EP0806946A2 - Utilisation de carotinoides pour preparer des medicaments destines au traitement des dermatoses - Google Patents

Utilisation de carotinoides pour preparer des medicaments destines au traitement des dermatoses

Info

Publication number
EP0806946A2
EP0806946A2 EP96902950A EP96902950A EP0806946A2 EP 0806946 A2 EP0806946 A2 EP 0806946A2 EP 96902950 A EP96902950 A EP 96902950A EP 96902950 A EP96902950 A EP 96902950A EP 0806946 A2 EP0806946 A2 EP 0806946A2
Authority
EP
European Patent Office
Prior art keywords
treatment
carotenoids
carotene
minutes
histamine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP96902950A
Other languages
German (de)
English (en)
Inventor
Wolfgang Schmutzler
Karl Kolter
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
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
Priority claimed from DE1995103604 external-priority patent/DE19503604A1/de
Priority claimed from DE1995139743 external-priority patent/DE19539743A1/de
Application filed by BASF SE filed Critical BASF SE
Publication of EP0806946A2 publication Critical patent/EP0806946A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • 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
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to the use of carotenoids for the production of medicaments for the treatment of inflammatory diseases which are not caused by an infection with microorganisms and not by exposure to light, in particular abacterial, non-light-induced dermatoses.
  • Inflammatory diseases in the sense of this invention can be both allergic and non-allergic in nature, the inflammatory reaction of the affected tissues not being caused by an infection with microorganisms and not being induced by exposure to light.
  • Dermatoses for example contact urticaria, urticaria pigmentosa
  • cutan-vascular forms of allergy such as, for example, neurodermatitis or urticaria or hyperkeratosis such as, for example, psoriasis
  • Reactive oxygen species or singlet oxygen most likely play an important role in the pathogenesis of various allergic and non-allergic inflammations. It is also suspected that such species are involved in the degranular tion with release of mediators from mast cells. What is certain is that degranulation of the mast cells and the basophilic granulocytes in the blood is the first step in the initiation of an allergic reaction.
  • histamine One of the most important mediators of allergic reactions is histamine and the inhibition of its release or action is an important principle in the therapy of allergic-inflammatory diseases.
  • glucocorticoids and hi-antagonists have been used so far, the latter being only suitable for systemic use.
  • Bronchial spasmolytics, cromones or steroid therapeutic agents are used in the treatment of bronchial asthma.
  • steroids or immunosuppressants are mostly used.
  • retinol vitamin A
  • retinoic acid derivatives for the treatment of some inflammatory dermatoses.
  • retinol was used for the therapy of juvenile acne and psoriasis, this therapy proving to be unsuitable because of the signs of overdose.
  • retinoids isotretinoin and etretinate are also suitable in principle for the treatment of acne and inflammatory hyperkeratoses such as psoriasis, but like retinol they easily lead to overdose symptoms.
  • etretinate can be classified as very problematic due to its strong teratogenic effect.
  • retinoids isotretinoin and etretinate can inhibit histamine release in human mast cells (D. Eichelberg and W. Schmutzler, Arch. Dermatol. Res., 280, 155-157 (1988)).
  • these active ingredients are not necessarily recommended for therapeutic use.
  • cartoinoids such as ß-carotene (Provita ⁇ min A) or canthaxanthin have been used for the therapy of light-induced dermatoses such as erythropoietic protoporphyria and sunlight urticaria as well as pigment disorders (vitiligo) (A. Hollander, "News from American dermatology ", The dermatologist, pp.
  • the object of the present invention was to expand the treatment options for certain inflammatory diseases, in particular dermatoses, by providing new means for this purpose.
  • carotenoids inhibit histamine release and are suitable for the use defined at the outset.
  • carotenoids used according to the invention are also canthaxanthin, zeaxanthin, citranaxanthin, astaxanthin or lycopene.
  • the carotenoids are preferably used in the form of solubilizates.
  • the carotenoids can be used both in topical and in systemically active preparations.
  • dosage forms customary for this purpose such as ointments, creams, gels, lotion, emulsions or solutions, are suitable in principle.
  • the carotenoids can both be injected and administered orally. All usual forms are suitable as oral dosage forms, e.g. Capsules, coated tablets, tablets or liquid preparations.
  • Dosage forms for topical use can contain 0.05 to 15, preferably 0.2 to 4% by weight of carotenoids. Depending on the severity of the illness to be treated, the dosage can be in wide limits can be varied, since side effects are virtually excluded due to the good tolerability of the carotenoids.
  • Daily doses of 5 to 750, preferably 10 to 300 mg are recommended for systemic therapy.
  • carotenoids are suitable for the production of medicaments for the treatment of allergic-inflammatory diseases of the nasal mucosa and the intestinal mucosa. Furthermore, they are suitable for the treatment of systemic allergic-inflammatory diseases. Preference is given to the production of medicaments for the treatment of skin diseases not induced by the action of light.
