JP7444707B2 - Livestock colostrum quality improving agent and method - Google Patents

Description

The present invention relates to a colostrum quality improving agent for livestock and a method thereof. Specifically, an agent that simply and effectively increases the immunoglobulin content and/or improves N-acetyl-β-D-glucosaminidase (NAGase) activity and/or increases the lactoferrin content in colostrum of livestock. The present invention relates to feeding agents, feed compositions, feeding methods, etc.
In particular, a central feature of the present invention is that it is a technology for colostrum, that is, milk immediately after parturition of livestock, among other drugs, feed compositions, feeding methods, etc. for livestock.

For livestock such as cows, pigs, sheep, and goats whose milk and/or meat are commercial products, poor physical condition or illness of the individual being raised is a serious and direct management issue for dairy farmers and livestock farmers. It becomes a problem. However, due to the emphasis on productivity and cost, large-scale and intensive breeding environments are often adopted, and it is extremely difficult to prevent infectious diseases caused by such breeding environments.
Under these circumstances, the present invention focuses on infants having the following characteristics, and aims to improve the quality of colostrum that is particularly effective for infants. It can be said that the technical field is different from ordinary livestock preparations, feed compositions, feeding methods, etc. for mature animals.

In other words, especially in young livestock, their immune function is immature from birth to weaning, and they are affected by changes in the feed they are fed and stress caused by transportation and environmental changes, leading to diarrhea, respiratory diseases, and various other diseases. susceptible to infections. For example, calf diarrhea is the most common disease, accounting for approximately 75% of calf diseases, and is a cause of extremely large economic losses for livestock farmers.

Normally, immune substances such as immunoglobulin are fed from each mother's colostrum to supplement the immature immune function of the offspring. However, since the content of immune substances contained in colostrum varies greatly depending on the mother stock, even if the amount of colostrum fed is appropriate, it may not be possible to feed the necessary and sufficient amount of immune substances to the offspring. In that case, the baby is at a very high risk of contracting various infectious diseases until its own immune system develops.

Among the immune substances in colostrum, immunoglobulin plays the most important role in preventing various infectious diseases before the immune function of the baby has developed. In view of the above-mentioned background technology, there is a need in the art for a method for producing colostrum of better quality with a higher immunoglobulin content, or for a method for increasing the ability of infants to absorb immunoglobulin.

As a case in which the immunoglobulin content in colostrum increased, a case has been reported in which carrots high in β-carotene were fed to Japanese black cattle cattle that were deficient in β-carotene (Non-Patent Document 1). On the other hand, as a method of increasing the immunoglobulin absorption ability of calves, it is known to feed selenium compounds together with colostrum to calves (Patent Document 1).

N-acetyl-β-D-glucosaminidase (NAGase) is a hydrolase contained in lysosomes, a component of cells, and has the function of decomposing N-acetyl-β-D-glucosaminid, a component of bacterial cell walls. have It is known that when dairy cows are infected with mastitis, NAGase exerts the effect of decomposing bacteria when mammary gland epithelial cells phagocytose the bacteria, and has an antibacterial effect.

In addition, NAGase (derived from Bifidbacterium longum subsp. Infantis ATCC 15697) efficiently produces N-linked glycans that have physiological activities such as increasing the number of beneficial bacteria in the intestinal tract by reacting with glycoproteins in colostrum whey. (Non-patent Document 2).

There is no scientifically clear definition of colostrum, and there are various interpretations such as only the first milk after delivery, up to 5 days after delivery, up to 1 week after delivery, and up to 10 days after delivery. In Japan, it is prohibited to distribute milk as food up to five days after calving, regardless of the type of livestock.
In this application, colostrum refers to colostrum up to the fifth day of delivery.

Vitamin K is considered to be an essential nutritional component in the post-translational modification process of blood coagulation factors and bone matrix proteins. Vitamin K3 (menadione), vitamin K4 (sodium menadiol diphosphate), vitamin K5 (4-amino-2-methyl-1-naphthol), etc. are present. Among these, vitamin K1, vitamin K2, and vitamin K4 are approved for use in humans.

Although vitamin K3 is prohibited for human use, its use for livestock is permitted, and for example, it is added to milk replacer as a feed additive for suckling calves. There is also a report that the immune function of ruminant livestock such as cows, sheep, and goats can be activated by providing vitamin K3 (Patent Document 2). However, there are currently no reports that have investigated the effects of vitamin K on the immunoglobulin content in colostrum of livestock.

