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WO2019061491A1 - Peptide pour soins oculaires, composition et procédé d'utilisation de celui-ci - Google Patents

Peptide pour soins oculaires, composition et procédé d'utilisation de celui-ci Download PDF

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Publication number
WO2019061491A1
WO2019061491A1 PCT/CN2017/104991 CN2017104991W WO2019061491A1 WO 2019061491 A1 WO2019061491 A1 WO 2019061491A1 CN 2017104991 W CN2017104991 W CN 2017104991W WO 2019061491 A1 WO2019061491 A1 WO 2019061491A1
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WO
WIPO (PCT)
Prior art keywords
peptide
eye
composition
migration
subject
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2017/104991
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English (en)
Inventor
Min-Chuan Huang
Syue-Ting Chen
Yu-Chun Liu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pro Sunfun Biotech Research And Development Co Ltd
Original Assignee
Pro Sunfun Biotech Research And Development Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pro Sunfun Biotech Research And Development Co Ltd filed Critical Pro Sunfun Biotech Research And Development Co Ltd
Priority to PCT/CN2017/104991 priority Critical patent/WO2019061491A1/fr
Publication of WO2019061491A1 publication Critical patent/WO2019061491A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates generally to a peptide effective for keeping eye health, its composition and method of using the same.
  • a peptide having the amino acid sequence of ArgAsnProLeuGluGluThr (SEQ ID NO: 1) has an effect in enhancing the migration of corneal epithelial cells, which is beneficial to eye care or eye health.
  • the present invention provides in one aspect a synthetic peptide consisting of the amino acid sequence of SEQ ID NO: 1, which is also named as “Peptide No. 12” herein.
  • the peptide provides an effect in enhancing the migration of corneal epithelial cells.
  • the present invention provides a composition or a pharmaceutical composition benefic to eye care or eye health, comprising an effective amount of the peptide of SEQ ID NO: 1, and a pharmaceutically acceptable carrier.
  • the composition of the invention is formulated in a systemic or topical form.
  • the composition is formulated in a topical form, such as eye drop.
  • the present invention provides an eye-care method for preventing eye damage, which comprises administering to a subject in need thereof the peptide having the amino acid sequence of SEQ ID NO: 1 in an amount effective to enhance the migration of corneal epithelial cells in the subject.
  • the peptide is topically administered to the subject.
  • Fig. 1A and Fig. 1B show that Peptide NO. 12 enhanced migration of HCEC corneal epithelial cells for 24 hours; wherein Fig. 1A provides some representative images of cell migration for 24 hours analyzed by Transwell migration assay in HCEC cells treated with different concentrations of Peptide NO. 12 for 24 hours (Scale bar, 1 mm) ; and Fig. 1B provides the results of the statistic analysis of migration for 24 hours (*: P ⁇ 0.05) .
  • Fig. 2A and Fig. 2B show that Peptide NO. 12 enhanced migration of HCEC corneal epithelial cells for 48 hours; wherein Fig. 2A provides some representative images of cell migration in which the cells were treated with different concentrations of Peptide NO. 12 and analyzed by Transwell migration assay in HCEC cells for 48 hours (Scale bar, 1 mm) ; and Fig. 2B provides the results of the statistic analysis of migration for 48 hours (**: P ⁇ 0.01) .
  • Fig. 3 shows that Peptide NO. 12 did not significantly affect viability of HCEC cells for 24 hours; wherein the HCEC cells were treated with different concentrations of Peptide NO. 12 for 24 hours and then analyzed by MTT assays.
  • Fig. 4 shows that Peptide NO. 12 did not significantly affect viability of HCEC cells for 48 hours; wherein the HCEC cells were treated with different concentrations of Peptide NO. 12 for 48 hours and then analyzed by MTT assays.
  • peptide is used herein in its conventional sense, i.e., a polymer in which the monomers are amino acids and are joined together through amide bonds, alternatively referred to as a polypeptide.
  • amino acids are ⁇ -amino acids
  • either the L-optical isomer or the D-optical isomer may be used.
  • unnatural amino acids for example, ⁇ -alanine, phenylglycine and homoarginine are also meant to be included. Standard abbreviations for amino acids are used.
  • the term “subject” refers to a vertebrate or vertebrates, preferably mammals, including, for example, humans, laboratory animals such as rats and mice, and farm animals, such as horses and cows; particularly humans.
  • a human serving as a subject is specifically referred to as a “human subject. ”
  • carrier or “cosmetically or pharmaceutically acceptable carrier” refers to any material commonly used on the formulations of cosmetic or pharmaceutical compositions used to enhance stability, sterility and deliverability.
  • the delivery system is in an acceptable carrier, preferably an aqueous carrier.
  • aqueous carriers may be used, e.g., water, buffered water, 0.8%saline, 0.3%glycine, hyaluronic acid and the like.
  • compositions may contain physiologically acceptable auxiliary substances as required to approximate physiological conditions, such as pH adjusting and buffering agents, tonicity adjusting agents, wetting agents and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc.
  • physiologically acceptable auxiliary substances such as pH adjusting and buffering agents, tonicity adjusting agents, wetting agents and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oleate, etc.
