JP5594684B2 - Birth rate improvement accelerators applied to mammals, tranquilizers applied to mammals, and livestock feed - Google Patents

Description

  The present invention relates to a birthrate improvement promoter applied to mammals, a tranquilizer applied to mammals, and livestock feed.

  In the animal breeding industry such as livestock and pet breeders, improving the “birth rate per mother (parturition rate)” is one of the most important issues. In order to achieve this improvement in the birth rate, it is important to prevent accidents during childbirth, increase the growth of mothers and children, and increase the probability of becoming pregnant.

  In the prior art, it is known that n-3 polyunsaturated fatty acids such as EPA and DHA and vitamin E are effective as a breeding feed to increase the birth rate. Is desired. In addition, in the prior art, feeds containing saccharides mainly composed of oligosaccharides are also known.

  Furthermore, restraint, electric shock method, etc. may be used for pets with aggressive personalities such as barking and biting when raising pets etc., but this is not desirable from the viewpoint of animal welfare, There is a need to develop more pet-friendly breeding methods.

JP-A-8-23889

  Therefore, the present invention has been made to solve the above-mentioned problems of the prior art, and can be applied to mammals that can increase the probability of conception and delivery of mammals including livestock and pets. It is an object to provide an improvement accelerator.

  The present invention has been made to solve the above-mentioned problems of the prior art, and stabilizes the mental state of mammals including livestock and pets (having a relaxing effect), and makes aggressive behavior. It is an object to provide a tranquilizer that can be suppressed and applied to mammals.

  Furthermore, a feed for livestock that has been made to solve the above-described problems of the prior art and that can increase the probability of conception and delivery of livestock, stabilize the mental state, and suppress aggressive behavior. The issue is to provide.

This invention is made | formed in order to solve the said subject, The birth-rate improvement promoter concerning the 1st aspect contains an isoprenoid compound, It is characterized by the above-mentioned. More specifically, it is a promoter for improving the birth rate applied to mammals, characterized by containing at least one substance selected from geranylgeranoic acid, geranylgeraniol, geranylgeranial, and geranylgeranyl pyrophosphate. It is characterized by.

In addition, the birthrate improvement promoter according to the second aspect of the present invention is the first aspect, wherein the isoprenoid compound is geranylgeranoic acid, farnesoic acid, geranylgeranylamine, farnesylamine, geranylamine, geranylgeraniol, geranyl. It is characterized by being at least one substance selected from geranial, geranylgeranyl pyrophosphate, and 4,5-didehydrogeranylgeranoic acid. More specifically, it is characterized by being a birth rate improvement promoter applied to mammals, characterized by containing geranylgeranoic acid.

Furthermore, this invention is made | formed in order to solve the said subject, The tranquilizer concerning the 3rd aspect contains an isoprenoid compound, It is characterized by the above-mentioned. More specifically, a tranquilizer for oral administration applied to mammals, comprising at least one substance selected from geranylgeranoic acid, geranylgeraniol, geranylgeranial, and geranylgeranyl pyrophosphate. It is characterized by being.

The tranquilizer according to the fourth aspect of the present invention is the tranquilizer according to the third aspect, wherein the isoprenoid compound is geranylgeranoic acid, farnesoic acid, geranylgeranylamine, farnesylamine, geranylamine, geranylgeraniol, geranylgeranii. It is at least one substance selected from R, geranylgeranyl pyrophosphate, and 4,5-didehydrogeranylgeranoic acid. More specifically, it is a tranquilizer for oral administration applied to mammals, characterized by containing geranylgeranoic acid.

  Furthermore, as a method of using the birthrate improvement promoter according to the present invention, a method of mixing about 0.0001% to 5% isoprenoid compound in feed is preferable when administering to livestock or pets. More preferred is a method in which about 0.01% to 0.1% of isoprenoid compound is mixed in the feed. More specifically, for example, a method in which geranylgeranoic acid is mixed in the feed by about 0.05% to 0.06% and is introduced into livestock or pets is preferable.

