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Title:
METHOD OF INCREASING THE PRODUCTION AND IMPROVING THE QUALITY OF SEMEN
Document Type and Number:
WIPO Patent Application WO/1999/029313
Kind Code:
A1
Abstract:
A method of increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males, is described. The method comprises administration of an effective dosage of a human or veterinary preparation containing at least one type of xanthophylls, such as astaxanthin, to said males. Preferably, the astaxanthin exists in a form esterified with fatty acids, e.g. in the form of algal meal produced by culturing of the alga Haematococcus sp. Further, the use of at least one type of xanthophylls, such as astaxanthin, for the preparation of a human or veterinary preparation for increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males, is disclosed.

Inventors:
LIGNELL AAKE (SE)
INBORR JOHAN (SE)
NICOLIN CURT (SE)
Application Number:
PCT/SE1998/002138
Publication Date:
June 17, 1999
Filing Date:
November 26, 1998
Export Citation:
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Assignee:
ASTACAROTENE AB (SE)
LIGNELL AAKE (SE)
INBORR JOHAN (SE)
NICOLIN CURT (SE)
International Classes:
A23K1/16; A23L1/30; A61K31/122; A61K31/22; A61K36/02; A61P15/08; (IPC1-7): A61K31/12; A61K31/07; A23K1/16; A23L1/30
Domestic Patent References:
WO1997035491A11997-10-02
WO1996008977A11996-03-28
Foreign References:
SE9300901A
Other References:
FILE WPI, Derwent Accession No. 92-396782, BIOCHEM. INST. et al., "Medium for Dilution Cryopreservation of Farm Animals Sperm Contains Sugar, Complex Salt of Ethylene di: Amine Tetra: Acetic Acid, Egg Yolk, Chlorophyll, Glycerine and Water"; & SU,A1,1 706 608 (23-01-92) DW9248.
STN INTERNATIONAL, File Caplus, CAPLUS Accession No. 1990:52954, PARAMONOVA L. et al., "Interaction of Carotenoids with the Superoxide Anion Radical in Relation to Their Stabilizing Effect During Cryoconservation of Sperm"; & DOKL. VSES. AKAD. S-KH. NAUK IM. V. I. LENINA, (1989), (11), 30-2.
Attorney, Agent or Firm:
Nilsson, Brita (AB Stockholms PatentbyrÄ AB Zacco & Bruhn P.O. Box 23101 S- Stockholm, SE)
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Claims:
CLAIMS
1. Method of increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males, comprising administration of an effective dosage of a human or veterinary preparation containing at least one type of xanthophylls to said males.
2. Method according to claim 1, wherein the type of xanthophyll is astaxanthin.
3. Method according to claim 2, wherein the astaxanthin exists in a form esterified with fatty acids.
4. Method according to claim 3, wherein the esterified astaxanthin is in the form of algai meal produced by culturing of the alga Haematococcus sp.
5. Method according to claim 3 or 4, wherein the effective dosage of the preparation contains 0.01 to 1 mg astaxanthin per kg body weight per day.
6. Use of at least one type of xanthophylls for the preparation of a human or veterinary preparation for increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males.
7. Use according to claim 6, wherein the type of xanthophyll is astaxanthin.
8. Use according to claim 7, wherein the astaxanthin exists in a form esterified with fatty acids.
9. Use according to claim 8, wherein the esterified astaxanthin is in the form of algal meal produced by culturing of the alga Haematococcus sp.
10. Use according to claim 8 or 9, wherein the amount astaxanthin in the preparation is 0.01 to 1 mg per kg body weight.
Description:
METHOD OF INCREASING THE PRODUCTION AND IMPROVING THE QUALITY OF SEMEN The present invention relates to a method of increasing the production and improving the quality of semen. More precisely, the invention relates to a method of increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males. The method comprises administration of an effective dosage of a human or veterinary preparation containing at least one type of xanthophylls, such as astaxanthin, to the males.

The invention also relates to the use of at least one type of xanthophylls, such as astaxanthin, for the preparation of a human or veterinary preparation for increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males.

Background The quality of semen is of vital importance for the reproduction of both humans and animals. From an economical point of view the production of animals, by natural mating or artificial insemination, is of great importance in the food, poultry, livestock, animal breeding and domestic animal industry.

Our published International patent application WO 97/35491 relating to an agent for increasing the production of/in breeding and production mammals, discloses experiments wherein sows were given feed supplemented with astaxanthin during a period prior to parturition resulting in e. g. more piglets born alive. The mating boars did not receive any xanthophyll supplementation of their feed.

Astaxanthin, and other xanthophylls, are known to exhibit antioxidative properties, and hence possesses the ability to scavenge so-called free radicals.

However, in biological tests astaxanthin has been shown to possess clearly the

best antioxidative properties compared to other carotenoids (Miki W., 1991, Pure and Appl Chem 63 (1): 141-146).

Description of the invention The present invention is directed to a method of increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males, comprising administration of an effective dosage of a human or veterinary preparation containing at least one type of xanthophylls to said males.

