WO1998006409A2 - Composition renfermant de la vitamine a et son utilisation, en particulier contre les dermatoses - Google Patents

Composition renfermant de la vitamine a et son utilisation, en particulier contre les dermatoses Download PDF

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Publication number
WO1998006409A2
WO1998006409A2 PCT/EP1997/004446 EP9704446W WO9806409A2 WO 1998006409 A2 WO1998006409 A2 WO 1998006409A2 EP 9704446 W EP9704446 W EP 9704446W WO 9806409 A2 WO9806409 A2 WO 9806409A2
Authority
WO
WIPO (PCT)
Prior art keywords
composition according
vitamin
polyanion
skin
polysulfate
Prior art date
Application number
PCT/EP1997/004446
Other languages
German (de)
English (en)
Other versions
WO1998006409A3 (fr
Inventor
Albert Landsberger
Malte Landsberger
Original Assignee
Albert Landsberger
Malte Landsberger
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 Albert Landsberger, Malte Landsberger filed Critical Albert Landsberger
Publication of WO1998006409A2 publication Critical patent/WO1998006409A2/fr
Publication of WO1998006409A3 publication Critical patent/WO1998006409A3/fr

Links

Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/07—Retinol compounds, e.g. vitamin A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • 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
    • A61K8/67—Vitamins
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof

