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WO2004056370A1 - Utilisation d'une composition a base d'acides gras pour le traitement de la sterilite masculine - Google Patents

Utilisation d'une composition a base d'acides gras pour le traitement de la sterilite masculine Download PDF

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Publication number
WO2004056370A1
WO2004056370A1 PCT/IB2003/006083 IB0306083W WO2004056370A1 WO 2004056370 A1 WO2004056370 A1 WO 2004056370A1 IB 0306083 W IB0306083 W IB 0306083W WO 2004056370 A1 WO2004056370 A1 WO 2004056370A1
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WO
WIPO (PCT)
Prior art keywords
dha
epa
fatty acid
acid composition
composition
Prior art date
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Ceased
Application number
PCT/IB2003/006083
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English (en)
Inventor
Morten Bryhn
Gudrun Skuladottir
Arnar Hauksson
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Pronova Biopharma Norge AS
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Pronova Biocare AS
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Priority claimed from SE0203841A external-priority patent/SE0203841D0/xx
Application filed by Pronova Biocare AS filed Critical Pronova Biocare AS
Priority to AU2003288606A priority Critical patent/AU2003288606A1/en
Publication of WO2004056370A1 publication Critical patent/WO2004056370A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • 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
    • A61K31/21—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
    • A61K31/232—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 having three or more double bonds, e.g. etretinate
    • 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
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention comprises a number of aspects.
  • a use of a pharmaceutical composition for prevention or treatment of male infertility is disclosed.
  • a use of a pharmaceutical composition for prevention or treatment of asthenozoospermia is disclosed.
  • a use of a pharmaceutical composition for prevention or treatment of teratozoospermia is disclosed.
  • a use of a pharmaceutical composition for prevention or treatment of a condition due to decreased concentration of DHA in sperm is disclosed.
  • a use of a dietary foodstuff for non-medical prevention or treatment of male infertility is disclosed.
  • a use of a dietary foodstuff for non-medical prevention or treatment of asthenozoospermia is disclosed.
  • a use of a dietary foodstuff for non-medical prevention or treatment of teratozoospermia is disclosed.
  • a use of a dietary foodstuff for non-medical prevention or treatment of a condition due to decreased concentration of DHA in sperm is disclosed.
  • a method for prevention or treatment of male infertility is disclosed.
  • a method for prevention or treatment of asthenozoospermia is disclosed.
  • a method for prevention or treatment of teratozoospermia is disclosed.
  • a method for prevention or treatment of a condition due to decreased concentration of DHA in sperm is disclosed.
  • a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA: DHA in the fatty acid composition is 1:X, where X is > 1, or a fatty acid composition comprising at least one of EPA or DHA, to be administered to a human or an animal together with DHA in the case where the composition comprises EPA, or EPA in the case where the composition comprises DHA, wherein the total administered amount of DHA is > EPA.
  • sperms takes place in the Leydig cells of the testicles. Their development from diploid stem cells into mobile, haploid sperm is governed by several hundred genes in which the cell nucleus becomes the sperm head while portions of the Golgi , mitochondrial , and cytoplasmic material become the tail and the sheet .
  • the tail and head each have distinctive functions where the tail is responsible for movement in the epididymis and, after ejaculation, in the female genital tracts.
  • the head with its acrosome plays an important role in capacitation and the acrosome reaction that renders the sperm capable of fusing with the egg plasma membrane, penetrating the egg for fertilisation and transferring the genetic material.
  • sperm heads and tails have been characterised in detail [Holger H, et al . The protein complexi ty of the cytoskeleton of bovine and human sperm heads . Exp Cell Res 1995 ; 218 : 174 -182] but certain lipids also seem to play an important role in the constitution and function of sperms. Great differences in the composition of sterols, fatty acids, and the phospholipid molecular species between heads and tails have been observed in monkeys [Connor WE, et al . Uneven distribution of desmosterol and docosahexaenoic acid in the heads and tails of monkey sperm . J Lipid Res 1998;39 : 1404 -1411] .
  • these differences in membrane lipid composition may contribute to the unique functions of the sperms.
  • the most striking difference between heads and tails were in the concentration of the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3)). Over 99% of the DHA was localised in the tails. The reason for this selective accumulation of DHA is not known but since high concentrations of DHA in cell membranes are correlated with membrane fluidity it is possible that this selective concentration of a polyunsaturated fatty acid (PUFA) in the tail is necessary to provide for the bending and flexing for motility of sperms.
