EP1292295A1 - Supplement visant augmenter la fertilite - Google Patents

Supplement visant augmenter la fertilite

Info

Publication number
EP1292295A1
EP1292295A1 EP01940729A EP01940729A EP1292295A1 EP 1292295 A1 EP1292295 A1 EP 1292295A1 EP 01940729 A EP01940729 A EP 01940729A EP 01940729 A EP01940729 A EP 01940729A EP 1292295 A1 EP1292295 A1 EP 1292295A1
Authority
EP
European Patent Office
Prior art keywords
supplement
dha
admixture
spermatozoa
antioxidant
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Withdrawn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
EP01940729A
Other languages
German (de)
English (en)
Inventor
Ray Clifford Noble
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.)
JSR Clover Ltd
Original Assignee
JSR Clover Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by JSR Clover Ltd filed Critical JSR Clover Ltd
Publication of EP1292295A1 publication Critical patent/EP1292295A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23Esters, 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
    • A61K31/232Esters, 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic 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
    • A61K31/352Heterocyclic 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 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355Tocopherols, e.g. vitamin E
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/30Boraginaceae (Borage family), e.g. comfrey, lungwort or forget-me-not
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis

Definitions

  • This invention is concerned with the provision of a supplement by oral or other means and in particular one that exhibits properties for promoting and enhancing fertility and reproductive output in mammals such as livestock and particularly pigs.
  • spermatozoa and associated seminal plasma contain lipids (fat) which have been found to be unique in their composition and fatty acid constituents when compared with almost all other tissues within the male animal body.
  • lipids fat
  • fatty acid constituents when compared with almost all other tissues within the male animal body.
  • all tissues have a requirement to maintain significant levels of essential polyunsaturated fatty acids.
  • These usually exist as C18 components, linoleic and alpha-linolenic acids, which are distributed between phospholipid and neutral lipid fractions.
  • Such acids are also accompanied by varying, but usually very much lower, concentrations of longer chain acids of higher polyunsaturation.
  • long chain acids can either be derived directly through nutrition or indirectly through synthesis by processes within the tissues themselves involving interrelated desaturation (introduction of more double bonds) and chain elongation (addition of more carbon atoms) of both linoleic and alpha-linolenic acid.
  • a selection of C20 and C22 polyunsaturates can arise from linoleic acid and these are known collectively as n-6 or omega-6 polyunsaturates.
  • n-6 or omega-6 polyunsaturates a series of C20 and C22 polyunsaturates arise from alpha-linolenic acid and are collectively known as n-3 or omega-3 polyunsaturates.
  • the male pig has a substantial level of polyunsaturates present within its spermatozoa and seminal fluid which is characteristically dominated by docosahexaenoic acid (DHA) of which its chain length is 22 carbon atoms with 6 double bonds in n-3 configuration and docosapentaenoic acid (DPA) of which its chain length is 22 carbon atoms with 5 double bonds in n-6 configuration.
  • DHA docosahexaenoic acid
  • DPA docosapentaenoic acid
  • the present invention was developed to address the issues of maximising financial gain from commercial pig breeding by way of optimising male fertility whilst additionally increasing female reproductive output.
  • the object of the present invention was to produce a supplement for easy use and which was adapted to maximise the fertility and reproductive output in pigs.
  • a supplement for the promotion of fertility and reproductive output in animals comprising an admixture of an enriched triacylglycerol source of Docosahexaenoic acid (DHA) accompanied by at least one antioxidant and selenium as the major cationic enzyme co-factor to protect the DHA.
  • DHA Docosahexaenoic acid
  • a supplement for the promotion of fertility and reproductive output in humans comprising an admixture of an enriched triacylglycerol source of Docosahexaenoic acid (DHA) accompanied by at least one antioxidant and selenium as the major cationic enzyme co-factor to protect the DHA.
  • DHA Docosahexaenoic acid
  • GLA gamma-linolenic acid
  • a supplement for the promotion of fertility and reproductive output in animals comprising an admixture of an enriched triacylglycerol source of Docosahexaenoic acid (DHA) accompanied by at least one antioxidant, selenium as the major cationic enzyme co-factor to protect the DHA and gamma-linolenic acid (GLA).
  • DHA Docosahexaenoic acid
  • GLA gamma-linolenic acid
  • a supplement for the promotion of fertility and reproductive output in humans comprising an admixture of an enriched triacylglycerol source of Docosahexaenoic acid (DHA) accompanied by at least one antioxidant, selenium as the major cationic enzyme co-factor to protect the DHA and gamma-linolenic acid (GLA).
  • DHA Docosahexaenoic acid
  • GLA gamma-linolenic acid
  • the DHA is present in the admixture at a level of 63-90g/kg.
  • the GLA is present in the admixture at a level of 4-10g/kg and advantageously is introduced in the form of oil from the Evening Primrose or Starflower.
  • the antioxidant is alpha-tocopherol and present in the admixture at a minimum of lOOOmg/kg.
  • the selenium is present in the admixture at a minimum 2.75mg/kg.
  • stearadonic acid an n-3 C18 polyunsaturated acid
  • n-3 C18 polyunsaturated acid may be added to the admixture.
  • the admixture can be introduced into the animal by way of a suitable carrier for ingestion by the animal such as feedstuff s or by gelatin bolus.
  • a suitable carrier for ingestion by the animal such as feedstuff s or by gelatin bolus.
  • the fatty acids, antioxidants and cationic cofactors can be supplied intramuscularly, intraperitonealy, intravenously or subcutaneously for slow release and appropriate tissue targeting as chelates, chemical complexes and adjuncts.
  • the properties of the supplement promote increased fertility in both the male and female animals.
  • the properties of the supplement increased significantly a wide range of qualitative and quantitative biochemical/ physiological parameters of the semen and its spermatozoa resulting in the promotion of the t fertilising capacity of the ejaculate.
  • the application to gilts/ sows of such semen from boars supplemented with the admixture resulted in a significant elevation to female reproductive output and efficiency with appropriate substantial economic returns in terms of progeny.