  • systemic refers to a route of administration of medication or other substance into the circulatory system so that the entire body of a subject to be administered is affected.
  • the administration may take place via enteral administration (through which the absorption of the medication or other substance through gastrointestinal tracts) or parenteral administration such as injection, infusion or implantation.
  • Topical or “topically” is used herein its conventional sense as referring to a spot which can be in or on any part of the body, including but not limited to an eye or eyes, or any other part of the body.
  • Topical administration or application means the direct contact of the peptide with tissue, such as a cornea.
  • the term “effective amount” as used herein refers to a sufficient amount of the peptide according to the invention to provide desired therapeutic or healthcare effects, or the induction of a particular type of response.
  • the effective amount required varies from subject to subject, depending on the disease state, physical conditions, age, sex, species and weight of the subject, etc. However, an appropriate effective amount can be determined by one of ordinary skill in the art using only routine experimentation.
  • the peptide according to the invention may be administered systemically or topically.
  • pharmaceutically acceptable carrier encompasses any of the standard pharmaceutical carriers.
  • Such carriers may include, but are not limited to: saline, buffered saline, dextrose, water, glycerol, ethanol, propylene glycol, cremophor, nanoparticles, liposome, polymer, and combinations thereof.
  • a pharmaceutical composition of the present invention may be supplemented with one or more excipients that are normally employed in common standard formulations, such as surfactants, solubilizers, stabilizers, emulsifiers, thickeners, and preservatives. Such excipients are well known to those skilled in the art.
  • the peptide having the amino acid sequence of SEQ ID NO: 1 which may be artificially synthesized by a standard method or in any manner commonly used or known to one of ordinary skill. It was confirmed to have an effect in enhancing the migration of corneal epithelial cells, but not the growth of the cells. Therefore, the invention also provides a an eye-care method for preventing eye damage, which comprises administering to a subject in need thereof the peptide having the amino acid sequence of SEQ ID NO: 1 (also named as “Peptide No. 12) in an amount effective to enhance the migration of corneal epithelial cells in the subject.
  • the present invention provides the use of the peptide of the invention for manufacturing a pharmaceutical or healthcare composition benefic to eye care or eye health.
  • the invention provides a composition or a pharmaceutical composition benefic to eye care or eye health, comprising an effective amount of the peptide of SEQ ID NO: 1, and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition of the present invention may be constituted with one or more pharmaceutically acceptable carriers into any form suitable for the mode of administration selected, including systemic and topical administrations via enteral or parenteral administration such as injection, infusion or implantation, oral, transdermal or topical administration.
  • the composition may be formulated with a pharmaceutically or cosmetically acceptable carrier as a topical formulation in a solution, ointment, gel, serum, cream, lotion, powder, emulsion or any form for administration.
  • the formulation may be administered in a form of eye drop.
  • the peptide consisting of the sequence of ArgAsnProLeuGluGluThr (SEQ ID NO: 1) was synthesized by MDBio, Inc. (Taipei, Taiwan) and the purity and composition of peptide was confirmed by high performance liquid chromatography (HPLC) and mass spectrometry. Peptide stock was stored at -20°C after dissolving 10 mg of lyophilized peptide powder in 250 ⁇ l of double deionized water (dd H 2 O) .
  • Human corneal epithelial cell line, HCEC was cultured in complete KSF containing keratinocyte-serum free medium, 5 ng/ml human recombinant EGF, 0.05 mg/ml bovine pituitary extract, 0.005 mg/ml insulin and 500 ng/ml hydrocortisone under 5%CO 2 at 37 °C.
  • HCEC corneal epithelial cells were treated with 0, 2, 5, 10 and 25 ⁇ g/ml of Peptide NO. 12, for 24 and 48 hours respectively, and then was analyzed by transwell migration assay.
  • Peptide NO. 12 enhanced the migration of HCEC corneal epithelial cells.
  • Peptide NO. 12 in either of the concentrations of 5, 10, 25 and 50 ⁇ g/ml did not significantly affect viability of HCEC cells for 24 and 48 hours, respectively.
  • the peptide of SEQ ID NO: 1 provide an unexpected efficacy in the enhancement of the migration of migration of corneal epithelial cells, instead of the cell viability f corneal epithelial cells.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un peptide synthétique constitué d'une séquence d'acides aminés de ArgAsnProLeuGluGluThr (SEQ ID NO : 1). L'invention concerne également une composition pharmaceutique bénéfique pour le soin ou la santé oculaire comprenant le peptide, et un procédé de cicatrisation des plaies à l'aide du peptide.
PCT/CN2017/104991 2017-09-30 2017-09-30 Peptide pour soins oculaires, composition et procédé d'utilisation de celui-ci Ceased WO2019061491A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2017/104991 WO2019061491A1 (fr) 2017-09-30 2017-09-30 Peptide pour soins oculaires, composition et procédé d'utilisation de celui-ci