  • PUFA polyunsaturated fatty acid
  • DHA is the most unsaturated fatty acid of the omega- 3 series with 6 double bonds (Fig. 1) .
  • the omega-3 fatty acids are essential to animals and humans meaning that they have to be provided in the diet .
  • the omega-3 fatty acid with the " shortest chain length alfa- linolenic acid (ALA, 18:3n-3) may be converted to DHA through the intermediate eicosapentaenoic acid (EPA,
  • DHA docosahexaenoic acid
  • desaturase is the rate-limiting enzyme and the conversion rate from ALA is slow in humans .
  • delta-6-desaturase insufficiency could be the factor responsible for male infertility, at least in people not eating fatty fish containing DHA.
  • Seldom intake of fish is a common dietary habit throughout the Western World today.
  • Oxidative damage of DHA has been suggested as another mechanism for low DHA concentration with possibly reduction of sperm viability [Ottero M, et al . Variation of docosahexaenoic acid content in subsets of human spermatozoa at different stages of maturation : implication for sperm lipoperoxidative damage . Mol Reprod & Devel 2000;55 : 326-334 , Zalata AA, et al . Whi te blood cells cause oxidative damage to the fatty acid composi tion of phospholipids of human spermatozoa] .
  • DHA supplementation had no effects on sperm motility or sperm concentration.
  • WO 9966877 a method and a dietary supplement for increasing fertilitiy in an aniaml is presented.
  • the method comprising feeding the animal a omega-3 fatty acid containing component, which omega-3 fatty acid containing component is preferably of plant, animal or single cell oil origin.
  • Method for prevention or treatment of teratozoospermia 11. Method for prevention or treatment of teratozoospermia . 12. Method for prevention or treatment of a condition due to decreased concentration of DHA in sperm.
  • a fatty acid composition comprising at least (all-Z omega-3) -5, 8, 11, 14, 17-eicosapentaenoic acid (EPA) and (all-Z omega-3) -4 , 7 , 10, 13 , 16, 19- docosahexaenoic acid (DHA) , wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1.
  • a fatty acid composition comprising at least one of EPA or DHA, to be administered to a human or an animal together with DHA in the case where the composition comprises EPA, or EPA in the case where the composition comprises DHA, wherein the total administered amount of DHA is > EPA.
  • the invention relates to the use of a fatty acid composition
  • a fatty acid composition comprising at least (all-Z omega-3) -5, 8, 11, 14, 17- eicosapentaenoic acid (hereafter abbreviated EPA) and (all-Z omega-3) -4, 7, 10, 13 , 16, 19-docosahexaenoic acid
  • the invention relates to the use of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, for the manufacture of a pharmaceutical composition for prevention or treatment of male infertility.
  • a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, for the manufacture of a pharmaceutical composition for prevention or treatment of asthenozoospermia .
  • the invention relates to the use of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, for the manufacture of a pharmaceutical composition for prevention or treatment of teratozoospermia .
  • the invention relates to the use of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is ⁇ 1, for the manufacture of a pharmaceutical composition for prevention or treatment of a 'Condition due to decreased concentration of DHA in sperm.
  • the prevention or treatment of male infertility includes especially prevention or treatment of male infertility due to at least one of asthenozoospermia, teratozoospermia, and a decreased concentration of DHA in sperm or any combinations of these conditions.
  • the effect of the invention is accomplished by the combination of at least the two fatty acids EPA and DHA, wherein the amount of DHA is > EPA.
  • DHA itself had no effect on sperm motility or sperm concentration, but the administration of a fatty acid composition according to the invention comprising at least EPA and DHA, wherein the weight ratio of EPA: DHA is 1:X, where X is > 1, showed a surprisingly synergetic effect.
  • a most preferred effect of the invention is accomplished by a fatty acid composition rich in DHA, but still containing at least EPA.
  • the term rich herein includes a fatty acid composition there the amount (weight or volume) of DHA is equal or larger than EPA.
  • a pharmaceutical composition comprising at least EPA is to be administered together with DHA, and then the pharmaceutical composition comprising at least DHA, EPA is to be administered together with DHA, wherein the total administered amount of DHA is > EPA, in both cases for prevention or treatment of male infertility, especially male infertility due to at least one of asthenozoospermia, teratozoospermia, a decreased concentration of DHA in sperm or any combinations of these conditions.