  • the admixture is fed at 250g/male pig/ day.
  • Figure 1 graph showing the spermatozoa concentration in semen from control and supplemented boars according to Group 2 in Table A;
  • Figure 2 graph showing mean spermatozoa concentration and total sperm number in the semen from control and supplemented boars according to Group 2 in Table A;
  • Figure 3 graph showing total born and born alive progeny to gilts inseminated with semen from control and supplemented boars according to Group 2 in Table A;
  • Figure 4 graph showing farrowing rate and fecundity for gilts inseminated with semen from control and supplemented boars according to Group 2 in Table A;
  • Figure 5 graph showing mean obtainable artificial inseminations per ejaculate for control and supplemented boars according to Group 2 in Table A.
  • the experimental groups consisted of matched (age, weight etc.) boars and gilts, from the same genetic stock and maintained under the conditions referred to above.
  • the diets were fed for 16 weeks with individual semen samples taken at day 0 and 4 week intervals thereafter for appropriate qualitative and quantitative investigations.
  • the major fatty acid components of the standard (basal) diet, the enriched DHA oil and GLA source (Evening Primrose Oil) are given below in Table 1.
  • Fatty acid compositions (wt. per cent of total fatty acids) of the basal diet and the supplemental high DHA and GLA oils.
  • the spermatozoa were harvested from the semen by gentle centrifugation as per standard commercial procedures well known in the art. The physiological and chemical measurements were then undertaken immediately and the parameters measured according to standard procedures well known in the art of semen production and spermatozoa physiology and biochemistry. Those parameters measured were as follows:
  • Total lipid content was extracted from the spermatozoa by an established procedure involving an exhaustive extraction with organic solvents. Lipid separation and quantification was then subsequently performed by thin layer chromatography. Fatty acid analysis of the lipids was performed again by established procedures involving transesterification and appropriate application to capillary gas liquid chromatography.
  • the fertilising capacity of the semen was measured in vivo by artificial insemination of gilts as per commercial practice and conception rates, fecundity (piglet numbers, born alive /dead etc.) recorded on an individual boar and gilt basis.
  • Table 2 shows the long chain polyunsaturated fatty acid compositional changes that occurred within the spermatozoa as a result of the supplemental addition outlined in this group. It can be seen that there was a substantial elevation in the level of DHA at the expense of a proportional reduction in that of DPA. In the supplemented group the level of DPA:DHA in the spermatozoa (in the supplemented boars at 16 weeks of feeding) was 13.8:45.5(wt per cent of total fatty acids) versus 25.1:32.8 in those fed the standard diet.
  • Fatty acid composition (wt. per cent of total fatty acids) of the phospholipid fraction of the spermatozoa from the control and DHA supplemented boars at 16 weeks of feeding.
  • antioxidants can also be used, such as plant extracts.
  • other fatty acids such as Stearadonic acid (n-3) also have been found to enhance fertility in accordance with this invention.
  • the pig is unique in displaying for one reason or another a high proportion of DPA at the expense of DHA within the lipid of the spermatozoa.
  • One of the advantages of the present invention is that now the promotion of male fertility in the pig under present intensive commercial production systems can be promoted through enhanced supplemental DHA availability to maximise the DHA level within the spermatozoa and its metabolic involvement in spermatozoa output, quality and functionality.
  • the present invention clearly demonstrates the ability to increase substantially the level of DHA at the expense of DPA in the spermatozoa of the modern commercial male breeding pig through supplemental dietary means.
  • supplemental polyunsaturates to be accompanied by additional dietary selenium which was accompanied by an enhanced glutathione peroxidase activity (group 2).
  • group 3 A further improvement on the spermatozoa features was effected by supplemental inclusion also of GLA (group 3).
  • the supplement herein described be used for livestock, in particular pigs, it is to be understood that due to the well known similarity between pigs and human biochemistry and physiology , the supplement would also find application in maximisation of human fertility and reproductive output.
  • the advantages of the present invention include the fact that the addition of a supplement based on a unique formulation of a high DHA containing oil and alpha-tocopherol influenced significantly the C22 polyunsaturate acid proportions within the spermatozoa and the proportion of DHA was considerably increased at the sole expense of DPA. Under these conditions there was a trend for a positive effect upon a range of spermatozoa features associated with fertilising capacity. With the addition of selenium to the supplement the effect of the fatty acid changes on the full range of spermatozoa fertilising features were all highly significant.
  • administering the semen from boars receiving the DHA/ a-T/ selenium supplement to gilts via artificial insemination effected a significant increase in fertilisation and progeny output as judged on a range of commercial parameters.
  • incorporation of GLA into the supplement further enhanced the semen quality of the boar.
  • the admixture provided by this application significantly extends, under semen storage conditions appropriate to artificial insemination, the maintenance within the spermatozoa of several features important to fertilising capacity.
  • the supplementation resulted in a highly significant increase in financial return.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Reproductive Health (AREA)
  • Pregnancy & Childbirth (AREA)
  • Gynecology & Obstetrics (AREA)
  • Emergency Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un supplément comprenant un adjuvant contenant une source triacylglycérol enrichie d'acide docasahexanoïque (DHA), accompagnée d'au moins un antioxydant et de sélénium intervenant comme co-facteur majeur d'enzyme cationique destiné à protéger le DHA, et convenant pour favoriser la fertilité et l'issu de la reproduction chez l'homme et les autres animaux.
EP01940729A 2000-06-17 2001-06-18 Supplement visant augmenter la fertilite Withdrawn EP1292295A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0014758A GB2363331B (en) 2000-06-17 2000-06-17 Supplement to enhance fertility
GB0014758 2000-06-17
PCT/GB2001/002640 WO2001097802A1 (fr) 2000-06-17 2001-06-18 Supplément visant à augmenter la fertilité

