Classifications

• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
  • A23K20/184—Hormones
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
  • A23K20/163—Sugars; Polysaccharides
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
  • A23K20/168—Steroids
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K50/00—Feeding-stuffs specially adapted for particular animals
  • A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
• • 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
  • A61P15/08—Drugs 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 in the field of animal food, in particular food for female animals in their reproductive phase.
• Food according to the invention improves the fertility of animals and increases their chances on a pregnancy.
• Clomiphene citrate is a commonly prescribed fertility drug. It stimulates the brain to release luteinizing hormone, which causes egg maturation and release from the ovary. The drug is taken for just a few days and then stopped. A brief fertile period may follow. A drawback is that more than one egg may be released, resulting in a multiple pregnancy. In addition, nearly half of all pregnancies achieved in this way result in spontaneous abortion. Perhaps the miscarriage rate is so high because such medications only force ovulation without correcting underlying deficiencies or hormonal abnormalities.
• Botanical medicines nourish and support the female reproductive system to restore hormonal balance.
• Many dietary supplements have been described that function in improving the fertility of man and animals.
• Vitamin E has previously been labeled the anti-sterility vitamin. Vitamin E is crucial to proper reproductive function in both men and women. In fact, the chemical name for vitamin E, "tocopherol,” originated from the Greek words tokos, which means “offspring,” and phero, which means “to bear.” One of the body's main antioxidant nutrients, vitamin E protects hormones from oxidation. As vitamin E becomes less available in processed foods and exposure to harmful oxidizing agents increases, supplementation with 400-800 IU a day may improve fertility for some men. Arginine has been shown to raise sperm counts and sperm motility. The recommended dosage is 2-4 g a day. Taurine, another amino acid that may enhance sperm production and motility, is supplemented at 2-4 g a day.
• Chaste tree berry (Vitex agnus-castus): This herb stimulates the release of luteinizing hormone (LH) from the pituitary gland in the brain. This, in turn, promotes ovulation. Chaste tree berry may restore normal periods in women with amenorrhea (lack of menstrual periods).
• LH luteinizing hormone
• Dong quai Angelica sinensis: Widely used for female complaints, including menstrual irregularities and infertility, dong quai can tone a weak uterus by promoting metabolism within the organ, 12 regulating hormonal control and improving the rhythm of the menstrual cycle.
• Red clover blossoms (Trifolium pratense): These beautiful little flowers are categorized in many herbals as fertility promoters. Chemical analysis shows that the herb is rich in coumestans and isoflavones, estrogenlike compounds that may promote fertility, particularly in women who are deficient in estrogen.
• Licorice (Glycyrrhiza glabra): This plant contains hormonally active compounds categorized as saponins.
• a Japanese study found licorice-based medicines improved menstruation in women with infrequent periods. The study also found that licorice helped women with elevated testosterone and low estrogen levels, as commonly occurs in polycystic ovary disease.
• Siberian ginseng (Eleutherococcus senticosus): This and other tonic botanicals can improve fertility by enhancing overall health and vitality. Siberian ginseng also acts on the brain to promote regulation of reproductive hormones.
• the fertility of animals may be improved by feeding the animal with a certain amount of naturally occurring immune enhancing ingredients such as beta-glucans and/or phytohormones like auxin or gibberellic acid. Also, combinations of these substances, in particular the combination of beta-glucans and phytohormones, were shown to have a synergistic effect in that they improved the fertility of the animal, even more than these individual components on their own.
• immune enhancing ingredients such as beta-glucans and/or phytohormones like auxin or gibberellic acid.
• the invention therefore relates to the use of an animal feed comprising between 0.05 and 500 milligram of beta-glucans per kilogram of feed and/or between 0.1 and 1000 milligram of phytohormones per kilogram of feed for improving the fertility of animals.
• infertile animals or animals with impaired fertility is used herein to refer to animal populations that have difficulties in getting pregnant.
• the term is used to indicate individual animals that have difficulties in getting pregnant.
• the invention proved particularly useful for getting animals into heat earlier, so that they produced offspring earlier resulting in an increased number of offspring of the total population. It was also observed that the number of newborns per parent animal increased by using the method according to the invention. This is particularly useful in commercial stock farming where even small increases in the productivity of the stock may contribute significantly to the commercial profits.
• Improving the fertility of animals as used herein also relates to increasing the number and/or quality of the offspring of animals, in particular vertebrate animals, more in particular domestic animals such as farm animals.
• Farm animals are animals that are kept for profit, such as for instance animals selected from the group consisting of cattle such as cows, pigs, horses, rabbits, deer, ostrich or fur-animals like mink.
• cattle such as cows, pigs, horses, rabbits, deer, ostrich or fur-animals like mink.
• the term animals as used herein is particularly intended to exclude humans.
• Phytohormones are herein defined as molecules that function to coordinate plant growth and development.
• the compounds that have been considered as plant hormones are for instance: indole-3-acetic acid (auxin), cytokinin, gibberellin, ethylene, abscisic acid.
