WO1996016669A1 - Use of human recombinant epidermal growth factor in the manufacture of a medicament for treating acne - Google Patents
Use of human recombinant epidermal growth factor in the manufacture of a medicament for treating acne Download PDFInfo
- 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
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- WIPO (PCT)
- Prior art keywords
- egf
- growth factor
- epidermal growth
- manufacture
- medicament
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- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000036346 tooth eruption Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 235000002374 tyrosine Nutrition 0.000 description 1
- 150000003668 tyrosines Chemical group 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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
Use of Epidermal Growth Factor in the manufacture of a medicament for treating acne and acneiform dermal disorders. The EGF may be human recombinant EGF. Pharmaceutical composition for topically treating acne and acneiform dermal disorders by applying to the skine a cream or ointment containing this active principle.
Description
Title: Use of human recombinant epidermal growth factor in the manufacture of a medicament for treating acne
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.
Acne usually occurs during adolescence. It can persist or develop during adulthood, but the disease normally disappears at around 20 years of age, leaving scars in some cases. Due to these characteristics and the frequency of this disease, it is considered to be the most esthetically compromising illness for young people.
At present the etiology of this disease can only be viewed from a multifactorial standpoint, involving the androgenic stimulation of sebaceous glands, abnormal differentiation of the follicular epithelium, proliferation of the follicular micro- flora, particularly Propionibacterium acnes, and the variable inflammatory response of the host. Acne is characterized by both non-inflammatory lesions (comedones) and inflammatory lesions
(pimples, pustules and nodulocysts) . With the first pathological changes, a differentiation of the follicular epithelium gives rise to a hyperkeratosis caused by follicular retention and formation of a microcomedo that can either remain as a non- inflammatory lesion or evolve towards the different inflammatory expressions.
The mechanisms that control the transformation of a micro¬ comedo into a ripe blackhead or an inflammatory lesion are not known. However, recent studies suggest that the free fatty acids in the follicle can contribute to the inflammatory process, due to their chemotaxic and cytostatic response to polymorphonuclear leukocytes and monocytes.
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. Finally, 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. As a result, 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.
Histological studies show the presence of different elements which correspond to the different etiopathogenic stages.
According to Lever (Lever, WF. Histopathology of the skin , 5ta Ed. Phyladelphia, IB Lippincott Co. 1975; Pp: 344) 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. During the healing process, 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.
Many substances have been used to treat Acne (both topical and systemic). Among the principal topical substances used are: sulfur including all types of mud packs, resorcinol, salicylic acid, zinc among other exfoliating and anti-seborrheic chemical substances (Andrews Domonkos, A Tratado de Dermatologia, 5ta Ed. V.l. Lababana: Cientifico Tόcnica 1984; Pp 276, Quiroga, M; Guillot CF. Cosmέtica Dermatolόgica Prάctica . 5ta Ed. Buenos Aires, Ateneo 1985, Pp: 220).
At present, and in spite of the favorable results, the use of antibiotics, benzoyl peroxide, retinoic acid, hormones and other drugs, has been limited, due to their precise indications and undesired adverse reactions.
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 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
Biochem 1979; 48: 193-216; Fisher DA, Lakshmanan J.J. Metabolism and effects of epidermal growth factor and related growth factors in mammals. Endocrine Reviews 1990; 11 (3): 418-442). It has also been detected in tissue extracts, from practically all of the organs in the body, excepting skeletal muscle fibers and
erythrocytes (Merlino GT. Epidermal growth factor receptor relation and function. Semin Cancer Biol 1990; 1; 277-284).
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, Kamerath CG, Wolt TB, Woodward SC. Sustained release of Epidermal Growth Factor accelerates wound repair.
Proc Natl Sci USA 1985; 82: 7340-7344; Gross I, Dynia D, Rooney S, Smart DA, Warshaw JB, SJssom JF Hoath SB. Influence of epidermal growth factor on fetal rat lung development in vitro. Pediatr Res 1986; 20: 473). The most well known in vivo effect of EGF is its capacity to promote epithelial cell proliferation (Carpenter G, Cohen S. Epidermal Growth Factor. Ann Rev Biochem 1979; 48: 193-216).