  Moreover, as a method of using the tranquilizer according to the present invention, a method of mixing about 0.0001% to 5% of isoprenoid compound in feed is preferable when administering to a domestic animal or pet. More preferred is a method in which about 0.01% to 0.1% of isoprenoid compound is mixed in the feed. More specifically, for example, a method in which geranylgeranoic acid is mixed in the feed by about 0.05% to 0.06% and is introduced into livestock or pets is preferable.

  Furthermore, the present invention has been made to solve the above problems, and the livestock feed according to the fifth aspect is a livestock feed in which an isoprenoid compound and a feed body are mixed, and the isoprenoid compound is 0.0001% to 5% is mixed. More specifically, a configuration in which the isoprenoid compound is mixed in an amount of 0.05% to 0.06% is preferable.

  In this livestock feed, the isoprenoid compound contains geranylgeranoic acid, farnesoic acid, geranylgeranylamine, farnesylamine, geranylamine, geranylgeraniol, geranylgeranial, geranylgeranyl pyrophosphate, and 4,5-didehydrogeranylgeranoin It is preferably at least one substance selected from acids.

  In addition, when configuring this livestock feed, microcapsules are used in combination with antioxidants such as vitamin E in order to increase the stability of isoprenoid compounds (eg, geranylgeranoic acid). It is preferable.

  In addition, when the above-mentioned birth rate improvement promoter and tranquilizer are applied to humans (for example, when these are used as health foods), they may be used by mixing with edible oils, soft capsules, etc. It is preferable that it can be ingested appropriately.

  ADVANTAGE OF THE INVENTION According to this invention, the birth-rate improvement promoter applied to the mammal which can raise the probability of conception and the delivery of the mammal including a domestic animal, a pet, etc. can be obtained. Moreover, according to this invention, the tranquilizer applied to the mammal which can stabilize the mental state of mammals including a domestic animal, a pet, etc., and can suppress aggressive behavior can be obtained. Furthermore, according to the present invention, it is possible to obtain livestock feed that can increase the probability of conception and delivery of livestock, stabilize the mental state, and suppress aggressive behavior.

The main composition component (and its compounding quantity) of the feed for 1st comparison (CE-2) and the feed for 2nd comparison (CA-1) used at the time of the experiment of the 1st Example concerning embodiment of this invention is shown. It is a table. Using each feed (first comparative feed (CE-2), second comparative feed (CA-1), example feed (CE-2 + GGA)) in the first example according to the embodiment of the present invention. It is the table | surface which showed the difference in the birth rate at the time of raising a mouse. Using each feed (first comparative feed (CE-2), second comparative feed (CA-1), example feed (CE-2 + GGA)) in the first example according to the embodiment of the present invention. It is the table | surface which showed the difference in the average number of weanlings and a production index at the time of raising a mouse | mouth. Mice in the case of breeding using each feed according to the embodiment of the present invention (first comparative feed (CE-2), second comparative feed (CA-1), example feed (CE-2 + GGA)) It is the table | surface which showed the difference in action. FIG. 2 shows a schematic diagram of a mouse head and a partial enlarged view of the brain (enlarged view of the hippocampus). Mice in the case of breeding using each feed according to the embodiment of the present invention (first comparative feed (CE-2), second comparative feed (CA-1), example feed (CE-2 + GGA)) Fig. 6 (a) shows a partially enlarged schematic diagram of the hippocampus (localization and expression level of BDNF) in Fig. 6 (a) when fed with the first comparative feed (CE-2). Fig. 6 (c) shows the case where it was raised with the feed for example (CE-2 + GGA).

  In the process of studying the physiological action of geranylgeranoic acid, which is one of the isoprenoid compounds, the present inventors have increased the delivery rate (birth rate) of animals (mammals). The inventors discovered for the first time that they are effective in suppressing the aggressiveness of animals (mammals) (stabilizing the spirit of mammals), and completed the present invention.