In mouse and human immune cells, vitamin K3 suppresses redox-dependent inflammatory reactions and immune reactions (Non-Patent Document 3), and vitamin K3 and vitamin K5 inhibit the proliferation response of activated T cells. There are experimental reports such as weakening T cell-mediated immunity by inducing apoptosis (Non-Patent Document 4), and it can be said that all of these suggest the ability of vitamin K to suppress immune function.

Japanese Patent Application Publication No. 2006-160661 Japanese Patent Application Publication No. 2018-174729 Animal Science Journal (2017) 88, 653-658 Biotechnol Prog. 2015 Sep-Oct;31(5):1331-9. Free Radical Research Vol.45, 975-985. (2011) Life Science Vol. 99, 61-68 (2014)

The present invention provides nutritional and physiological techniques (oral administration or feeding ingredients, feed compositions, feeding methods, etc.) that can improve the quality of colostrum produced by livestock such as cows, pigs, sheep, goats, and horses. It was made for the purpose of providing.
As mentioned above, the health maintenance functions of young animals are immature, and the loss of economic value is particularly large when they die or become ill, so they are very different from those of mature livestock. Special care and care are required. The present invention is specialized in solving this problem, and for this purpose, it focuses on improving the quality of colostrum. Therefore, the problem to be solved is also very different from the treatment and feeding of mature livestock.
It should be noted that calves, especially newborn calves, do not have resistance to diseases. Immunity from the mother is transferred passively through the calf's ingestion of colostrum. Most of the immunoglobulin transferred from the mother's blood to the colostrum is IgG, which is absorbed from the calf's intestinal tract and transferred to the bloodstream, where it acts as an antibody to protect against infection. In addition, antibodies transferred into the bloodstream are re-secreted into the intestinal tract and act to protect against local infection in the intestinal tract. Insufficient intake of high-quality colostrum is said to result in failure of passive immune transmission, leading to increased disease incidence and mortality. Since the transfer of IgG ingested by a calf from the intestinal tract to the bloodstream stops within 24 hours after birth, the component content of colostrum that is given within 24 hours at worst, preferably within 12 hours, and preferably within 6 hours is important. This is because, as mentioned above, the composition of colostrum components greatly affects the calf's resistance and survival rate. Therefore, the present invention can also be said to have particular significance in improving the quality of colostrum used for feeding within 24 hours, preferably within 6 hours, immediately after delivery.

In order to achieve the above object, the present inventors conducted extensive research and found that a feed composition containing vitamin K as an active ingredient, such as vitamin K1 (phylloquinone), vitamin K2 (menaquinone), vitamin K3 (menadione), etc., was formulated for livestock. It has been discovered that by orally administering or feeding a substance to livestock, it is possible to easily and effectively increase the immunoglobulin content of colostrum produced by livestock, improve NAGase activity, and further increase lactoferrin content. , we have completed the present invention.

That is, embodiments of the present invention are as follows.
(1) A method for improving the quality of colostrum in livestock, which comprises orally administering or feeding vitamin K such as vitamin K3 to the livestock from 21 days before (scheduled) parturition until parturition.
Due to the characteristics of the technical field of the present application, the administration/feeding period may be changed depending on the condition of the mother cow, the climate of the previous year, etc. For example, the effect of the present invention can be achieved starting from about 28 days before scheduled delivery, or from about 30 days before scheduled delivery until delivery. In addition, administration and feeding may be performed during all periods before and after 60 days of the dry period.
(2) Livestock characterized by orally administering or feeding vitamin K such as vitamin K3 to the livestock from 21 days (around) before parturition until parturition, together with the feed normally given to the livestock during the dry period. How to improve colostrum quality.
(3) The method according to (1) or (2), wherein the vitamin K is at least one selected from vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). .
(4) The quality improvement of colostrum is characterized by at least one of increasing the immunoglobulin content contained in colostrum, improving N-acetyl-β-D-glucosaminidase (NAGase) activity, and increasing lactoferrin content. The method described in any one of (1) to (3).
(5) Quality improvement requires that the immunoglobulin concentration on the third day of delivery is (approximately) 8.0 g/L or more, 7.9 g/L or more, and that the NAGase activity on the third day of delivery is (approximately) 55.0 nmol. /min/mL or higher, the immunoglobulin concentration immediately after delivery is 116.4 to 163.6 g/L, and the lactoferrin content immediately after delivery is 70.3 to 172.5 μg/mL or higher. The method according to (4), characterized in that the method is at least one of the following.
(6) The method according to any one of (1) to (5), wherein the livestock is at least one selected from cows, pigs, sheep, goats, and horses.
(7) The method according to any one of (1) to (6), characterized in that vitamin K is orally administered or fed in an amount of 10 to 200 mg/head per day.
(8) The method according to any one of (1) to (7), wherein the vitamin K is at least one selected from purified products, crude products, and contained products.
(9) A colostrum quality improving agent for livestock containing vitamin K such as vitamin K3 as an active ingredient.
(10) The colostrum quality improvement is characterized by at least one of increasing the immunoglobulin content contained in the colostrum, improving NAGase activity, and increasing the lactoferrin content (9) The agent described in.
(11) The agent according to (9) or (10), wherein the livestock is at least one selected from cows, pigs, sheep, goats, and horses.
(12) The agent according to (9) to (11), which contains at least one or more selected from vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione) as an active ingredient.
(13) The agent according to any one of (9) to (12), wherein the active ingredient is at least one selected from purified products, crude products, and contained products.
(14) A method for improving colostrum quality of livestock, comprising orally administering or feeding the agent according to any one of (9) to (13).