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. Ann Rev Biochem 1981; 43: 251-265). The receptor is a glycoprotein product of the cellular c- erb I proto-oncogene formed by 1,186 amino acids, 621 of which make up an extracellular domain containing the site that binds to the EGF. It also has a transmembrane region, with 23 predominantly hydrophobic amino acids and a cytoplasmic region of 542 amino acids with tyrosine kinase activity which is activated by the EGF-receptor interaction, as the result of an
auto-phosphorylation reaction in the cytoplasmic portion (Yarden Y, Schlessinger J. Epidermal growth factor induced rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry 1989; 26: 1443-1451; Helin K, Velu T, Martin P, Vass WC, Allevato G, Lowy DR, Beguinot L. The biological activity of the human epidermal growth factor receptor is positively regulated by its c-terminal tyrosines. Oncogene 1991, 625-832).
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. As a result of the first bioassay to which EGF was submitted, it was concluded that 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. The
EGF induces mitotic activity in the cells of the epidermis, sebaceous glands and dermal fibroblasts. In vivo experimental systems for assessing the effect of the factor on the healing of
I wounds and burns show that the topical application of EGF stimulates the cicatrization process and improves its quality
(Martin P Hopkinson-Woolley J, McCluskey J. Growth factors and cutaneous wound repair. Progr Growth Factor Res 1992; 4: 25-44). In fibroblasts and endothelial cells an increase has been observed in the production of cell surface proteins or
fibronectine, which provides the necessary substrate for the growth and differentiation of the epidermis (Gospodarowicz D. Epidermal and nerve growth factors in mammalian development. Ann Rev Biochem 1979; 43: 251-265). One of the reasons for such intensive research has been done on the biology of EGF and its receptor is due to their relationship with the skin aging process. Human dermal diploid fibroblasts, in spite of the physiological level of expressed receptors, become dysfunctional with the consequent drop in tyrosine kinase activity.
Apparently, the number of 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.
The invention also provides a pharmaceutical composition useful for treatment of acne and/or acneiform dermal disorders comprising between 2-50 μg/g of EGF, preferably approximately
10 μg/g, and an appropriate excipient. Preferably, it will be in the form of a cream or ointment for topical application.
Using EGF it is possible to obtain an efficacious product for the treatment of this chronic disease of the skin with psychological and esthetic implications. It was demonstrated in a double blind clinical trial using the eight point scale of the
English Medical College, at the beginning of the trial, 45 days later, and at the end of treatment, in sixty patients. The treatment consisted of the topical application of EGF cream or placebo (inert cream) daily during a period of 90 days. Patients treated with EGF showed significant improvement (p < 0.01) when compared to the placebo group. The final results show a general improvement in 23 patients (79.3%) in the EGF group: 15 were considered to be much better (51.7%) and 8 (27.5%) better. None of the patients worsened. This invention could be useful as an alternative therapy for acne treatment.
The 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 μg/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.
Sixty patients with acne were included in the clinical trial (30 patients per group). The treatment consisted of the topical application of EGF cream or placebo (inert cream) daily during a period of 90 days. The grade of severity was determined according to the 8 point scale of the English Medical College, at the beginning of the trial, 45 days later and at the end of treatment.
Patients treated with EGF showed significant improvement (p < 0.01) when compared to the placebo group. The final result showed a general improvement in 23 patients (79.3%) in the EGF group: 15 were considered to be much better (51.7%) and 8 (27.5%) better. None of the patients worsened. Only 2 patients (6.66%) in the placebo group were considered to be much better and 15 (50%) better. A total of 13 (36.6%) patients responded negatively; and 3 (10%) became worse.
The mean values of the subjects who improved in the placebo group were equal to 0.5 degrees while for the EGF group the figure was.1.31 degrees.