  • the histamine-inhibiting effect is described in the experiments below.
  • the carotenoid used was ⁇ -carotene in the form of a solubilizate, consisting of 4% by weight of ⁇ -carotene, 22% by weight of ethoxylated 12-hydroxystearic acid as a solubilizer and water ad 100% by weight.
  • the experiments were carried out on adenoid mast cells, skin mast cells and peripheral monocytes.
  • the stimulation was done with Concanavalin A or the inflammation mediator C5a.
  • Adenoid vegetation (pharyngeal tonsil) is placed in Hanks buffer immediately after the operation and passed through the complete test within 90 to 120 minutes.
  • the tissue is first comminuted with an "Mclwain and Buddle science chopper" (literature: Handbuch der experimental Pharma ⁇ kologie, vol. 18/1, 342, 1966).
  • a part by weight of adenoid is taken up in a 5-fold volume of Hanks buffer and placed in an ice bath.
  • the suspension is now drawn up five times with a plastic syringe (without a cannula) and squeezed out again. After resting in the ice bath for 10 minutes, the same process is repeated again.
  • the ZeilSuspension is filtered through three layers of gauze, then centrifuged for 5 minutes at 125 xg. The supernatant is suctioned off, the sediment is resuspended in 1 ml Hanks buffer and made up with 10 ml Hanks buffer. The cell suspension is filtered through a Vyon filter with 100 ⁇ pore size (W. Kopp cell rubber, Aachen), centrifuged again, resuspended and again filtered through Vyon filters.
  • the mixture was centrifuged at 4 ° C. and the histamine in the supernatant and sediment were determined separately using the radioimmunoassay (Dianova-Immunotechmaschinesgesellschaft, Hamburg).
  • the monocytes are isolated with a purity of approx. 85% from leukocyte concentrates (buffy coats) by centrifugal centrifugation.
  • the buffy coats are distributed over 2 tubes and brought to a total volume of 30 ml with spinner medium (Gibco, Paisley, Scotland).
  • This suspension is carefully layered over 20 ml of Ficoll (Pharmacia, Freiburg i. Brsg.) And centrifuged at 532 x g at 20 ° C. for 40 minutes. The band over the Ficoll is removed (the rest is discarded) and made up to 50 ml with spinner medium.
  • the sediment After 10 minutes of centrifugation at 299 x g and 4 ° C, the sediment is resuspended in 10 ml of spinner medium and centrifuged again. The sediment is resuspended in 3 ml and placed on a prepared 55% Percoll gradient (300 to 600 million mononuclear cells / tubes). After centrifugation at 532 x g for 40 minutes and 20 ° C., the monocytes are found in the upper band and the lymphocytes in the lower band. The upper band is removed and washed three times in spinner (resuspend sediment in spinner), make up to 50 ml and centrifuge at 299 x g for 10 minutes). After the second wash, the number of living monocytes is determined by a vitality count with trypan blue and, after the last wash, set to a cell number of 3 million cells per 200 ⁇ l of Iscoves medium.
  • the sediment is then resuspended in such a way that 200 ⁇ l contain approx. 3 ⁇ 10 6 living cells.
  • Iscoves medium 200 ⁇ l of Iscoves medium (Gibco, Paisley, Scotland) are added to the mixture, 50 ⁇ l of a dilution of beta-carotene or placebo solution in Iscoves medium in order to obtain the desired final concentration. After 60 minutes of equilibration, either 50 ⁇ l buffer or 50 ⁇ l C5a solution (Sigma,
  • the mixture is centrifuged and the histamine content is determined separately in the supernatant and sediment using the radioimmunoassay (Dianova-Immunotech, Hamburg).
  • DMEM buffer Dulbecco's Minimum Essential Medium
  • the skin mast cells are isolated from foreskin tissue, which is placed in buffer immediately after the operation and processed within 24 hours.
  • the tissue is crushed manually and washed twice by suspending the tissue with 10 ml DMEM buffer / 1 g tissue, centrifuging for 5 minutes at 4 ° C. and 1000 rpm and separating from the buffer. This is followed by treatment with Collagenase I (Washington / Cell Systems, Remagen; 142 U / mg) and hyaluronic type IS (Sigma; 440 U / mg), 10 ml DMEM buffer containing 1.5 mg / g per gram of tissue. ml collagenase and 0.5 mg / ml hyaluronidase can be used.
  • the mixture is incubated for 60 minutes at 37 ° C. in a shaking bath. After the incubation, a suspension is produced by mechanical dispersion using a syringe, which is filtered through 3-layer gauze and then centrifuged for 5 minutes at 4 ° C. and 1000 rpm. The supernatant is decanted, the cell pellet suspended in 1 ml DMEM buffer and made up to 10 ml with buffer and again under the conditions mentioned above. centrifuged. This process is repeated two more times and the cell pellet is taken up in 1 ml of DMEM buffer.
  • the cell pellets were equilibrated with 2 ml of a CaCl 2 -containing DMEM buffer (2.8 mmolar of CaCl) and the various concentrations of beta-carotene in a water bath at 37 ° C. After 5 minutes, 50 mg of substance P (neuropeptide; Sigma company) were added in a volume of 50 ⁇ l, so that the final volume was 500 ⁇ l. After a further 10 minutes of incubation at 37 ° C., the mixture was centrifuged at 4 ° C. and the histamine in the supernatant and sediment were determined separately using the radioimmunoassay (Dianova-Iirauumotechmaschinesgesellschaft, Hamburg).
  • substance P neuropeptide