• auxin indole-3-acetic acid
• cytokinin cytokinin
• gibberellin cytokinin
• ethylene ethylene
• abscisic acid abscisic acid
• brassinosteroids, jasmonic acid and salicylic acid have been shown to have important growth regulating activities and are considered to function as phytohormones.
• the invention therefore particularly relates to a method wherein the phytohormone is selected from the group consisting of indole-3-acetic acid (IAA, auxin), cytokinin, gibberellin, gibberellic acid, ethylene, abscisic acid, brassinosteroids, jasmonic acid and salicylic acid.
• IAA indole-3-acetic acid
• auxin auxin
• cytokinin gibberellin
• gibberellic acid ethylene
• abscisic acid brassinosteroids
• jasmonic acid jasmonic acid and salicylic acid.
• Free IAA and conjugated IAA are known compounds. Free IAA is a naturally-occurring plant growth phytohormone which has been extensively studied. In plants, most of the IAA occurs in a conjugated form (Slovin et al. 1999, Biochemistry and molecular biology of plant hormones, Elsevier, Amsterdam. P115-140), either conjugated to sugars via ester linkages or to amino acids and peptides via amide linkages.
• Free IAA is readily available as a commercial product. It may be synthesised chemically or prepared in a biological way. IAA producing micro-organisms are widespread in nature. Yeast, fungi and many bacteria as well as plants are known to convert precursors of IAA into free IAA. In addition to the L-tryptophan conversion by bacteria, also L-tryptophan independent biochemical routes towards free IAA are described extensively (J. Plant Growth Regul (2001) 20: 198-216).
• a well known bacterium, capable of producing free IAA is Azospirillum Brasilense (AB).
• AB Azospirillum Brasilense
• a small amount of synthetic free IAA may be added to the media.
• the micro-organism may be lysed and a powder enriched in free IAA may be obtained by spray drying or any other convenient way of drying the culture broth. Other techniques may be used to remove liquids partly or completely.
• free IAA is used herein to indicate that the free IAA is in the free or acid form, whereas the term “conjugated IAA” refers to IAA that is conjugated via ester linkages or via amide linkages.
• EP 1.296.676 describes the use of free IAA as a pharmaceutical, in particular for treating neoplastic disease in humans.
• WO 02/080906 describes the use of free IAA for treating endometriosis in women.
• Nachson et al. (Feed and Chemical Toxocology 41 , 745-752) reported the effect of some free IAA derivates (indole-3-carbinol and 3,3'-diindolylmethane) on the proliferation and induction of apoptosis in human prostate cancer cell lines whereas Rossiter et al.
• the amount of free IAA in the ready to use feed has to be adjusted in order to supply the animal with an effective amount of free IAA.
• an estimate has to be made of the feed intake of an animal or animal group.
• the feed intake per day is between 0.5 and 10% of the body weight of the animal, with occasional exceptions as high as 20 %.
• Elderly animals tend to eat less and are considered to have a feed intake per day between 0.1 and 5 %, typically of 1% of their body mass.
• the invention therefore also relates to a process for improving the fertility of an animal wherein the animal is fed with free IAA provided in the feed in the range of 0.004 and 40 mg per kilogram life weight per day (mg/kglw/day).
• 1 ,3 and 1 ,6 beta glucans were very useful to improve the fertility of animals.
• a particularly good source of such 1 ,3 and 1 ,6 beta glucans may be found in preparations of Agaricus blazei murill (ABM) or yeast cell walls. Animal feed supplemented with 1 to 1000 mg/kglw/day of dried Agaricus blazei murill was found to produce the desired effect of improving the fertility of animals. This corresponds to approximately 0.1 to 100 mg/kglw/day of 1 ,3 and 1 ,6 beta glucans.
• the invention therefore also relates to a process for improving the fertility of an animal wherein the animal is fed with 1 ,3 and 1,6 beta glucans in the range of approximately 0.1 to 100 mg/kglw/day.
• WO 02/091850 A discloses an animal feed which comprises 100-1000mg of beta-glucans per kilogram of feed.
• WO 02/37988, WO 2004/066863, WO 2004/014320 and US 2005/020490 A1 disclose compositions which comprise beta-glucans, and which may be suitable for use as an animal feed in the present invention.
• Such animal feed has also been described in Hiss and Sauerwein, Journal of animal physiology and animal nutrition, 87, 2003, pp2-11, Deblackwell, Berlin.
• the effect of improving the fertility of animals was also observed when the feed of animals was supplemented with Gibberelin or Gibberellic acid.
• the optimal concentrations here were found to be within the range of 0.0004 and 4 mg/kglw/day.
• the effect of improving the fertility of animals was particularly pronounced in the range of 0.004 and 0.4 mg/kglw/day.
• Optimal results were achieved between 0.01 and 0.1 mg/kglw/day, such as 0.04 mg/kglw/day.
• the invention is therefore also directed towards the use of any of the substances described above, for the preparation of a medicament for improving the fertility of animals.
