JP5248438B2 - Ruminant milk production improver - Google Patents

Description

  The present invention improves milk production for ruminants containing difructose anhydride III (hereinafter also referred to as DFA III) and / or difructose anhydride IV (hereinafter also referred to as DFA IV) as an active ingredient. It relates to the agent.

  Ruminants have four stomachs, most of which are digested by rumen microorganisms, particularly in the rumen. Therefore, few foods reach the intestines without being broken down.

  The source of calcium to milk of ruminant dairy cows is calcium in the blood, which is transferred from body tissues such as calcium and bone in the feed. The calcium concentration in the blood of dairy cows, which are representative of ruminants, is usually 9 to 11 mg / dl. If excessive calcium is supplied, absorption from the intestinal tract decreases and the amount of excretion in the urine increases. As a result, the calcium in milk is kept almost constant, although it is affected by the breed of dairy cows and milk components.

  In dairy cows, the calcium concentration in the blood decreases during the perinatal period before and after calving and presents with a pathological condition of hypocalcemia. In hypocalcemia, when the blood calcium concentration is 7 mg / dl or less and 5 mg / dl or less, it becomes impossible to stand and death in severe cases. It is also called milk fever and affects about 6% of dairy cows in the United States, and is susceptible to mastitis (E. coli) and metabolic diseases such as ruminal displacement, placental stagnation and ketosis. In addition, latent hypocalcemia, which does not lead to clinical symptoms, occurs in about 66% of parous cows and causes anorexia in cows immediately after calving, as well as milk fever, ketosis, placental stagnation, It makes it easy to cause diseases such as displacement of the stomach and mastitis.

  Furthermore, when hypocalcemia is prolonged, the calcium concentration of the milk itself may decrease. Although there are various foods as a source of calcium necessary for human nutrition, the daily intake (about 600 mg) of Japanese is less than the necessary amount. Milk, which is one of the sources of calcium, is important as a source of calcium because it contains about 227 mg of calcium per cup (200 ml).

  As a method to improve hypocalcemia in dairy cows, an anion salt is supplied during the dry period, and intravenous administration of calcium preparations is generally given to dairy fever cows. There are known cases that are difficult to maintain. In addition, the milk production capacity has increased due to the improvement of transmission, and the amount of milk produced after parturition is also high. These causes further increase in the number of cattle with hypocalcemia, and cause serious conditions such as inability to stand up. There is a long-awaited desire to overcome calcium deficiency in these cows.

  On the other hand, for DFA III and DFA IV, which are oligosaccharides formed by binding two fructose molecules, a calcium absorption enhancing composition containing DFA III as an active ingredient and a calcium absorption enhancing composition containing DFA IV as an active ingredient have already been obtained. (For example, refer to Patent Document 1 and Patent Document 2). However, it is not described that it is effective in preventing and treating calcium deficiency and edema in domestic animals. Among them, the physiological effects of DFA III and DFA IV on ruminants having four stomachs, particularly dairy cows, have not been clarified at all. Furthermore, there is no mention of DFA III, IV not being decomposed in these stomachs, and also being effective in the prevention and / or treatment of calcium deficiency and edema. There is no mention of even ruminants.

Japanese Patent Laid-Open No. 11-43438 JP 2000-204042 A

In view of the present state of the art, the present invention increases the calcium content in milk as food, and restores and maintains the blood calcium concentration after delivery of dairy cows, and also prevents perinatal diseases and milk production. The object of the present invention is to develop a veterinary veterinary medicine and / or feed composition that improves the above.

  The present invention has been made in order to solve the above-mentioned problems, and the present inventors have studied from various directions that, as a result of diligent research, DFA III and DFA IV are different from normal mammals in four types. It has been found for the first time in cattle with a unique digestive system with a stomach that it does not break down despite the complex and unique stomach configuration. As a result of further research based on this new useful knowledge, DFA III and DFA IV increase calcium absorption, increase blood calcium level, and as a result, increase the calcium concentration of milk, It was found for the first time that it had a very useful action of improving the symptoms, and it was confirmed that these actions were performed reliably and reproducible.

  In general, dairy cows have a low risk of blood calcium, especially after delivery, and as a result, they are prone to various diseases, and there is a high risk of lowering productivity. However, productivity has been reduced, and there has been a demand for solutions to the problems peculiar to cattle, especially dairy cows. However, the present invention solves the problems peculiar to these cows. It is the first success. Therefore, the administration of DFA III, IV according to the present invention to cattle, particularly perinatal dairy cows before and after calving, is extremely effective.

Moreover, it discovered newly that the above-mentioned effect peculiar to a cow could be heightened by calcium and vitamin D.

  The present invention has been made on the basis of many new and useful findings, and it has been confirmed for the first time that the above-mentioned novel action is exerted not only on cattle but also on ruminants. Further, as a result of further research, the present invention relates to a ruminant drug containing DFA III and / or DFA IV as an active ingredient, and also relates to a ruminant feed composition.