According to the present invention, it is possible to simply and effectively increase the immunoglobulin content in the colostrum of livestock and at the same time improve NAGase activity. It is also possible to increase the lactoferrin content in colostrum. This makes it possible to produce high-quality colostrum, thereby reducing the disease rate of young livestock and stabilizing dairy farming and livestock management.

1 shows the immunoglobulin (IgG) concentration (g/L) in milk on the third day of delivery in Example 1. White squares indicate the control group, and black squares indicate the vitamin K3-supplemented group. 1 shows the NAGase activity (p-nitrophenol nmol/min/mL) in milk on the third day of calving in Example 1. White squares indicate the control group, and black squares indicate the vitamin K3-supplemented group. The lactoferrin concentration (μg/mL) in milk on the third day of delivery in Example 1 is shown. White squares indicate the control group, and black squares indicate the vitamin K3-supplemented group.

The present invention will be explained in detail below.

In the present invention, vitamin K is used as an active ingredient for improving the quality of colostrum of livestock. Vitamin K types include natural vitamin K such as vitamin K1 (phylloquinone) and vitamin K2 (menaquinone-4 to 14), and synthetic vitamin K such as vitamin K3 (menadione), vitamin K4 (sodium menadiol diphosphate), and vitamin K5 (4 to 4). -amino-2-methyl-1-naphthol) can be used, and 1,4-naphthoquinone and 1,4-dihydroxy-2-naphthoic acid (DHNA), which have a chemical structure similar to vitamin K, can also be used. In particular, it is preferable to use one or more selected from vitamin K1, vitamin K2 (preferably menaquinone-4 and/or menaquinone-7), and vitamin K3.

Regarding these vitamin Ks, it is preferable to use pure dried products, but crudely purified products (pastes, diluted products, emulsions, suspensions, etc.) can also be used. It is also possible to use formulations made by adding excipients such as starch or dextrin and granulating them, or making them into tablets or liquid preparations. Furthermore, it is also possible to use one coated with oil or fat to prevent decomposition in the rumen.

These vitamin Ks can be used as active ingredients as feed additives, feeds, feed compositions, and other agents. It is also possible to provide feed additives, feeds, and feed compositions by adding and mixing commonly used feed ingredients. When preparing such feed compositions, in addition to feed ingredients, other nutritional components (protein, lipids, minerals (potassium, sodium, magnesium, etc.), vitamins other than vitamin K (vitamin A, vitamin E, etc.) should be added. etc.)) can be used together. Furthermore, veterinary pharmaceutical preparations containing these as active ingredients can also be provided. In this case, the formulation may be formulated according to a conventional method for veterinary pharmaceutical preparations, and active ingredients having other physiological functions may also be used in combination.

In the case of veterinary pharmaceutical preparations, they are administered orally in various forms. Examples of the administration form include oral administration using tablets, capsules, granules, powders, syrups, and the like. These various preparations are prepared in the field of formulation technology for veterinary drugs, such as excipients, binders, disintegrating agents, lubricants, flavoring agents, solubilizing agents, suspending agents, coating agents, etc., in accordance with conventional methods. It can be formulated using known adjuvants that are commonly used. Incidentally, it is also possible to use pure dried active ingredients such as vitamin K as they are as a preparation.

The product formulated in this way can not only be used as a veterinary drug, but also as a feed additive, etc., and can be used directly as a feed composition for livestock. It can be fed, or it can be added and mixed with other feed materials as a feed additive to form a feed composition.

