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WO1991007166A1 - Compositions et procedes de reduction du risque de cancer de la peau induit par la lumiere solaire et les rayons ultraviolets - Google Patents

Compositions et procedes de reduction du risque de cancer de la peau induit par la lumiere solaire et les rayons ultraviolets Download PDF

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Publication number
WO1991007166A1
WO1991007166A1 PCT/US1989/005178 US8905178W WO9107166A1 WO 1991007166 A1 WO1991007166 A1 WO 1991007166A1 US 8905178 W US8905178 W US 8905178W WO 9107166 A1 WO9107166 A1 WO 9107166A1
Authority
WO
WIPO (PCT)
Prior art keywords
protease enzyme
proteases
enzyme inhibitors
class
approximately
Prior art date
Application number
PCT/US1989/005178
Other languages
English (en)
Inventor
Clarence A. Ryan
Original Assignee
Washington State University Research Foundation, Inc
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 Washington State University Research Foundation, Inc filed Critical Washington State University Research Foundation, Inc
Priority to PCT/US1989/005178 priority Critical patent/WO1991007166A1/fr
Publication of WO1991007166A1 publication Critical patent/WO1991007166A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • 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
    • A61K38/55—Protease inhibitors
    • 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
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • compositions and Methods for Reducing the Risk of Sunlight and Ultraviolet Induced Skin Cancer Technical Field
  • the technical field of this invention is compositions and methods for treating skin to reduce the risk of skin cancer caused by sunlight or other sources of ultraviolet radiation.
  • Skin cancer is a prevalent disease in humans caused by overexposure to ultraviolet radiation from the sun and other sources. It is commonly known that people with dark skin, or skin that easily tans, are less likely to develop skin cancer due to sunlight exposure. This reduced risk of sunlight-induced cancer is apparently due to the protective nature of melanin against ultraviolet light, and the relatively higher concentrations of melanin in the skin of darker skinned peoples.
  • Current methods for reducing the risk of skin cancer caused by sunlight usually involve the control or elimination of sunlight exposure. Examples include mechanical blocking of the sun's rays, or chemical screening of the sun's rays, such as by using the ultraviolet sunscreen ingredient para-amino benzoic acid (PABA). Although such approaches appear to reduce the risk of sunlight and other ultraviolet radiation induced skin cancer, there remains a need for additional methods of treatment, particularly methods which are effective for treatment after exposure to the ultraviolet light. Disclosure of the Invention and Best Modes for Carrying Out the Invention
  • the present invention includes the discovery that at least some types of protease inhibitors can be used in relatively minute concentrations to treat skin and thereby reduce the risk of skin cancer associated with exposure to sunlight.
  • the protease inhibitors can be applied prospectively to interrupt or reverse the biochemical processes in the skin which are caused by sunlight or ultraviolet exposure and that lead to skin cancer. Retrospective application of the protease inhibitors is also effective in reducing the risk of skin cancer.
  • the protease inhibitors act to inhibit the production of, or the presence or activity of, at least certain types of protease enzymes (proteolytic enzymes) which are contributing factors in sunlight and ultraviolet induced skin cancer initiation.
  • the inhibition or reduction of the protease enzymes, or their activities reduces the likelihood that a tumorigenic reaction will occur in a cell, or that any tumorigenic reaction will not become effective to cause malignant cell reproduction.
  • the action of the protease inhibitors thus reduce the overall likelihood and rate of sunlight-induced skin cancer in humans.
  • protease inhibitors are useful in this invention.
  • Preferred classes of protease inhibitors useful in this invention include those that inhibit the serine class and the metallo- class of proteases. Inhibitors of cysteine and aspartyl proteases are also believed effective.
  • the protease inhibitors useful in the invention generally include most or all known protease inhibitors derived from plants, animals or microorganisms, as well as synthetic protease inhibitors.
  • Preferred types of serine protease inhibitors include the chymotrypsin and trypsin families of protease inhibitors derived from plants, such as from potatoes and soybeans.
