EP2635266A1 - Composition et médicament contenant des acides gras oméga-3 ainsi qu'un modulateur - Google Patents

Composition et médicament contenant des acides gras oméga-3 ainsi qu'un modulateur

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Publication number
EP2635266A1
EP2635266A1 EP11776342.5A EP11776342A EP2635266A1 EP 2635266 A1 EP2635266 A1 EP 2635266A1 EP 11776342 A EP11776342 A EP 11776342A EP 2635266 A1 EP2635266 A1 EP 2635266A1
Authority
EP
European Patent Office
Prior art keywords
acid
oil
composition
composition according
group
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Withdrawn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
EP11776342.5A
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German (de)
English (en)
Inventor
Ute Steinfeld
Frank Holzer
Hyeck Hee Lee
Markus Mahler
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.)
F Holzer GmbH
Original Assignee
F Holzer GmbH
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Filing date
Publication date
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Publication of EP2635266A1 publication Critical patent/EP2635266A1/fr
Withdrawn legal-status Critical Current

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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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • 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]

Definitions

  • the present invention relates to a composition
  • a composition comprising at least one ⁇ -3 fatty acid and at least one modulator, e.g. an inhibitor, antagonist, etc. of the NF-B transcription factor.
  • This composition is suitable as a medicament or pharmaceutical base formulation, in particular for the prophylaxis or treatment of inflammations.
  • the medicament is preferably suitable for topical application or inhalation for the fields of ophthalmology, ear-nose-throat (ENT) as well as for the areas of the mouth and throat area and the lung area for prophylaxis and therapy.
  • ophthalmic compositions for example in the form of eye drops or lens storage fluids, which ⁇ -3 fatty acids. This is on the
  • WO 2006/007510 Al and WO 2007/130960 A2 verwie ⁇ Sen lie in front of an oil-in-water emulsion ⁇ , the compositions described therein are optimized such that they are stable 01- in-water emulsions. Although these compositions show some efficacy in the treatment and prevention of dry-eye syndrome (DSE), these compositions are not suitable for treating or preventing inflammatory diseases, for example of the eye or the skin.
  • DSE dry-eye syndrome
  • compositions which can be used as a medicament, with which a sustainable treatment of epithelial surfaces of the eye, nose, lung, throat and throat and ear is possible. It is also an object of the present invention to provide a composition and a corresponding medicament which allows a sustained release of ⁇ -3-fatty acids ("sustained release") in the abovementioned ranges for incorporation into the cell membranes of epithelia and deeper tissue layers. Furthermore, it should thus be an increased residence time and an improved effect on the epithelia or an improved uptake by the epithelia or improved uptake into "adjacent compartments", such as the lungs, pharyngeal areas and tissues of the brain when applied to the nose, can be achieved.
  • composition comprising a) at least one omega-3 fatty acid, a lipid derived therefrom, a carboxylate salt, an ester, a triglyceride or amide thereof or another pharmacologically acceptable carboxylic acid derivative, and
  • At least one modulator e.g. Inhibitor, antagonist, etc. of the NF-B transcription factor.
  • Immunological processes, processes in inflammatory processes and wound healing processes form a closely interwoven combination of irritation, inflammation and healing processes and are inextricably linked.
  • Modulators are therefore substances which have a regulating / modulating effect on this complex interaction and thus support the optimal functioning of the immune system and / or exert a positive effect on the prophylaxis or treatment of irritation, inflammation and / or wound healing.
  • modulator in claim 1 The following modulators of physiological processes, such as irritations, inflammatory processes and / or wound healing, are known from the prior art and according to the invention comprises the term modulator in claim 1:
  • Coenzyme Q10 (Q10, ubiquinone-10).
  • Q10 is essential at the mitochondrial level for optimal Function of the immune system (Folkers K, Wolaniuk A, Research on coenzyme Q10 in clinical medicine and in immunomodulation, Drugs Exp Clin Res., 1985; 11 (8): 539-45).
  • Q10 acts in inflammatory processes at the level of gene expression. It exerts, inter alia, anti-inflammatory effect on the influence on NFkappaBl-dependent gene expression (Schmelzer C, Lindner I, Rimbach G, Niklowitz P, Menke T, Döring F., Functions of coenzymes Q10 in inflammation and gene expression, Biofactors 2008, -32 (1-4): 179-83).
  • Q10 can be used in a concentration of 1-100 ⁇ m, preferably in a concentration of 2-10 ⁇ M;
  • Taurine occurs in immune cells and modulates certain immune cell functions, e.g. Regulation of inflammatory aspects of the immune response. It also acts as a protective agent in its function as antioxidants (Fazzino F, Obregon F, Lima L. Taurine and proliferation of lymphocytes in the physically restrained rats, J Biomed Sei. 2010 Aug 24; 17 Suppl 1: S24) and as an osmoregulator ( Shioda R., Reinach PS, Hisatsune T., Miyamoto Y. Osmosensitive taurine transporter expression and activity in human corneal epithelial cell, IOVS, Sept. 2002, Vol 43, No 9). Taurine can be used in a concentration of 0.1-50 mM, preferably 0.1-5 mM;
  • Carboxymethylcellulose (CMC). CMC binds to human epithelial cells and is a modulator of corneal epithelial wound healing (Invest).