  • the EPA and the DHA may be administered subsequently to each other.
  • the fatty acid composition is administered to a human.
  • the pharmaceutical composition according to the invention is preferably intended to be administered to humans, but the invention also relates to use of a pharmaceutical composition according to the invention that may be administered to animals, preferably animals such as domestic animals, livestock and/or cattle.
  • the fatty acid composition is obtained from at least one of vegetable, microbial and animal or combinations thereof.
  • the EPA is obtained from at least one of vegetable, microbial and animal origins or combinations thereof
  • the DHA is obtained from at least one of vegetable, microbial and animal origins or combinations thereof. Namely, it is possible that DHA and EPA may independently of each other come from different origins.
  • At least part of the EPA and/or the DHA is produced from a marine oil, preferably a fish oil.
  • both DHA and EPA is obtained from fish oil.
  • the fatty acid composition is presented in at least one of esterified form, ethyl ester form, salt form and free acid form, or any combinations thereof.
  • the fatty acid composition comprises at least DHA and EPA in the forms of triglycerides, re-esterified triglycerides with content of * di- and mono-glycerides, ethyl esters, salts and/or free fatty acids or any combinations of the above mentioned forms.
  • the rest of the fatty acid composition is preferably comprised of omega-3 -fatty acids other than DHA and EPA that have 20-22 carbon atoms in any of the above mentioned forms.
  • the fatty acid composition may additionally also comprise at least one of arachidonic acid (ARA) , docosapentaenoic acid, heneicosapentaenoic acid and octadecatetraenoic acid.
  • ARA arachidonic acid
  • the combination of EPA:DHA are present in the composition in an EPA:DHA ratio from about 1 : 1 to 1 : 6.
  • the weight ratio of EPA: DHA in the fatty acid composition is about 1:6.
  • 15% to 80% by weight of the fatty acid composition is comprised of EPA and DHA.
  • 60% to 80% by weight of the fatty acid composition is constituted by EPA and DHA.
  • about 60% by weight of the fatty acid composition is constituted by a combination of EPA and DHA.
  • the fatty acid composition also comprises (all-Z omega-3) - 7, 10, 13 , 16, 19-docosapentaenoic acid (DPA) , in an amount of about 10% to 40% of the amount of DHA in the composition.
  • DPA docosapentaenoic acid
  • the fatty acid composition being administered in amount providing a daily dosage of 0,5g to 6,0g of said fatty acid composition, preferably between 2g and 4g, to a human or an animal.
  • the pharmaceutical composition or pharmaceutical preparation or medicinal product may preferably be produced for oral administration in the form of for instance a pill, a soft capsule or the like.
  • the pharmaceutical composition or pharmaceutical preparation or medicinal product may also be produced for administration through any other route where the active ingredients may be efficiently absorbed and utilized, e.g. intravenously, subcutaneously, intramuscularely, intranasally, rectally, vaginally or topically.
  • the pharmaceutical composition according to the invention may also comprise other substances, in addition to the EPA and DHA active ingredients, such as vehicle, one or more acceptable carrier, fillers, stabilizers, extenders, binders, humidifiers, surfactants, lubricants etc., which all are well known to persons skilled in the art.
  • one or more pharmaceutical acceptable antioxidants for example hydroxytoluene, butyrate, quinone, tocopherol , ascorbic acid etc., preservatives, colouring agents, perfumes, flavourings and other pharmaceutically agents may be used.
  • preservatives for example hydroxytoluene, butyrate, quinone, tocopherol , ascorbic acid etc.
  • preservatives for example hydroxytoluene, butyrate, quinone, tocopherol , ascorbic acid etc.
  • colouring agents for example hydroxytoluene, butyrate, quinone, tocopherol , ascorbic acid etc.
  • preservatives for example hydroxytoluene, butyrate, quinone, tocopherol , ascorbic acid etc.
  • colouring agents for example hydroxytoluene, butyrate, quinone, tocopherol , ascorbic acid etc.
  • preservatives for example hydroxytoluen
  • the invention relates to the use of a fatty acid composition
  • a fatty acid composition comprising at least (all-Z omega-3) - 5, 8, 11, 14, 17-eicosapentaenoic acid (EPA) and (all-Z omega-3) -4, 7, 10 , 13 , 16, 19-docosahexaenoic acid (DHA), wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, for the manufacture of a dietary foodstuff for non-medical prevention or treatment of male infertility.