  • the soybean-derived Bowman Birk inhibitor family and the potato inhibitor 1 family are appropriate families of inhibitors for use in the novel compositions and methods of this invention. Also appropriate are inhibitors of elastase and other inhibitors of pancreatic proteolytic enzymes. Appropriate protease inhibitors from the metallo- class of protease inhibitors in particular include the carboxy-peptidase inhibitors. These and other protease inhibitors are commercially available and can be prepared using a variety of production techniques known in the art or hereafter developed. The protease inhibitors used in the compositions and methods according to this invention are preferably included in amounts sufficient to provide effective inhibition of at least one of the proteases present in skin cells being treated.
  • Concentrations as low as approximately 10 picograms per milliliter of applied topical mixture are believed effective to provide at least some reduction of the risk of sunlight- induced skin cancer.
  • Protease inhibitor concentrations ranging from that value to approximately 10 milligrams per milliliter, or higher, in the applied topical mixture are believed effective and appropriate for use in the novel methods and compositions.
  • the active protease inhibitors are included in amounts sufficient to provide concentrations ranging from approximately 1 nanogram per milliliter to approximately 1 milligram per milliliter. Still more preferred are concentrations of approximately 0.1 milligrams per milliliter of topical mixture. Variations in the relative effectiveness of differing protease inhibitors cause the preferred concentrations to vary.
  • compositions according to this invention preferably include the desired protease inhibitors in combination with one or more suitable topical ointments, creams, lotions or similar topical vehicles allowing for relatively even and dilute application of the active ingredient or ingredients to exposed surfaces of healthy skin.
  • suitable topical ointments, creams, lotions or similar topical vehicles allowing for relatively even and dilute application of the active ingredient or ingredients to exposed surfaces of healthy skin.
  • suitable topical vehicles are appropriate for use in this invention.
  • the topical vehicle should preferably be of a type which does not cause significant degradation of the protease inhibitors and any additives used in the skin treatment compositions of this invention.
  • Topical vehicles suitable for use in this invention can be selected from water-in-oil and oil-in-water emulsions of mineral, vegetable, animal and synthetic oils; petrolatum; glycerol; mineral; vegetable, animal and synthetic oils; propylene glycol; other aliphatic and aromatic alcohols which can be tolerated by the skin and many other vehicles suitable for topical application to skin.
  • the compositions according to this invention can also be enhanced by including other suitable additives in the topical mixtures.
  • One preferred class of anti-carcinogenic skin treatment compositions according to this invention uses a suitable protease inhibitor in combination with a suitable chemical sunscreen, in particular sunscreens which are effective at reducing the intensity of ultraviolet radiation which reaches the skin.
  • Sunscreens which may be suitable for use in the novel skin treatment compositions include in particular para- amino benzoic acid (PABA).
  • PABA is preferably included in the novel compositions in amounts sufficient to provide concentrations ranging from none to approximately 100 milligrams of PABA per milliliter of the topical anti-carcinogenic mixtures.
  • Concentration of the ultraviolet screening agent in amounts sufficient to provide sunscreen factors ranging from approximately 1 to approximately • 30 are also indicative of the concentration of PABA or other ultraviolet screening agent which may be included.
  • Other sunscreens which do not cause significant degradation of the active protease inhibitors and which are tolerated by the skin are also suitable for use in this invention.
  • sunscreens examples include octyl dimethyl PBA, octyl salicylate, palmitate O, oxybenzone, and others.
  • PABA or other suitable ultraviolet screening agent or agents are advantageously included to provide a combined sunscreen and anti-carcinogenic effect which is particularly effective and easy to apply in a routine manner prior to or during exposure to sunlight.
  • a variety of other additives may also be included in skin treatment compositions according to this invention for a variety of purposes. Ingredients for enhancing or providing humectant properties, spreadability, non-greasiness, fragrance, absorbability and many other desirable attributes of the novel skin treatment compositions can also be included.
  • any such additive ingredients are preferably selected, to be without deleterious effect on the particular protease inhibitors used and their stability within the particular skin treatment compositions.
  • the novel compositions are preferably made by selecting, buying or manufacturing a suitable cream, lotion, ointment or other topical vehicle and then mixing the desired active ingredient or combination of active ingredients into the vehicle in the desired proportions.