That is, the embodiment of the present invention is as follows.
(1) A milk production improving agent for a postpartum feed composition , characterized by comprising difructose anhydride III and / or difructose anhydride IV as an active ingredient.
(2) The agent according to (1), wherein the improvement in milk production is an increase in milk yield.
(3) A method for improving milk production of lactating cows after parturition , comprising orally administering an agent comprising difructose anhydride III and / or difructose anhydride IV as an active ingredient to lactating cows after parturition .
(4) The method according to (3) , wherein the milk production improvement is an increase in milk yield.

The use of the pharmaceutical or feed composition for ruminants comprising the DFA III and / or DFA IV of the present invention as an active ingredient increases the calcium content in ruminant milk and reduces hypocalcemia during delivery. This not only improves the disease, but also increases the productivity of milk and reduces perinatal disease.

The change of DFA III and DFA IV content by rumen culture is shown. However, as the change, the difference between the culture broths was not observed, so the average value of both culture broths was used.

  In the present invention, DFA III and / or IV is used as an active ingredient, and calcium and / or vitamin D is also used in combination as desired. DFA III (difructose anhydride III) used as an active ingredient in the present invention is a disaccharide (di-D-fructofuranose-1, 2 ': 2) in which two molecules of fructose are linked by 1, 2' and 2, 3 '. , 3 'dianhydride). DFA III has recently been in industrial production. In addition, DFA IV (difructose anhydride IV) used as an active ingredient is a disaccharide (di-D-fructfuranose-2, 6: 6,2) in which two fructose molecules are bound at 2,6 ′ and 6,2 ′. 'dianhydride). The active ingredients include DFA III and / or DFA IV refined products, crude refined products, intermediate products produced in the manufacturing process, waste products, and processed products (concentrate, pasted product, dried product, diluted product). At least one selected from the group consisting of a product, a suspension, and an emulsion.

  Calcium preparations are all approved for use as feed and food. Specifically, for example, calcium glucuronate, calcium propionate, calcium carbonate, monobasic calcium phosphate, dibasic calcium phosphate, tribasic calcium phosphate, oyster shell, bone powder and the like are exemplified without limitation.

  The vitamin D agent contains vitamin D2, vitamin D3, and precursors thereof, and can be used for the purpose of complementing or enhancing the calcium absorption enhancing effect of DFA III and DFA IV.

  In the present invention, in addition to the above-described active ingredients, extenders such as starch and dextrin, sugars other than the above that enhance palatability and bifido effects, and the like can be mixed as necessary. Examples of the saccharide include molasses, raffinose, melibiose, fructose, lactose, and sucrose.

  According to the present invention, feed compositions (including beverages) and / or veterinary medicines (nutrient enhancing agents, oral administration agents, etc.) are prepared using the above-mentioned active ingredients, in which case DFA III and / or DFA IV When the feed is fed as a feed or a drink, it is 10 mg to 1000 mg, preferably 100 to 300 mg per kg body weight of the animal per day. In the case of a nutrition enhancer or an oral administration agent, the dose is 10 mg to 1000 mg, preferably 100 to 300 mg per kg body weight of the animal, and is preferably fed 1 to 3 times a day. These salary amounts are not limited to the range shown here, and may deviate from this range.

  In addition, DFA III and / or DFA IV used as an active ingredient in the present invention is 0.1 to 2 times or more in weight ratio when fed as feed or beverage with respect to calcium in feed or pharmaceutical composition, Preferably, it is 0.5 to 1.5 times. In addition, in the case of a nutrition enhancer and an oral administration agent, the weight ratio is 0.2 to 3 times or more, preferably 1 to 2 times. However, if a long-term salary or improvement effect on illness is expected, there is no problem even if it deviates from the above range.

  When used as a feed and beverage type composition, the active ingredient (its processed product) can be used as it is or in combination with other feeds or feed ingredients as appropriate. The composition according to the present invention using the present active ingredient can be administered in solid form (powder, granule, tablet), paste form, liquid form, suspension form, and other forms.

  When used as a nutritional enhancer and orally administered type pharmaceutical composition, the active ingredient is administered in various forms. The dosage form may be solid or liquid as a dosage unit so as to contain a certain amount of the active ingredient, for example, powder, powder, tablet, capsule, solvent, suspension and the like. As long as it can be taken orally or parenterally, there are no restrictions on the form. According to the usual method of preparation, excipient, binder, disintegrant, lubricant, sweet potato odorant, solubilizer It is formulated into an orally administered medicine or injection or suppository or other parenteral medicine using adjuvants commonly used in the pharmaceutical technology field of human and veterinary medicine, such as pills, suspensions, coating agents and emulsifiers. .

  The content of the active ingredient is as described above. However, when it is taken for the purpose of prevention or health, the content may be smaller than the above range, and the active ingredient is originally a natural product. Since it is also the origin and there is no problem with safety, even if it is used in a larger amount than the above range, there is no problem. In fact, in a 10-day acute toxicity test using mice, neither DFA III nor IV was found dead even when administered orally at 1000 mg / kg.

  In the present invention, ruminants include not only cattle, but also wild ruminants as well as livestock such as goats, sheep, camels, and buffalos. Ruminants are unique animals that have a unique digestive system that is different from ordinary mammals, such as those that have ruminants, and are often unable to apply common technical knowledge in ordinary mammals. is there.