  Embodiments of the present invention will be described below based on examples and test examples.

<First Example>
In the first embodiment, a case where an isoprenoid compound is used as a birth rate improvement accelerator will be described. More specifically, the case where the isoprenoid compound is geranylgeranoic acid will be described.

  In this example, AKR / J mice purchased from Japan SLC Co., Ltd. (Shizuoka) were used, and a breeding experiment was performed under different dietary conditions. As a method for changing the dietary conditions, three feeds were prepared.

  First, as a first comparative feed, a mouse breeding feed (pellet form) (hereinafter referred to as “CE-2”) manufactured by CLEA Japan (Tokyo) was prepared, and as a second comparative feed, Nippon Claire Corporation A mouse breeding feed (in the form of pellets) (hereinafter referred to as “CA-1”) manufactured by the company (Tokyo) was prepared. In addition, CE-2 (the “feed body” of the present invention) was used as a feed containing the fertility improvement promoter according to the present example (corresponding to “livestock feed” of the present invention, hereinafter referred to as “Example Feed”). "Corresponding") was prepared by mixing 0.06% of geranylgeranoic acid (GGA) which is one of the isoprenoid compounds (hereinafter referred to as "CE-2 + GGA").

  In conducting the experiments, the mice were divided into three groups so as to have the same initial conditions. Specifically, two female mice and one male mouse aged 6 to 8 weeks were placed in one plastic cage to form one unit group, and a plurality of unit groups were prepared. The plurality of unit groups are roughly divided into three groups (hereinafter also referred to as “A group”, “B group”, and “C group”). In this embodiment, each group is composed of about 4 to 5 unit groups.

  Each group was fed with water and one of the three diets (different diets) for free for one week, and then each female mouse was reared in a separate plastic cage for three weeks. At that time, the feed to be fed was continuously given without changing the feed given at the beginning. In this example, Group A was given “First Comparative Feed (CE-2)”, Group B was given “Second Comparative Feed (CA-1)”, and Group C was given “Example Feed ( CE-2 + GG) ".

  Further, about 3 weeks later (20 to 23 days later), in the plastic cage where birth was confirmed, the type of feed was not changed until the weaning period (3 weeks after delivery), and the same feed was continuously given.

  Here, FIG. 1 is a table showing the main composition components (and their blending amounts) of the first comparative feed (CE-2) and the second comparative feed (CA-1) according to this example. .

  As is clear from FIG. 1, the composition of the first comparative feed (CE-2) and the second comparative feed (CA-1) has many similar parts. The EPA and DHA contents of fatty acids are particularly different. Specifically, the second comparative feed (CA-1) contains about twice the amount of polyunsaturated fatty acids EPA and DHA in comparison with the first comparative feed (CE-2). ing.

  In contrast to these comparative feeds (CE-2, CA-1), the Example feed (CE-2 + GGA) according to this example is obtained by mixing GGA with the first comparative feed, which is a feed for breeding mice. It is configured. Specifically, the Example feed is configured by mixing 0.05% to 0.06% GGA to the first comparative feed.

FIG. 2 shows a comparison of the birth rates when mice are raised using three types of feed as in the first embodiment described above. That is, FIG. 2 is based on each feed in the first example of the present invention (first comparative feed (CE-2), second comparative feed (CA-1), and example feed (CE-2 + GGA)). It is a table showing the difference in the birth rate. Here, the birth rate is calculated by the following <Formula 1>.
<Formula 1>
Birth rate = number of birth parents / number of matings x 100

  As is apparent from FIG. 2, when the mice were raised using the first comparative feed (CE-2), which is a feed for raising mice, the birth rate was 20%, whereas When mice were raised using the second comparative feed (CA-1), which was a feed, the birth rate was significantly increased to 50%.