Definitions

  • composition containing vitamin A and its use in particular against skin diseases Composition containing vitamin A and its use in particular against skin diseases
  • the invention relates to a new vitamin A-containing composition and its use.
  • Triggers can be pathogens, such as b eispielnger bacteria, fungi, viruses; Foreign matter, b eispielmud care and drug or Irritation and G iftscher such as insecticides.
  • Be orld Behan d skin diseases both systemic (oral) as well as locally, in particular with Sub b ereitungen in the form of creams, ointments or gels.
  • the drugs used also have a number of undesirable effects.
  • creams administered frequently result in reddening, drying out, itching, desquamation as well as burning and stinging on the treated skin areas.
  • the corticoids administered in a number of dermatoses can lead to changes in skin pigmentation and / or to folliculitis, favor secondary infections and delay wound healing.
  • Oral drugs used to treat severe cornification disorders can, in extreme cases, lead to osteoporosis, onicholysis and epidermal necrolysis.
  • the present invention was based on the technical problem of having a preparation, in particular for skin diseases well tolerated, rapid onset of action possible an d provide higher efficiency than the previously available preparations.
  • composition which contains at least one polyanion, in particular a linear polyanion, a vitamin A and / or a precursor of vitamin A.
  • the basic building block of the polyanion preferably forms a disaccharide, in particular a glycosaminoglycan or derivative thereof. So is preferred as the polyanion
  • Chondroitin polysulfate the atan polysulfate, pentosan polysulfate or heparin are used.
  • High molecular weight poly anions such as chondroitin polysulfates and dermatan polysulfates have an average molecular weight of 20,000 to 60,000 daltons.
  • Further polyanions which can be used according to the invention have a molecular weight of more than 5000 to 15000, in particular in the range from 8000 to 12000.
  • the low molecular weight polyanions which can also be used, such as pentosan polysulfate have a molecular weight in the range from 1500 to 5000 daltons.
  • Vitamin A and provitamin A can be of synthetic or natural origin; According to the invention, retinol, in particular retinol palmitate, is preferably used as vitamin A, and beta-carotene in particular is used as the precursor of vitamin A.
  • the preparation according to the invention is very well suited for the treatment of a number of skin diseases, in particular for the treatment of excessive scarring and cornification, hardening of connective tissue, superficial inflammation (boils), virus-related skin symptoms such as herpes simplex labialis, poorly healing skin tears (Rhagaden) and skin fungus diseases.
  • skin diseases in particular for the treatment of excessive scarring and cornification, hardening of connective tissue, superficial inflammation (boils), virus-related skin symptoms such as herpes simplex labialis, poorly healing skin tears (Rhagaden) and skin fungus diseases.
  • Rhagaden poorly healing skin tears
  • skin fungus diseases at Inflammation of superficial veins, caused by cytostatic chemotherapy drugs, the symptoms subside after an unusually short time. With the rare progressive generalized scleroderma, already hardened skin areas become supple again.
  • composition according to the invention can also be used for the treatment of superficial tissue degeneration: in the case of superficial colonization of organ cancers, an at least partial regression with subsequent normal new skin formation can be achieved.
  • preparation is also suitable as a cosmetic and also has beneficial effects as a body or skin care product.
  • Linear polyanions not only attack tumor cells directly (Landsberger A.: The effect of heparinoids on the Ehrlich ascites tumor in mice; Med. Welt 22, 1963, pages 1222 to 1233), but also enhance the rectified effect of other substances.
  • Appropriate therapeutic preparations containing anionic linear polymers and cytostatic chemotherapeutics have already been patented (DE 3220326C2 and 3249658C2, US-A-4, 710, 493 and 4,738,955; CDN-B-1227427; EP 0176769B1) and are currently in clinical pharmacology h en testing (Landsberger A., M. Landsberger.:.
  • the diverse, experimentally proven effects of anionic linear polymers include: inhibiting the multiplication of certain viruses (Baba M. et al.: Sulfated Polysaccharides are Potent and Selective Inhibitors of Various Enveloped Viruses, Including Herpex Simplex Virus, Cytomegalovirus, Vesicular Stomatitis Virus, and Human Immunodeficiency Virus; Antimicrobial Agents and Chemoth. 32, 11, 1988, pages 1742 to 1745; Museteanu C, H.
  • Voss Sulfated glycosaminoglycans as virus inhibitors, 3rd communication: to determine the basics of a therapy for viral diseases with glycosaminoglycan polysulfates in animal experiments; Zbl. Bakt. Hyg., I. Dept. Orig. A231, 1975, pages 375 to 388), enhancing the effect of growth factors (Nagasaki T., MA Lieberman: Heparin Potentiates the Action of Plasma Membrane-Associated Growth Stimulatory Activity; J. of Cellular Phys. 133, 1987, pages 365 to 371) and the blocking of enzymes which spread to the inflammation and tumor contribute by breaking down constituents of the basic substance of the connective tissue (Greiling H., M. Kaneko: The inhibition of lysosomal enzymes by a glycosaminoglycan polysulfate; Pharm. Forsch. (Drug Res.) 23, 593, pages 597 to 1973).
  • linear polyanions from disaccharide units are themselves an essential component of the basic substance. They are found in the connective tissue of humans as