  • CMC binding to the matrix stimulates the attachment, migration and re-epithelialization of corneal wounds in HCEC;
  • Resolvin (especially the E and D series).
  • Resolvin El (RvEl) induces an increase in cell migration and thus accelerated epithelial wound healing (Zhang et al, IOVS, Vol. 51, No. 11, November 2010);
  • Protectine as resolvins, De ⁇ derivatives of eicosapentaenoic acid and
  • Docosahexaenoic acid exerts anti-inflammatory effects (Curr Opin Clin Nutr Metab Care. 2011 Mar; 14 (2): 132-7. Docosahexaenoic acid, protectins and dry eye., Cortina MS, Bazan HE).
  • hyaluronic acid dexpanthenol (pantothenol, D-panthenol or
  • Panthenol pantothenic acid (vitamin B5), hypotaurine, castor oil, ricinoleic acid, limonene, pinene, rosemary oil, piperine, capsaicin, flavonoids, triterpenoids, tmian extracts, green tea extract, ginko extract, caffeine, caffeic acid (and their Derivative caffeic acid phenethyl ester), L-carnitine, lutein, vitamin D (eg vitamin D2 ergocalciferol and vitamin D3 cholecalciferol) and carnesol.
  • vitamin D eg vitamin D2 ergocalciferol and vitamin D3 cholecalciferol
  • composition according to the invention in particular as a drug or medical device, on the one hand, the development of tissue irritation and damage allergies or inflammation can be efficiently prevented and avoided, and can be intervened in the inflammatory events already occurred damage, wherein achieve very good results, also in relation to wound healing.
  • tissue irritation or damage occurs, be it through environmental noxae, mechanical stimuli, such as friction, Pressure, through bacteria, Trauraa, chemicals, heat and / or excessive immune reactions, such as allergies, etc., will initially lead to activity changes in certain cellular signaling pathways, which in turn lead to specific changes in the gene expression pattern.
  • inflammatory mediators are released in the affected tissues, initiating and maintaining inflammatory processes.
  • the entirety of these complex tissue changes is called inflammation.
  • Regulated inflammatory processes play an important role in wound healing processes.
  • composition according to the invention intervenes in these complex processes for avoidance, modulation or inhibition at various levels: influencing the lipid composition of cell membranes in the area of application
  • lipid composition of the membranes depends on the lipid composition of the membranes. This, in turn, may be influenced by topical application due to application or inhalation of the composition described herein.
  • the fatty acid composition of the membrane also continues to influence its permeability and fluidity.
  • the ⁇ -3 fatty acid in combination with a modulator uses the NF-KB transcription factor
  • a modulator eg an inhibitor, antagonist, etc.
  • the emergence of anti-inflammatory mediators is favored prophylactically or therapeutically to prevent inflammation.
  • the healing of already existing inflammations was also observed.
  • NF- ⁇ transcription factor NF- ⁇
  • NF- ⁇ transcription factor NF- ⁇
  • cytokines such as IL-1, TNF-alpha
  • enzymes such as COX-2, iNOS, cell adhesion molecules, etc., which promote propagation of the inflammatory response to other cells and their enhancement often in the sense of positive feedback.
  • the modulation of the activation of NF- ⁇ represents another possibility with which the inventive composition can intervene in the inflammatory process.
  • modulators of the NF-kappa B transcription factor can act directly on NF-kappa B, or indirectly via the signaling cascade on NF-kappa B.
  • Antioxidants for example, can inhibit components of the NF-kappa B signal transduction pathway, including the TNF receptor and the proteasome ,
  • the modulation of NF-kappa B may result in a modulation (in particular suppression) of the tumor necrosis factor alpha (TNF- ⁇ ).
  • TNF-a is a signal substance of the immune system and plays in diseases such as Sjögren's syndrome, the
  • Keratoconjunctivitis sicca disorders of the meimoma gland a major role.
  • the superoxide radical in immune cells is formed by membrane-bound NADPH oxidases and released into the extracellular milieu.
  • NADPH oxidases membrane-bound NADPH oxidases and released into the extracellular milieu.
  • the normally low level of superoxide formation increases tenfold ("oxidative burst") .
  • the formation of this species is not only responsible for the killing of bacteria, but also serves to recruit leukocytes to the site of inflammation.
  • reactive oxygen species at the transcriptional level interfere with the production of enzymes, such as NOS-II, and activate transcription factors, such as the NF-BB family and protein kinases, while retaining protein tyrosine. Inactivate phosphatases.
  • the reactive nitrogen compound nitrogen Noxide is formed enzymatically and strictly controlled in a number of tissues.
  • the starting substance is the amino acid L-arginine, from which the free radical is formed by the enzyme NO-synthase (NOS).
  • NOS NO-synthase
  • Granulocytes after stimulation, the inducible NOS (iNOS) can be expressed.
  • Stimuli are primarily triggers of inflammatory reactions, such as bacteria or their constituents, inflammatory cytokines, etc.
