WO2018029762A1 - Matériau absorbable par voie transdermique, produit cosmétique absorbable par voie transdermique et médicament absorbable par voie transdermique - Google Patents

Matériau absorbable par voie transdermique, produit cosmétique absorbable par voie transdermique et médicament absorbable par voie transdermique Download PDF

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Publication number
WO2018029762A1
WO2018029762A1 PCT/JP2016/073350 JP2016073350W WO2018029762A1 WO 2018029762 A1 WO2018029762 A1 WO 2018029762A1 JP 2016073350 W JP2016073350 W JP 2016073350W WO 2018029762 A1 WO2018029762 A1 WO 2018029762A1
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WIPO (PCT)
Prior art keywords
peptide
skin
transdermally absorbable
solution
gly
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PCT/JP2016/073350
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English (en)
Japanese (ja)
Inventor
衣織 前田
知広 引間
健 野瀬
Original Assignee
国立大学法人 九州工業大学
株式会社Ｅ＆Ｃヘルスケア
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Application filed by 国立大学法人 九州工業大学, 株式会社Ｅ＆Ｃヘルスケア filed Critical 国立大学法人 九州工業大学
Priority to PCT/JP2016/073350 priority Critical patent/WO2018029762A1/fr
Publication of WO2018029762A1 publication Critical patent/WO2018029762A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids

