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
  • A61K31/33—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 
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/39—Convolvulaceae (Morning-glory family), e.g. bindweed
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
  • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

• This invention relates to combinations of vasoactive substances which are useful in the treatment of sexual dysfunctions associated with poor local blood supply and/or insufficient lubrication.
• Loss of erectile capacity in men is an event which adversely affects the physical, emotional and social sphere of the sufferer.
• men come to expect yet another “failure” whenever they have sexual intercourse, thus generating a particular state of mind which is both cause and effect of a problem that was originally only physical.
• Acetylcholine (Ach), for example, is the best-known parasympathetic neurotransmitter. In vitro, it causes relaxation of smooth muscle striations previously contracted by noradrenaline, and contraction of smooth muscle cell isolates.
• Ach nitric oxide
• VIP nitric oxide receptor 1
• CGRP calcitonin gene-related peptide
• Nitric oxide is synthesised from L-Arginine through the action of the enzyme NOs (nitric oxide synthetase).
• NOs nitric oxide synthetase
• the two sources of NO in the penis and clitoris are represented by the parasympathetic nerve endings and the endothelium, synthesised by different NOs enzymes: nNOs (neuronal NOs), which is present in the cytoplasm of the parasympathetic nerves, and eNOs (endothelial NOs), found in the endothelium of the blood vessels and trabecular tissue, which mainly seems to bond to the cell membranes.
• the Ach released by the parasympathetic fibres bonds to muscarinic receptors present on the endothelial cell membranes and the smooth muscle cell membranes. In the endothelium, this bond promotes the activation of eNOs with subsequent release of NO and inhibition of noradrenaline (NA). Inhibition of NA release is essential to the physiology of the erection.
• NA released by the sympathetic nerve endings, bonds with ⁇ 1-adrenergic membrane receptors (in the cavernous tissue, type ⁇ receptors outnumber type ⁇ receptors by a ratio of 10:1), leading to an increase in the activity of phospholipase C (PLC), which converts phosphatidylinositol (PIP) into inositol triphosphate (IP3) and diacylglycerol (DAG).
• PLC phospholipase C
• PIP3 phosphatidylinositol
• IP3 inositol triphosphate
• DAG diacylglycerol
• the NO released by the parasympathetic nerve endings and the endothelium is a lipophilic molecule, and therefore able to cross the smooth muscle cell membrane.
• cGMP cyclic guanosine monophosphate
• VIP like the prostanoids (PGE1), mainly acts via specific receptors on the surface of the smooth muscle cell, stimulating the enzyme adenylate cyclase (a membrane enzyme). This enzyme converts ATP into cyclic AMP (cAMP), which in turn causes a reduction in the intracellular calcium concentration and relaxation of the smooth muscles.
• PGE1 prostanoids
• This invention relates in particular to combinations of vasoactive substances useful in the treatment of sexual dysfunctions associated with poor local blood supply to the male and female sex organs.
• compositions according to the invention contain:
• Visnadine is a coumarin mainly found in the seeds of Ammi visnaga , a plant traditionally used to treat anginoid disorders.
• the compound has recently been used in the pharmaceutical field as a coronary dilator. We have demonstrated on various occasions that this compound, when applied topically, has a strong vasokinetic action on the precapillary arteries and arterioles, increasing the blood flow and tissue perfusion (EP 0418806).
• the supply of arterial blood to the erectile tissues induces the start of the erection and maintains it for as long as the compound is present in the tissues.
• Visnadine also has an anti-phosphodiesterase activity useful to maintain the cyclic nucleotides.
• Esculoside a coumarin glucoside present in many plants, such as Aesculus hippocastanum, Fraxinus communis , etc., possesses a vasokinetic action and venotropic activity at both venous and arterial levels.
• Icarin and its derivatives act on cGMP phosphodiesterase V. High levels of cGMP are required to maintain the erection in the male and female genital organs and therefore the performance necessary for sexual intercourse.