  • Tissue damage e.g. Lipid peroxidation
  • reactive oxygen species e.g. Lipid peroxidation
  • a prophylactic or therapeutic effect thus takes place at different levels of the process.
  • composition according to the invention therefore preferably contains in accordance with e.g. lipophilic and gel-forming components that can form a moisturizing, nourishing film on epithelia, such as the nasal mucosa or the cornea.
  • components of the described composition will access one or more levels, e.g. Gene transcription, qualitative and / or quantitative modulation of the release of mediator molecules, modulation of signal transduction, etc., in e.g. the
  • the selection and the composition of the ⁇ -3 fatty acids in the pharmaceutical composition may favor the development of anti-inflammatory mediators to prophylactically or therapeutically prevent disorders and diseases.
  • disorders are irritation, irritation and swelling of the mucous membranes, eye burning, dry cough, bronchitis, pneumonia, asthma, disorders of the immune system, especially allergies and inflammation, wound healing, treatment of keratoconjunctivitis sicca, Sjörgen's syndrome, diseases of the meibomian gland etc ,
  • the at least one modulator is an inhibitor or antagonist of the NF- ⁇ B transcription factor and preferably selected from natural sources, in particular from the group consisting of allicin, curcumin, EGCD, genistein, melatonin, quercetin, resveratrol, silymarin, Sulphoraphanen, vitamin A, vitamin C, vitamin E or mixtures thereof, and / or b) from the group consisting of synthetic inhibitors, in particular pyrrolidinedicarbamate, 2-chloro-4- (trifluoromethyl) pyrimidin-5- ⁇ - (3 ', 5 4 - bis (trifluoromethyl) phenyl) carboxamide and / or mixtures thereof.
  • natural sources in particular from the group consisting of allicin, curcumin, EGCD, genistein, melatonin, quercetin, resveratrol, silymarin, Sulphoraphanen, vitamin A, vitamin C, vitamin E or mixtures thereof, and / or b) from
  • Vitamin A includes vitamin AI (retinol), vitamin A2 (3-dehydroretinol), vitamin A acid, vitamin A derivatives (retinyl palmitate, retinyl acetate, etc.), all-trans retinoic acid (ATRA, aRA, tretinoin). , 13-cis retinoic acid or retinoic acid (isotretinoin), vitamin A analogs such as the all-trans retinoic acid.
  • Vitamin C includes ascorbic acid, ascorbyl palmitate and ascorbyl acetate
  • vitamin E includes gamma-tocotrienol and 6-hydroxy-2, 5,7, 8-tetramethylchroman-2-carboxylic acid (Trolox).
  • modulators of NF-kB activation from natural sources are: alpha-lipoic acid (thioctic acid) and dihydrolipoic acid, 2-amino-1-methyl-6-phenylimidazo (4,5-bpyridine ( PhIP), N-acetyldopamindimers (from P. cicadae), allopurinol, anetholdithiolthiones, apocynin, Aretemsia p7F
  • Carotenoids e.g., beta-carotene
  • carvedilol e.g., carvedilol
  • catechol derivatives e.g., catechol derivatives
  • Centaurea L (Asteraceae) extracts e.g., Centaurea L (Asteraceae) extracts
  • Chalcone chlorogenic acid, 5-chloroacetyl-2-amino-1,3-selenazoles, cholestin, chroman-2-carboxylic acid N-substituted phenylamides, polyphenols for example from Cocoa or Crataegus pinnatifida, Coffee extract (3-methyl-1, 2-cyclopentanediones), curcumin
  • DHEA dehydroepiandrosterone
  • DDC Diethyldithiocarbamate
  • DMDTC Diethyldithiocarbamate
  • EGTA eupatilin, fisetin, flavonoids
  • flavonoids Crataegus; Boerhaavia diffusa root; xanthohumol; Eupatorium arnottianum; genistein; kaempferol; quercetin, daidzein; flavone; isor amnetin; naringenin;
  • Seabuckthorn fruit berry Seabuckthorn fruit berry
  • sesquiterpene lactones e.g. Helenalin, for example, from arnica extracts, foil acid, gamma-glutamylcysteine synthetase (gamma-GCS),
  • Ganoderma lucidum polysaccharides Garcinol (from extract of Garcinia indica fruit cow), Ginkgo biloba extract, Glutathione, Guaiacol (2-methoxyphenol), Hematein, Hinokitiol, Hydroquinone, 23-hydroxyursolic acid, IRFI 042 (Vitamin E-like Compound), Iron tetrakis, isoflavones, isosteviol, isovitexin, isoliquitinitin, kallistatin, Kangen-karyu extract, L-cysteines, lacidipines, lazaroids, ligonberries,
  • synthetic sources are the following: cortisones and glucocorticoids, and also their esters, eg 16a, 17- [(R) -cyclohexylmethylenedioxy] -lithium, 21-dihydroxypregna-l, 4-diene-3, 20- dion-21-isobutyrate), salicylanilide inhibitors, 3,4-dihydro-1, l-dimethyl-2H-1,2-benzoselenazines; Declopramide and dexlipotam, N- (acetylphenyl) -2-hydroxy-5-iodophenylcarboxamide; N- (2,4-difluorophenyl) -2-hydroxy-5-nitrophenylcarboxamide; N- (2,4-difluorophenyl) -2-hydroxy-5-iodophenylcarboxamide, or a pharmaceutically acceptable salt, hydrate or solvate thereof.