Definitions

  • the present invention relates to a percutaneous absorption material comprising a specific peptide, a percutaneous absorption cosmetic and a transdermal drug containing the same.
  • elastin is known as a protein constituting animal tissue. Elastin is secreted from cells as a protein called tropoelastin, and then self-assembles around and around the microfibrils and crosslinks between molecules to form insoluble elastic fibers. This is due to self-assembling ability of elastin, so-called coacervation, and a peptide based on the amino acid sequence of elastin is considered to have coacervation (see Patent Document 1).
  • the present invention has been made in view of such circumstances, and consists of a peptide based on the amino acid sequence of elastin, a transdermal material having skin permeability and substance inclusion, and a transdermal absorption type comprising the same. It aims at providing cosmetics and a transdermal drug.
  • the percutaneous absorption material according to the first invention in accordance with the above object is a first peptide having an amino acid sequence in which the sequence of Phe-Pro-Gly-Val-Gly is repeated 2 to 10 times, or the first peptide On the other hand, it consists of a second peptide in which 40% or less of amino acids have been deleted, substituted, or added. It was verified that the first and second peptides have skin permeability and substance inclusion.
  • the percutaneous absorption cosmetic according to the second invention that meets the above-mentioned object is a first peptide having an amino acid sequence in which the sequence of Phe-Pro-Gly-Val-Gly is repeated 2 to 10 times, or the first peptide
  • a transdermal absorption material comprising a second peptide in which 40% or less of amino acids have been deleted, substituted, or added to the peptide is provided.
  • the transdermally absorbable drug according to the third invention that meets the above-mentioned object is a first peptide having an amino acid sequence in which the sequence of Phe-Pro-Gly-Val-Gly is repeated 2 to 10 times, or the first peptide
  • a transdermal absorption material comprising a second peptide in which 40% or less of amino acids have been deleted, substituted, or added to the peptide is provided.
  • the transdermally absorbable material according to the first invention is effective as a material that allows the substance to penetrate from the skin into the body because the first and second peptides have skin permeability and inclusion of the substance. From this, the transdermal absorption cosmetic according to the second invention provided with the transdermal absorption material according to the first invention and the third invention provided with the transdermal absorption material according to the first invention are also provided.
  • the percutaneous absorption type medicine according to the above can penetrate the active ingredient into the body through the skin.
  • the transdermally absorbable material has a sequence of SEQ ID NO: 1, that is, a sequence of Phe-Pro-Gly-Val-Gly (hereinafter sometimes expressed as “FPGVG”) 2 to 10
  • a transdermally absorbable material comprising a first peptide having an amino acid sequence repeated twice or a second peptide comprising 40% or less of the amino acid deleted, substituted, or added to the first peptide. It is a skin absorbing material.
  • “Phe”, “Pro”, “Gly”, and “Val” are phenylalanine, proline, glycine, and valine, respectively. Deletion of an amino acid means that no amino acid is present.
  • the second peptide has X1 as tryptophan, tyrosine, valine, isoleucine or cyclohexylalanine, X2 as alanine, X3 as phenylalanine, leucine or isoleucine, X4 as alanine, X1-Pro-X2-X3-X4 And a peptide in which 40% or less of amino acids are substituted with respect to the first peptide.
  • the second peptide examples include those having a repeating sequence of Ile-Pro-Gly-Val-Gly.
  • a peptide that repeats the sequence of Ile-Pro-Gly-Val-Gly 5 times and a peptide that repeats the same sequence 10 times include and releases a substance (a dye in the experiment).
  • the C-terminus of the first peptide may be any of a carboxy group (—COOH), a carboxylate (—COO ⁇ ), an amide (—CONH 2 ), and an ester (—COOR).
  • R is a C 1-6 alkyl group such as methyl, ethyl or n-propyl, a C 3-8 cycloalkyl group such as cyclopentyl or cyclohexyl, or a C 3 such as phenyl. Examples thereof include 6-12 aryl groups and aromatic alkyl groups such as benzyl.
  • the N terminal of the 1st peptide may be protected by protecting groups, such as an acetyl group, a formyl group, and a fatty acid, for example.
  • the first peptide has the inclusion property of the substance, the skin permeability, and the release property for releasing the included substance. Therefore, the first peptide can be employed as a percutaneous absorption material that allows an active ingredient to penetrate the human body through the skin and be released in the body.
  • a peptide having one FPGVG sequence cannot contain a substance.
  • the peptide having 11 or more repetitions of FPGVG has reduced water solubility and cannot secure the stability of penetration from the skin into the human body.
  • the first peptide specifically, a second peptide in which 40% or less of amino acids are deleted, substituted, or added to the first peptide (for deletion, 30% or less is preferable, and 20% or less is more preferable), it has been confirmed by verification that the substance has inclusiveness, release and skin permeability.
  • the inclusion and release of substances are considered to be performed by the coacervation ability of the peptide.
  • Numerous publicly known documents eg, “Woohyun Kim, Elliot L.
  • the second peptide can also be employed as a percutaneous absorption material that allows the active ingredient to penetrate into the human body through the skin and be released in the body, like the first peptide. Furthermore, it was confirmed that the first and second peptides also have the property of moisturizing the skin (skin moisturizing property).
  • the transdermal absorption material composed of the first peptide or the transdermal absorption composed of the second peptide Since the first and second peptides have skin permeability, substance inclusion and release properties, the transdermal absorption material composed of the first peptide or the transdermal absorption composed of the second peptide.
  • Cosmetics and drugs containing (ie, comprising) materials can stably deliver active ingredients from the skin to the body. Therefore, the percutaneous absorption material consisting of the first peptide or the percutaneous absorption material consisting of the second peptide is contained in the percutaneous absorption cosmetics and percutaneous absorption medicines according to other examples of the present invention. It is effective to be used.
  • the percutaneous absorption type cosmetic contains one or both of the first and second peptides and an active ingredient of the cosmetic (for example, whitening ingredient), and is a type that penetrates the active ingredient of the cosmetic from the skin.
