JPH07309750A - Central nervous stabilizer for ruminant - Google Patents

Abstract

PURPOSE:To obtain a central nervous stabilizer for ruminants containing lysin as an active ingredient and capable of readily suppressing or preventing ruminants from exiting. CONSTITUTION:Lysin in a form of L body or a salt is included as an active ingredient and as necessary, proper excipient etc., are blended therein and the blend is prepared in a solid or liquid formulation according to a conventional method. Lysin and/or methionine in a form protected from action of the first stomach of ruminants (e.g. cow or sheep) is included as an active ingredient to prepare a feed additive for ruminants. The central nervous stabilizer or the feed additive is administered to ruminants and the administered ruminants are bred. Thereby, the behavior of the ruminants is stabilized during breeding and efficiency of base feed is improved to promote the growth of the ruminants. The behavior of milch cow is also stabilized and production of milk is stabilized for a long period and high production of milk can be kept and the behavior of beef cattle is similarly also stabilized and the growth of the beef cattle is promoted and production of meat is improved.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a central nervous system stabilizer for ruminants containing lysine as an active ingredient.

[0002]

BACKGROUND OF THE INVENTION Ruminants are animals having a compound stomach consisting of four morphologically different stomachs, which are the rumen, the reticulum, the abomasum and the abomasum. The former three are derived from the distal part of the esophagus, and only the abomasum is considered the true stomach. Food is returned to the mouth in part after entering the first two stomachs. The rumen and the rumen are the parts that perform fermentation,
Bacteria, protozoa, and fungi coexist, and the fiber (plant tissue) in food is also digested by cellulase, xylase, cellobiase, etc. secreted by these microorganisms (symbiotic digestion).

In ruminants such as cattle and sheep, problems arise when biologically active substances are administered, for example orally. That is, a substantial part of the administered substance (protein, amino acid, etc.) is decomposed into ammonia and volatile fatty acids by the microorganisms in the rumen, and is finally utilized for the synthesis of protein in the microorganism. Therefore, the utilization efficiency of proteins and amino acids contained in the feed is slightly lower for ruminants than for monogastric animals. Thus, ruminants lose some of their nutrients due to retention and formation of rumen microorganisms. On the other hand, if some of the nutrients (proteins, etc.) contained in the feed flow down to the lower digestive tract without being digested, it also contributes to the nutrition of the ruminant, but other nutrient sources of the ruminant are It is a microbial-derived protein in the rumen that reaches the digestive tract. Therefore, it is important to maintain a ruminal microbial population that constantly provides a source of this type of protein.

When a specific nutrient or drug capable of being absorbed and metabolized is orally administered to a ruminant, these substances are removed from the rumen environmental conditions (for example, environmental conditions such as microbial decomposition and weakly acidic or alkaline pH). It is important to protect, so that the active state of the substances can be maintained until these substances reach the intended digestive or absorption site. That is, the digestion and absorption of the feed by the animal itself is carried out in the abomasum and small intestine, so that certain nutrients and drugs should not be affected by microorganisms while reaching the rumen through the rumen. Is desirable.
Regarding protection technology for nutrients, for example, US Patents
4,976,976, 4,937,083, 3,619,200, 5,093,128, 4,
837,004, 3,959,493, 4,842,863, 5,023,091, 4,95
7,748, 4,797,288, 5,064,665, 5,244,669 and 5,22
7,166, and further, JP-A-59-66842, 5
8-175449, 63-317053, 60-168351 and 59-198946,
In addition, JP-A 2-027950, 2-128654, 2-128655, 3-05675
5, 3-155756, 3-155757, 4-079844 and 5-023114.

All proteins in the animal body consist of a combination of 20 or more amino acids. Of these, 10 essential amino acids are not synthesized in the animal body (in the case of immature rats) and must be ingested from the outside. I have to. Amino acids that make up certain proteins are specific to that protein and cannot be replaced by other amino acids. Therefore, the amount of protein produced by an animal is adjusted by the amino acid (restricted amino acid) that is the least supplied of the essential amino acids. When essential amino acids are deficient in the amino acids absorbed from the intestine, they negatively affect the growth of ruminants and milk production.

As is well known, mainly lysine and / or methionine are the limiting amino acids because of the current worldwide supply of ruminant feed and the amino acid composition of microbial proteins. Various forms of lysine and / or methionine protected from the action of are commercially available as feed additives for ruminants.