  • cortisones and glucocorticoids and also their est
  • ⁇ -3 Fatty acids are selected from the group consisting of steroidal acid, eicosatetracenoic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid and mixtures or combinations thereof.
  • ⁇ -3 fatty acids are polyunsaturated fatty acids and are among the essential fatty acids that are usually taken with food and incorporated into the body in cell membranes.
  • the derivatives of these fatty acids are tissue hormones and are considered the body's own regulatory wirksa ⁇ me fabrics. They influence numerous metabolic processes and functions.
  • the ⁇ -3 and ⁇ -6 fatty acids are released from the membrane lipids and made available for the biosynthesis of these tissue hormones, the eicosanoids.
  • the fatty acid composition also influences the permeability and fluidity of the membranes. Especially sense organs, such as skin, eye, ear, nose and mouth and the adjacent areas, such as the throat and pharynx, lungs and bronchi, are constantly in contact with the outside world and thus exposed to environmental influences.
  • particulate Noxen such as suspended dust, viruses, bacteria, fungal spores and / or pollen can lead to environment-induced disorders and diseases, such as irritation of the mucous membranes, eye burning, dry cough, decline in lung function, shortness of breath, bronchitis, pneumonia, asthma, disorders of the immune system, especially allergies and inflammation, etc.
  • Topical application of selected omega-3 fatty acids in the pharmaceutical composition according to the invention is intended to prevent the formation of anti-inflammatory drugs.
  • favor diators for example by incorporating these fatty acids in the cell membranes at the site of application. Since inflammatory mediators are newly synthesized directly from membrane fatty acids after the stimulus and the type of fatty acids present a direct
  • fatty acids used and the oils they contain should serve as natural membrane constituents also as a protective coat and care for the irritated and dry tissues.
  • Another conceivable function is that of a barrier function to prevent the contact of harmful noxious agents, e.g. particulate noxae, with the affected tissues, e.g. Nose or eye epithelium to avoid.
  • the ⁇ -3 fatty acids can be used as pure substances, but also in the form of vegetable or animal
  • oils are in particular selected from the group consisting of algae oil, fish oil, perilla oil, shi oil, linseed oil, rapeseed oil, olive oil,
  • Preferred contents of the at least one omega-3 fatty acid and / or the derivative thereof here are, based on the total composition, between 0.1 and 50% by weight, preferably between 1 and 30% by weight, more preferably between 2 and 10% by weight.
  • the composition contains at least one pharmacologically suitable carrier, in particular fatty acid esters, such as isopropyl palmitate; Isopropyl myristate, shingolipids such as ceramides, cerobroside, phosphatidylethanolamines, glycerol, neutral oils such as miglyol, ethyl oleate, caprylic-capric acid triglyceride, miglyol; waxes; fats; Vaseline; paraffins; Mineral oil; Vegetable oils such as castor oil, almond oil; and / or water, preferably in an amount between 50 and 95 wt .-%, preferably between 75 and 90 wt .-%, based on the total composition.
  • fatty acid esters such as isopropyl palmitate
  • Isopropyl myristate shingolipids such as ceramides, cerobroside, phosphatidylethanolamines, glycerol, neutral oils
  • the composition contains at least one antioxidant, preferably in an amount of between 0.01 and 5% by weight, based on the total composition.
  • antioxidants are terpenoids (monoterpenoid, sesquiterpenoid, diterpenoid, triterpenoid), carotenoids (- and .beta.-carotene), hydroxytyrosol, zeathin, lutein, lycopene, anthocyanins, cryptoxanthines, xanthophylls, epicatechin, quercetin, punica lagine and ellagic acid; Chlorogenic acid, bile acid,
  • Ferulic acid caffeic acid, ⁇ -tocopherol, ⁇ -tocopherol ester, ascorbic acid, ascorbic acid ester (myristate, palmitate and stearate), ⁇ -carotene, cysteine, acetylcysteine (N-acetyl-L-cysteine also simultaneously constitutes a mucolytic agent ), Coenzyme Q, idebenone
  • the antioxidants can be added directly or in the form of oils or essential oils.
  • Wheat germ oil contains e.g. Tocopherols, carotenoids, ergocalciferol, folic acid (vitamin B9), pantothenic acid, phytosterols and phenols, such as dihydroquercetin, etc.
  • the content of the optionally added antioxidants is preferably from 0.001 to 10% by weight, more preferably from 0.01 to 5% by weight, based on the
  • the composition also contains at least one gelling agent selected from the group consisting of natural or synthetic polymers, preferably in an amount between 0.01 and 5 wt .-%, based on the total composition.
  • at least one gelling agent selected from the group consisting of natural or synthetic polymers, preferably in an amount between 0.01 and 5 wt .-%, based on the total composition.
  • Gel formers suitable for the compositions of the invention preferably comprise natural or synthetic polymers.