  • a transdermal drug includes one or both of the first and second peptides and an active ingredient (for example, an analgesic ingredient), and means a drug of a type that sends an active ingredient of a drug from the skin into the body. To do.
  • ⁇ Skin moisture retention test In the skin moisturizing test, first, based on a peptide in which the sequence of FPGVG was repeated 5 times (hereinafter also referred to as “peptide of F5”), distilled water (hereinafter referred to as “DW”) as a solvent.
  • 0.1 w / w% solution solution containing 0.1 g of the peptide of the experimental example with respect to 100 g of solution, hereinafter, also simply referred to as “0.1% solution”
  • 1.0 w / W% solution a solution containing 1.0 g of the peptide of the experimental example with respect to 100 g of the solution, hereinafter, also simply referred to as “1.0% solution”.
  • the cultured skin on which 200 ⁇ L each of 0.1% solution and 1.0% solution was applied (supplied) to the surface was kept at 32 ° C. with a constant temperature shaker and shaken for 30 minutes.
  • the solution on the cultured skin was wiped off with a paper waste and dried in an environment of 32 ° C. for 1 hour.
  • the above-described cycle from application of the solution to the surface of the cultured skin until the completion of drying for 1 hour was repeated three times (total 3 cycles were performed), and then the weight of the cultured skin after the drying treatment (hereinafter referred to as “the dried skin”).
  • the cultured skin was dried for 24 hours with a dryer, and the weight of the cultured skin (hereinafter also referred to as “dry weight”) was measured.
  • Moisture content (%) ⁇ (wet weight ⁇ dry weight) / wet weight ⁇ ⁇ 100 (Formula 1) Moreover, since it compares with a 0.1% solution and a 1.0% solution, it does not contain a peptide. W. Also, the same treatment as in the case of 0.1% solution and 1.0% solution cultured skin was performed, and the moisture content in the cultured skin was measured.
  • p ⁇ 0.05 in FIG. 1 means p value of t test. Since the moisture content of the cultured skin not subjected to any treatment including drying treatment was 76.3 ⁇ 1.8%, the cultured skin to which the 1.0% solution was applied was not subjected to any treatment. It was found that the water content recovered to the same level. Therefore, it was revealed that the solution containing the peptide of F5 has a skin moisturizing property that maintains or increases the moisture content of the cultured skin.
  • the solution containing the peptide is also referred to as “peptide solution”.
  • ⁇ Skin permeability test In the skin permeability test, first, 200 ⁇ L of the peptide solution was placed on the cultured skin placed in the culture cup, and the cultured skin was housed in a constant temperature shaker set at 32 ° C. In this test, an F5 peptide solution (concentration: 0.1%) and a peptide (hereinafter also referred to as “F10 peptide”) solution (concentration: 0.05%) in which the FPGVG sequence was repeated 10 times were used as subjects. did.
  • the cultured skin from which the peptide solution has been wiped off with a waste cloth is washed with a 0.1% TFA + 50% CH 3 CN solution, wiped well, and then placed in a sample tube together with a 0.1% TFA + 50% CH 3 CN solution. , Stirred. And the density
  • the peptide extracted from the cultured skin did not penetrate into the cultured skin, and the peptide extracted from the cultured skin could be said to have penetrated into the cultured skin, the peptide extracted from the cultured skin The amount can be treated as the amount of peptide that has penetrated into the cultured skin. It is confirmed that the total amount of the peptide extracted from the waste and the amount of the peptide extracted from the cultured skin is first equal to the amount of the peptide given on the cultured skin. . In addition, the procedure described above is performed even when the time for accommodating the cultured skin in a constant temperature shaker set at 32 ° C. is extended to 15 minutes, 30 minutes, and 60 minutes after placing the peptide solution. Was used to derive the amount of peptide that had penetrated into the cultured skin.
  • FIG. 2 shows that both the peptide solution of F5 and the peptide solution of F10 tend to increase the amount of penetration of the peptide into the cultured skin with the passage of time, and the peptide of F5 is cultured skin compared to the peptide of F10. It was found that there was a lot of penetration. Therefore, it was confirmed that the peptide penetrated into the skin in both the F5 peptide solution and the F10 peptide solution.
  • the target of the inclusion release test of the dye was a solution containing a peptide having an amino acid sequence of FPGVG (hereinafter also referred to as “F1 peptide”), a peptide in which the FPGVG sequence was repeated twice (hereinafter referred to as “F2 peptide”).
  • Solution containing FPGVG sequence hereinafter also referred to as “F3 peptide”
  • F4 peptide peptide repeating FPGVG sequence four times
  • a peptide in a liquid state and a dye in a liquid state were mixed to prepare a peptide solution containing a predetermined amount of each of the peptide and the dye.
  • the prepared peptide solution was allowed to stand for 24 hours in an environment of 4 ° C., and then allowed to stand at 37 ° C. for 24 hours, thereby including the dye in the peptide in the peptide solution. Centrifugation was performed at 10,000 rpm for 3 minutes in an environment at 0 ° C., and the supernatant was collected.
  • the absorbance at a predetermined wavelength was measured for the collected supernatant, and the amount of dye contained in the peptide was determined based on the measurement result. Then, 1 ml of water was added to the residue of the peptide solution from which the supernatant was recovered, and the mixture was allowed to stand at 37 ° C. for 24 hours, and then the supernatant was recovered again, and the absorbance at a predetermined wavelength was measured for the recovered supernatant. The procedure of calculating the amount of dye released from the peptide was repeated every day to determine the cumulative amount of dye released.
  • FPGAA Phe-Pro-Gly-Ala-Ala
  • FPAVA Peptides and amino acids obtained by repeating 5 times the sequence of Phe-Pro-Ala-Val-Ala
  • FIG. 7A shows the experimental results for a peptide solution in which FPGAAA was repeated 5 times (the concentration of the peptide was 100 mg / mL) and the experimental results for the peptide solution in which FPVA was repeated 5 times (the concentration of the peptide was 5 mg / mL).
  • B respectively. From the results shown in FIGS. 7A and 7B, both of the two types of peptides have a phenomenon in which the turbidity on the vertical axis rapidly increases at a predetermined temperature at a predetermined wavelength of light (coacervation). Mean), and it was found that there was at least an inclusion effect of the substance. In addition, since it is not common that the contained substance is not released, it is considered that the two types of peptides also have an action of releasing the contained substance.
  • the active ingredient is delivered into the body through the skin, for example, in medicine, beauty, etc. Expected to be used in industry.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