Publications (1)

Publication Number Publication Date
EP1292295A1 true EP1292295A1 (fr) 2003-03-19

Family

ID=9893789

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01940729A Withdrawn EP1292295A1 (fr) 2000-06-17 2001-06-18 Supplement visant augmenter la fertilite

Country Status (4)

Country Link
EP (1) EP1292295A1 (fr)
AU (1) AU2001274232A1 (fr)
GB (1) GB2363331B (fr)
WO (1) WO2001097802A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003288606A1 (en) * 2002-12-20 2004-07-14 Pronova Biocare As Use of a fatty acid composition for treatment of male infertility
JP2013032288A (ja) * 2009-10-20 2013-02-14 Idemitsu Kosan Co Ltd 精子活力向上剤、受胎率向上剤、精子活力向上方法、及び受胎率向上方法
DE102015109352A1 (de) * 2015-06-12 2016-12-15 K. D. Pharma Bexbach Gmbh Anwendung von Omega-3- und/oder Omega-6-Fettsäure(n)
IL303815A (en) * 2020-12-22 2023-08-01 Purdue Research Foundation A method for selecting a young pig for breeding

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU204199B (en) * 1987-03-18 1991-12-30 Caola Kozmetikai Process for producing pharmaceutical compositions containing unsaturated fatty acids and selenium as active components
HU202088B (en) * 1987-03-18 1991-02-28 Caola Kozmetikai Method for producing dietetic preparation
HU210122B (en) * 1988-03-23 1995-02-28 Biorex Kutato Fejlesztoe Kft Process for production of composition against thromboembolytic conditions of circulating system and heart
WO1995026646A1 (fr) * 1994-04-01 1995-10-12 Abbott Laboratories Produit nutritif utilise dans le traitement de la rectocolite hemorragique et son utilisation
WO1998000125A1 (fr) * 1996-06-29 1998-01-08 The Scottish Agricultural College Amelioration de la fertilite male au moyen d'antioxydants et/ou d'acides gras polyinsatures
FR2761887B1 (fr) * 1997-04-11 1999-06-18 Roland Asmar Medicament visant a la prevention multifactorielle des maladies cardiovasculaires
ZA994296B (en) * 1998-04-01 2000-01-10 Agricultural Research Council A method of improving the reproductive performance of a sow.
IL125097A (en) * 1998-06-25 2003-01-12 Israel State Dietary manipulation to increase fertility
AU5791400A (en) * 1999-06-07 2000-12-28 Omegatech Inc. Methods for improving the functional status of sperm

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0197802A1 *

Also Published As

Publication number Publication date
GB2363331A8 (en) 2002-01-17
GB2363331A (en) 2001-12-19
WO2001097802A1 (fr) 2001-12-27
AU2001274232A1 (en) 2002-01-02
GB0014758D0 (en) 2000-08-09
GB2363331B (en) 2003-02-05

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