  • the active ingredients include the desired protease inhibitors and any suitable ultraviolet screening agent. Any desired additional additives such as described above are also mixed into the topical mixture in the desired concentrations.
  • the invention also includes novel methods for treating skin to reduce the risk of skin cancer induced by sunlight or other source of ultraviolet radiation.
  • the methods are useful in treating mammals, more particularly primates, especially humans, both male and female.
  • the novel methods include obtaining or preparing a suitable anti- cancer cream or other composition, such as described hereinabove.
  • the compositions are applied to the skin in amounts sufficient to create effective application rates from approximately 1 picogram to approximately 10 milligrams or higher of the active protease inhibitors per square centimeter of treated exposed skin area.
  • the novel compositions are most preferably applied to healthy skin not opened by wound, disease or other affliction.
  • the novel compositions are spread evenly onto the skin by the user's hands or with the aid of a suitable applicator, such as a brush, wand or other implement.
  • Example 1 Example 1
  • An anti-carcinogenic topical lotion according to this invention can be prepared by mixing 10 milliliters of U.S.P. grade glycerol into 40 milliliters of distilled water to produce a relatively homogeneous mixture.
  • a suitable protease inhibitor such as potato inhibitor 1
  • potato inhibitor 1 is then mixed into the glycerol and water mixture by slowly stirring the mixture and adding 5 milligrams of the potato inhibitor 1.
  • the resulting glycerol, water and protease inhibitor mixture can be stored at room temperatures.
  • the mixture is advantageously used in the manner typical of lotions by spreading a moist even layer over the user's skin and allowing it to be absorbed into the skin.
  • the anti- carcinogenic mixture is preferably applied to the skin to produce applied surface concentrations of roughly 1 milliliter of lotion to 10 square centimeters of skin, to thus produce surface concentrations of the protease inhibitor roughly equal to 0.01 milligrams per square centimeter.
  • the anti-carcinogenic mixture can be applied after exposure to ultraviolet rays to assist the reconstructive processes of any damaged cells and thereby reduce the risk of tumorigenesis.
  • Example 2 A commercially available suntan lotion known by the brand name
  • SEA AND SKI with sun protection factor of 6 is selected.
  • the listed ingredients are: octyl dimethyl PBA and octyl salicylate as sunscreen agents; cyclomethicone, ethylcellulose, dimethicone, trimethylsiloxysilicate, and fragrance are listed as other ingredients.
  • the soybean-derived Bowman Birk inhibitor Into this suntan lotion is mixed the soybean-derived Bowman Birk inhibitor in amounts sufficient to produce concentrations of the protease inhibitor eq ⁇ al to 1 milligram per milliliter of suntan lotion. The resulting combination is mixed to homogeneity. The resulting anti-carcinogenic lotion is then applied to the skin in suitable amounts such as roughly 1 milliliter per 10 square centimeters.
  • Example 3 Another commercially available suntan lotion sold under the brand name COPPERTONE-CREAM is selected. The cream has an indicated sun protection factor of 8.
  • the listed ingredients include: palmitate O and oxybenzone as sunscreen agents; and sorbitansesquioleate, sorbitol, glyceryl stearate SE, isopropylmyristate, triethanolamine, octadecene/maleic anhydride copolomer, benzyl alcohol, lanolin, jajoba oil, cocoa butter, aloe extract, methylparaben, propylparaben, vitamin E acetate, fragrance, and water are listed as other ingredients.
  • Into 50 milliliters of said lotion is mixed 1 milligram of commercially available elastase inhibitor.
  • the constituents are mixed to homogeneity to produce protease inhibitor concentration of approximately 20 micrograms per milliliter of the anti-carcinogenic lotion.
  • the lotion is then applied to the skin to reduce the risk of ultraviolet-exposure-induced skin cancer.
  • a commercially-available after sun lotion sold under the brand name HAWAIIAN TROPIC AFTER SUN MOISTURIZER CREAM was obtained.
  • the listed ingredients included: mineral oil; propylene glycol; glycerol stearate; polyethylene glycol stearate; cetyl alcohol; triethanolamine; methylparaben; cocoa butter; hydrogenated vegetable oil; coconut oil; avocado oil; vitamin E acetate; extracts of mango, papaya, guava and passion fruit; and fragrance.
  • Into 100 milliliters of the cream is mixed approximately 1 milligram of carboxy-peptidase inhibitor to the point of homogeneity.
  • the resulting anti-carcinogenic after sun moisturizing cream is then applied in the usual fashion to moisturize the skin and reduce the risk of cancer caused by sunlight exposure.
  • Industrial Applicability The novel compositions and methods of this invention are applicable for the treatment of human skin to reduce the risk of skin cancer.