  • the invention relates to the use of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, for the manufacture of a dietary foodstuff for non-medical prevention or treatment of asthenozoospermia.
  • the invention relates to the use of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, for the manufacture of a dietary foodstuff for prevention or treatment of teratozoospermia.
  • the present invention relates to the use of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, for the manufacture of a dietary foodstuff for non-medical prevention or treatment of a condition due to decreased concentration of DHA in sperm
  • the invention relates to a dietary foodstuff comprising a mixture containing at least EPA and DHA, wherein the amount of DHA > EPA, for non-medical prevention or treatment of male infertility, especially male infertility due to asthenozoospermia, teratozoospermia, low DHA concentration in sperm or combinations of these conditions.
  • the effect of the invention is also here accomplished by the use and administration of a fatty acid composition comprising at least a combination of EPA and DHA, wherein the weight ratio of EPA: DHA in the fatty acid composition is 1:X, where X is > 1.
  • a fatty acid composition comprising at least a combination of EPA and DHA, wherein the weight ratio of EPA: DHA in the fatty acid composition is 1:X, where X is > 1.
  • An advantage of manufacturing and selling a dietary food stuff according to the invention for prevention and/or treatment of male infertility, especially male infertility due to asthenozoospermia, teratozoospermia, low DHA concentration in sperm or any combinations of these conditions, is that such a dietary product will be more easily accessible for men around the world. They preferably can buy the product or supplement in a health food store and/or a supermarket, and don't need to visit a doctor in the first place.
  • the dietary foodstuff according to the invention is produced in such way that the EPA part of the composition is separate from the DHA part of the composition.
  • an EPA- containing composition is to be administered together with DHA and a DHA-containing composition is to be administered together with EPA, but still the total administered amount of DHA is equal or larger than the amount of EPA.
  • the EPA and the DHA may be administered subsequently to each other.
  • the weight ratio of EPA:DHA is also here 1:X, where X is equal or larger than 1. Please note that X being one of an integer or non-integer.
  • the dietary foodstuff according to the invention is preferably intended to be administered to humans, but it may also be administered to animals, preferably animals such as domestic animals, livestock and cattle.
  • the fatty acid composition is obtained from at least one of vegetable, microbial and animal or combinations thereof.
  • DHA is obtained from at least one of vegetable, microbial and animal origins or any combinations thereof. Further, DHA and EPA may independently of each other come from different origins. In a more preferred embodiment at least part of the EPA and/or the DHA is produced from a marine oil, preferably a fish oil. In a most preferred embodiment of the invention both DHA and EPA is obtained from fish oil .
  • the dietary foodstuff comprising a mixture containing at least a fatty acid composition comprising EPA and DHA, wherein the amount of DHA is ⁇ EPA, and DHA and EPA is at least in one of the form of triglycerides, re-esterified triglycerides with content of di- and mono-glycerides, ethyl esters, salts, free acids or in any combinations thereof.
  • the rest of the fatty acid composition is preferably comprised of omega-3-fatty acids other than DHA and EPA that have 20-22 carbon atoms in any of the above mentioned forms, preferably arachidonic acid (ARA) in any of the above mentioned forms.
  • ARA arachidonic acid
  • the fatty acid composition may additionally also comprise at least one of arachidonic acid (ARA) , docosapentaenoic acid, heneicosapentaenoic acid and octadecatetraenoic acid.
  • ARA arachidonic acid
  • 15% to 80% by weight of the fatty acid composition is comprised of EPA and DHA.
  • 60% to 80% by weight of the fatty acid composition is constituted by EPA and DHA.
  • the weight ratio of EPA:DHA in the fatty acid composition is about 1:6.
  • about 60% by weight of the fatty acid composition is constituted by a combination of EPA and DHA.
  • a cod-liver oil or a tuna fish-liver oil may be used.
  • the fatty acid composition also comprises (all-Z omega-3) - 7, 10, 13 , 16, 19-docosapentaenoic acid (DPA) , in an amount of about 10% to 40% of the amount of DHA in the composition.
  • DPA docosapentaenoic acid
  • the fatty acid composition being administered in amount providing a daily dosage of 0,5g to 6,0g of said fatty acid composition, preferably between 2g and 4g.
  • the dietary food stuff is in form of a gelatine capsule, which capsule is flavoured.
