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    • 专利摘要:
    Dinoprost tromethamine to increase the probability of gestation in calves. Use of dinoprost tromethamine for the preparation of a veterinary drug intended for the treatment of infertility of female mammals, such as calves that have never given birth, increasing their probability of gestation at the time of insemination. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2683868A1
    申请号:ES201700478
    申请日:2017-03-28
    公开日:2018-09-28
    发明作者:Jesús MUINELO GONZÁLEZ
    申请人:Jesús MUINELO GONZÁLEZ；
    IPC主号:
    专利说明:


    DINOPROST TROMETAMINE TO INCREASE THE PROBABILITY OF MANAGEMENT IN TERNERAS

    OBJECT OF THE INVENTION 5

    The object of the present invention is in the state of the art of the use of the active substance dinoprost tromethamine in the veterinary field.
     10
    More specifically, the present invention relates to the veterinary therapeutic use of the active substance dinoprost tromethamine for the gestation of female mammalian animals, increasing the probability of pregnancy in calves or heifers. fifteen

    BACKGROUND OF THE INVENTION

    The active substance dinoprost tromethamine (according to INN nomenclature) is a structural analogue of prostaglandin F2α (PGF2α). PGF2α is a derivative of unsaturated fatty acids produced naturally by cells of the mammalian organism. The metabolic systems associated with dinoprost already exist in the body and are the same as those that follow organic PGF2α. 25 PGF2α is rapidly distributed throughout the body and, as it passes through the lungs, more than 90% of the circulation is eliminated. The liver and kidneys degrade metabolites and final products that are eliminated by bile and urine respectively. 30

    Dinoprost tromethamine causes the induction of heat in females of normal estrous cycle or persistent corpus luteum, and in gestation states it induces labor or abortion. Its spasmodic effect on smooth muscles also causes side effects such as, 5 constrictions, increased blood pressure and stimulation of the intestinal and urinary smooth muscles in some species of mammals. Most natural prostaglandins are susceptible to metabolism. 10

    The rate of gestation, and therefore of reproduction, in calves is a determining factor in the management of livestock farms, such as those of milk cows. Therefore, there are numerous methods that try to detect, induce and even synchronize over time the heat of the calves to maximize the probability of pregnancy. Many of these methods use the active substance dinoprost tromethamine, which is a luteolytic agent that causes the morphological and functional regression of the corpus luteum, the stimulation of the uterine smooth musculature and a relaxing effect on the cervix of the calves.

    Dinoprost has been authorized by the health authorities of several countries for the following veterinary therapeutic uses or indications in several target species:

    Cows: 30

    - Silent zeal.

    - Coadjuvant treatment of chronic endometritis and pyometra.

    - Induction to childbirth.
     5
    - Induction to abortion.

    - Induction and synchronization of estrus (IATF).

    - For the control of reproduction in 10 cyclic dairy cows:

    Estrous synchronization

     Ovulation synchronization in combination with GnRH or GnRH analogs as part of the fixed-time insemination protocols.

    Sows: 20

    - Induction of labor.

    - Reduction of weaning-heat intervals and fertile weaning / covering. 25

    - Increase in the number of piglets born alive in the next delivery.

    Mares: 30

    - Persistent corpus luteum treatment.

    - Induction of estrus.

    There is numerous scientific and patent literature based on the use of dinoprost for the authorized uses listed above. For example, patent CN104873298 5 proposes the injection of PGF2α two hours before insemination in a cow that is in heat (0.2 mg in 2 ml of prostaglandin is suctioned into the seminiferous duct and injected into the cervix; two hours later, artificial insemination is performed ”). 10 Other patents describe the use of prostaglandin to increase the rate of insemination or for the induction and synchronization of estrus (uses authorized by the drug agency for dinoprost): Patent CN105613423 describes the use of injected prostaglandin 15 in a procedure to increase the fertility rate of artificial insemination of cows; US2002128313 describes an invention that reduces the number of attempts at artificial insemination by mixing dinoprost next to semen; and Spanish patent ES2235654 describes aspects of the use of dinoprost in a method of induction and synchronization of estrus (from ovulation for systematic artificial insemination in goats).
     25

    DESCRIPTION OF THE INVENTION

    A first aspect of the present invention relates to the veterinary therapeutic use of the active substance 30 dinoprost tromethamine for the gestation of female mammalian animals, especially calves, at the time of insemination.