  • Natural polymers are preferably selected from the group consisting of agar-agar, alginic acid, alginate, amidated pectin,
  • Gellan Gellan, ghatti gum, gum arabic, spruce juice gum, locust bean gum, karaya gum, keratin, konjac flour, L-HPC, locust bean gum, mastic, pectin,
  • Preferred synthetic polymers which can be used as gelling agents for the composition according to the invention are selected from the group consisting of acrylic acid polymers, carbomers, polyacrylamides and alkylene oxide polymers.
  • the gelling agents are preferably used in an amount of from 0.1 to 5% by weight, based on the total weight of the composition according to the invention.
  • the composition contains at least one thickener, preferably in an amount of between 0.5 and 5 wt .-%, based on the total composition.
  • Thickeners which may preferably be present in the compositions according to the invention include, for example, candelilla and carnauba wax and microcrystalline waxes, carbomer, polyethylene oxide thickeners, poloxamers, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose, povidone,
  • Hyaluronic acid polylactic acid and derivatives thereof.
  • the thickener is preferably used in an amount of 0.5 to 5 wt .-%, based on the total weight of the pharmaceutical composition according to the invention.
  • microemulsion gels and in situ gels or in situ microemulsion gels e.g. Lecithin organogel or
  • Lecithin organogel is preferably lecithin with a high content of phosphatidylcholine (> 92%) from natural sources such as soy or egg yolk used.
  • At least one vegetable extract is included.
  • herbal extracts are:
  • Herbal substances with antioxidant, anti-inflammatory and / or antiallergic action e.g. individual vegetable substances, mixtures of substances, a liquid or solid extract, a distillate or an oil or essential oil derived from plants, e.g. the following genera or species is:
  • Antioxidants selected from the group consisting of tannins, essential oils, azulenes, proteas, bisabolols, bisabolites, flavonoids (eg rutin, quercetin), flavones, anthocyanins, triterpenes, monoterpene alcohols, phenolcarboxylic acids, polyphenols, unsaturated fatty acids, hypericin, carotenoids, allantoin , Bromelain, glycyrrhizin, glycyrrhizic acid and salts of glycyrrhizic acid; Anti-inflammatory agents selected from the group consisting of vitamin A, carotenes, carotenoids, eg .beta.-carotene, .alpha.-carotene,
  • Lycopene ⁇ -cryptoxanthin, lutein, zeaxanthin, tretinoin, tocopherols (vitamin E) and biotin, vitamins A, C, D, K, Q10, pangamic acid, honey, royal jelly, casein;
  • Vegetable oils with anti-inflammatory action preferably selected from the group consisting of perilla oil, chi oil, fish oil,
  • Anti-inflammatory, antioxidant substances selected from the group consisting of vegetable tannins and synthetic tannins.
  • the composition contains at least one humectant, e.g. Glycerine, glycols, sorbitol. These not only increase the moisture in the tissue but also have a biostatic effect.
  • humectant e.g. Glycerine, glycols, sorbitol.
  • the composition contains at least one further active ingredient, which may be natural, synthetic or biotechnologically produced.
  • This additional active ingredient may be selected from the group consisting of antibiotics, decongestant drugs, non-steroidal anti-inflammatory drugs, antivirals, antiseptics, cortisone, antiallergic agents, prostaglantin analogues, drugs from the drug class of antihistamines and / or corticosteroids, antiallergic agents, pantothenic acid derivatives, non-steroidal anti-inflammatory drugs, vasoconstrictors and / or anti-glaucoma drugs, FP prostanoid receptor antagonists, prostamide receptor Antagonists and / or natural or synthetic inhibitors or antagonists of TNF alpha.
  • the active ingredients may be selected from natural, synthetic or biotechnologically produced active ingredients. Specific examples are given below:
  • Polypeptide antibiotics bacitracin, polymyxin B, gramicidin,
  • Aminoglycosides neoraycin, framycetin, gentamicin, tobramycin,
  • Sulfonamides sulfoacetamide
  • decongestants such as naphazoline, phenylephrine, tetryzoline, tramazoline, xylometazoline;
  • Non-steroidal anti-inflammatory drugs such as diclofenac, indomethacin
  • antivirals such as acyclovir
  • antiseptics such as cortisone, such as hydrocortisone, rimexolone;
  • Anti-allergic antihistamines corticosteroids, synthetic mast cell anti-granulation agents and leukotriene receptor antagonists;
  • corticosteroids triamcinolone, dexamethasone, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone buteprate, prednisolone, betamethasone, methyl prednisolone, clobetasone, flumetasone, fluocortin, fluperolone, fluorometholone, flupredniden, desonide, triamcinolone, alclometasone, dexamethasone, Clocortolone, betamethasone, fluclorolone, desoxymetasone, fluocinolone acetonide, fluocortolone, diflucortolone, fludroxycortide, fluocinonide, budesonide, diflorasone, amcinonide, halomethasone, mometasone, methylprednisolone aceponate, beclomethasone, hydro
  • At least one antiallergic active ingredient from the group cromoglycic acid, spaglumic acid, lodoxamide, nedocromil, montelukast and
  • non-steroidal inflammatory e.g.