• Icarin derivatives include 7-hydroxyethyl-icarin or 7-aminoethyl-icarin, 7-hydroxyethyl-3-0-ramnosyl-icarin, 7-aminoethyl-7-desgluco-3-ramnosyl-icarin, 8-dihydro-icarin and its glucosides in 7 and 3, and 7-hydroxyethyl-7-desgluco-icarin.
• Amentoflavone is a biflavone present in modest amounts in numerous plants, such as Gingko biloba, Brakeringea zanguebarica and Taxus sp.
• the addition of amentoflavone is particularly useful in some formulations, and is one of the subjects of this invention, because it acts as a very powerful inhibitor of phosphodiesterase and on the release of oxytocin, which is a known aphrodisiac at low doses.
• Forskolin, and the extracts which contain it, is a known adenylate cyclase agonist.
• a purified extract of Coleus forskolii is particularly preferred.
• Extracts of plants of the genus Ipomea also possess a significant activity on adenylate cyclase; the standardised lipophilic extracts of Ipomea hederacea, Ipomea parassitica and Ipomea batatas are particularly preferred.
• the formulations according to the invention improve sexual performance, especially in women.
• a combination in gel form containing 1% esculoside, 0.2% forskolin and 1% ethyl ximenynate was administered to a group of 10 female volunteers of child-bearing age.
• the efficacy test in which the blood flow parameters in the external genital organs were instrumentally measured by a non-invasive method (Laser Doppler and optical probe videocapillaroscopy), demonstrated that the blood flow increased by up to 200% of the basal value; as regards subjective sensations, the patients reported general well-being, and sexual excitement within half an hour.
• application of the formulations according to the invention leads to a rapid erection which is prolonged for as long as required to complete the act of sexual intercourse.
• Esculoside 1.00 g Ethyl ximeninate 2.00 g Coleus purified extract >80% 0.20 g Polyethylene 400 10.00 g Ethoxydiglycol (Transcutol - Gattefossé) 10.00 g Caprylic/Capric PEG-6 glycerides 10.00 g (Softigen 767 - Huls) Sorbitol 10.00 g Polysorbate 20 8.00 g Carbomer (Ultrez 10 - B F Goodrich) 1.00 g Imidazolidinyl urea 0.30 g Xanthane gum (Keltrol TF - Kelco) 0.30 g Methyl paraben 0.20 g Disodium EDTA 0.10 g Hydroxytoluene butoxide 0.05 g 10% sol. sodium hydroxide 2.00 g Perfume (Jenny - Dragoco) 0.01 g Water q.s. to 100 g
• Visnadine 1.00 g 7-hydroxyethyl-7-desgluco-icarin 1.00 g Forskolin 0.20 g Amentoflavone 0.20 g Ethyl ximeninate 2.00 g Polyethylene 400 10.00 g Ethoxydiglycol (Transcutol - Gattefossé) 10.00 g Caprylic/Capric PEG-6 glycerides 10.00 g (Softigen 767 - Huls) Sorbitol 10.00 g Polysorbate 20 8.00 g Carbomer (Ultrez 10 - B F Goodrich) 1.00 g Imidazolidinyl urea 0.30 g Xanthane gum (Keltrol TF - Kelco) 0.30 g Methyl paraben 0.20 g Disodium EDTA 0.10 g Hydroxytoluene butoxide 0.05 g 10% sol. sodium hydroxide 2.00 g Perfume (Jenny - Dragoco
• Esculoside 1.00 g 7-Hydroxyethyl-7desgluco-icarin 1.00 g Ipomea hederacea lyophilic standardized extract 0.20 g Gingko biloba dimeric flavones 0.20 g Ethyl ximeninate 1.00 g Polyethylene 400 10.00 g Ethoxydiglycol (Transcutol - Gattefossé) 10.00 g Caprylic/Capric PEG-6 glycerides 10.00 g (Softigen 767 - Huls) Sorbitol 10.00 g Polysorbate 20 8.00 g Carbomer (Ultrez 10 - B F Goodrich) 1.00 g Imidazolidinyl urea 0.30 g Xanthane gum (Keltrol TF - Kelco) 0.30 g Methyl paraben 0.20 g Disodium EDTA 0.10 g Hydroxytoluene butoxide 0.05 g 10% Sol. sodium

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• Health & Medical Sciences (AREA)
• Natural Medicines & Medicinal Plants (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Medical Informatics (AREA)
• Microbiology (AREA)
• Mycology (AREA)
• Botany (AREA)
• Biotechnology (AREA)
• Alternative & Traditional Medicine (AREA)
• Organic Chemistry (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Endocrinology (AREA)
• Reproductive Health (AREA)
• Gynecology & Obstetrics (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines Containing Plant Substances (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Saccharide Compounds (AREA)
• Pyrane Compounds (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

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• 2003
  • 2003-07-11 IT IT001428A patent/ITMI20031428A1/it unknown
• 2004
  • 2004-07-06 RU RU2006100305/15A patent/RU2356568C2/ru not_active IP Right Cessation
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