  • the active compounds according to the dietary foodstuff of the invention may be administered in one of the possible forms and ways as mentioned before for the pharmaceutical composition according to the invention.
  • the dietary foodstuff according to the invention may comprise, in addition to the EPA and DHA ingredients, at least one of the same substances as mentioned before according to a pharmaceutical composition, but also other suitable agents such as vitamins and/or minerals.
  • the invention relates to a method for prevention or treatment of male infertility, wherein a therapeutically active amount of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, is administrated to a patient in a need of said treatment.
  • the invention relates to a method for prevention or treatment of asthenozoospermia, wherein a therapeutically active amount of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, is administrated to a patient in a need of said treatment.
  • the invention relates to a method for prevention or treatment of teratozoospermia, wherein a therapeutically active amount of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, is administrated to a patient in a need of said treatment .
  • the invention relates to a method for prevention or treatment of a condition due to decreased concentration of DHA in sperm, wherein a therapeutically active amount of a fatty acid composition comprising at least EPA and DHA, wherein the weight ratio of EPA:DHA in the fatty acid composition is 1:X, where X is > 1, is administrated to a patient in a need of said treatment.
  • the invention in another embodiment, relates to a method for prevention and/or treatment of male infertility, especially male infertility due to asthenozoospermia, teratozoospermia, decreased concentration of DHA in sperm or combinations of these conditions, wherein a therapeutically or pharmaceutically active amount of at least a fatty acid composition comprising EPA and DHA, wherein the amount of DHA is > EPA, is administrated to a patient in a need of the mentioned treatment.
  • the effect of the invention is accomplished by preferably the combination of the two fatty acids EPA and DHA, but the amount of DHA may be equal or larger than EPA.
  • a therapeutically or pharmaceutically active amount of a fatty acid composition comprising at least EPA is to be administered together with DHA, and then the composition comprising at least DHA, EPA is to be administered together with DHA, wherein the total administered amount of DHA is > EPA, in both cases for prevention or treatment of male infertility, especially male infertility due to at least one of asthenozoospermia, teratozoospermia, a decreased concentration of DHA in sperm or any combinations of these conditions.
  • At least one of EPA and DHA is obtained from at least one of vegetable, microbial and animal origins or combinations thereof.
  • at least part of the EPA and/or the DHA is produced from a marine oil, preferably a fish oil.
  • the therapeutically or pharmaceutically active amount of a fatty acid composition comprising at least EPA and DHA is administrated to a patient, wherein the DHA and EPA is in one of the forms of triglycerides, re-esterified triglycerides with content of di- and mono-glycerides, ethyl esters, salts, free acids or any combinations thereof.
  • the rest of the fatty acid composition is preferably comprised of omega-3-fatty acids other than DHA and EPA that have 20-22 carbon atoms in any of the above mentioned forms.
  • 15% to 80% by weight of the fatty acid composition is comprised of EPA and DHA.
  • 60% to 80% by weight of the fatty acid composition is comprised of EPA and DHA.
  • the fatty acid composition also comprises (all-Z omega-3) - 7, 10, 13 , 16, 19-docosapentaenoic acid (DPA) , in an amount of about 10% to 40% of the amount of DHA in the composition.
  • the pharmaceutically or therapeutically active composition is administered in amount providing a daily dosage of 0,5 to 6,0 grams of the fatty acid composition according to the invention.
  • the fatty acid composition is administered in a daily dosage of 2 to 4g and most preferably about 3g.
  • the pharmaceutically active composition is administered in a daily dosage comprising about 450-850mg EPA and about l,7-3,0g DHA.
  • the dosage of EPA is about 0,8g and the dosage of DHA is about l,9g.
  • the pharmaceutically active compound according to the invention is administered in a food product or as a dietary foodstuff.
  • the analysis in % by weight is based on the ethyl esters even if other derivatives of salts or the acids themselves are a part of the present invention.
  • the term manufacture is interpreted to include production of a pharmaceutical composition and/or a medicinal product.
  • asthenozoospermia means poor sperm forward motility.
  • pharmaceutical means pharmaceutical preparations and/or compositions and medical food.
  • a pharmaceutical preparation according to the present invention may also comprise other substances such as an inert vehicle or a pharmaceutically acceptable adjuvance, carriers, preservatives etc., which all are well-known to those skilled in the art.