  • Aminoarylcarboxylic acid derivatives e.g, enfenamic acid, etofenamate, levenamic acid, isonixin, meclofenamic acid, mefenamic acid, niflumic acid, tallowlfumate, tofenfenamate, toifenamic acid
  • arylacetalic acid derivatives eg aceclofenac, acemetacin, alclofenac, amfenac, amtolmetinguacil, Bromfenac, Bufexamac Cinmetacin, Clopirac, Diclofenac Sodium,
  • Etodolac felbinac, fenclozinic acid, fentiazac, glucametacin, ibufenac, indomethacin,
  • Isofezolac Isoxepac, Ionazolac, Metiazinic Acid, Mofezolac, Oxametacin, Pirazolac, Proglumetacin Sulindac, Tiaramide, Tolmetin, Tropesin,
  • aryl-butyric acid derivatives e.g., bumadizone, butibufen, fenbufen, xenbucin
  • arylcarboxylic acid e.g., clidanac, ketorolac, tinoridine
  • arylpropionic acid derivatives e.g.
  • Pyrazoles e.g., difenamizole, epirizole
  • Pyrazolones e.g., apazones, benzpiperylones,
  • salicylic acid derivatives eg Acetaminosalol, aspirin, benorylates, bromosaligenin, calcium acetylsalicylates, diflunisal, eggsalates, fendosal, gentisic acid, glycolates, imidazolesalicylates, lysine acetylsalicylates, mesalamines, morpholinesalicylates, 1-naphthylsalicylates, olsalazines, parsalmides, phenylacetylsalicylates, phenylsalicylates, salacetic amides, salicylamide o-acetic acid, salicylsulfonic acid, salsalates, sulfasalazines), thiazinecarboxamides (eg, ampiroxicam, droxicam, isoxicam, lornoxicam, piroxicam, ten
  • NSAIDs non-steroidal anti-inflammatory drugs
  • cyclooxygenase inhibitors e.g. selective inhibitors of type II cyclooxygenase, e.g.
  • Celecoxib and etodolac platelet activating factor (PAF) antagonists, such as Apafant, Bepafant, Minopafant, Nupafant, and Modipafant; PDE (phosphodiesterase) IV inhibitors such as Ariflo, Torbafylline, Rolipram, Filaminast Piclamilast, Cipamfylline and Roflumilast; Inhibitors of cytokine production, such as inhibitors of NF- ⁇ B transcription factor; or other known anti-inflammatory agents.
  • PAF platelet activating factor
  • the erfxndungswashe pharmaceutical composition may contain from the group of vasoconstrictors, for example, oxy ⁇ metazoline, xylometazoline, tretryzoline, naphazoline, tramazoline and / or their derivatives as Wirkstoffkom- component.
  • vasoconstrictors for example, oxy ⁇ metazoline, xylometazoline, tretryzoline, naphazoline, tramazoline and / or their derivatives as Wirkstoffkom- component.
  • fatty acids may optionally also anti-glaucoma drugs, such as
  • beta-blockers timolol, levobunolol
  • Alpha-2-adrenoceptor agonist clonidine, brimo- nidine, carbonic anhydrase inhibitor: brinzolamide, dorzolamide and acetazolamide,
  • Prostaglandins latanoprost, travoprost, bimato- prost, tafluprost, can be added to exert even greater influence on the effect.
  • the concentration of the alternative agents included in the present invention may vary depending on the agent and type of disease.
  • the concentration should be sufficient, e.g. to treat or prevent inflammation in the treated tissue.
  • the concentrations are typically in the range from 0.0001 to about 5% wt / wt (or alternatively at 0.01 to about 2% wt / wt, or from about 0.05% to 1% wt / wt, or from about 0.01% to about 0.5% wt / wt).
  • modulators of COX-2 are included as active ingredients.
  • natural inhibitors are basil, berberine, curcumin, EGCG, ginger, hops (Humulus lupulus), fish oil, oregano, quercetin, resveratrol, rosemary and vitamins A and E.
  • Preferred administration forms of the composition according to the invention are in liquid, viscous or semisolid form, in particular in the form of a gel, a thixotropic gel, a lipogel, a
  • Organogel a microemulsion gel, a hydrogel, a spray gel, a throat spray, but also formulated as lozenges, lozenges, or gelatin preparations such as soft gelatin capsules for the treatment in the oropharynx, a water-in-oil emulsion, an oil in-water emulsion, cream, ointment or in situ gel or in situ microemulsion gel.
  • the invention also provides a pharmaceutical composition based on a composition according to the invention as described above, i. this composition includes.
  • the drug may include other additional substances, but also be formed from this composition. In particular, the drug is suitable for topical application.
  • the medicament or medical product according to the invention is for the prophylaxis and / or treatment of irritations
  • Inflammations inflammatory diseases and other diseases of the eye, nose, throat and throat, lungs and ears, allergies, conjunctivitis (conjunctivitis), corneal inflammation (blepharitis), dry eye, eye injuries, eg burns, siccaemia Syndrome, glaucoma, dry nose, dry runny nose, rhinitis sicca, atrophic rhinopathy, rhinitis as inflammation of the nasal cavity, sinusitis, bronchial asthma, cold with cold, allergic rhinitis, nasal enteroscopy, rhinophyma, otitis media dia), inflammation of the external auditory canal, paucomatous infusion, inflammation in the mouth and pharynx, eg pharyngitis, cataract, neurodermatitis and atopic dermatitis.
