WO1996016669A1 - Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne - Google Patents

Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne Download PDF

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Publication number
WO1996016669A1
WO1996016669A1 PCT/NL1995/000392 NL9500392W WO9616669A1 WO 1996016669 A1 WO1996016669 A1 WO 1996016669A1 NL 9500392 W NL9500392 W NL 9500392W WO 9616669 A1 WO9616669 A1 WO 9616669A1
Authority
WO
WIPO (PCT)
Prior art keywords
egf
growth factor
epidermal growth
manufacture
medicament
Prior art date
Application number
PCT/NL1995/000392
Other languages
English (en)
Inventor
Tania GONZÁLES-LÓPEZ
José RODRÍGUEZ-MACHADO
Guillermo FERNÁNDEZ-ARAGÓN
Maria Dolores Castro-Santana
Francisco HERNÁNDEZ-BERNAL
Arturo DÍAZ DE LA ROCHA-QUEVEDO
Pedro Antonio LÓPEZ-SAURA
Original Assignee
Centro De Ingeniería Genética Y Biotecnología
Kambeel, Robert, Wilhelmus
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 Centro De Ingeniería Genética Y Biotecnología, Kambeel, Robert, Wilhelmus filed Critical Centro De Ingeniería Genética Y Biotecnología
Publication of WO1996016669A1 publication Critical patent/WO1996016669A1/fr

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Classifications

    • 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
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1808—Epidermal growth factor [EGF] urogastrone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/86—Products or compounds obtained by genetic engineering

Definitions

  • This invention is related with Medicine boughs, specifi ⁇ cally with the use of human recombinant Epidermal Growth Factor in the manufacture of a medicament for topically treating acne and acneiform dermal disorders.
  • Acne is a chronic skin disease, with psychological and esthetic implications, that affects 90% of adolescents. It is characterized by a polymorphous lesion syndrome caused principally by the interaction of predisposing hormonal and genetic factors which act on the sebaceous apparatus. It generally affects the face, neck and upper part of the arms and trunk. The most affected areas on the face are the cheeks, forehead, nose and chin.
  • Free intrafollicular fatty acids are mainly the result of the hydrolysis of sebaceous triglycerides by the follicular microflora, especially Propionibacterium acnes, since it is the only one with a lipase capable of hydrolyzing them.
  • This microbe also has other functions that lead to the production of a variety of extracellular products which intervene in the inflammatory response.
  • the inflammatory process can be modulated by the variable response of the host, particularly by the neutrophils that play a very important role, since they represent more than 90% of the leukocyte population.
  • all treatments currently in use are aimed at lowering the inflammatory response by modulating the response of the host and of the aforementioned factors that intervene in this process.
  • a blackhead contains keratinized sebaceous cells and some micro ⁇ organisms.
  • the follicular papules caused by acne are characterized by a perifollicular lymphocyte infiltrate.
  • the intrafollicular pustules which mostly contain neutrophils, usually form after the wall of the follicle has been ruptured.
  • the nodules occur at the site of follicular rupture, where the sebaceous free fatty acids, bacteria and keratinized cells have escaped from the follicle towards the dermis.
  • the perifollicular infiltrate can form a.cyst containing numerous neutrophils, in addition to plasma cells, mononuclear cells and giant cells which react to foreign bodies.
  • the inflammatory infiltrate is replaced by a fibrosis and the epidermis of the follicular wall can extend around and encapsulate part of the inflammatory mass.
  • the EGF is a single chain polypeptide with 53 amino acids, an isoelectric point of 4.6 and a molecular weight of 6,045 daltons. It contains 6 cysteine residues that form disulfide bonds, giving rise to 3 peptide loops which give the molecule its characteristic stability (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979, 48; 193-216; Savage Cr, Jr, Hash JH, Cohen S. Epidermal Growth Factor. J Biol Chem 1973; 248: 7669-7672).
  • EGF EGF was isolated by Cohen and Carpenter from human urine, with use of an antibody to mouse EGF (Cohen S, Carpenter G. Human Epidermal Growth Factor, Isolation and Chemical and Biological Properties, Proc Natl Acad Sci USA 1975; 72: 1317- 1321). Since then, its presence has been reported in many human body fluids such as sera, salive, calostrum, amniotic fluid and semen (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev
  • EGF is a powerful mitogenic agent for a great variety of cells, including the keratinocytes, conjunctive and pharyngeal tissues, corneal endothelial cells, smooth muscle cells in the vessels, condrocytes, hepatocytes, cells from the thyroid follicle and the mammary glands (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979; 48: 193-216; Buckley A, Davidson JM, toneth CG, Wolt TB, Woodward SC. Sustained release of Epidermal Growth Factor accelerates wound repair.
  • EGF epidermal growth factor
  • the action of EGF is exerted by binding to a specific receptor on the cell membrane.
  • the presence of this receptor has been reported in many human cell lines with exception of the hematopoietic cells.
  • the receptors are also found in relative abundance in the brain, thyroid, lungs, skin, placenta and fetal membranes (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979; 48: 193-216; O'Keefe E, Hollenberg MD, Cuatrecasas P. EGF characteristics of specific binding in membranes from liver, placenta and other tissues. Arch Biochem Biophys 1974;164: 51-52; Gospodarowicz D. Epidermal and nerve growth factors in mammalian development.
  • EGF epithelial restoration role
  • salivary glands The ancestral instinct in animals to lick their wounds and skin lesions have been associated to the epithelial restoration role of EGF, based on the high concentration of this protein in the salivary glands.
  • EGF's unusual capacity to stimulate teething and opening of the eyelids was due to its ability to stimulate the migration, maturation and keratini- zation of the epidermis (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979; 48: 193-216).
  • EGF and its receptor have been detected in a variety of skin cells.
  • Keratinocytes cells in the ducts of the sudoriferous glands, hair follicles, myoepithelial cells, smooth muscle epithelium, and muscle cells responsible for the raising of hairs, all contain a large number of receptors (Martin P, Hopkinson-Woolley J, McCluskey J Growth factors and cutaneous wound repair. Proc Growth Factor Res 1992, 4: 25-44).
  • Another interesting aspect is the fact that as differentiation or keratinization of the epithelial cells increases, the number of expressed EGF receptors decreases.
  • EGF induces mitotic activity in the cells of the epidermis, sebaceous glands and dermal fibroblasts.
  • EGF receptors decreases in the skin cells of patients suffering from progeria and other forms of early skin involution.
  • Other studies have reported disorders in the functional capacity of the intra-cytoplasmic domain of the EGF receptor in patients with psoriasis (Elder JT, Fisher GJ, Lindquist PB, Bennett GL, Pittelkow MR, Coffey RJ, Jr Ellingsworth L, Derynck R, Voorhees JJ. Overexpression of transforming growth factor alpha in psoriatic epideris. Science 1989, 243; 811-813).
  • the present invention relates to the use of EGF in the manufacture of a composition for topically treating acne and acneiform dermal disorders.
  • a preferred embodiment of the invention is the use of human recombinant Epidermal Growth Factor (EGF) in the manufacture of a pharmaceutical composition for topically treating acne and/or acneiform dermal disorders by applying to the skin a cream or ointment containing this active principle.
  • EGF Epidermal Growth Factor
  • the invention also provides a pharmaceutical composition useful for treatment of acne and/or acneiform dermal disorders comprising between 2-50 ⁇ g/g of EGF, preferably approximately
  • EGF effect in the improvement of active acne was showed in a double blind clinical trial.
  • a EGF cream was compared with placebo.
  • the concentration of EGF in the cream was 10 ⁇ g/g and the other components were stearic acid as thickener, anhydrous potassium carbonate as emulsifier and thickener, methylparaben and propylparaben for antimicrobial preservation, glycerine as humidifier and purifier water as solvent.
  • Pacient 1 grade 6 at the beginning, and 3.5 at the end.
  • Pacient 2 grade 5.5 at the beginning, and 3.5 at the end.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Birds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne l'utilisation du facteur de croissance épidermique (EGF) dans la production d'un médicament destiné à traiter l'acné et des dermatoses acnéiformes. L'EGF utilisé peut être l'EGF humain recombiné. L'invention concerne également des compositions pharmaceutiques permettant le traitement topique de l'acné et de dermatoses acnéiformes par application sur la peau d'une crème ou d'un onguent contenant ledit principe actif.
PCT/NL1995/000392 1994-11-25 1995-11-17 Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne WO1996016669A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CU1994136A CU22613A1 (es) 1994-11-25 1994-11-25 Uso de factor de crecimiento epidérmico para el tratamiento del acne
CU136/94 1994-11-25

