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    • 专利摘要:
    Veterinary composition for the manufacture of a seminal stimulant useful for artificial insemination in animals. The present invention relates to a composition for the manufacture of a seminal additive characterized in that it contains oxytocin, lecireline and caffeine. The seminal additive is useful to increase fertility and prolificacy in artificial insemination in animals, specifically in mammals, in cases of low seminal concentration, asthenospermia or in seminal doses stored during a prolonged period of time in refrigeration. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2608935A1
    申请号:ES201631536
    申请日:2016-11-30
    公开日:2017-04-17
    发明作者:Juan Carlos Domínguez Fernández De Tejerina；Beatriz ALEGRE GUTIÉRREZ；José Ramiro GONZÁLEZ MONTAÑA；Marta Elena ALONSO DE LA VARGA；Felipe Martínez Pastor
    申请人:Universidad de Leon；
    IPC主号:
    专利说明:

    VETERINARY COMPOSITION FOR THE MANUFACTURE OF AN ADDITIVEUSEFUL SEMINAL FOR ARTIFICIAL INSEMINATION IN ANIMALS
    5 FIELD HEARS THE INVENTIONThe present invention belongs to the technical field of veterinary medicine, and morespecifically to artificial insemination applied to the pig sector. The invention isrefers in particular to a composition for the manufacture of a seminal additive useful inartificial insemination of animals, specifically of swine females in order to
    10 increase fertility and prolificacy.
    BACKGROUND OF THE INVENTION
    15 The objective of artificial pig insemination is to achieve a lower operating cost and greater time and labor organization savings, to achieve high rates of pregnancy and a percentage lower than 15% of repetitions, since each jealousy that is lost, or pregnancy that it is not achieved negatively affects the productive effectiveness that is required, since the labor-new conception period is increased by another 21 days.
    One of the disadvantages of artificial insemination is that it may require a higher level of handling than in natural riding. For example, in artificial insemination there is a greater chance of human errors occurring than with natural riding. When a stallion pig or boar rides the female, the semen is not exposed to large
    25 environmental changes, and is usually deposited in the female more than once, during a period that includes the optimal time for fertilization.
    However, in artificial insemination, it is possible that, while semen is collected, diluted, transported and then artificially deposited, many occur
    30 environmental changes The insemination must be done correctly and at the optimum time. To obtain a high percentage of gestations and numerous litters, the detection of estrus must be done carefully and without failures.
    The efficiency of artificial pig insemination depends on both the prediction of the ovulation time and the insemination protocol. Current artificial insemination protocols are based on the application of sperm within 24 hours prior to ovulation, with the added disadvantage that ovulation in the sow is serial and not simultaneous for all the oocytes available in each cycle.
    5 Artificial swine insemination almost exclusively involves the use of semenrefrigerated collected between 1 and 7 days before use, although numerous studiesindicate that optimal fertility requires insemination within 48 hoursfollowing the seminal collection, whether short or thinner diluents are usedLong conservation
    Seminal freezing would eliminate the restrictions of time and space for the use of seminal doses. However, insemination with cryopreserved semen has a lower reproductive performance than that obtained with refrigerated semen, both in the percentage of deliveries and in the size of the litter. From
    In fact, only acceptable fertility percentages are observed when insemination is carried out in the interval of 4 hours before each ovocitary hatching.
    It is believed that the damage suffered by the cryopreservation process could induce an effect on sperm similar to training or premature aging,
    20 associated with an increase in DNA fragmentation. Therefore, the control of training and premature sperm aging represents a point of interest for the improvement of fertility associated with the use of pig cryopreserved semen.
    25 Seminal stimulants, also known as seminal enhancers or additives, are those substances that, not being necessary for seminal preservation, improve fertility and / or semen prolificity when applied to seminal doses at the time immediately prior to insemination. of the female, either acting on the intrinsic characteristics of the semen (increasing
    30 motility, favoring sperm training, etc.), or involving in the organism of the inseminated female favorable reactions for the successful fertilization of insemination.
    The use of seminal stimulants has been described in the prior art. The 35 seminal dilution media can be classified into three categories: extenders (increase seminal volume), protectors (preserve and protect semen) and implementers (improve fertilization conditions and embryonic viability). Specifically, in relation to the seminal dilution media of the latter group, express reference is made to two specific substances such as hyaluronidase
    5 (favoring the conjugation of the game) and oxytocin (stimulating the uterotubic contractions involved in sperm transport).