• Example 1 Microbiological production of a preparation containing free IAA
• Azospirillum brasilence Sp7 was obtained as an agar culture in a culture tube. LB medium was used to grow the strain overnight at 28 °C at 175 rpm. Glycerol was added to the culture up to 10 %, mixed and divided over Nalgene creovials and frozen at - 80 °C. Stocks were stored at - 80 °C in creovials.
• a 10 litre fermentor was rinsed with water and the pH electrode was calibrated.
• Nine litre of LB medium was prepared and 1 g/l L-Tryptophan and 0.1 g/l free IAA was added.
• the medium was entered into the fermentor together with 2 ml of anti foam.
• the fermentor was sterilised for 30 min at 121 0 C. After cooling down to 28 °C, the 02 probe is calibrated with N2 and 02, 0 and 100 % air saturation respectively.
• the seed culture is transferred to the fermentor via a flask and tubing which are separately sterilised in an autoclave.
• the tubing and flask are removed and the fermentation is started with the following parameters:
• a pig feed according to the invention was prepared by vacuum impregnating ten kilogram of the usual commercially available pig feed with 100 ml of the oil suspension. Control feed was prepared by vacuum impregnating the same amount of feed with only olive oil.
• An amount of the spray dried formulation as described in example 1 corresponding to 400 milligram of free IAA was suspended in 100 ml of olive oil.
• a pig feed according to the invention was prepared by vacuum impregnating ten kilogram of the usual commercially available pig feed with 100 ml of the oil suspension.
• Control feed was prepared by vacuum impregnating the same amount of feed with only olive oil.
• An amount of 50 gram of dried Agaricus Blazei Murill (Agaricus Farm), a natural source of beta-glucans and an amount of the spray dried formulation as described in example 1 corresponding to 400 milligram of free IAA were suspended in 100 ml of olive oil.
• a pig feed according to the invention was prepared by vacuum impregnating ten kilogram of the usual commercially available pig feed with 100 ml of the oil suspension.
• Control feed was prepared by vacuum impregnating the same amount of feed with only olive oil.
• the weaning period of porcine species constitutes a particularly delicate moment from the physiological, metabolic and endocrine point of view. Numerous studies reported that few days before the weaning as well as few days after that, a greater energetic and amino acid food contribution is fundamental in order to adequately stimulate follicular and ovulatory dynamics and therefore to obtain a better reproductive efficiency with favourable implications, mainly on management.
• the experiment was performed in three well-managed animal farms specialised in pork production for the traditional pork butchery (ham, for example). Forty lactating sows were randomly distributed into four groups of 10 sows, three groups were fed with feed according to the invention, one group received control feed. The animals received the feed the 3 last days of lactation until 3 days after weaning.
• the BCS is not comprised in the inclusion criteria; backfat will not be considered.
• the administration of the feed supplement was performed in the morning in concentrations indicated in table 1. After weaning, the pigs were placed in "fecundation" cages and stimulated two times per day with boars skilled for oestrous detection. Oestrous sows were then inseminated by a technician following the classical protocol.
• Sows were diagnosed for pregnancy in the 3 rd or 4 th week after insemination using ultrasonography. The prolificacy of each sow was registered after parturition.

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• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Polymers & Plastics (AREA)
• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Food Science & Technology (AREA)
• Zoology (AREA)
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• Endocrinology (AREA)
• Reproductive Health (AREA)
• Organic Chemistry (AREA)
• Public Health (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• General Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Veterinary Medicine (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Birds (AREA)
• Gynecology & Obstetrics (AREA)
• Pregnancy & Childbirth (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Fodder In General (AREA)

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• 2005
  • 2005-04-21 EP EP05075950A patent/EP1714674A1/en not_active Withdrawn
• 2006
  • 2006-04-19 DK DK06743345.8T patent/DK1871482T3/da active
  • 2006-04-19 EP EP06743345A patent/EP1871482B1/en not_active Expired - Lifetime
  • 2006-04-19 SI SI200631403T patent/SI1871482T1/sl unknown
  • 2006-04-19 JP JP2008507074A patent/JP5198254B2/ja not_active Expired - Lifetime
  • 2006-04-19 PT PT06743345T patent/PT1871482E/pt unknown
  • 2006-04-19 WO PCT/EP2006/061673 patent/WO2006111546A1/en not_active Ceased
  • 2006-04-19 EA EA200702289A patent/EA013541B1/ru not_active IP Right Cessation
  • 2006-04-19 CN CNA2006800132502A patent/CN101163521A/zh active Pending
  • 2006-04-19 PL PL06743345T patent/PL1871482T3/pl unknown
  • 2006-04-19 US US11/918,749 patent/US8084440B2/en not_active Expired - Fee Related
  • 2006-04-19 CA CA2604774A patent/CA2604774C/en not_active Expired - Lifetime
  • 2006-04-19 ES ES06743345T patent/ES2389252T3/es not_active Expired - Lifetime
• 2012
  • 2012-09-13 CY CY20121100839T patent/CY1113285T1/el unknown

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