    This first aspect refers to the use of dinoprost tromethamine for the preparation of a veterinary medicinal product intended for the treatment of infertility of female mammalian animals. 5

    A second aspect of the present invention relates to the dinoprost tromethamine product to increase the likelihood of a female mammalian animal becoming pregnant, this dinoprost tromethamine product is used with a method comprising the following sequence of steps: detection that the animal is in heat, then natural or artificial insemination of the animal, and finally parenteral supply of dinoprost tromethamine. fifteen

    These aspects of the invention are achieved thanks to the action of dinoprost on the uterine musculature causing natural contractions produced by the veal itself thanks to the hormones estrogen and oxitocinam 20 causing inseminated sperm to move faster and better. In this way, as they have been proven in the field studies in which this method has been tested, a high gestation rate is ensured.
     25
    The female mammal animal is preferably a calf or heifer without morphological or genetic defects that has a natural zeal, and that has never given birth.

    Thus, the inventor of the present invention has developed and proven, by means of field tests, that a method or treatment protocol, typically using an intramuscular injection of dinoprost
    tromethamine immediately after the natural or artificial insemination of a calf in heat, is effective to significantly increase the chances that the treated calves or heifers remain pregnant at the time of such insemination. In 5 the rest of the ages have a similar effect but it is not as evident and exponential because of a greater uterine mass.

    In order to apply a drug parenterally, it will be necessary to pass through the skin, so that the medication passes into the bloodstream directly or through the different tissues where it is administered. More specifically, in the present invention, the preferred form of delivery of the preferred dinoprost tromethamine is via a 25 mg single dose (using the 5 mg / ml concentration presentation) injected intramuscularly into the upper part, preferably the part right, from the rump of the animal, due to greater proximity to the bovine uterus. There is a presentation of 20 12.5 mg / ml, with which the dose to be applied would be 2 ml (the important thing is that the final dose is 25 mg dinoprost, regardless of its concentration).

    Thus, in the estrous cycle that lasts approximately 21 days 25 a series of hormonal processes occur, estrogens are the first to cause the animal to go out in heat, which are produced in the mature follicle. After this, the corpus luteum that produces progesterone will grow at the site of the follicle and 30 prepares the uterus for pregnancy and prevents the animal from returning to heat by inhibiting the production of FSH (stimulating follicle) and LH (luteinizing hormone).
    After this, if the animal had not been inseminated we want the heat to return. Thus, between days 16 and 18 of the estrous cycle, if the uterus does not detect the presence of the embryo (it is not pregnant) it begins to produce prostaglandin in its "first wave" and destroys the corpus luteum to stop producing progesterone. In addition, the pituitary gland increases the secretion of gonadotropins by stimulating the follicle to produce estrogens and returning the animal to heat, thus completing the estrous cycle. Thus, the 10 dinoprost tromethamine product is applied in an animal that is already in heat, dinoprost does not have to act on the corpus luteum and thus the whole active principle focuses on uterine contractions causing an effect as a “second wave” of Typical effects of prostaglandin 15 PGF2α (which in normal conditions do not have) and that causes contractions of the uterine smooth musculature.

    The method indicated above is carried out with the product 20 dinoprost tromethamine and is especially advantageous for the veterinarian and the farmer, since it achieves:

    - Reduce the time it takes for the heifers to produce, by several repetitions of jealousy. 25

    - It allows the use of semen doses of greater economic value and therefore genetic, without risking that the treated calves are not pregnant, wasting time and investments. This is especially useful if the assembly or insemination is artificial; or even not to waste semen of the male mammalian animal that performs the ride.

    - Avoid in a large number of cases having to sacrifice heifers because they are not pregnant with the consequent economic loss.
     5
    - In terms of health, the active substance used has a suppression period in meat of two days and in milk of less than one day.