  • dietary foodstuff is interpreted to include food and food supplement to animals and/or humans, fortification of food, dietary supplement, functional food and nutrient supplement.
  • the term patient relates to any human or non-human mammal in need of treatment with the medicinal product or method according to the invention.
  • marine oil includes oil from fish, seals, cetaceans, sea shell and sea mammals.
  • fish oil is e.g. Menhaden oil, Cod Liver oil, Herring oil, Capelin oil, Sardine oil, Anchovy oil and Salmon oil.
  • the fish oils mentioned above may be recovered from fish organs, e.g. cod liver oil, as well as from the meat of the. fish.
  • microbial oils also includes "single cell oils” and blends, or mixtures, containing unmodified microbial oils.
  • Microbial oils and single cell oils are those oils naturally produced by micro organisms during their lifespan.
  • the term treatment means both treatment having a curving or alleviating purpose and treatment having a preventive purpose.
  • the treatment can be made either acutely or chronically.
  • Treatment can be given to both humans and animals.
  • Non-limiting examples of such animals is e.g. domestic animals, livestock and cattle .
  • the term prevention means actions having a preventive purpose to prevent a condition to appear. Preventive actions can be given to both humans and animals.
  • Figure 3 shows the levels (%) of DHA in plasma total phospholipid.
  • Figure 4 shows the levels (%) of DHA in sperm total phospholipid .
  • Figure 5 shows the effect on sperm motility.
  • Figure 6 shows the effect on abnormal morphology.
  • Figure 7 shows the relationship between total sperm count (mill) and DHA (%) in sperm total phospholipid.
  • figure 8 shows the relationship between DHA (%) in sperm total phospholipid and DHA (%) in plasma total phospholipides .
  • a fatty acid composition according to the present invention In order to evaluate the effect of a fatty acid composition according to the present invention on male infertility, 16 asthenozoospermia men, aged 30-40 years and living in the Reykjavik, Island, area, with sperm motility lower than 30% of normal value volunteered to participate in an open intervention using a 60% of weight omega-3 concentrate from fish.
  • the concentrate (EPAX 2050TG) contained 20% eicosapentaenoic acid (EPA) and 50% docosahexaenoic acid (DHA) as re-esterified triglyceride with a triglyceride content of 50-55%, diglyceride content of 40-45% and monoglyceride content of about 5%.
  • a fatty acid composition comprising at least EPA and DHA, wherein the amount of DHA is larger than EPA, was used.
  • the participants had not consumed any other omega-3 preparation or cod liver oil at least two years prior to the trial. They did not use medication and none were heavy smokers or drinkers .
  • Blood and semen samples were collected two weeks before study start (A) , the day the trial started (B) , at 10 weeks (C) and at 20 weeks (D) after study start. After completion of the study, the participants were controlled after two (E) and 10 weeks (F) . All together the participants were controlled six times. The frequent controls were warranted to compensate for anticipated large variations in study parameters .
  • the participants were given six capsules of the omega-3 concentrate daily, each capsule containing 750 mg oil, during 20 weeks.
  • the daily dose of EPA was 0,81 g and DHA 1,89 g.
  • the following parameters were measured for each sample: Sperm count, sperm motility, sperm morphology, semen viscosity, fatty acid composition of sperm phospholipids, fatty acids in blood plasma and lipid peroxides.
  • the study shows that the supplementation with a fatty acid composition comprising at least EPA and DHA, wherein the amount of DHA is larger than EPA, increases the average concentration of DHA in the plasma phospholipids, as evident from figure 3. Moreover, the distribution of the amount of DHA in sperm phospholipides in patients at study start, after 10 weeks and 20 weeks of treatment respectively 10 weeks after the completion of the study, is shown in figure 4. The best effect seems to be obtained after 10 weeks of treatment.
  • Figure 7 shows that the total sperm count (mill) is correlated to the level (%) of DHA in sperm total phospholipid.
  • participant 1 and three the treatment with a fatty acid composition according to the invention had an effect on the DHA level of sperm total phospholipid as well as the sperm count.
  • figure 8 illustrates the relationship between DHA (%) in sperm total phospholipid and DHA (%) in plasma total phospholipid after 20 weeks of treatment according to the invention. Discussion
  • a fatty acid compositions according to the present invention are potentially valuable for the treatment and prophylaxis of male infertility or multiple factors with influence on male infertility, such as asthenozoospermia, teratozoospermia, low concentration of
  • the doses of the composition of this invention needed for therapeutic or prophylactic effect will vary with the type of administration, body size, and the seriousness of the condition to be treated.