On the other hand, the following facts are fragmentarily known about the physiological action of pipecolic acid and the fate of lysine in the rumen of ruminants.

[0008] That is, regarding the physiological action of pipecolic acid, in mice and the like, pipecolic acid crosses the blood-brain barrier, and therefore, when the blood concentration of pipecolic acid increases, the brain concentration also increases (Handbook of Neurochemistry).
(2nd ed.), Vol.3, pp. 583 ~ 605, Prenum Press, New
York (1983)), and that the higher the brain concentration of pipecolic acid, the higher the concentration of GABA (γ-aminobutyric acid) in the brain (Neurochemical Research, vol.14, No.5, p.
p.405-408 (1989)) are known. And for mammals, GA is associated with inhibitory neurons in the cerebrospinal area.
Many neurons use BA as a messenger.
ABA-acting neurons act as pre- or post-synaptic inhibitory systems for excitatory transmission synapses in the cerebrospinal system ("New Edition Animal Pharmacology," page 135, Yokendo Co., Ltd. Version)) is known.

Regarding the fate of lysine in the rumen of ruminants, conversion of lysine to pipecolic acid by protozoa of the rumen (Agr. Biol. Chem., Vol. 36,
No. 11, pp.1989-1995 (1972)) is known.

However, from these facts alone, the feeding of lysine stabilizes the behavior of ruminants,
That is, it cannot be easily inferred that lysine has a central nervous system stabilizing action on ruminants.

[0011]

SUMMARY OF THE INVENTION Under the background of the prior art described in the preceding paragraph, the present invention provides a central nervous system stabilizer for ruminants containing lysine as an active ingredient, and uses such a central nervous system stabilizer. An object of the present invention is to provide an advantageous method for raising ruminant livestock.

[0012]

Means for Solving the Problems The present inventor observed cases in which the behavior of animals was noticeably stable during the course of various feeding tests of amino acids such as lysine and methionine for ruminant livestock. Upon pursuing the cause, it was found that lysine has an action of stabilizing the central nerves of the ruminant, and the present invention has been completed based on such findings.

That is, first, the present invention relates to a central nervous system stabilizer for ruminants, which comprises lysine as an active ingredient.

The ruminant referred to in the present invention is not particularly limited, and broadly includes goats, sheep, buffalos, etc. in addition to cows.

Lysine as an active ingredient is L-form because it requires bioassimilation, but it does not have to be in a free state, and in the form of a salt such as hydrochloride which is a usual commercially available form of lysine for feed. Of course, it is possible.

There is no particular limitation on the dosage form of the central nervous system stabilizer, and it can be in conformity with the usual dosage form for oral administration agents for domestic animals, for example, with or without the use of suitable excipients, In addition, it can be prepared into a solid or liquid dosage form, if necessary, together with other feed additives. The usage will be described later in relation to the breeding method of the present invention.

Secondly, the invention relates to lysine and lysine in a form protected from the action of the rumen of ruminants and / or
Alternatively, the present invention relates to a feed additive for ruminants, which comprises methionine as an active ingredient.

Lysine and / or methionine in a form protected from the action of the rumen of ruminants (hereinafter referred to as RPAA)
(Rumen-protected amino acid) is sometimes abbreviated. ) Has already been manufactured by US
Patents 4,996,067, 4,937,
Some are proposed in 083 and the like.

RPAA is usually used in addition to the basic feed. The amount of RPAA feed additive added to the basic feed is
It depends on a number of factors, but is calculated from the difference between the amino acid requirement of the ruminant and the amount of amino acid supplied from the feed and held by the animal. Generally, RPAA
The amount added is an amount corresponding to the amount required for the development, maintenance, productivity and health of the ruminant. This required amount can be based on experience, research data of universities and the like. For example, H
einbeck has developed and proposed a computational model that incorporates the dietary composition of dairy cows on the basis of amino acids (De
gusa Technical Symposium, Saskatoon, Sa
skatoon, Saskatchewan, Cana
da, September 12, 1989). In addition, as another effective method for calculating the amino acid requirement of ruminants and the feed amino acid supply, a Cornell model (Search: Agricultu
re. Ithaca, NY: Cornell Univ. Arg. Exp. Sta. No. 3
4, 128pp.1990, ISSN 0362-2754).