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

On utilise des carotinoïdes pour préparer des médicaments destinés au traitement de maladies inflammatoires non provoquées par exposition à la lumière ou par une infection due à des micro-organismes.
EP96902950A 1995-02-03 1996-02-02 Utilisation de carotinoides pour preparer des medicaments destines au traitement des dermatoses Withdrawn EP0806946A2 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE1995103604 DE19503604A1 (de) 1995-02-03 1995-02-03 Verwendung von Carotinoiden zur Herstellung von Arzneimitteln zur Behandlung von Dermatosen
DE19503604 1995-02-03
DE19539743 1995-10-25
DE1995139743 DE19539743A1 (de) 1995-10-25 1995-10-25 Verwendung von Carotinoiden zur Herstellung von Arzneimitteln zur Behandlung von entzündlichen Erkrankungen
PCT/EP1996/000381 WO1996023489A2 (fr) 1995-02-03 1996-02-02 Utilisation de carotinoides pour preparer des medicaments destines au traitement des dermatoses

Publications (1)

Publication Number Publication Date
EP0806946A2 true EP0806946A2 (fr) 1997-11-19

Family

ID=26012140

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96902950A Withdrawn EP0806946A2 (fr) 1995-02-03 1996-02-02 Utilisation de carotinoides pour preparer des medicaments destines au traitement des dermatoses

Country Status (6)

Country Link
US (1) US5886053A (fr)
EP (1) EP0806946A2 (fr)
JP (1) JPH10513444A (fr)
AU (1) AU4715796A (fr)
CA (1) CA2210957A1 (fr)
WO (1) WO1996023489A2 (fr)