In a preferred embodiment the type of xanthophylls is astaxanthin. In a particularly preferred embodiment the astaxanthin exists in a form in which it is esterified with fatty acids. The last mentioned form of astaxanthin may be in the form of algal meal produced by culturing of the alga Haematococcus sp.

An effective dosage of the preparation contains e. g. 0.01 to 1 mg astaxanthin per kg body weight per day.

The invention is also directed to the use of at least one type of xanthophylls for the preparation of a human or veterinary preparation for increasing the volume, the total sperm count and the reproductive performance of semen from human and animal males.

Here again, in a preferred embodiment the type of xanthophylls is astaxanthin.

In a particularly preferred embodiment the astaxanthin exists in a form in which it is esterified with fatty acids. The last mentioned form of astaxanthin may be in the form of algal meal produced by culturing of the alga Haematococcus sp.

For example, the amount astaxanthin in the preparation is 0.01 to 1 mg per body weight of the human or animal male.

In the present invention the human and veterinary preparations may comprise a mixture of different types of xanthophylls or different forms of the same xanthophyll, such as a mixture of synthetic astaxanthin and naturally produced astaxanthin.

The human and veterinary preparation of the invention may comprise additional ingredients which are pharmacologically acceptable inactive or active, such as flavoring agents, excipients, diluents, carriers, etc., and it may be presented in a separate unit dose or in admixture with food or feed. Examples of separate unit doses are tablets, gelatin capsules and predetermined amounts of solutions, e. g. oil solutions, or emulsions, e. g. water-in-oil or oil-in-water mulsions.

Examples of food in which the preparation of the invention may be incorporated is dairy products, such as yogurt, chocolate and cereals.

Description of experiments The preparation used in the experiments contained the xanthophyll astaxanthin which was produced via the alga Haematococcus sp. by AstaCarotene AB, Gustavsberg, Sweden, and the experimental animal model was boars.

Naturally produced astaxanthin can be obtained also from fungi and crustaceans, in addition to from alga. Astaxanthin from other sources, and other xanthophylls as well, are expected to be similarly useful for the purposes of the invention. An advantage of using astaxanthin from alga is, however, that the astaxanthin exists in a form esterified with fatty acids [Renström B. et al, 1981, Phytochem 20 (11): 2561-2564], which esterified astaxanthin thereby is more stable during handling and storage than free astaxanthin.

The experiment was conducted with boars for the purpose of establishing whether astaxanthin supplemented feed increases semen production and improves the reproductive performance even though the breeding sows do not receive such astaxanthin supplemented feed.

Experimental design A total of 37 boars of several breeds used for Al (artificial insemination) were divided into two groups and randomly allocated to one of the two dietary treatments. The boars were fed a standard boar feed either with (3 g/day) or without added NOVASTA (the trade name of AstaCarothene AB for the algal meal preparation for animals) for 16 weeks. NOVASTA was fed as a top dressing (150 g NOVASTA, containing 1% astaxanthin, mixed with 850 g ground wheat) once daily.

Boars were collecte as part of the normal routine of the boar shed. On average boars were collecte once per week. Collection was by the gloved hand technique whilst boars were mounted on a dummy sow. Ejaculates were collecte into warmed collection container after filtering to remove the gel fraction of the ejaculate. Each ejaculate was weighed to provide an estimate of the volume collecte.

During the statistical analysis of the data the age of the boar at the time of collection was included as a covariate.

The semen produced by the boars was then used for mating sows of the commercial herd. There were 1036 mating carried out, 513 matings to NOVASTA supplemented boars and 523 matings to boars from the control group.

Results of the experiments Semen production Control NOVASTA Period 1 (0-6 weeks) Volume (mi) 151.250a 211. 400b Sperm density (x 109/ml) 0. 636a 0. 509b Total sperm count (x 109) 93.515a 104. 000a Period 2 (7-16 weeks) Volume (ml) 150.395a 178 775b Sperm density (x 109/ml) 0.650a 0. 568b Total sperm count (x 109) 95.294a 96. 404a a means not sharing superscripts differ significantly (P<0.05) Reproduction Control NOVASTA P-value Farrowing rate, % 71 76 0.11 Born alive, pigs/sow 9.2 9. 7 0.009 Born dead, pigs/sow 0.8 0. 9 0.24 Born in total, pigs/sow 10.0 10. 6 0.003 From the above results it is evident that NOVASTA significantly (P<0.05) increased semen volume and in boars during a 16 week period Total sperm count increased by on average 6.2 per cent (P>0.05) in boars fed NOVASTA

Feeding NOVASTA to AI boars significantly (P<0.05) increased the number of piglets born alive by 5.4 per cent in sows mated with their semen The response to NOVASTA in terms of semen volume was much more dramatic in the first 6-weeks of the experiment than in the subsequent 10-week period.

The number of sperms produced decreased for both treatment groups during the latter period. However, boars fed NOVASTA produced higher number of sperms in both periods. This was not statistically significant.

The matings resulted in 378 farrowings out of 513 matings of sows mated with boars fed NOVASTA and 359 farrowings out of 523 matings of sows mated with boars of the control group.