By the way, the present inventor relates to a method for supplementing an amino acid in a ruminant, and particularly to a rumen.
The feed additive containing methionine and / or lysine protected so as not to be influenced by the action of the microorganism of the present invention to the feed, and the invention relating to the method for feeding the ruminant from before or after the birth to the lactation period (This method remarkably enhances the ruminant's milk production by supplementing the feed with digestible amino acids that are effectively used to feed the ruminant, and further enhances the ruminant's health and appetite. (Patent application No. 6-18543).

As described above, the ruminant feed additive of the present invention has two components, lysine and RPAA, as essential components. Needless to say, this action of lysine as a central nervous system stabilizer and RPAA. The aim is to achieve both effects of the nutritional source of.
Therefore, the feed additive for ruminants of the present invention must be such that the blending amounts and blending ratios of the above two components are suitable for achieving such an object, but there is no special limitation other than this, and The shape, the preparation method and the like can be appropriately adapted to known methods.

Such a feed additive is incompletely protected from the action of the rumen of the ruminant, for example, RPAA (Lys) or R having a protection rate of 30 to 80%.
When PAA (Lys + Met) is used, it is not necessary to add lysine because lysine leaking from RPAA in the rumen acts as the above-mentioned essential component, lysine.

Incidentally, the above-mentioned protection rate is measured as follows.

That is, about 1 g of the prepared sample was added to 300
It is put into a ml Erlenmeyer flask and Mc equivalent to rumen fluid
Inject 200 ml of Dougall buffer, 39 ° C
It was shaken for 24 hours. After shaking, the elution amount of the biologically active substance was analyzed, the ratio to the total amount was calculated, and the value obtained by subtracting this ratio from 1 was taken as the protection rate in the rumen.

The Mc Dougall buffer is a buffer prepared by dissolving the following reagents in 1000 ml of water. That is, 7.43 g of sodium hydrogen carbonate, 7.00 g of disodium phosphate dodecahydrate, 0.34 sodium chloride
g, g chloride, 0.43 g of potassium chloride, 0.10 g of magnesium chloride hexahydrate, and 0.05 of calcium chloride
g.

Thirdly, the present invention relates to a method for raising a ruminant, which comprises administering the ruminant central nervous system stabilizer or the ruminant feed additive of the present invention as described above.

As described above, the RPAA feed additive is used in addition to the basic feed, but it is convenient to use the central nervous system stabilizer of the present invention and the feed additive in addition to the basic feed. Good.

With regard to lysine, the dosage is
An amount of lysine that acts as a central nervous system stabilizer, that is, an amount sufficient to sedate an agitated animal or pre-administered to an animal at risk of agitation to prevent agitation or to stabilize behavior This is an amount sufficient to maintain, and this amount can be easily obtained by those skilled in the art by referring to past experience, examples described later, simple preliminary trials, etc., depending on a given specific case. It can be determined, but for example, about 10 to 100 g per animal per day
It can be a degree.

Similarly for RPAA, in short,
This is an amount sufficient to reach the purpose of administration of RPAA, but for example, it is about 30 g or less per day in terms of lysine, and about 10 in total in terms of lysine and methionine.
It can be 0 g or less. In addition, the above-mentioned Japanese Patent Application No. 6-1
8543 discloses an example of administering RPAA for the purpose of increasing milk production.

The administration of the central nervous system stabilizer of the present invention stabilizes the behavior of heifers, and the administration of the feed additive of the present invention stabilizes the behavior of heifers and the feed of the basic feed. Efficiency is improved and growth is promoted. In the case of lactating cows, the behavior is stabilized by the administration of the central nervous system stabilizer, and the addition of R by addition of the feed additive.
Due to the action of PAA, milk production is stable for a long period of time and a high production amount can be maintained. In the case of beef cattle, similarly, the behavior is stabilized, the feed efficiency of the basic feed is improved, and the fattening is promoted, so that the meat production amount is improved.

The inspection example 1 (Table 2) described later is L-
The effects of lysine hydrochloride administration are shown, of which the results of day 1 (no administration history) and day 15 (no administration for the previous 7 days) are shown on the day of administration of L-lysine hydrochloride.
At this time, the pipecolic acid concentration in plasma was increased by 35.9 and 31.9 nmol / ml in the test group, whereas it was 11.1 nmol / m in the control group.
1 increase and 7.9 nmol / ml decrease.