    The increase in fertility in the cow and the sow with these seminal stimulants has been described in the state of the art. In the 70s, with the development of "in vitro" (IVF) fertilization, substances such as methylxanthines began to be used
    or calcium ionophores, to promote hyperkinesis and sperm training necessary for fertilizing success, especially oligospermic and hypokinetic semen. An example of methylxanthine is caffeine, which is of practical utility to improve the fertilizing capacity of chilled or frozen semen of
    15 pig, improving its motor vigor, acting as activator of sperm cells.
    Oxytocic substances are extremely important in the formulation of seminal stimulants, specifically in the sow the beneficial effect on fertility improvement after their addition to pig semen has been described, since there is a `` lack of coital stimuli '' in the moment of the insemination of the females, which translates into a decrease in the oxytocic discharges that the mechanical act of intercourse entails and therefore a decrease in the contractility of the genital apparatus decreasing its semen absorption capacity towards the area from
    25 his encounter with the oocytes (oviduct).
    On the other hand, another of the groups of important compounds in artificial insemination are hormones. The most frequently used reproductive hormones are included in the following groups: gonadotropin s, progestogens, analogs of the
    30 gonadotropin releasing factor (GnRH) and prostaglandins. In general, it can be said that gonadotropins would be indicated for heat stimulation, progestogens for synchronization thereof, GnRH analogs for ovulation control and prostaglandins for labor synchronization or for the improvement of Uterine involution processes.
    Specifically, synthetic GnRH are about 50 times more potent than natural ones, Lecirelina being an example, which binds more persistently to Pituitary GnRH receptors and is characterized by very high potency.
    5 However, there is no composition in the state of the art that combines the ability to increase fertility and prolificacy in artificial pig insemination. It was therefore desirable a composition of seminal stimulants that provide greater efficiency of the process of artificial pig insemination against the natural mount, avoiding the drawbacks existing in the state of the art.
    DESCRIPTION OF THE INVENTION
    The present invention solves the problems existing in the state of the art by means of a composition for the manufacture of a seminal additive comprising
    15 a combination of seminal stimulants, which applied together, allows lower dosages compared to when used individually, ensuring consistent and consistent results, with high repeatability, while inducing the seasonal adjustment of the "summer" effect on the drop in fertility, typical of pigs (summer infertility syndrome).
    The present invention is a veterinary composition for the manufacture of a seminal additive comprising oxytocin, lecireline and caffeine.
    Said veterinary composition for the manufacture of a seminal additive comprises
    25 (per milliliter) an oxytocin concentration between 1 and 3 Ul / ml, lecireline concentration between 0.2 and 0.8 IJg / ml and caffeine in a concentration between 1 and 3 mM.
    Preferably, in the composition of the invention, the selected lecireline is lecireline acetate.
    The veterinary composition of the invention contains an excipient, which give the composition characteristics of "self-sterility". In a preferable embodiment, the excipient is chloretone 8110%.
    The veterinary composition is presented in aqueous liquid form.
    The veterinary composition can be packaged in multi-dose containers, easily applied in the daily practice of artificial insemination of animals.
    Another aspect of the invention relates to the use of the composition as a seminal additive.
    5 useful for artificial insemination in animals. The three active substances mentioned have,each one in particular, different properties that, added together, act in a wayeffective as a seminal additive in artificial insemination of animals.
    An embodiment is the composition of the invention, wherein said veterinary composition is administered directly in seminal doses at the time prior to artificial insemination of animals.
    An embodiment is the composition of the invention, wherein said animals are mammals.
    A further embodiment is the composition of the invention, wherein said animals are selected from the group consisting of sows, cows, goats and sheep.
    The composition of the invention can be used in cases of low concentration
    20 seminal, certain cases of asthenospermia, and in seminal doses stored for a prolonged period of time in refrigeration (greater than two days) in which there is always a decrease in fertility.
    25 BRIEF DESCRIPTION OF THE FIGURES
    Figure 1 is the effect of the seminal stimulant on fertility / fertility and prolificacy, in 2014, of a group of females who receive the seminal stimulant against those who do not receive stimulant (Control group).

    PREFERRED MODES OF EMBODIMENT
    Example 1. Preparation of the pharmaceutical compositionBatch of 2,000 doses were prepared, where each dose is carried in 1 ml,5 obtaining total volumes of 2,000 ml. In a volumetric Erlenmeyer flask of
    2,000 ml, perfectly clean and dry, the following products were added: 4000 IU of Oxytocin (Facilpart®. Laboratorios Syva SAU, presentation 10 IU / ml). 1000 I-Ig of Lecirelina acetate (Dalmarelin®. Fatro Ibérica S.L., presentation 25
    10 ~ g / ml).
    38.8 9 Caffeine (Caffeine -1, 3,7-Trimethylxanthine-Sigma-Chemistry, ref.C0750).Excipient (Chloretone at a final concentration of 10%)
    and physiological serum is added until it reaches a volume of 2000 ml.
