2016-12-08 |
EP4014987A3 (en) | 2022-07-06 |
AU2021202995A1 (en) | 2021-06-10 |
TW201708247A (zh) | 2017-03-01 |
JP2021073234A (ja) | 2021-05-13 |
US20180066020A1 (en) | 2018-03-08 |
KR20180010267A (ko) | 2018-01-30 |
JP2023096139A (ja) | 2023-07-06 |
EP4014987A2 (en) | 2022-06-22 |
US20210277062A9 (en) | 2021-09-09 |
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