  • compositions according to the present invention are being well tolerated, not giving any severe side effects.
  • the rest of the fatty acid composition is preferably essentially comprised of omega-3 -fatty acids other than DHA and EPA that have 20-22 carbon atoms in any of the above mentioned forms, preferably at least DPA.
  • the capsule may be micro- or macro incapsulated. Further, the capsule may be constituted by one of bovine gelatine, fish gelatine or pig gelatine. Alternatively, a vegetable capsule may be used. The active ingredients and the excpeciants are weighed an homogenized on a high speed stirrer. The mixture is then colloid milled and dereated in a stainless steel vessel ready for encapsulation. The mixture is filled in soft gelatine capsules of size 20 oblong (average weight 1.2 g) using a standard capsulation machine.

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Abstract

L'invention concerne un composition d'acides gras comprenant un acide eicosapentaénoïque (all-Z oméga-3)-5,8,11,14,17 (EPA) et un acide docosahexaénoïque (all-Z oméga-3)-4,7,10,13,16,19 (DHA), le rapport de poids EPA:DHA dans la composition d'acides gras étant de 1:X, avec X = 1. Cette composition entre dans la fabrication d'une composition pharmaceutique ou d'un produit alimentaire diététique destinés à prévenir ou à traiter la stérilité masculine. La présente invention concerne également une méthode de traitement de la stérilité masculine à l'aide de ladite composition d'acides gras.
PCT/IB2003/006083 2002-12-20 2003-12-19 Utilisation d'une composition a base d'acides gras pour le traitement de la sterilite masculine Ceased WO2004056370A1 (fr)

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Cited By (9)

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JPWO2009004999A1 (ja) * 2007-06-29 2010-08-26 武田薬品工業株式会社 シームレスカプセル
WO2010103402A1 (fr) * 2009-03-09 2010-09-16 Pronova Biopharma Norge As Compositions comprenant un mélange oléagineux à base d'acides gras comportant de l'epa et du dha sous forme d'acide libre et un tensioactif, et procédés et utilisations associés
WO2013013979A1 (fr) * 2011-07-26 2013-01-31 Gonadosan Gmbh Utilisation de citrulline et association médicamenteuse pour améliorer la fécondité masculine
US9050308B2 (en) 2012-01-06 2015-06-09 Omthera Pharmaceuticals, Inc. DPA-enriched compositions of omega-3 polyunsaturated fatty acids in free acid form
US9452135B2 (en) 2012-03-20 2016-09-27 Particle Dynamics International, Llc Gelling agent-based dosage form
US9492545B2 (en) 2012-05-07 2016-11-15 Omthera Pharmaceuticals Inc. Compositions of statins and omega-3 fatty acids
DE102015109352A1 (de) * 2015-06-12 2016-12-15 K. D. Pharma Bexbach Gmbh Anwendung von Omega-3- und/oder Omega-6-Fettsäure(n)
WO2019110097A1 (fr) * 2017-12-06 2019-06-13 Laboratoire Des Granions Composition comprenant de la l-carnitine pour le traitement de l'infertilite masculine
IT202000026798A1 (it) 2020-11-10 2022-05-10 Univ Degli Studi Di Perugia Acidi grassi poliinsaturi ω-3 per l’uso nella prevenzione e nel trattamento dell’infertilità maschile in soggetti pre-puberi candidati a terapie gonado-tossiche.