  On the other hand, when the mice were bred using the example feed (CE-2 + GGA) according to the present embodiment, it became clear that the birth rate was higher than that of the second comparative feed (CA-1). It was. Specifically, when Example feed (CE-2 + GGA) was used, the result showed a high birth rate of 62.5%.

FIG. 3 shows the respective feeds (first comparative feed (CE-2), second comparative feed (CA-1), and experimental feed (CE-2 + GGA)) in the first embodiment of the present invention. It is the table | surface which showed the difference in the average number of weanlings and a production index at the time of raising a mouse | mouth. Here, the average number of weaned babies and the production index are calculated by the following <Equation 2> and <Equation 3>.
<Formula 2>
Average number of weaned infants = number of weaned infants / number of birth parents <Formula 3>
Production index = number of weanlings / number of matings

  As is clear from FIG. 3, the number of weaned babies per mother (average number of weaned babies) is not so different between the three feeds (due to the difference in feed). However, among them, the case of breeding using the example feed (CE-2 + GGA) tends to be slightly higher than the case of breeding using the other two comparative feeds (average number of weanlings = 6. 8 animals) were revealed.

  As described above, there was no significant difference in the average number of weaned babies, but it became clear that there was a marked difference when compared with the number of weaned children per mating number, that is, the production index. Specifically, as shown in FIG. 3, the production index when the mice were raised using the first comparative feed (CE-2) was 1.2, whereas the second comparative feed When the mice were raised using (CA-1), the production index was 2.5, which was almost doubled. In addition, when the mice were bred using Example Feed (CE-2 + GGA), the production index was further improved to 4.25.

  According to the present example, from the results of FIG. 2 and FIG. 3, the isoprenoid compound (one of which is GGA) can effectively function as a birth rate improvement promoter that increases the probability of conception and delivery of mammals. It became clear. In addition, according to this example, an example feed (corresponding to “livestock feed” of the present invention) in which an isoprenoid compound (one of which is GGA) and a feed main body (CA-1) is mixed is a livestock. It has been found that it effectively increases the probability of conception and delivery.

<Second Example>
Next, a second example of this embodiment will be described. In this second embodiment, the case where an isoprenoid compound is used as a tranquilizer will be described. More specifically, the case where the isoprenoid compound is geranylgeranoic acid will be described.

  The experiment performed by the second embodiment is basically the same as the first embodiment described above. That is, the following results could be obtained based on the breeding experiment conducted in the first example.

  In this example, during the breeding period of the mouse in the above experiment, the respective feeds used for breeding (first comparative feed (CE-2), second comparative feed (CA-1), and example feed (CE). -2 + GGA)), a significant difference was observed in the behavior of the mice when changing the flooring. The result is shown in FIG.

  FIG. 4 is reared using each feed according to the embodiment of the present invention (first comparative feed (CE-2), second comparative feed (CA-1), and example feed (CE-2 + GGA)). It is the table | surface which showed the difference in the mouse | mouth action (The action of the mouse | mouth at the time of replacement | exchange of floor coverings) in the case of doing.

  As is clear from FIG. 4, when the first comparative feed (CE-2) or the second comparative feed (CA-1) was used for breeding, when the flooring was changed, the mouse jumped, There were several occasions that showed behavior that attacked human hands.

  On the other hand, when the mice were bred using the example feed (CE-2 + GGA), there were few actions that jumped or attacked human hands even when the flooring was replaced.

  That is, when a mouse is bred with the first comparative feed (CE-2) or the second comparative feed (CA-1), the frequency of jumping or attacking human hands when replacing the flooring. In contrast, there were few jumps, and there was little jumping, and it was excellent in human hands and did not cause any attack reaction only when raised with the example feed (CE-2 + GGA). In other words, a reduction in aggressiveness was observed in the mice bred using the example diet (CE-2 + GGA).

  The present inventors have made various studies on the reason why such a result (decrease in aggressiveness) could be obtained. As a result, it was thought that the developmental state of the mouse brain was the factor. This will be specifically described below.