When this result is displayed based on the control section, L
-The effects of lysine hydrochloride administration (increased pipecolic acid concentration) are 14.8 and 49.8 nmol / ml, respectively.
This clearly shows that the metabolism of L-lysine to pipecolic acid is expressed immediately on the day of administration, and thus the central nervous system stabilizing effect is expressed.

Also on the 7th day (7 days of continuous administration), the effect of administration of L-lysine hydrochloride is 37.0 nmol / ml, expressed on the same basis. This indicates that not only the same day administration but also continuous administration for several days has a central nervous system stabilizing effect.

Therefore, when shipping grown adult cattle,
The shipping cattle may be strangely excited, but in such a case, it is appropriate to arrive at the destination immediately before the shipping movement, that is, on the same day, the day before or two days before, or even before, for example, 2 to 5 weeks before. By administering the central nervous system stabilizer or feed additive of the present invention for a short period of time, it is possible to reduce shipping labor and reduce excitement (stress) of a moving cow. In addition, when shipping fattened beef cattle, in addition to such merits, stable meat quality can be maintained.

As will be described later, the action of lysine, which is the active ingredient of the central nervous system stabilizer of the present invention, is considered to be due to the conversion of lysine into pipecolic acid by the action of microorganisms in the rumen. It should be added that administration of the central nervous system stabilizer or feed additive of the present invention does not exert a central nervous system stabilizing effect on pups aged 1 to 2 months with undeveloped rumen.

[0036]

The central nervous system stabilizing effect of the ruminant central nervous system stabilizing agent and feed additive of the present invention is different from RPAA in that the active ingredient lysine inoculated with the feed is different from RPAA in view of the conventional state of the art described above. Since it has not been treated to be protected from the action of ruminant rumen microorganisms, it is converted to pipecolic acid by rumen microorganisms and is then contained in rumen fluid. It is presumed that this is due to the fact that it further enters the brain, increases the GABA concentration in the brain, and eventually suppresses the excitability of the animal to stabilize the behavior.

[0037]

EXAMPLES The present invention will be further described below with reference to examples.

Example 1 (lysine) Six Holstein cows (three in each of the test group and the control group) about 12 months old were selected, and L-lysine hydrochloride was added per day to the test group. The concentrated feed (Miyazaki Prefecture No. 10, No. 10, once a day, 2 kg per dose) was mixed and fed to give 10 g, and the feeding was continued for 4 months.

During this period, the type and intake of roughage were recorded,
In addition, samples were taken several times, body weight and BCS (body condition score) were measured on the day of sampling, and rumen fluid properties and rumen microorganisms were analyzed.

It has been observed that after entering such a feed, the animals in the test plots had markedly more stable behavior than those in the control plots, compared to before feeding. It was Regarding the change in body weight, the change in the average value of the three animals in each group was as shown in Table 1 below.

[0041]

[Table 1]

Inspection Example 6 Six heifers same as those used in Example 1 were used, and they were fed in the same manner as in Example 1 at another time thereafter. However, the L-lysine hydrochloride was fed for 7 consecutive days from a certain day (the first day), and then the rest was given for 7 days before the final feeding.

During this period, on the first day, the seventh day, and the fifteenth day, the concentration of pipecolic acid in plasma immediately before and 1 hour after the administration of L-lysine hydrochloride was measured by an improved method devised by the present inventor. Was quantified by The results are shown in Table 2 below.

[0044]

[Table 2]

From the results shown in the above table, in the test group, the blood pipecolic acid concentration was clearly increased after the feeding at the same time as the administration of lysine. On the other hand, in the control group containing no lysine, the blood pipecolic acid concentration did not always increase even after feeding,
The cause was not clear, but it tended to decrease.

That is, it can be presumed that the administration of lysine metabolized lysine to produce pipecolic acid, which was absorbed in the digestive tract and transferred to blood. It is considered that this pipecolic acid increased the brain concentration and contributed to the central nervous system stabilizing action of cattle.

On the other hand, from the results of weight measurement in Table 1 above, the weight gain of the test group was about 4% higher than that of the control group at the end of the administration of lysine hydrochloride, and if the administration of lysine hydrochloride was the only stable central nervous system, the cattle were raised. It can be said that it also contributes significantly to development.

Example 2 (Lysine + RPAA) (1) Test animals: All Holstein dairy cows tested were introduced from the Tokachi and Obihiro districts of Hokkaido. The cows were selected so that the following conditions were satisfied. That is, 1. Perform a herd test and have a record of lactation results. 2.305 days total milk production 750
Be a high-yielding dairy cow weighing 0 kg or more. 3. Milk fat percentage is 3.5% or more on average annually. 4. The next delivery is the third or fourth birth. 5. The expected delivery date is from early May to early August.