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

Abstract

Compositions et procédés de réduction du risque de cancer de la peau. Les nouvelles compositions comprennent au moins un inhibiteur de protéase efficace. Les inhibiteurs de protéase préférés comprennent les inhibiteurs d'enzyme de protéase de la class sérine de protéases; les inhibiteurs d'enzymes de protéase de la classe cystéine de protéases; les inhibiteurs d'enzymes de protéase de la classe asparyle de protéases; les inhibiteurs d'enzymes de protéase de la classe métallo de protéases; les inhibiteurs d'enzymes de protéase de la classe carboxy-peptidase de protéases; les inhibiteurs d'enzymes de protéase de la classe trypsine de protéases; les inhibiteurs d'enzymes de protéase de la classe chymotrypsine de protéases; les inhibiteurs d'enzymes de protéase des protéases pancréatiques; les inhibiteurs d'enzymes de protéase de la classe élastase de protéases; les inhibiteurs d'enzyme de protéase de la famille d'inhibiteurs de Bowman Birk; les inhibiteurs d'enzymes de protéase de la famille 1 d'inhibiteurs de la pomme de terre. Les inhibiteurs de protéase sont inclus de préférence dans des concentrations allant de 10 picogrammes à 10 milligrammes environ par millilitre des mélanges appliqués localement sur la peau. Les mélanges d'application locale comprennent de préférence un véhicule ou excipient local approprié tel qu'une crème, une lotion ou une pommade. Une classe de compositions anticarcinogènes pour le traitement de la peau, de cette invention, comprend de préférence les inhibiteurs de protéase désirés en combinaison avec un agent ou des agents de protection solaire appropriée, tels que l'acide para-aminobenzoïque de manière à obtenir des compositions particulièrement avantageuses réduisant le risque du cancer de la peau induit par la lumière solaire.
PCT/US1989/005178 1989-11-16 1989-11-16 Compositions et procedes de reduction du risque de cancer de la peau induit par la lumiere solaire et les rayons ultraviolets WO1991007166A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US1989/005178 WO1991007166A1 (fr) 1989-11-16 1989-11-16 Compositions et procedes de reduction du risque de cancer de la peau induit par la lumiere solaire et les rayons ultraviolets

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1989/005178 WO1991007166A1 (fr) 1989-11-16 1989-11-16 Compositions et procedes de reduction du risque de cancer de la peau induit par la lumiere solaire et les rayons ultraviolets

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WO1991007166A1 true WO1991007166A1 (fr) 1991-05-30

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999009065A1 (fr) * 1997-08-16 1999-02-25 Eberhard-Karls-Universität Tübingen Universitätsklinikum Peptide a effet radioprotecteur
GR1003080B (el) * 1997-11-21 1999-02-25 Συντηρηση ενζυμων σε κοιλο πωμα φιαλιδιων για χρηση τους σε καλλυντικα σκευασματα
WO2000050057A1 (fr) 1999-02-22 2000-08-31 Bernstein Eric F Compositions et procedes de prevention du photovieillissement
JP2001081011A (ja) * 1999-07-27 2001-03-27 Johnson & Johnson Consumer Co Inc 皮膚の色素沈着を処理するための方法
US6638909B1 (en) 1996-11-01 2003-10-28 Ethicon, Inc. Wound healing compositions containing alpha-1-antitrypsin
US7012100B1 (en) 2002-06-04 2006-03-14 Avolix Pharmaceuticals, Inc. Cell migration inhibiting compositions and methods and compositions for treating cancer
US7192615B2 (en) 2001-02-28 2007-03-20 J&J Consumer Companies, Inc. Compositions containing legume products
US7309688B2 (en) 2000-10-27 2007-12-18 Johnson & Johnson Consumer Companies Topical anti-cancer compositions and methods of use thereof
US8093293B2 (en) 1998-07-06 2012-01-10 Johnson & Johnson Consumer Companies, Inc. Methods for treating skin conditions
US8106094B2 (en) 1998-07-06 2012-01-31 Johnson & Johnson Consumer Companies, Inc. Compositions and methods for treating skin conditions
US8431550B2 (en) 2000-10-27 2013-04-30 Johnson & Johnson Consumer Companies, Inc. Topical anti-cancer compositions and methods of use thereof
US12233073B2 (en) 2017-06-09 2025-02-25 Regents Of The University Of Minnesota Skin care formulations and skin cancer treatment