Publications (1)

Publication Number Publication Date
WO1996016669A1 true WO1996016669A1 (fr) 1996-06-06

Family

ID=46093359

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NL1995/000392 WO1996016669A1 (fr) 1994-11-25 1995-11-17 Utilisation du facteur de croissance epidermique humain recombine dans la production d'un medicament contre l'acne

Country Status (3)

Country Link
AR (1) AR002002A1 (fr)
CU (1) CU22613A1 (fr)
WO (1) WO1996016669A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015182905A1 (fr) * 2014-05-29 2015-12-03 Daewoong Pharmaceutical Co., Ltd. Composition pharmaceutique destinée à la prévention ou au traitement d'éruptions cutanées

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0140998A1 (fr) * 1983-11-02 1985-05-15 Nihon Chemical Research Kabushiki Kaisha Préparations ophtalmiques
WO1991002533A1 (fr) * 1989-08-16 1991-03-07 Levin Robert H Composition topiques contenant du lycd et d'autres ingredients medicaux actifs au niveau topique
CN1083371A (zh) * 1993-01-03 1994-03-09 周至惠 痤疮、毛囊炎、皮疹特别护理剂

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0140998A1 (fr) * 1983-11-02 1985-05-15 Nihon Chemical Research Kabushiki Kaisha Préparations ophtalmiques
WO1991002533A1 (fr) * 1989-08-16 1991-03-07 Levin Robert H Composition topiques contenant du lycd et d'autres ingredients medicaux actifs au niveau topique
CN1083371A (zh) * 1993-01-03 1994-03-09 周至惠 痤疮、毛囊炎、皮疹特别护理剂

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE INVESTEXT; FILE SERVER STN IN KARLSRUHE, ACCESION NUMBER 89:314028 SACCO, G.R. ET AL: BIOPHARMACEUTICALS -INDUSTRY REPORT, 1989 *
DATABASE WPI Section Ch Week 9524, Derwent World Patents Index; Class B04, AN 95-179722 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015182905A1 (fr) * 2014-05-29 2015-12-03 Daewoong Pharmaceutical Co., Ltd. Composition pharmaceutique destinée à la prévention ou au traitement d'éruptions cutanées
CN106659768A (zh) * 2014-05-29 2017-05-10 株式会社大熊制药 用于预防或治疗皮疹的药物组合物

Also Published As

Publication number Publication date
CU22613A1 (es) 2000-02-10
AR002002A1 (es) 1998-01-07

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