  As described above, in the present embodiment, after delivery, the breastfeeding period is also continuously used as the mother's feed, the first comparative feed (CE-2), the second comparative feed (CA-). 1) Or the Example feed (CE-2 + GGA).

  Then, the brain of a one-week-old mouse was removed, embedded in a Cryo-embedding compound, frozen sections were prepared, and fluorescence using an anti-BDNF (brain-derived neurotrophic factor) antibody was prepared. After staining with an antibody method, the localization and expression level of BNDF were observed with a confocal laser scanning fluorescence microscope.

  Here, FIG. 5 shows a schematic diagram of the head of the mouse and a partial enlarged view of the brain (enlarged view of the hippocampus).

  In FIG. 5, a schematic diagram of the head of mouse M (the brain B in the head of mouse M and the hippocampus H constituting brain B) and the brain B of mouse M (one of the brain regions) A partial enlarged view of the hippocampus H is shown. In the hippocampus H shown in FIG. 5, the neural network of the hippocampus is described in a simplified manner, and hatched portions indicate the dentate gyrus DG and the Ammon angle CA (CA1, CA3).

  FIG. 6 is reared using each feed (first comparative feed (CE-2), second comparative feed (CA-1), example feed (CE-2 + GGA)) according to an embodiment of the present invention. The partial expansion schematic diagram (localization and expression level of BDNF) of the hippocampus H of the mouse M in the case of doing is shown. Here, FIG. 6 (a) shows the case of breeding with the first comparative feed (CE-2), FIG. 6 (b) shows the case of breeding with the second comparative feed (CA-1), and FIG. c) shows the case of breeding with Example Feed (CE-2 + GGA). That is, FIG. 6 shows the result of observing the localization and expression level of BDNF described above.

  As shown in FIG. 6, localization of BNDF was observed in granule cells and pyramidal cells, which are neurons of the dentate gyrus DG and Ammon angles CA1 and CA3 of the hippocampus H, which is considered to be the center of memory. . As a result, compared with the case where the first comparative feed (CE-2) is given (see FIG. 6A), the case where the second comparative feed (CA-1) is given (see FIG. 6B). ) Showed a slight increase in the expression level of BDNF in granule cells and cone cells.

  On the other hand, when Example feed (CE-2 + GGA)) is given (see FIG. 6C), the first comparative feed (CE-2) or the second comparative feed (CA-1) is used. Compared with the case of giving, the expression level of BDNF in granule cells and cone cells was greatly increased. This was particularly noticeable in dentate granule cells.

  BDNF is known as a factor that suppresses apoptosis of nerve cells, and an increase in the expression level of BDNF during an important period of brain development is important as ensuring the healthy development of the brain. That is, as shown in FIG. 6, according to the present example, it is possible to increase the expression level of BDNF by giving the example feed (CE-2 + GGA). By doing so, it is possible to achieve healthy brain development, stabilize the mental state of the mouse, and suppress aggressive behavior.

  According to the present example, from the result of FIG. 6, the isoprenoid compound (one of which is GGA) is effective as a tranquilizer capable of stabilizing the mental state of mammals and suppressing aggressive behavior. It became clear that it could function functionally. In addition, according to this example, an example feed (corresponding to “livestock feed” of the present invention) in which an isoprenoid compound (one of which is GGA) and a feed main body (CA-1) is mixed is a livestock. It became clear that it was possible to stabilize mental states and suppress aggressive behavior.

  From the above, in this embodiment, it is possible to obtain a birth rate improvement accelerator applied to mammals that can increase the probability of conception and delivery of mammals including livestock and pets. Moreover, according to this embodiment, the tranquilizer applied to the mammal which can stabilize the mental state of mammals including domestic animals, pets, etc., and can suppress aggressive behavior can be obtained. Furthermore, according to the present embodiment, it is possible to obtain livestock feed that can increase the probability of conception and delivery of livestock, stabilize the mental state, and suppress aggressive behavior.