L'invention concerne un matériau absorbable par voie transdermique comprenant un premier peptide ayant une séquence d'acides aminés dans laquelle la séquence Phe-Pro-Gly-Val-Gly est répétée 2 à 10 fois, ou un second peptide obtenu par la délétion, la substitution ou l'addition d'au plus 40 % des acides aminés du premier peptide. L'invention concerne également un produit cosmétique absorbable par voie transdermique pourvu du matériau absorbable par voie transdermique, et un médicament absorbable par voie transdermique pourvu du matériau absorbable par voie transdermique.
PCT/JP2016/073350 2016-08-08 2016-08-08 Matériau absorbable par voie transdermique, produit cosmétique absorbable par voie transdermique et médicament absorbable par voie transdermique WO2018029762A1 (fr)

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PCT/JP2016/073350 WO2018029762A1 (fr) 2016-08-08 2016-08-08 Matériau absorbable par voie transdermique, produit cosmétique absorbable par voie transdermique et médicament absorbable par voie transdermique

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PCT/JP2016/073350 WO2018029762A1 (fr) 2016-08-08 2016-08-08 Matériau absorbable par voie transdermique, produit cosmétique absorbable par voie transdermique et médicament absorbable par voie transdermique

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115991732A (zh) * 2022-11-21 2023-04-21 北海黑珍珠海洋生物科技有限公司 一种具有抗炎作用的珍珠贝活性肽及其应用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011219427A (ja) * 2010-04-13 2011-11-04 Kyushu Institute Of Technology 水溶性エラスチンのナノ粒子の製造方法と該ナノ粒子からなる皮膚透過性担体
WO2011155565A1 (fr) * 2010-06-10 2011-12-15 国立大学法人九州工業大学 Feuille sensible à la température qui affiche des propriétés réversibles et procédé de production de feuille cellulaire utilisant celle-ci
JP2012126713A (ja) * 2010-11-25 2012-07-05 Kyushu Institute Of Technology ペプチドおよびその自己集合方法、その集合体、これらを用いた細胞培養基材、並びに、細胞シートの製造方法
JP2013249272A (ja) * 2012-05-31 2013-12-12 Sanyo Chem Ind Ltd 皮膚弾性向上材及び皮膚弾性向上用タンパク質溶液
JP2015013850A (ja) * 2013-04-30 2015-01-22 国立大学法人九州工業大学 ペプチドおよびその自己集合方法、その集合体、これらを用いた細胞培養基材、並びに、細胞シートの製造方法
JP2016147830A (ja) * 2015-02-12 2016-08-18 国立大学法人九州工業大学 経皮吸収素材、並びに、経皮吸収式化粧品、及び、経皮吸収式薬剤

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011219427A (ja) * 2010-04-13 2011-11-04 Kyushu Institute Of Technology 水溶性エラスチンのナノ粒子の製造方法と該ナノ粒子からなる皮膚透過性担体
WO2011155565A1 (fr) * 2010-06-10 2011-12-15 国立大学法人九州工業大学 Feuille sensible à la température qui affiche des propriétés réversibles et procédé de production de feuille cellulaire utilisant celle-ci
JP2012126713A (ja) * 2010-11-25 2012-07-05 Kyushu Institute Of Technology ペプチドおよびその自己集合方法、その集合体、これらを用いた細胞培養基材、並びに、細胞シートの製造方法
JP2013249272A (ja) * 2012-05-31 2013-12-12 Sanyo Chem Ind Ltd 皮膚弾性向上材及び皮膚弾性向上用タンパク質溶液
JP2015013850A (ja) * 2013-04-30 2015-01-22 国立大学法人九州工業大学 ペプチドおよびその自己集合方法、その集合体、これらを用いた細胞培養基材、並びに、細胞シートの製造方法
JP2016147830A (ja) * 2015-02-12 2016-08-18 国立大学法人九州工業大学 経皮吸収素材、並びに、経皮吸収式化粧品、及び、経皮吸収式薬剤

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115991732A (zh) * 2022-11-21 2023-04-21 北海黑珍珠海洋生物科技有限公司 一种具有抗炎作用的珍珠贝活性肽及其应用

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