Non inflammatory lesions responded best to the EGF treatment (blackhead) and among the inflammatory lesions, the best results were observed in cases of pimples and pustules. Improvement in case of nodules was not as marked as in the case of the aforementioned.
More chronic lesions (cysts and abcesses) did not present a significant improvement; some cases did not report any improvement whatsoever. Regarding blackheads, the number of patients with many lesions of this nature at the beginning of the treatment was 24, but dropped to only 7 patients by the end of the treatment.
Of the 23 patients with pimples at the beginning of the treatment only 6 still had them at the end of the study. The number of patients with pustules dropped from 20 at the beginning of the study to only 6 at the conclusion.
Example of patients treated with EGF
• 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.
These results indicate that EGF can influence the correction of skin disorders implicated in the physiopathology of acne.
Claims
1. Use of Epidermal Growth Factor in the manufacture of a medicament for treating acne and acneiform dermal disorders.
2. A pharmaceutical composition useful for treatment of acne and acneiform dermal disorders comprising between 2-50 μg/g of EGF and an appropriate excipient.
3. A pharmaceutical composition according to claim 2, wherein the EGF concentration is approximately 10 μg/g.
4. A pharmaceutical composition according to claim 2 or 3 in the form of a cream or ointment for topical application.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CU1994136A CU22613A1 (en) | 1994-11-25 | 1994-11-25 | USE OF EPIDERMIC GROWTH FACTOR FOR THE TREATMENT OF ACNE |
| CU136/94 | 1994-11-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996016669A1 true WO1996016669A1 (en) | 1996-06-06 |
Family
ID=46093359
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/NL1995/000392 WO1996016669A1 (en) | 1994-11-25 | 1995-11-17 | Use of human recombinant epidermal growth factor in the manufacture of a medicament for treating acne |
Country Status (3)
| Country | Link |
|---|---|
| AR (1) | AR002002A1 (en) |
| CU (1) | CU22613A1 (en) |
| WO (1) | WO1996016669A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015182905A1 (en) * | 2014-05-29 | 2015-12-03 | Daewoong Pharmaceutical Co., Ltd. | Pharmaceutical composition for preventing or treating skin rash |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0140998A1 (en) * | 1983-11-02 | 1985-05-15 | Nihon Chemical Research Kabushiki Kaisha | Ophthalmic preparations |
| WO1991002533A1 (en) * | 1989-08-16 | 1991-03-07 | Levin Robert H | Topical compositions containing lycd and other topically active medicinal ingredients |
| CN1083371A (en) * | 1993-01-03 | 1994-03-09 | 周至惠 | Acne, folliculitis, erythra special nursing agent |
-
1994
- 1994-11-25 CU CU1994136A patent/CU22613A1/en unknown
-
1995
- 1995-11-17 WO PCT/NL1995/000392 patent/WO1996016669A1/en active Application Filing
- 1995-11-24 AR ARP950100314A patent/AR002002A1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0140998A1 (en) * | 1983-11-02 | 1985-05-15 | Nihon Chemical Research Kabushiki Kaisha | Ophthalmic preparations |
| WO1991002533A1 (en) * | 1989-08-16 | 1991-03-07 | Levin Robert H | Topical compositions containing lycd and other topically active medicinal ingredients |
| CN1083371A (en) * | 1993-01-03 | 1994-03-09 | 周至惠 | Acne, folliculitis, erythra special nursing agent |
Non-Patent Citations (2)
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015182905A1 (en) * | 2014-05-29 | 2015-12-03 | Daewoong Pharmaceutical Co., Ltd. | Pharmaceutical composition for preventing or treating skin rash |
| CN106659768A (en) * | 2014-05-29 | 2017-05-10 | 株式会社大熊制药 | Pharmaceutical composition for preventing or treating skin rash |
Also Published As
| Publication number | Publication date |
|---|---|
| AR002002A1 (en) | 1998-01-07 |
| CU22613A1 (en) | 2000-02-10 |
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