  • conjunctivitis conjunctivitis
  • corneal inflammation blepharitis
  • dry eye eye injuries, eg burns, siccaemia Syndrome, glaucoma, dry nose, dry runn
  • Rhinophymitis otitis media, inflammation of the external auditory canal, drenching, inflammation of the mouth and throat, e.g. Pharyngitis, neurodermatitis and atopic dermatitis. Further indications are e.g. Irritations,
  • Further additives which may be present in the composition according to the invention are, for example, viscosity enhancers, spreading agents, wetting agents, wetting agents, auxiliaries and also buffers, stabilizers, surfactants and co-surfactants such as ethyl alcohol, sorbitan fatty acid residues, polysorbates etc. Osmolarticiansregler, such as NaCl, sorbitol, glucose, glycerol, polyethylene glycol, fructose or mixtures thereof, preservatives, etc.
  • castor oil has proven to be particularly advantageous in combination with omega-3 fatty acids, because in this combination, surprisingly, an odor-binding occurs and the fishy odor of some omega-3 fatty acids is suppressed.
  • Oil (mineral oil or oil ad 100
  • Lecithin (Epikuron 200) 7.5 (up to 15)
  • Miglyol 90,8-89,4 (depending on water and DHA / EPA amount)
  • Retinol (or Retinylpalmic 0, 05
  • Citric acid 0, 005
  • Citric acid 0, 005
  • Citric acid 0, 005
  • FIG. 1 contains additional examples 7 to 19 for organogels.
  • Figure 2 includes Examples 20 to 25, which relate to various formulations.
  • FIG. 3 gives Examples 26 to 31 for further formulations.

Abstract

La présente invention concerne une composition qui comporte au moins un acide gras ω-3 ainsi qu'au moins un inhibiteur du facteur de transcription NF-κB. Cette composition convient comme médicament ou formulation de base pharmaceutique, en particulier pour la prophylaxie ou le traitement d'inflammations. De préférence, le médicament convient pour la prophylaxie et la thérapie en application topique ou en inhalation dans les domaines de l'ophtalmologie, de l'oto-rhino-laryngologie (ORL) ainsi que dans les domaines de la cavité buccale et de la cavité de la gorge et dans le domaine des poumons.
EP11776342.5A 2010-11-05 2011-09-27 Composition et médicament contenant des acides gras oméga-3 ainsi qu'un modulateur Withdrawn EP2635266A1 (fr)

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DE102010050570A DE102010050570A1 (de) 2010-11-05 2010-11-05 Zusammensetzung und Arzneimittel enthaltend ω-3-Fettsäuren sowie einen Inhibitor des NF-κB-Transkriptionsfaktors
PCT/EP2011/004836 WO2012059158A1 (fr) 2010-11-05 2011-09-27 Composition et médicament contenant des acides gras oméga-3 ainsi qu'un modulateur

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2778503C1 (ru) * 2021-12-15 2022-08-22 Общество с ограниченной ответственностью "АЙБИОФАРМ" Композиция для проведения гигиенической обработки век

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20120510A1 (it) * 2012-03-29 2013-09-30 Bio Lo Ga Srl Vitamina e e suoi esteri per l'uso nel trattamento topico di affezioni faringo-laringee
EP4008355A1 (fr) 2012-05-03 2022-06-08 Kala Pharmaceuticals, Inc. Nanoparticules pharmaceutiques permettant un transport muqueux amélioré
JP6360040B2 (ja) 2012-05-03 2018-07-18 カラ ファーマシューティカルズ インコーポレイテッド 粘液浸透性被覆粒子、組成物、医薬組成物、医薬製剤、及びそれらの形成方法
US11596599B2 (en) 2012-05-03 2023-03-07 The Johns Hopkins University Compositions and methods for ophthalmic and/or other applications
US9827191B2 (en) 2012-05-03 2017-11-28 The Johns Hopkins University Compositions and methods for ophthalmic and/or other applications
EP2664329A1 (fr) * 2012-05-15 2013-11-20 F. Holzer GmbH Système de véhicule ophtalmologique
EP2664330A1 (fr) * 2012-05-15 2013-11-20 F. Holzer GmbH Composition et médicament comprenant des acides gras oméga 3 ainsi qu'un glycosaminoglycane
DE102012020542A1 (de) 2012-10-19 2014-04-24 Ingo Schmidt-Philipp Lokale NF-kB-Modulation durch topisches Tocotrienol
WO2014127214A1 (fr) 2013-02-15 2014-08-21 Kala Pharmaceuticals, Inc. Composés thérapeutiques et utilisations de ceux-ci
EP2767293A1 (fr) 2013-02-19 2014-08-20 Paul Hartmann AG Composition destinée à la cicatrisation accélérée de plaies de tissu lésé