The animals targeted by the present invention are livestock whose milk, meat, etc. are sold as commercial products. For example, dairy cows (particularly Holstein breeds, Jersey breeds, etc.), beef cattle (Japanese cattle, etc.), pigs, sheep, goats, etc. are exemplified as more suitable target animals. However, it does not matter if the target is a buffalo, a camel, a yak, a horse, etc.

The amount of oral administration or feeding of the active ingredient of the present invention to livestock is, for example, in the case of dairy cows, vitamin K is 10 to 200 mg, preferably 10 to 100 mg, more preferably 10 to 100 mg per day. 10 to 50 mg is preferred. This amount of oral administration or feeding is preferably divided into about two times per day. If the amount of the active ingredient to be orally administered or administered is higher than the above range, there will be no particular problem in terms of safety or effectiveness, but from the viewpoint of cost etc. it is preferably within the above range. Further, if the amount is less than the above range, the effects of the present invention may not be sufficiently exhibited, which is not preferable.
Note that oral administration or feeding amounts for other livestock may also be determined by taking into consideration their body weight, but oral administration or feeding amounts other than those listed above, including for dairy cows, are not completely excluded.

In this application, as is clear from the above-mentioned problem to be solved, the timing of the salary is an important factor. Usually, especially in cows, the lactation period begins with parturition and continues until about 60 days before the next parturition. During this period, mother cows are given multivitamin supplements to prepare them for safe and healthy calving.

Next, the dry period begins approximately 60 days before the next calving until the next calving. The present invention provides (administers) vitamin K compounds during this dry period. Preferably, for example, during the last 21 days of this period or 21 days before calving (scheduled), the central significance of the present invention is to provide vitamin K in order to improve the quality of postpartum colostrum. During this period, it is common to feed mixed feed, bypass protein, vitamins A, C, E, methionine, lysine, etc. In the present invention, vitamin K may be fed alone or together with the above-mentioned normal feed during this period.
Finally, milk produced for up to 5 days after calving is referred to as colostrum in this application.

The present invention aims to directly confirm the effectiveness of vitamin K (increasing the immunoglobulin content in colostrum of livestock and improving NAGase activity) not only at the laboratory level but also directly using living livestock at actual production sites. It can be said that it is extremely practical and has been proven.

In addition, in the present invention, the "colostrum quality improvement effect" of livestock refers to improving/improving at least one of the following effects: increase in immunoglobulin content, improvement in NAGase activity, and increase in lactoferrin content contained in colostrum of livestock. It means to cause.

Examples of the present invention will be described below, but the present invention is not limited to these examples, and various modifications can be made within the technical idea of the present invention.

Forty dry cows selected from four dairy farms were used. They were divided into 19 animals in the control group and 21 animals in the vitamin K3-fed group.The control group received conventional feed, and the vitamin K3-fed group received a preparation containing 1% vitamin K3 in the conventional feed from 3 weeks before parturition (scheduled). They were fed 5 g per day (ie 50 mg per day as vitamin K3) and milk samples were collected 3 days after parturition. Immunoglobulin (IgG) concentration, lactoferrin content and NAGase activity were measured on milk samples. These measurement methods were performed according to the ELISA method and the colorimetric method, respectively.

The results (average values) are shown in FIGS. 1, 2, and 3. In the vitamin K3-fed group, the immunoglobulin (IgG) concentration in milk on the third day of calving significantly increased (p<0.05), and at the same time, NAGase activity also significantly improved (p<0.05). Lactoferrin concentration also increased. Therefore, it has been revealed that feeding vitamin K3 to dry cows increases the immunoglobulin content in colostrum, improves NAGase activity, and increases lactoferrin concentration.

In other words, the IgG concentration in the control group was about 2 to 3 g/L, while in the vitamin K3 supplement group it was about 7 to 8 g/L, which was about 3 to 4 times higher than in the control group. . Therefore, from the viewpoint of those skilled in the art, it is considered possible to achieve an IgG concentration as high as 9 to 10 g/L according to the present invention.
The IgG concentration in colostrum is highest immediately after delivery, and then rapidly decreases. This can be said to be the significance of the effect of improving the quality of colostrum immediately after delivery according to the present invention.
Therefore, since the IgG concentration on the third day of delivery is as shown in FIG. 1, it is recognized by those skilled in the art that the IgG concentration immediately after delivery is extremely high. In fact, this point is demonstrated in Example 2.