    - This is an easy procedure to execute and that does not require control or planning over several weeks or days.


    PREFERRED EMBODIMENT OF THE INVENTION 15

    The inventor of the present invention has been conducting field studies for more than ten years developing the aspects claimed in the present invention.
     twenty
    For example, the following procedure is carried out with the product dinoprost tromethamine in a set of 104 heifers that have never given birth, and for 11 months:

    - Those that are jealous by any method known in the state of the art are detected.

    - An insemination or natural riding of the heifers to which the heat is detected is carried out.
     30
    - Each inseminated heifer is given a single dose of 25mg (presentation with a concentration of 5 mg / ml) of the dinoprost tromethamine product by
    route of an intramuscular injection in the upper right part of the rump.

    The results observed are: of those 104 heifers, 95 are pregnant in the first application of the 5 procedure, 8 remain pregnant in the second application, and one is not pregnant after several attempts.

    In general, it has been observed that 95% of heifers 10 remain pregnant in their first insemination, much of the remaining 5% in the next heat.

    In another alternative field test, observing 9 very repetitive heifers (with a number of 15 previous high inseminations, but which have never given birth) and that have never been treated with dinoprost tromethamine, in its next insemination and using the method of the first test from the field described above, very high gestation rates are achieved: 7 in the first 20 application and the remaining 2 in the second.

    In both field tests it was observed that the reduced percentage of heifers that did not remain pregnant after treatment, had some kind of genetic or morphological problem such as freemartinism, aplasias, etc. that were later confirmed.

    Other derivatives of prostaglandin dinoprost tromethamine such as cloprostenol or chloroprostenol have not achieved the desired results in the field tests performed. This would be because its mode of action is very different, since dinoprost tromethamine
    (administered as described above) by having a shorter half-life, once injected, acts more rapidly and bluntly on the uterine smooth musculature.
     5
    权利要求:
    Claims (8)
    [1]


    1. Use of dinoprost tromethamine for the preparation of a veterinary medicinal product intended for the treatment of infertility of female mammals.

    [2]
    2. Use of dinoprost tromethamine for the preparation of a medicament for veterinary use for the treatment of infertility of female mammals, according to the preceding claim, characterized in that said treatment occurs at the time of insemination of the animal. fifteen

    [3]
    3. Use of dinoprost tromethamine for the preparation of a medicament for veterinary use for the treatment of infertility of female mammalian animals, according to any of the preceding claims, characterized in that said female mammalian animal has not previously given birth.

    [4]
    4. Use of dinoprost tromethamine for the preparation of a medicament for veterinary use for the treatment of infertility of female mammals, according to any of the preceding claims, characterized in that said female mammalian animal is a calf.
     30
    [5]
    5. Use of dinoprost tromethamine for the preparation of a veterinary medicinal product intended for the treatment of infertility of mammalian animals
    female, according to any of the preceding claims, characterized in that said dinoprost tromethamine is administered in a dose of 25 mg.

    [6]
    6. Use of dinoprost tromethamine for the preparation of a medicament for veterinary use for the treatment of infertility of female mammals, according to any of the preceding claims, characterized in that said treatment is by injectable administration. 10

    [7]
    7. Product comprising dinoprost tromethamine, characterized in that it is administered parentally after the detection that the animal is in heat and its natural or artificial insemination. fifteen

    [8]
    8. Product according to the preceding claim, characterized in that said parenteral administration is administered in a single dose of 25 mg injected intramuscularly into the upper part, preferably the right part, of the animal's rump.
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    同族专利:
    公开号 | 公开日
    ES2683868B1|2019-07-05|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    WO2002004006A2|2000-07-10|2002-01-17|Pharmacia & Upjohn Company|Method for improving the efficacy of artificial insemination of non-human animals|
    法律状态:
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    ES201700478A|ES2683868B1|2017-03-28|2017-03-28|Dinoprost tromethamine to increase the probability of pregnancy in calves|ES201700478A| ES2683868B1|2017-03-28|2017-03-28|Dinoprost tromethamine to increase the probability of pregnancy in calves|
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