A pre-purchase survey table, pedigree registration certificate, and test notification table for each individual were obtained for all dairy cows. At the time of introduction, live IBR vaccine was inoculated for the purpose of preventing bovine infectious rhinotracheitis (IBR), and the levamisole preparation was transdermally absorbed from the dorsal part for the purpose of exterminating parasites (nematodes and lungworms).

Test test cows 10 are shown in Tables 3 and 4 below.
The individual numbers of the heads (5 heads × 2 wards), preparatory results, milk yield at the 5th week in this test, the number of deliveries, and the date of delivery were shown. The division was performed so that the total milk yield before delivery, milk quality, the number of deliveries, the date of delivery, and the amount of milk produced during the preliminary breeding period (5 weeks after delivery) were as equal as possible.

[0051]

[Table 3]

[0052]

[Table 4]

(2) Breeding method: Lysine and methionine (abbreviated as RPLys and RPMet in this example, respectively) in a form protected from the action of the rumen of ruminants were added to the feeds shown in Table 5 below. In addition, it was given to morning and evening cows (administration group E: the present invention). The amount of dry matter consumed by the cow at this time is also shown in the same table. Also, as a control, RP
The same procedure as in the present invention was performed except that Lys and RPMet were not added (control group). The composition of the mixed feed in Table 5 is shown in Table 6. Also, in order to supplement the amino acid composition and deficiency in the feed when this feed was given, RPLys was added at 30 g /
Day (Lys 15.7g equivalent) and RPMet 10g
/ Day (equivalent to 6.4 g of Met) was used, and 20 g of lysine was added as the hydrochloride salt.

[0054]

[Table 5]

[0055]

[Table 6]

The content (g / kg) of each mineral per kg of the mineral mix is Mg30, K149,
Cu 1.65, Zn 8.60, Mn 4.17 and I 0.16, the content of vitamins per gram of vitamin mix is 50,000 IU of vitamin A, 5,000 IU of vitamin D ₃ and 30 mg of dl-α-tocopherol acetate. Met.

The cumulative milk yield due to such breeding is calculated as
Shown in the table.

[0058]

[Table 7]

In addition, it was observed that the cows in the test section were generally more stable in behavior than the cows in the control section throughout the entire breeding period.

Example 3 (RPAA) Using RPAA (Lys), which has a low protection rate to leak lysine to some extent in the rumen of dairy cows, the effect of this lysine on central nervous stability was examined.

Holstein dairy cows (latest calving date April 2
From 1st to 21st July, 2 to 4 heifers (10 heifers) are divided into 5 test groups and 5 control groups. The test group has a protection rate of 70% after the first week from the day of calving. RPAA (Lys) was given until the 4th week, and then the protection rate of 40% RPAA (Lys) was administered to the test group for 3 weeks from the 7th week to the 9th week.

As a result, the average milk yield (weekly average) of each section is
Throughout the entire test period, the test plots exceeded the control plots throughout. However, the difference between the two slightly decreased during the suspension period (5th and 6th weeks) of RPAA (Lys).

It was observed that the cows in the test section were generally more stable in behavior than the cows in the control section throughout the entire breeding period.

[0064]

INDUSTRIAL APPLICABILITY According to the present invention, it becomes possible to easily suppress or prevent the excitement of ruminants (effect of unprotected lysine), and in addition, improve feed efficiency and milk production. Can be easily performed (effect of RPAA). Industrial advantages in dairy farming and beef cattle fattening based on these factors are extremely large.

Claims (5)

[Claims] 1. A central nervous system stabilizer for ruminants, which comprises lysine as an active ingredient. 2. A feed additive for ruminants, which contains lysine and lysine and / or methionine in a form protected from the action of the rumen of a ruminant as an active ingredient. 3. The rumen protection rate of ruminants is 30.
A feed additive for ruminants, which comprises as an active ingredient lysine or lysine and methionine in a form protected from the action of the rumen of ruminants in an amount of -80%. 4. A method for raising a ruminant, which comprises administering the central nervous system stabilizer according to claim 1 or the feed additive according to claim 2 or 3. 5. The breeding method according to claim 4, wherein the ruminant is a rearing cow, a lactating cow or a beef cow.