  • Glycosaminoglycans especially chondroitin sulfate, predominantly bound to protein bodies to form proteoglycans or glycoproteins. They influence the entire mass exchange between the supplying blood vessels and the cells, determine with the water content, the ion and metabolite concentration, act as a selective filter and have a defense function. They promote the cohesion of the fibers of the basic substance and are probably also involved in the formation of collagen fibers from microfibrils (Bucher 0., H. Wartenberg: Cytology, Histology and Microscopic Anatomy of Humans; pages 146 to 163, publisher Hans Huber, Bern, Stuttgart, Toronto 1989; Junqueira, L. C, J. Carneiro: Histology, cytology, histology and microscopic human anatomy; pages 151 to 171, Springer Verlag, Berlin, Heidelberg, New York, Tokyo 1991).
  • heparin and heparin-like substances are mainly used in the prevention and treatment of diseases.
  • the substances are injected for prophylaxis against thrombosis and embolism, for the treatment of fresh vascular occlusions, for coagulation inhibition during operations with extracorporeal circulation, for consumption coagulopathy, for circulatory disorders and hyperlipidemia; They are administered locally for superficial vein changes, including inflammatory in nature, circulatory disorders, blunt trauma, frost damage, hemorrhoids, tendonitis, insect bites and for herpes simplex labialis, especially in the early stage of development.
  • Fixed combinations e.g. B. with zinc sulfate or anti-inflammatory plant extracts (Federal Association of the Pharmaceutical Industry (ed.): Red List 1996; ECV, Editio Cantor, Aulendorf / Württ. 1996).
  • vitamin A regulates the growth of superficial tissues (epithelia) and connective tissue cells and supports the regular differentiation of the cell organelles. Vitamin A is also an essential component of the cell membrane and influences the formation of mucus-secreting cells. These cells produce glycoproteins, the sugar content of which is mainly derived from glycosaminoglycans (formerly known as mucopolysaccharides referred to). The sulfur required for the biosynthesis of anionic linear polymers may be activated by vitamin A (Sailer S .: Digestion, Vitamins; in: Functional Pathology; Ed .: Wick G.
  • Vitamin A deficiency symptoms include night blindness, excessive cornification of the skin surfaces, drying out of the conjunctiva and cornea of the eye, clouding and softening of the cornea, infection, blindness, growth disorders, inability to conceive, malformations.
  • overdosing of vitamin A can also lead to disorders such as headache, nausea, nausea, itching, detachment of the skin and mucous membranes and malformations (Wolfram G.: body and environment, nutrition; in: Hierholzer K., RF Schmidt ( Ed.): Pathophysiology of humans; pages 38.1 to 14, Ed.Medicine, VCH publishing company, Weinheim, Basel, Cambridge, New York 1991).
  • vitamin A and its derivatives are used therapeutically, especially when there are changes in the outer and inner skin surfaces, e.g. B. acne, seborr oe, hyperkeratosis and dyskeratosis, injuries to the cornea of the eye and to promote wound healing. Attempts are also being made to increase the sensitivity of malignant tumors to ionizing radiation and cytostatics through vitamin A. Vitamin A is administered both systemically (orally) and topically (drops, oils, ointments). Fixed combinations are common, e.g. B.
  • composition according to the invention is preferably administered cutaneously, ie externally by application to the skin, in particular in the form of a dermatological preparation.
  • Dermatological preparations include, for example, envelopes and pastes, but preferably ointments, gels, lotions or powders, optionally with additional auxiliaries. When such preparations are applied topically, the active ingredients are absorbed by the cornea in a concentration which is sufficient, for example, to reduce excessive cornification to a normal level.
  • the required dosage of the active ingredients is determined by the doctor depending on common factors, such as the nature and severity of the disease.
  • the composition according to the invention preferably contains 10 to 15000 mg, in particular 50 to 1000 mg, very particularly preferably 100 to 300 mg polyanion per 250,000 I.U. up to 10 million IU Vitamin A.
  • a further preferred embodiment relates to compositions which can be administered parenterally, such as solutions which are suitable for injection and which contain the composition according to the invention.
  • solutions which are suitable for injection and which contain the composition according to the invention.
  • solutions can be introduced into the body by intravenous infusion. This type of administration is particularly indicated for the treatment of cancer.
  • Effective dosages for, for example, patients with advanced epithelial and esenchymal tumors ranged from 50,000 to 2,000,000 IU of vitamin A, preferably 150,000 to 1,200,000 IU of vitamin A, in an oily solution for intramuscular injection, still 50 to 1000 mg, preferably 200 to 600 mg of pentosan polysulfate are present in the infusion solution.
  • the vitamin-containing solution and the pentosan polysulfate-containing solution can also be administered separately from one another. When the vitamin A solution and the pentosan polysulfate solution are administered separately, the latter is, for example, in 250 ml 5% glucose or 250 ml isotonic saline infused.
  • the vitamin A-containing solution is administered intramuscularly while the pentosan polysulfate solution is administered intravenously.
  • the number of repetitions of the injections depends on the patient's condition, but a regimen with administration 1 to 2 times a week for 4 to 12 weeks has proven successful. In individual cases, treatments over a longer period are required.
  • Adverse effects were rare and were usually limited to skin symptoms such as itching or scaling, increased liver enzymes, GOT, GPT and ⁇ GT, and moderate pain symptoms that persisted for about 1 to 2 days. All undesirable side effects were fully reversible.