US9688688B2 (en) 2013-02-20 2017-06-27 Kala Pharmaceuticals, Inc. Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof
AU2014219024B2 (en) 2013-02-20 2018-04-05 KALA BIO, Inc. Therapeutic compounds and uses thereof
AU2014342042B2 (en) 2013-11-01 2017-08-17 KALA BIO, Inc. Crystalline forms of therapeutic compounds and uses thereof
US9890173B2 (en) 2013-11-01 2018-02-13 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
JP2018509412A (ja) 2015-03-10 2018-04-05 イーエルシー マネージメント エルエルシー 炎症を収束させるよう皮膚を処置するための方法および組成物ならびに炎症収束経路を刺激する活性物質のスクリーニング
CA3036336A1 (fr) 2016-09-08 2018-03-15 Kala Pharmaceuticals, Inc. Formes cristallines de composes therapeutiques et leurs utilisations
US10392399B2 (en) 2016-09-08 2019-08-27 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
BR112019004463A2 (pt) 2016-09-08 2019-05-28 Kala Pharmaceuticals Inc formas cristalinas de compostos terapêuticos, seus processos de obtenção e seus métodos de uso
CN106619553B (zh) * 2017-02-14 2019-09-03 赣州华汉生物科技有限公司 一种萝卜硫素微乳速释滴丸的制备方法
EP4093372B1 (fr) * 2020-01-23 2024-04-03 Visufarma S.p.A. Composition ophtalmique pour le traitement de la sécheresse oculaire
GB2624353A (en) * 2021-08-04 2024-05-15 Leiutis Pharmaceuticals Llp Novel Omega 3 carrier preparations for inhalation drug delivery for treating lung inflammation
CA3228281A1 (fr) * 2021-08-19 2023-02-23 Morse Laboratories L.P. Systeme d'administration topique anhydre pour des ingredients actifs solubilises dans des phases lipidique, aqueuse et alcoolique
CN114306328B (zh) * 2021-12-31 2022-10-21 苏州普乐康医药科技有限公司 一种含trpm8激动剂的组合物及其制备方法和应用
CN114748464A (zh) * 2022-03-23 2022-07-15 赣州华汉生物科技有限公司 一种萝卜硫素在制备治疗鼻炎的药物中的应用
CN115463089B (zh) * 2022-08-30 2023-10-20 宁夏医科大学 一种治疗干眼症的眼用微乳及其制备方法与应用

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1157269B (it) * 1982-03-19 1987-02-11 Seuref Ag Nuove formulazioni farmaceutiche contenenti il coenzima q10 adatte per la somministrazione topica
US5709855A (en) * 1995-09-22 1998-01-20 Bockow; Barry I. Compositions of spirulina algae and omega fatty acids for treatment of inflammation and pain
US5912006A (en) * 1996-08-28 1999-06-15 Eboc, Inc. Compositions and methods for alleviating discomforting menstrual pain
PT102509A (pt) * 2000-08-16 2002-02-28 Fundacao Essprit Icarus Composicoes farmaceuticas, cosmeticas e dermo-cosmeticas, de higiene, alimentares e para-alimentares a base de oleo de foca, e sua utilizacao
DE10056351A1 (de) * 2000-11-14 2002-05-29 Weylandt Karsten Henrich Pharmazeutisches Präparat
US20040043013A1 (en) * 2000-12-28 2004-03-04 Mccleary Edward Larry Metabolic uncoupling therapy
SK14502003A3 (en) * 2001-05-30 2004-10-05 Laxdale Ltd Coenzyme Q and eicosapentaenoic acid
US20030077336A1 (en) * 2001-10-10 2003-04-24 Maf Group, Llc Anti-inflammatory complex containing flaxseed oil
US20060251685A1 (en) 2003-03-18 2006-11-09 Zhi-Jian Yu Stable ophthalmic oil-in-water emulsions with Omega-3 fatty acids for alleviating dry eye
WO2005006890A2 (fr) * 2003-07-10 2005-01-27 Forest Carl A Aliments, boissons, condiments, epices et sauces pour salades a complements specialises
US20050074443A1 (en) * 2003-10-03 2005-04-07 Treadwell Benjamin V. Methods of attenuating autoimmune disease and compositions useful therefor
NZ552481A (en) * 2004-07-01 2008-12-24 Schepens Eye Res Compositions and methods for treating eye disorders and conditions
JP4378642B2 (ja) * 2005-07-12 2009-12-09 東洋カプセル株式会社 ゲンゲ科魚類に由来する栄養機能性食品
JP2007181408A (ja) * 2005-12-31 2007-07-19 Nippon Same No Kai Bussan Kk スクアレン加工食品
US20080146579A1 (en) * 2006-12-15 2008-06-19 N.V. Nutricia Treatment of patients with chronic pulmonary diseases and nutritional compositions therefore
AU2008100822A4 (en) * 2007-08-28 2008-10-16 Blackmores Limited Nutrition supplement

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2012059158A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2778503C1 (ru) * 2021-12-15 2022-08-22 Общество с ограниченной ответственностью "АЙБИОФАРМ" Композиция для проведения гигиенической обработки век

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