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WO1999066877A2 (fr) * 1998-06-25 1999-12-29 Agricultural Research Organization Manipulation alimentaire visant a accroitre la fertilite
WO2001097802A1 (fr) * 2000-06-17 2001-12-27 Jsr Clover Ltd Supplément visant à augmenter la fertilité

Patent Citations (2)

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WO1999066877A2 (fr) * 1998-06-25 1999-12-29 Agricultural Research Organization Manipulation alimentaire visant a accroitre la fertilite
WO2001097802A1 (fr) * 2000-06-17 2001-12-27 Jsr Clover Ltd Supplément visant à augmenter la fertilité

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102552213A (zh) * 2007-06-29 2012-07-11 武田药品工业株式会社 无缝胶囊
JPWO2009004999A1 (ja) * 2007-06-29 2010-08-26 武田薬品工業株式会社 シームレスカプセル
CN101801416B (zh) * 2007-06-29 2012-10-24 武田药品工业株式会社 无缝胶囊
EP2172225A4 (fr) * 2007-06-29 2011-04-27 Takeda Pharmaceutical Capsule sans soudure
US10596142B2 (en) 2009-03-09 2020-03-24 Pronova Biopharm Norge AS Compositions comprising a fatty acid oil mixture and a free fatty acid, and methods and uses thereof
US9532963B2 (en) 2009-03-09 2017-01-03 Pronova Biopharma Norge As Compositions comprising a fatty acid oil mixture and a free fatty acid, and methods and uses thereof
WO2010119319A1 (fr) * 2009-03-09 2010-10-21 Pronova Biopharma Norge As Compositions comprenant un mélange oléagineux à base d'acides gras et d'un acide gras libre, et procédés et utilisations associés
US11612579B2 (en) 2009-03-09 2023-03-28 Pronova Biopharma Norge As Compositions comprising a fatty acid oil mixture and a surfactant, and methods and uses thereof
US20120232141A1 (en) * 2009-03-09 2012-09-13 Svein Olaf Hustvedt Compositions comprising a fatty acid oil mixture and a free fatty acid, and methods and uses thereof
US11395811B2 (en) 2009-03-09 2022-07-26 Pronova Biopharma Norge As Compositions comprising a fatty acid oil mixture comprising EPA and DHA in free acid form and a surfactant, and methods and uses thereof
WO2010103402A1 (fr) * 2009-03-09 2010-09-16 Pronova Biopharma Norge As Compositions comprenant un mélange oléagineux à base d'acides gras comportant de l'epa et du dha sous forme d'acide libre et un tensioactif, et procédés et utilisations associés
US10028928B2 (en) 2009-03-09 2018-07-24 Pronova Biopharma Norge As Compositions comprising a fatty acid oil mixture and a free fatty acid, and methods and uses thereof
WO2013013979A1 (fr) * 2011-07-26 2013-01-31 Gonadosan Gmbh Utilisation de citrulline et association médicamenteuse pour améliorer la fécondité masculine
US9050309B2 (en) 2012-01-06 2015-06-09 Omthera Pharmaceuticals, Inc. DPA-enriched compositions of omega-3 polyunsaturated fatty acids in free acid form
US10117844B2 (en) 2012-01-06 2018-11-06 Omthera Pharmaceuticals, Inc. DPA-enriched compositions of omega-3 polyunsaturated fatty acids in free acid form
US9050308B2 (en) 2012-01-06 2015-06-09 Omthera Pharmaceuticals, Inc. DPA-enriched compositions of omega-3 polyunsaturated fatty acids in free acid form
US9452135B2 (en) 2012-03-20 2016-09-27 Particle Dynamics International, Llc Gelling agent-based dosage form
US9492545B2 (en) 2012-05-07 2016-11-15 Omthera Pharmaceuticals Inc. Compositions of statins and omega-3 fatty acids
DE102015109352A1 (de) * 2015-06-12 2016-12-15 K. D. Pharma Bexbach Gmbh Anwendung von Omega-3- und/oder Omega-6-Fettsäure(n)
US20180214406A1 (en) * 2015-06-12 2018-08-02 K.D. Pharma Bexbach Gmbh Omega-3 and/or omega-6 fatty acid(s) in impaired sphingolipid metabolism
US10744108B2 (en) 2015-06-12 2020-08-18 K.D. Pharma Bexbach Gmbh Omega-3 and/or omega-6 fatty acid(s) in impaired sphingolipid metabolism
WO2019110097A1 (fr) * 2017-12-06 2019-06-13 Laboratoire Des Granions Composition comprenant de la l-carnitine pour le traitement de l'infertilite masculine
IT202000026798A1 (it) 2020-11-10 2022-05-10 Univ Degli Studi Di Perugia Acidi grassi poliinsaturi ω-3 per l’uso nella prevenzione e nel trattamento dell’infertilità maschile in soggetti pre-puberi candidati a terapie gonado-tossiche.
WO2022101948A1 (fr) * 2020-11-10 2022-05-19 Universita' Degli Studi Di Perugia Acides gras polyinsaturés oméga-3 pour le traitement ou la prévention de l'infertilité masculine chez des candidats prépubaires pour des thérapies gonadotoxiques

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