Furthermore, the NAGase activity in the control group was approximately 20-25 in p-nitrophenol nmol/min/mL, whereas it was approximately 50-55 in the vitamin K3-supplemented group, which was approximately 2% of the control group. It has doubled. Therefore, from the perspective of those skilled in the art, it is considered possible to achieve a NAGase activity as high as 58 to 63 according to the present invention. Regarding lactoferrin concentration, it was about 150-200 μg/mL in the control group, while it was about 230-280 μg/mL in the vitamin K3-supplemented group, which was about 1.5 times higher than in the control group. There is. Therefore, even from the perspective of those skilled in the art, it is considered possible to achieve a lactoferrin concentration as high as 300 μg/mL according to the present invention.

Eleven dry cows selected from two dairy farms were used. They were divided into 5 animals in the control group and 6 animals in the vitamin K3-fed group. 50 mg per day as K3) during the period shown in the table (2019). Milk samples were collected at the time of delivery, and the IgG concentration was measured in each case. The results are shown in Table 1 below.

As is clear from the results of Table 1 (feeding vitamin K3 preparations (VK3: 50 mg/day) to the test group during the delivery period), according to the present invention, by administering vitamin K, colostrum When vitamin K3 is administered (fed) at 50 mg per day for 5 to 18 days, a high IgG content of 100 g/L or more can be obtained immediately after delivery, for example. , an IgG content of 120-130 g/L was obtained, an IgG content of 130-160 g/L was obtained, and a high IgG content of 163-164 g/L was actually confirmed. Therefore, from the viewpoint of those skilled in the art, it is considered possible to obtain an IgG content as high as 170 to 180 g/L or even more than 200 g/L according to the present invention.

The average value of IgG content in the test group (6 animals) administered with vitamin K3 was 137.3 g/L. On the other hand, the average value of the IgG content in the control group (5 animals) to which vitamin K3 was not administered was 79.3 g/L. Therefore, it was demonstrated that the test group achieved an extremely high IgG content of 1.73 times as compared to the control group.

Colostrum is very important for young livestock, and as is clear from the above, the present invention has succeeded in improving the quality of colostrum, particularly in significantly increasing the IgG content. As is clear from the results of Examples 1 and 2, it was demonstrated that this effect is strongly exerted by allowing the colostrum to be consumed by the offspring as soon as possible after delivery, within 6 hours after birth. Therefore, it is recommended to administer (feed) colostrum to the calf as soon as possible after birth, within 6 hours of birth.
As a result, the healthy growth of young livestock is ensured, which also makes an economic contribution to livestock farmers. As described above, the present invention is unique in that it focuses on colostrum, which is particularly targeted at young livestock, specializes in improving its quality, and has succeeded in doing so.

Lactoferrin content was also measured in the milk samples. The measurement method was performed according to the ELISA method.
Regarding the lactoferrin content, the average value of the test group (6 animals) was 248.5 μg/mL, while the average value of the control group (5 animals) was 122.0 μg/mL, which was higher than the control group. It was demonstrated that the test group was able to achieve a very high lactoferrin content of 2.03 times.

The present invention can be summarized as follows.

That is, the present invention simply and effectively increases the immunoglobulin content, NAGase activity, and lactoferrin content contained in colostrum produced by livestock such as cows, pigs, sheep, goats, and horses. The purpose is to provide nutritional and physiological techniques (oral administration or feeding components, feed compositions, feeding methods, etc.) that can be realized.

Then, by orally administering or feeding ruminant livestock with vitamin K such as vitamin K1 (phylloquinone), vitamin K2 (menaquinone), vitamin K3 (menadione), etc. as active ingredients in feed compositions, etc. Colostrum quality improvement can be achieved.

Claims (5)

Orally administering or feeding vitamin K, which is at least one selected from vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione), to livestock during the period from 21 days before scheduled parturition until parturition. A method for improving the quality of colostrum of livestock that improves at least one of the following: an increase in immunoglobulin content, an increase in N-acetyl-β-D-glucosaminidase (NAGase) activity, and an increase in lactoferrin content in the colostrum of livestock. . A feed in which vitamin K, which is at least one selected from vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione), is normally fed to livestock during the dry period from 21 days before expected parturition until parturition. At least one of increasing the immunoglobulin content, improving the N-acetyl-β-D-glucosaminidase (NAGase) activity, and increasing the lactoferrin content contained in the colostrum of livestock, characterized by orally administering or feeding with the A method for improving colostrum quality in livestock. 3. The method according to claim 1 , wherein the livestock is at least one selected from cows, pigs, sheep, goats, and horses. Claim 1 , characterized in that 10 to 200 mg/head of vitamin K , which is at least one selected from vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione), is orally administered or fed per day. 3. The method according to any one of items 3 to 3. The vitamin K, which is at least one selected from vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione), is at least one selected from purified products, crude products, and contained products. The method according to any one of claims 1 to 4 .