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* Cited by examiner, † Cited by third party
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DE19653410A1 (de) * 1996-12-20 1998-06-25 Basf Ag Verwendung von Carotinoid-Solubilisaten zum Färben von Lebensmitteln und pharmazeutischen Zubereitungen
SE522246C2 (sv) 1997-02-27 2004-01-27 Astacarotene Ab Oralt preparat för profylaktisk och terapeutisk behandling av Helicobacter Sp. infektion
AU752468B2 (en) 1997-04-04 2002-09-19 Phyllis E. Bowen Lutein esters having high bioavailability
SE512531C2 (sv) * 1997-09-04 2000-03-27 Astacarotene Ab Användning av åtminstone en typ av xantofyller för framställning av ett läkemedel för profylaktisk och/eller terapeutisk förbättring av muskelfunktionsdurationen hos däggdjur och/eller behandling av muskelstörningar eller - sjukdomar hos däggdjur
SE511237C2 (sv) 1997-12-16 1999-08-30 Astacarotene Ab Användning av åtminstone en typ av xantofyller för framställning av ett humant eller verinärmedicinskt läkemedel för profylaktisk behandling av mastit hos däggdjursmammor
SE524337C2 (sv) 1998-10-16 2004-07-27 Astacarotene Ab Användning av åtminstone en typ av xantofyller för framställning av ett läkemedel för profylaktisk och/eller terapeutisk behandling av matsmältningsbesvär
SE9903619D0 (sv) * 1999-10-07 1999-10-07 Astacarotene Ab Use and method of treatment
SE0001071D0 (sv) * 2000-03-27 2000-03-27 Astacarotene Ab Method of inhibiting the expression of inflammatory cytokines and chemokines
US7078040B2 (en) * 2000-03-27 2006-07-18 Fuji Chemical Industry Co., Ltd. Method of inhibiting the expression of inflammatory cytokines and chemokines
DE10221212A1 (de) * 2002-05-13 2003-11-27 Andreas Maack Sporopollenin enthaltende lösliche Zusammensetzung und Verwendung
US20050009788A1 (en) * 2002-07-29 2005-01-13 Lockwood Samuel Fournier Carotenoid ester analogs or derivatives for controlling connexin 43 expression
US20050059635A1 (en) * 2002-07-29 2005-03-17 Lockwood Samuel Fournier Carotenoid ester analogs or derivatives for controlling C-reactive protein levels
US7320997B2 (en) * 2002-07-29 2008-01-22 Cardax Pharmaceuticals, Inc. Pharmaceutical compositions including carotenoid ester analogs or derivatives for the inhibition and amelioration of disease
US20050059659A1 (en) * 2002-07-29 2005-03-17 Lockwood Samuel Fournier Carotenoid analogs or derivatives for controlling C-reactive protein levels
EP1532108B1 (fr) 2002-07-29 2016-06-29 Cardax Pharma, Inc. Esters d'astaxanthin pour l'inhibition et la reduction de maladie
US7723327B2 (en) * 2002-07-29 2010-05-25 Cardax Pharmaceuticals, Inc. Carotenoid ester analogs or derivatives for the inhibition and amelioration of liver disease
US7345091B2 (en) * 2002-07-29 2008-03-18 Cardax Pharmaceuticals, Inc. Carotenoid ether analogs or derivatives for the inhibition and amelioration of disease
US20050148517A1 (en) * 2002-07-29 2005-07-07 Lockwood Samuel F. Carotenoid ether analogs or derivatives for controlling connexin 43 expression
US7521584B2 (en) * 2002-07-29 2009-04-21 Cardax Pharmaceuticals, Inc. Carotenoid analogs or derivatives for the inhibition and amelioration of disease
US20050026874A1 (en) * 2002-07-29 2005-02-03 Lockwood Samuel Fournier Carotenoid ether analogs or derivatives for the inhibition and amelioration of liver disease
US20050143475A1 (en) * 2002-07-29 2005-06-30 Lockwood Samuel F. Carotenoid analogs or derivatives for the inhibition and amelioration of ischemic reperfusion injury
US20050004235A1 (en) * 2002-07-29 2005-01-06 Lockwood Samuel Fournier Carotenoid analogs or derivatives for the inhibition and amelioration of liver disease
US7375133B2 (en) * 2002-07-29 2008-05-20 Cardax Pharmaceuticals, Inc. Pharmaceutical compositions including carotenoid ether analogs or derivatives for the inhibition and amelioration of disease
US7763649B2 (en) * 2002-07-29 2010-07-27 Cardax Pharmaceuticals, Inc. Carotenoid analogs or derivatives for controlling connexin 43 expression
US20050049248A1 (en) * 2002-07-29 2005-03-03 Lockwood Samuel Fournier Carotenoid ether analogs or derivatives for controlling C-reactive protein levels
JP3780236B2 (ja) * 2002-08-07 2006-05-31 キヤノン株式会社 ガスが浸透した材料の保管方法
WO2004035884A1 (fr) * 2002-10-18 2004-04-29 Kolon Industries, Inc Fibres moussees microcellulaires et leur procede de preparation
US7691901B2 (en) * 2004-04-14 2010-04-06 Cardax Pharmaceuticals Inc. Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation
US20060058269A1 (en) * 2004-04-14 2006-03-16 Lockwood Samuel F Carotenoid analogs or derivatives for the inhibition and amelioration of inflammation
US7351424B2 (en) * 2004-07-22 2008-04-01 Bio Lut S.A. De C.V. Enhanced purity trans-lutein-ester compositions and methods of making same
US20060269497A1 (en) * 2005-05-27 2006-11-30 Yamaha Hatsudoki Kabushiki Kaisha Trichogenous agent
FR2935610B1 (fr) * 2008-09-05 2010-10-29 Lvmh Rech Composition cosmetique ou dermatologique contenant un melange d'huiles essentielles et son utilisation, notamment pour le soin des peaux sensibles ou sensibilisees
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FR2591105B1 (fr) * 1985-12-11 1989-03-24 Moet Hennessy Rech Composition pharmaceutique, notamment dermatologique, ou cosmetique, a base de phases lamellaires lipidiques hydratees ou de liposomes contenant un retinoide ou un analogue structural dudit retinoide tel qu'un carotenoide.
DE4031094A1 (de) * 1990-10-02 1992-04-09 Basf Ag Verfahren zur herstellung von stabilen injizierbaren (beta)-carotin-solubilisaten
FR2683722B1 (fr) * 1991-11-14 1995-05-24 Arkopharma Laboratoires Medicament pour le traitement de fond de l'asthme a base de beta-carotene.

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Also Published As

Publication number Publication date
US5886053A (en) 1999-03-23
WO1996023489A2 (fr) 1996-08-08
WO1996023489A3 (fr) 1996-10-03
CA2210957A1 (fr) 1996-08-08
JPH10513444A (ja) 1998-12-22
AU4715796A (en) 1996-08-21

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