Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-07-07
2003-06-10
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S929000, C424S641000, C424S643000
Reexamination Certificate
active
06576634
ABSTRACT:
The present invention relates to preparations and compositions for improving the fertility of, and/or for improving the quality of the semen produced by, male individuals of mammalian species, including but not limited to human beings.
More in particular, the invention concerns a pharmaceutical or dietetic preparation that after oral intake can increase fertility and improve sperm quality in male animals in general and men in particular.
The preparations and compositions of the invention can inter alia be used to prevent and/or treat, in male individuals of mammalian species including but not limited to human beings, low fertility, disorders in fertility and/or conditions of poor semen quality, including but not limited to phenomena such as low sperm count, aberrations in morphology of the sperm cells, low motility of the sperm cells, or generally low sperm quality.
In one aspect of particular interest, the preparations and compositions of the invention may be used to prevent and/or treat a condition known as male sub-fertility, by which herein is generally meant a failure to conceive after 1 year of unprotected intercourse with the same partner; and in particular with a sperm count of less than 20 million cells/ml and with more than 30% of sperm cells having normal morfology and more than 50% of sperm cells having normal motility.
In another aspect of particular interest, the preparations and compositions of the invention may be used to prevent and/or treat disorders of male fertility and/or conditions of poor semen quality—including but not limited to male subfertility—as may be caused by, and/or as may be associated with, drug therapy.
In yet another aspect of particular interest, the preparations and compositions of the invention are used in animal breeding, e.g. in breeding programs for livestock and other economically important animals, in horse breeding, in breeding of pets and/or in breeding of zoo animals.
Yet other aspects of the invention relate to methods for improving the fertility of, and/or for improving the quality of the semen produced by, a male individual of a mammalion species, including but not limited to human beings.
Further aspects of the invention will become clear from the description given hereinbelow.
Subfertility is a disorder in which a relatively low number of pregnancies (conceptions) result from a certain number of copulations. Subfertility is a major problem in society. More than 14% of the families in many countries of the Western hemisphere experience problems with fertility and it has been reported than this problem may increase in the near future when the decrease in sperm quality as observed in the last decades is extrapolated. Also in animal breeding subfertility has become a matter of concern. In intensive animal breeding programmes, as e.g. applied in horse, cattle and pig breeding an increase of spermcounts has a clear economical advantage.
Subfertility problems have to be distinguished from erectile or libido disorders. To our knowledge no associations have been published between disorders with libido and subfertility.
Subfertility in males may result from genetic disorders, hypothalamic disorders, undescended testis, clinical disorders [cancer of testis, variocele], germ cell aplasia, medical treatment [irradiation, drug treatment e.g. with sulphasalazine, beta-blockers, anabolic steroids], malnutrition (deficiencies in energy/protein or specific nutrition such as food very rich in phytocomponents), diabetes and environmental factors. Male subfertility is generally associated with decreased semen quality, characterised by a diminished number of sperm cells per semen volume (sperm count) and/or an altered morphology and motility of the sperm cells.
Generally, it is an object of the invention to provide a method for improving the fertility of, and/or for improving the quality of the semen produced by a male individual of a mammalian species, and also to provide preparations and/or compositions that can be used in such a method.
In the art, attempts have been made to improve fertility in animals via administration of dietetic preparations.
Landau B. et al., disclosed in Experientia, 1978, 34, (10), 1301-2 that administration of 10 mg folic acid over 30 days did not result in an increase in sperm counts and motility and DNA content of spermatozoa.
Bentivoglio et al. disclosed in Fertil Steril 1993, 60 (4), 698-701 titled “
folinic acid in the treatment of human male infertility”
that administration of 15 mg folinic acid per day during 3 months increases spermatozoa number and fertility in men suffering from round cell idiopathic syndrome. The authors do not refer to the potential effect of lower amounts of folinic acid or other folate sources nor to beneficial effects that could be obtained by administration of zinc.
Recommendations for folate are typically maximall 400 ug per daily dose except for pregnant women who have a history of neural tube defects in their offspring. Higher amounts can only be allowed when prescribed under medical supervision. It is desirable to decrease doses to avoid risks of underdiagnosing vit B12 deficiencies in persons suffering from perniceous anemia.
Considering the dose-response relationships that are typically observed in the pharmaceutical field, the prior art teaches the skilled person that it is highly questionable whether administration of low concentrations of folate alone is still effective in improving semen quality.
The use of a complex of zinc with an amino acid, in particular aspartate, or with orotate for improving libido has been reported in WO 00-011396. No effect on sperm quality is disclosed. Blesbois E. and Mauger I. have reported in Br.Poult.Sci. 1989, 30 (3), 677-685 that a concentration of zinc above 3 &mgr;g per ml storage medium reduced the fertility of fowl seminal plasma.
Sprenger et al, in Contributions to Nephrology (1984), 38, 103-28 disclosed the effect of zinc salts on sexual dysfunction. No reference is made to folic acid or sperm quality.
European patent application 0 194 710 discloses the use of a zinc salt of fructose-1,6 diphosphate for treatment of male infertility. Folic acid is not mentioned.
European patent application 0 534 033 discloses the use of an injected preparation of zinc gluconate to inhibit the generation, maturation, motality and viability of sperm. The teaching of this European application is therefore contrary to the teaching of the present application, in which zinc is used—in combination with folic acid—to increase the generation and/or the maturation and/or the viability of sperm cells. Also, according to the present application, oral administration is preferred.
Tikkiwal et al. disclose in Ind. J. Physiol. Pharmac., Vol. 31, no. 1, January-March 1987, pages 30 ff., that after administration of 220 mg zinc sulphate to males that suffer from idopathic oligospermia, that sperm and the number of spermatozoa having normal morfology and motility improved significantly. No reference is made to an additional effect that could be obtained by (co-)administering low doses of a source of folic acid.
Also, the amount of zinc sulfate administered according to Tikkiwal is very high, as administration of zinc salts is typically limited to amounts of maximally about 30 mg/day.
The research group of R. Steegers have reviewed published prior art literature in Wong, W. Y, et al, Fertil. Steril. 73, (3), 2000, pp 435-442) titled:
“Male factor subfertility; possible causes and the impact of nutritional factors”.
U.S. Pat. No. 5,523,087 discloses a pharmaceutical preparation for oral intake and treatment of diabetic male sexual dysfunction in terms of libido. It comprises 45-60 parts phytooestrogen (calculated as free aglycon), 10-50 parts beta-sitosterol, 30-100 parts Damiana leaf dry extract, and optionally up to 400 parts phosphatidyl choline, 15 parts vitamin A, 250 parts B1, 300 parts B6, 100 parts E, 300 parts Calcium, 750 parts Magnesium and 100 parts of Zinc.
In the International application WO 98-52555 it is disclosed that a preparation, h
Hageman Robert Johan Joseph
Nieuwenhuizen Arie
Steegers-Theunissen Regine Patricia Maria
Browdy and Neimark PLLC
Criares Theodore J.
N.V. Nutricia
LandOfFree
Pharmaceutical or dietetic preparation for improvement of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical or dietetic preparation for improvement of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical or dietetic preparation for improvement of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3104400