Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Reexamination Certificate
2000-02-17
2003-11-18
Padmanabhan, Sreeni (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
C514S108000
Reexamination Certificate
active
06649601
ABSTRACT:
The invention relates to a process for increasing the egg production and strengthening the eggshells of poultry.
The invention moreover relates to a process for manufacturing preparations which can be administered to poultry for increasing egg production and strengthening the shells.
The process of the invention consists in administering at least one bisphosphonic acid or a physiologically acceptable salt thereof.
Among the species which produce eggs for consumption, the hen is by far the main species. Constant progress in the fields of genetic selection and nutrition have led over the last 30 years to a steady increase in the number of eggs laid per hen. It is now common for a hen to lay more than 300 eggs in a laying year, which corresponds, in the most productive phase of the laying period, to one egg laid per day. Paradoxically, this change is accompanied by a reduction in the size of the animals and thus, in particular, in the volume of the calcium reserve represented by the skeleton. This reserve is essential for producing a good-quality shell. The decrease in the calcium available in the body to produce the shell has as a first consequence the production of more fragile shells which have defects in the organic mineralized frame. Secondly, if the phenomenon persists, the laying of the egg itself is compromised.
Bisphosphonic acid derivatives of medical interest are nowadays well known. Their pharmacological properties and their therapeutic applications are well described in the prior art in the case of mammals, in particular man. On account of their anti-resorptive properties on bone and their regulatory action on bone remodelling, bisphosphonic acid derivatives nowadays form part of the therapeutic arsenal available to medical practitioners for treating pathologies in man which are associated with disruptions in bone metabolism, such as osteoporosis, Paget's disease or malignant hypercalcaemias.
Conversely, few investigations have been carried out to date on birds. It appears that, in birds, bisphosphonic acid derivatives also exert their property of inhibiting bone resorption. Specifically, investigations carried out with alendronate (or [4-amino-1-hydroxybutylidene] bisphosphonate) in laying hens demonstrated the ability of this compound to limit bone resorption.
A first study reports the inhibitory effect of alendronate on the bone resorption which accompanies the acquisition of sexual maturity in laying hens when the product is administered subcutaneously at a dose of 0.01 mg/kg twice a week from the 16-week-old stage and up to the laying of the first egg (cf. Thorp B. H. et al., 1993
, Avian Pathol.,
22, 671-682).
A second study uses a slightly different administration protocol: alendronate is administered via the same route at a dose of 0.01 mg/kg at a rate of 6 administrations in total spread over 2 weeks from the 14-week-old stage (cf. Wilson S. et al.,
Res. Vet. Sci.,
1998, 64, 37-40). As in the previous study, this study demonstrates the inhibitory effect of alendronate on the bone resorption which precedes the laying of the first egg.
The studies reported above indicate that alendronate did not bring about any change in the age of onset of laying.
The use of compounds which can reduce the calcium mobilization required to produce the eggshell appears to be detrimental both as regards the production of good-quality shells and as regards the production of eggs. Due to their anti-resorptive action, bisphosphonic acid derivatives should in principle exert such detrimental effects.
In the two studies reported above, it was shown that the volume of the medullary bone is substantially lower in hens receiving alendronate compared with control hens, irrespective of the time of administration of the compound, i.e. before the onset of laying or during laying. Medullary bone is a bone which is specific to female birds; this bone acts as a calcium reservoir required to constitute the eggshell. At each cycle of laying, this bone undergoes a partial resorption allowing the release of calcium, followed by a new mineralization which is exploited in the next cycle. The results obtained regarding the decrease in medullary bone volume in the studies cited above thus suggest that the administration of bisphosphonic acid derivatives before the onset of laying or during laying is liable to compromise the mineralization of the eggshell and, consequently, the quality of the eggshell.
The study by Thorp et al. moreover demonstrates that the administration of alendronate during laying at doses of 0.01, 0.1 or 1 mg/kg can lead to a reduction, or even the stopping, of laying. Thus, the injection of a dose of 1 mg/kg subcutaneously every 2 days for 2 weeks, about 18 weeks after the onset of laying, brings about a complete stoppage of laying within a few days. Furthermore, the product is the cause of an adverse change in the quality of the shell, which is all the more pronounced the higher the dose.
Now, the present inventors have discovered, surprisingly, that compounds of bisphosphonate type are useful for increasing the production of eggs in poultry as well as for improving the quality of the shell of the eggs laid.
More specifically, the invention relates to a process for increasing the egg production and the strengthening eggshells of poultry, which comprises the administration to the animal of at least one bisphosphonic compound chosen from a bisphosphonic acid, a physiologically acceptable salt thereof, hydrates thereof and mixtures thereof.
The expression “bisphosphonic acid and salt of this acid” generally means a compound which has a P—C—P linkage.
The salts of this compound with pharmaceutically acceptable inorganic or organic acids or bases can also be used in the context of the invention. Examples of salts with acids are the hydrochloride, hydrobromide, sulphate, acetate, hydrogen sulphate, dihydrogen phosphate, methane-sulphonate, methyl sulphate, maleate, fumarate, sulphonate, 2-naphthalenesulphonate, glycolate, gluconate, citrate, isethionate, benzoate, salicylate, tartrate, succinate, lactate, glutarate, toluene-sulphonate and ascorbate salts. Examples of salts with inorganic or organic bases which may be mentioned are the ammonium salts or the salts of alkali metals such as, for example, the sodium salts.
The hydrates of these compounds can similarly be used according to the invention.
The compounds of bisphosphonic type described in the prior art as promoting bone resorption or recommended in the treatment of Paget's disease can be used in the context of the invention. More generally, the bisphosphonic acids and the salts of these acids described in the following patent applications fall within the context of the definition of bisphosphonic compounds which can be administered according to the invention: WO 87/03598, EP 325 482, BE 822 930; EP 304 961; U.S. Pat. No. 4,621,077; FR 2 826 223; WO 86/00902; EP 162 510; EP 186 405; U.S. Pat. No. 4,922,007; U.S. Pat. No. 4,578,376; BE 865 434; U.S. Pat. No. 4,134,969; DE 2 130 794 and BE 902 308.
In general, the bisphosphonic compound has the formula:
in which R
1
and R
2
are, independently, a hydrogen atom; a halogen atom; a hydroxyl group; a group —T; or a group —XT;
T is chosen from an aliphatic saturated or unsaturated hydrocarbon-based radical, optionally substituted and/or optionally interrupted with one or more O, S, N, N—CO, CO—N, CO, SO or SO
2
; a saturated, unsaturated or aromatic, optionally substituted carbocyclic or heterocyclic radical; a radical with both an aliphatic part as defined above and a carbocyclic and/or heterocyclic part as defined above, the said radical being optionally substituted and/or optionally interrupted with one or more O, S, N, N—CO, CO—N, CO, SO or SO
2
;
X is chosen from O, NH, NT, S, CO, CO—NT and NT—CO, in which T is as defined above;
or is a physiologically acceptable salt of this compound, or alternatively a hydrate thereof.
The expression “aliphatic radical” means a non-cyclic hydrocarbon-based radical such as alkyl, alkenyl and alkynyl, the latter groups be
Bardon Thierry
Thibaud Dominique
Ceva Sante Animale
Hui San-ming
Jacobson & Holman PLLC
Padmanabhan Sreeni
LandOfFree
Process for increasing the egg production and strengthening... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for increasing the egg production and strengthening..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for increasing the egg production and strengthening... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3146100