    15 Example 2. Effectiveness of the composition in field studies To examine the effect of the pharmaceutical composition prepared in Example 1 above for use in artificial pig insemination, field studies of the effects on fertility, fertility were carried out. at birth and prolificacy (average of total born piglets (alive or dead) by delivery). Tables 1 and 2 are presented
    20 the results of the studies carried out, observing how there are statistically significant differences in all the experimental groups with respect to the control groups.
    The statistical characteristics of fertility (% fertility), prolificacy (NT), number 25 of live births (NV) and mortality (% of NM vs. NT) a factorial ANOVA, LSD Fisher and the SAS package (Stalistica / Ana / ysis System).
    Table 1. Effects on fertility and fertility at birth
    Exp. CompositionExperimental groupsControl groups
    Fertility (%) Childbirth Fertility (%) Fertility (%)Childbirth Fertility (%)
    one Oxytocin (2 IU)90.2688.8983.2382.22
    2 Synthetic GnRH (0.5 ~ g)91.6789.9892.0787.95
    3 Pharmaceutical composition: Oxytocin (2 IU) + Lecirelina acetate (0.5 ~ g) + Caffeine (2 mM) + Excipient (Chloretone 10%)93.0290.0288.6287.0 1
    Table 2. Effects on prolificacy
    Exp. CompositionExperimental groupsControl groups
    (Mean ± • .5. (N))
    one Oxytocin (2 U1)14.30 ± 0.29 (154)12.75 ± 0.30 (161)
    2 Synthetic GnRH (0.5 ~ g)14.80 ± 0.31 (79)13.28 ± 0.26 (124)
    3 Pharmaceutical composition: Oxytocin (2 IU) + Lecirelina acetate (0.5 ~ g) + Caffeine (2 mM) + Excipient (Chloretone 10%)14.80 ± 0.12 (860)13.73 ± 0.09 (1824)
    权利要求:
    Claims (9)
    [1]
    one. Veterinary composition, characterized in that it comprises oxytocin, lecireline and caffeine.
    [2]
    2. Veterinary composition according to claim 1, characterized in that the concentration of oxytocin is between 1 and 3 Ul / ml, the concentration of lecireline is between 0.2 and 0.8 IJg / ml and the concentration of caffeine is between 1 and 3 mM .
    3. Veterinary composition according to claim 1 or 2, characterized in that it comprises lecireline acetate.
    [4]
    Four. Veterinary composition according to any one of claims 1 to 3, characterized in that it comprises an excipient.
    [5]
    5. Veterinary composition according to any of claims 1 to 4, characterized in that said excipient is 10% chloretone.
    [6]
    6. Veterinary composition according to any of claims 1 to 5, 20 characterized in that the composition is in aqueous liquid form.
    [7]
    7. Veterinary composition according to any of claims 1 to 6, characterized in that it is packaged in multi-dose containers.
    Veterinary composition according to any one of claims 1 to 7, characterized in that it is administered directly in the seminal doses at the time prior to insemination.
    [9]
    9. Use of the composition according to any of claims 1 to 8 as a seminal additive useful for artificial insemination in animals.
    [10]
    10. Use according to claim 9, characterized in that said animals are mammals.
    35 11. Use according to claim 10, characterized in that said mammals are selected from the group consisting of sows, cows, goats and sheep.
    [12]
    12. Veterinary composition according to any of claims 1 to 8 for use in artificial insemination in animals with low seminal concentration or asthenpermia or for use as an additive in seminal doses stored for a prolonged period of time in refrigeration.
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    RU2212233C2|2001-03-22|2003-09-20|Северо-Кавказский зональный научно-исследовательский ветеринарный институт|Method for treating some postpartum diseases in animals like cows|
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    ES201631536A|ES2608935B1|2016-11-30|2016-11-30|VETERINARY COMPOSITION FOR THE MANUFACTURE OF A SEMINAL ADDITIVE USEFUL FOR ARTIFICIAL INSEMINATION IN ANIMALS|ES201631536A| ES2608935B1|2016-11-30|2016-11-30|VETERINARY COMPOSITION FOR THE MANUFACTURE OF A SEMINAL ADDITIVE USEFUL FOR ARTIFICIAL INSEMINATION IN ANIMALS|
    EP17821666.9A| EP3530280B1|2016-11-30|2017-10-18|Veterinary composition for manufacturing a seminal additive useful for artificial insemination in animals|
    PCT/ES2017/070691| WO2018100214A1|2016-11-30|2017-10-18|Veterinary composition for manufacturing a seminal additive useful for artificial insemination in animals|
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