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2017/104991 WO2019061491A1 (fr) 2017-09-30 2017-09-30 Peptide pour soins oculaires, composition et procédé d'utilisation de celui-ci

Publications (1)

Publication Number Publication Date
WO2019061491A1 true WO2019061491A1 (fr) 2019-04-04

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PCT/CN2017/104991 Ceased WO2019061491A1 (fr) 2017-09-30 2017-09-30 Peptide pour soins oculaires, composition et procédé d'utilisation de celui-ci

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109912685A (zh) * 2017-12-13 2019-06-21 三凡生技研发股份有限公司 眼睛保护胜肽及其组合物及使用该胜肽的用途

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0914827A1 (fr) * 1996-06-26 1999-05-12 Santen Pharmaceutical Co., Ltd. Compositions medicamenteuses ophtalmiques
WO2013142229A1 (fr) * 2012-03-19 2013-09-26 President And Fellows Of Harvard College Conception de nouveaux peptides pour l'induction d'un assemblage de matrice de fibronectine
US8614103B2 (en) * 2006-10-27 2013-12-24 Lpath, Inc. Compositions and methods for treating sphingosine-1-phosphate (S1P) related ocular diseases and conditions
WO2016179007A1 (fr) * 2015-05-01 2016-11-10 Allysta Pharmaceuticals, Inc. Peptidomimétiques de l'adiponectine pour le traitement de troubles oculaires

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0914827A1 (fr) * 1996-06-26 1999-05-12 Santen Pharmaceutical Co., Ltd. Compositions medicamenteuses ophtalmiques
US8614103B2 (en) * 2006-10-27 2013-12-24 Lpath, Inc. Compositions and methods for treating sphingosine-1-phosphate (S1P) related ocular diseases and conditions
WO2013142229A1 (fr) * 2012-03-19 2013-09-26 President And Fellows Of Harvard College Conception de nouveaux peptides pour l'induction d'un assemblage de matrice de fibronectine
WO2016179007A1 (fr) * 2015-05-01 2016-11-10 Allysta Pharmaceuticals, Inc. Peptidomimétiques de l'adiponectine pour le traitement de troubles oculaires

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109912685A (zh) * 2017-12-13 2019-06-21 三凡生技研发股份有限公司 眼睛保护胜肽及其组合物及使用该胜肽的用途
CN109912685B (zh) * 2017-12-13 2022-05-06 三凡生技研发股份有限公司 眼睛保护胜肽及其组合物及使用该胜肽的用途

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