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, 1980, Volume 92, 213629f. *
CHEMICAL ABSTRACTS, 1982, Volume 96, 97304v. *
CHEMICAL ABSTRACTS, 1984, Volume 100, 46760j. *
CHEMICAL ABSTRACTS, 1984, Volume 101, 122650m. *

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6638909B1 (en) 1996-11-01 2003-10-28 Ethicon, Inc. Wound healing compositions containing alpha-1-antitrypsin
US6645934B1 (en) 1997-08-16 2003-11-11 Eberhard-Karls-Universität Tübingen Peptide with radio protective effect
DE19735587B4 (de) * 1997-08-16 2012-03-22 Eberhard-Karls-Universität Tübingen Universitätsklinikum Peptid mit radioprotektiver Wirkung, dieses enthaltende kosmetische oder pharmazeutische Zusammensetzung, für dieses kodierende Nukleinsäure, Herstellungsverfahren für dieses Peptid und die Verwendung als radioprotektives Agens
WO1999009065A1 (fr) * 1997-08-16 1999-02-25 Eberhard-Karls-Universität Tübingen Universitätsklinikum Peptide a effet radioprotecteur
GR1003080B (el) * 1997-11-21 1999-02-25 Συντηρηση ενζυμων σε κοιλο πωμα φιαλιδιων για χρηση τους σε καλλυντικα σκευασματα
WO1999026856A1 (fr) * 1997-11-21 1999-06-03 Katsikas, Marios Recipient de melange a compartiment double pour melanges renfermant des enzymes utiles pour traiter l'acne
US6627192B1 (en) 1997-11-21 2003-09-30 Spyros Tsakas Use of dual compartment mixing container for enzyme mixtures useful to treat acne
US8106094B2 (en) 1998-07-06 2012-01-31 Johnson & Johnson Consumer Companies, Inc. Compositions and methods for treating skin conditions
US8093293B2 (en) 1998-07-06 2012-01-10 Johnson & Johnson Consumer Companies, Inc. Methods for treating skin conditions
EP1162934A4 (fr) * 1999-02-22 2005-01-26 Eric F Bernstein Compositions et procedes de prevention du photovieillissement
JP2002537346A (ja) * 1999-02-22 2002-11-05 エリック・エフ・バーンスタイン 光老化の保護用組成物および保護方法
WO2000050057A1 (fr) 1999-02-22 2000-08-31 Bernstein Eric F Compositions et procedes de prevention du photovieillissement
EP1077063A3 (fr) * 1999-07-27 2003-02-12 JOHNSON & JOHNSON CONSUMER COMPANIES, INC. Méthodes pour agir sur la pigmentation de la peau
KR100778086B1 (ko) * 1999-07-27 2007-11-26 죤슨 앤드 죤슨 컨써머 캄파니스 인코포레이티드 보우만-버크 억제제를 포함하는 천연추출물을 투여하는 피부색소침착의 치료방법, 상기 천연추출물을 포함하는 피부색소침착을 치료하는 조성물 및 상기 천연추출물을 포함하는 피부색소침착을 치료하는 화장용 조성물
JP2001081011A (ja) * 1999-07-27 2001-03-27 Johnson & Johnson Consumer Co Inc 皮膚の色素沈着を処理するための方法
US7309688B2 (en) 2000-10-27 2007-12-18 Johnson & Johnson Consumer Companies Topical anti-cancer compositions and methods of use thereof
US8431550B2 (en) 2000-10-27 2013-04-30 Johnson & Johnson Consumer Companies, Inc. Topical anti-cancer compositions and methods of use thereof
US7192615B2 (en) 2001-02-28 2007-03-20 J&J Consumer Companies, Inc. Compositions containing legume products
US7897144B2 (en) 2001-02-28 2011-03-01 Johnson & Johnson Comsumer Companies, Inc. Compositions containing legume products
US7012100B1 (en) 2002-06-04 2006-03-14 Avolix Pharmaceuticals, Inc. Cell migration inhibiting compositions and methods and compositions for treating cancer
US7700615B2 (en) 2002-06-04 2010-04-20 Avolix Pharmaceuticals, Inc. Cell migration inhibiting compositions and methods and compositions for treating cancer
US12233073B2 (en) 2017-06-09 2025-02-25 Regents Of The University Of Minnesota Skin care formulations and skin cancer treatment

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