<Other embodiments>
The present invention is not limited to the above-described embodiments (examples), and can be carried out with various modifications as necessary within the scope that can meet the spirit of the present invention. Are included in the technical scope of the present invention.

  Although the case where geranylgeranoic acid is used as one of the isoprenoid compounds has been described in the above embodiment, the present invention is not limited to this configuration. Thus, for example, the isoprenoid compound is selected from geranylgeranoic acid, farnesoic acid, geranylgeranylamine, farnesylamine, geranylamine, geranylgeraniol, geranylgeranial, geranylgeranyl pyrophosphate, and 4,5-didehydrogeranylgeranoic acid As long as it is at least one substance.

  Moreover, in the said embodiment, although the manufacturing method of geranylgeranoic acid etc. was not demonstrated in particular, this invention is not limited to any manufacturing method. Therefore, for example, as a method for obtaining geranylgeranoic acid, it may be obtained as a compound by any chemical method, or may be obtained as a natural component from herbs or the like. There are various types of herbs. For example, it is preferable to use herbs such as turmeric, gomi, parsley, and lemongrass, and it is more preferable to use turmeric and basil.

  Furthermore, in the said embodiment, although the case where CE-2 was used as a feed main body which comprises livestock feed was demonstrated, this invention is not limited to this structure. Therefore, for example, at least one selected from solid, powder, or liquid may be used as the feed body constituting the livestock feed.

  Moreover, in the said embodiment, although the case where geranylgeranoic acid was used as an isoprenoid compound which comprises livestock feed was demonstrated, this invention is not limited to this structure. Thus, for example, isoprenoid compounds include geranylgeranoic acid, farnesoic acid, geranylgeranylamine, farnesylamine, geranylamine, geranylgeraniol, geranylgeranial, geranylgeranyl pyrophosphate, and 4,5-didehydrogeranylgeranoic acid At least one selected may be used.

  Furthermore, although the case where it uses about a mouse | mouth was demonstrated in the said embodiment, this invention is not limited to this structure, It is applicable also to another mammal as needed. When the above-mentioned birth rate improvement promoter and tranquilizer are applied to humans (for example, when these are used as health foods), they can be mixed with edible oils, soft capsules, etc. Is preferably able to be taken properly.

  In the animal husbandry industry such as livestock and pet breeders, improving the “birth rate per mother (parturition rate)” is one of the most important issues. To achieve this improvement in the birth rate Conventionally, various means have been taken. However, at present, no such solution has been found.

  Further, in breeding pets and the like, development of more friendly breeding methods and the like for pets having aggressive personalities such as barking and biting is required.

  In order to solve the above-mentioned problems of the prior art, the present inventors obtain a birth rate improvement promoter that realizes an improvement in the birth rate by using an isoprenoid compound (especially geranylgeranoic acid), and improve pet aggression. An inhibitory tranquilizer could be obtained. In addition, the present inventors have been able to obtain a livestock feed that can solve the above-mentioned problems of the prior art using an isoprenoid compound (particularly geranylgeranoic acid).

  That is, the present inventors have provided a fertility improvement promoter, a tranquilizer, and a livestock feed comprising an isoprenoid compound (especially geranylgeranoic acid) in the animal breeding industry. A periodical effect can be obtained.

M ... mouse B ... brain H ... hippocampus DG ... dentate gyrus CA (CA1, CA3) ... Ammon angle

Claims (4)

An agent for improving the birth rate applied to mammals, comprising at least one substance selected from geranylgeranoic acid, geranylgeraniol, geranylgeranial and geranylgeranyl pyrophosphate . Birth rate improvement promoter applied to mammals, characterized by containing geranylgeranoic acid . A tranquilizer for oral administration applied to mammals, comprising at least one substance selected from geranylgeranoic acid, geranylgeraniol, geranylgeranial and geranylgeranyl pyrophosphate . A tranquilizer for oral administration applied to mammals, characterized by containing geranylgeranoic acid .

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