Abstract

L'invention concerne une composition renfermant au moins un polyanion, en particulier un polyanion linéaire, une vitamine A et/ou un précurseur de vitamine A. Cette nouvelle composition peut en particulier être utilisée contre les dermatoses.
PCT/EP1997/004446 1996-08-14 1997-08-14 Composition renfermant de la vitamine a et son utilisation, en particulier contre les dermatoses WO1998006409A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1996132840 DE19632840A1 (de) 1996-08-14 1996-08-14 Vitamin A-haltige Zusammensetzung
DE19632840.3 1996-08-14

Publications (2)

Publication Number Publication Date
WO1998006409A2 true WO1998006409A2 (fr) 1998-02-19
WO1998006409A3 WO1998006409A3 (fr) 1998-03-26

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PCT/EP1997/004446 WO1998006409A2 (fr) 1996-08-14 1997-08-14 Composition renfermant de la vitamine a et son utilisation, en particulier contre les dermatoses

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DE (1) DE19632840A1 (fr)
WO (1) WO1998006409A2 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001089502A2 (fr) * 2000-05-22 2001-11-29 The Regents Of The University Of Michigan Compositions et procedes a utiliser contre l'inflammation induite par l'acne et les enzymes degradant la matrice dermique
AU2018276567B2 (en) * 2017-05-31 2021-09-16 Oji Holdings Corporation Moisturizing topical preparation
US11274165B2 (en) 2017-02-28 2022-03-15 Oji Holdings Corporation Pentosan polysulfate, pharmaceutical composition, and anticoagulant
US11286272B2 (en) 2016-08-31 2022-03-29 Oji Holdings Corporation Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide
US11312790B2 (en) 2016-08-31 2022-04-26 Oji Holdings Corporation Production method for pentosan polysulfate
US11344570B2 (en) 2017-12-20 2022-05-31 Oji Holdings Corporation Pentosan polysulfate and medicine containing pentosan polysulfate
US11390693B2 (en) 2017-09-12 2022-07-19 Oji Holdings Corporation Pentosan polysulfate and method for producing pentosan polysulfate

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2829388B1 (fr) * 2001-09-11 2005-09-02 Oreal Utilisation d'au moins un carotenoide dans une composition cosmetique

Citations (2)

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Publication number Priority date Publication date Assignee Title
FR2163352A1 (en) * 1971-12-15 1973-07-27 Fabre Sa Pierre Suppositories contg a central core - for admin of incompatible ingredients
US5484816A (en) * 1992-07-13 1996-01-16 Shiseido Company, Ltd. External skin treatment composition

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HU207656B (en) * 1989-03-30 1993-05-28 Beata Podanyi Process for producing cheloide creme
EP0637450A3 (fr) * 1993-08-04 1995-04-05 Collagen Corp Méthode et composition pour revigorer le tissu cicatriciel.
JP3689123B2 (ja) * 1993-10-22 2005-08-31 ライオン株式会社 ビタミンａ類可溶化水性点眼剤
JPH08157337A (ja) * 1994-12-05 1996-06-18 Shiseido Co Ltd 頭髪化粧料

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Publication number Priority date Publication date Assignee Title
FR2163352A1 (en) * 1971-12-15 1973-07-27 Fabre Sa Pierre Suppositories contg a central core - for admin of incompatible ingredients
US5484816A (en) * 1992-07-13 1996-01-16 Shiseido Company, Ltd. External skin treatment composition

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
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DATABASE WPI Section Ch, Week 9332 Derwent Publications Ltd., London, GB; Class B07, AN 93-251820 XP002051358 & HU 207 656 B (PODANYI B) , 28.Mai 1993 *
PATENT ABSTRACTS OF JAPAN vol. 095, no. 008, 29.September 1995 & JP 07 118147 A (LION CORP), 9.Mai 1995, *
PATENT ABSTRACTS OF JAPAN vol. 096, no. 010, 31.Oktober 1996 & JP 08 157337 A (SHISEIDO CO LTD), 18.Juni 1996, *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001089502A2 (fr) * 2000-05-22 2001-11-29 The Regents Of The University Of Michigan Compositions et procedes a utiliser contre l'inflammation induite par l'acne et les enzymes degradant la matrice dermique
WO2001089502A3 (fr) * 2000-05-22 2003-01-03 Univ Michigan Compositions et procedes a utiliser contre l'inflammation induite par l'acne et les enzymes degradant la matrice dermique
US11286272B2 (en) 2016-08-31 2022-03-29 Oji Holdings Corporation Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide
US11312790B2 (en) 2016-08-31 2022-04-26 Oji Holdings Corporation Production method for pentosan polysulfate
US11274165B2 (en) 2017-02-28 2022-03-15 Oji Holdings Corporation Pentosan polysulfate, pharmaceutical composition, and anticoagulant
AU2018276567B2 (en) * 2017-05-31 2021-09-16 Oji Holdings Corporation Moisturizing topical preparation
US11278485B2 (en) 2017-05-31 2022-03-22 Oji Holdings Corporation Moisturizing topical preparation
US11390693B2 (en) 2017-09-12 2022-07-19 Oji Holdings Corporation Pentosan polysulfate and method for producing pentosan polysulfate
US11344570B2 (en) 2017-12-20 2022-05-31 Oji Holdings Corporation Pentosan polysulfate and medicine containing pentosan polysulfate

Also Published As

Publication number Publication date
DE19632840A1 (de) 1998-02-19
WO1998006409A3 (fr) 1998-03-26

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