The present invention is effective in preventing and / or treating calcium deficiency in ruminants. Examples of calcium deficiency include inhibition of calcium absorption, reduction of blood calcium concentration, reduction of milk calcium content, and the like.

As described above, the present invention is effective for strengthening calcium in milk and improving hypocalcemia in lactating animals, and can also treat or prevent a decrease in blood calcium concentration. Therefore, the treatment and prevention of diseases caused by low calcium can be achieved. It is also possible to treat or prevent a decrease in calcium concentration due to labor, and the present invention is very effective particularly for lactating ruminants such as dairy cows.
Examples of the present invention will be described in detail below.

  In ruminants, in order for DFA III and DFA IV to enhance calcium absorption, they must escape the ruminant microorganisms and reach the intestinal tract. Therefore, the degradability of DFA III and DFA IV in the rumen was examined.

  Assuming nutritional management of dry cows, 4 kg of concentrated feed is fed, and Holstein steers equipped with a lumen cannula that feeds hay freely, and dairy cows with a milk yield of 30 kg and a concentrated feed ratio of 55% In each case, the rumen contents were collected and filtered through a quadruple gauze to obtain an inoculum.

  The buffer used was a 0.25M phosphate buffer (6.845 g of KH2PO4 + Na2HPO4 · 12H2O 26.8605 g / 500 ml, pH 7.0), and 1 g of DFA III or DFA IV was added per 100 ml of the buffer.

  To a 200 ml Erlenmeyer flask, 30 ml of inoculum and 20 ml of buffer solution were added, and the air inside was replaced with carbon dioxide gas. Then, the bottle was stoppered with a rubber stopper equipped with a Bunsen valve and cultured in a 39 ° C. incubator. Flasks were collected every 0, 1, 2, 4, 6, 8, 12, and 24 hours of culture and the culture was subjected to analysis.

  The culture broth contained in the flask was stirred, 20 ml was collected, and 0.1 ml of sulfosalicylic acid (20% solution) was added to deproteinize. After centrifugation at 8,000 rpm for 10 minutes, the mixture was filtered through 0.45 μm filter paper, and DFA III and DFA IV were analyzed by liquid chromatography.

  The amount of DFA III and DFA IV added to the culture solution was set to 400 mg / dl. As a result, DFA III and DFA IV were not decomposed when any inoculum was used, and almost all of the DFA III and DFA IV were recovered at each culture time (FIG. 1). It was confirmed that even in dairy cows, DFA III and DFA IV reach the intestinal tract and enhance calcium absorption if they are not degraded by rumen microorganisms.

  The effects of feeding DFA III and DFA IV on calcium metabolism, milk production and urinary excretion in lactating cows were examined.

  9 Holstein dairy cows (2-4, 90-120 days postpartum, average body weight 642kg, average milk yield 36kg) are divided into 3 groups, and 15 days in the first period (10 days in the preliminary period, 5 days in the current period) The test was carried out with a Latin square of x3.

  The daily feed is grass silage, corn silage, and beet pulp with a fixed amount of 3.4 and 2 kg of dry matter, respectively, and the mixed feed (crude protein content 18%, TDN content 74%) The amount was 1/3. Minerals and vitamins were not supplied, and the lack of food intake for each individual was compensated by feeding hay. These feeds had the same content for all cattle, and drinking water was freely consumed.

  The control group had only the above-mentioned salary, the DFA III group was fed with a feed + DFAIII 100 g, and the DFA IV group was fed with a feed + DFA IV 100 g.

  The dairy cows were housed in a metabolic test facility, milked twice at 5 and 17:00, and milk yield and milk components were analyzed for 5 days in this term. As for feces and urine, the whole amount was collected and weighed for 5 days, and a certain ratio was mixed for analysis.

  Table 1 shows the test results. As is clear from the results, there was no significant difference in dry matter intake and calcium intake in each section. Milk production increased about 1 kg in the DFA III and DFA IV groups over the control group. The milk fat rate and milk protein rate did not differ between the sections, but the milk calcium ratio significantly increased in both the DFA III and DFA IV groups compared to the control group (P <0.05). As for calcium excretion, in DFA III and DFA IV, excretion into feces was significantly decreased (P <0.05), and excretion into milk was significantly increased (P <0.05). . As a result, although the digestible amount of calcium was increased by feeding DFA III and DFA IV, there was no effect on the accumulated amount. Although there was no difference in drinking water in each section, urine volume increased significantly in both DFA III and DFA IV sections (P <0.05). In the table, TDN represents the total digestible nutrient amount.

  From the above, it was confirmed that DFA III and DFA IV had an excellent effect on calcium absorption by dairy cows, and also had an effect of increasing the calcium concentration of milk. An increase in urine volume was also confirmed.

  The effect of DFA III and DFA IV on blood calcium levels at delivery in dairy cows was examined.

The test cows used 5 or more Holstein calving cows from 2 or more calves. Immediately after delivery, blood was collected from the ridge, and 300 ml of hot water was orally administered in the control group, and DFA III and DFA IV groups were each orally administered by dissolving 100 g of DFA III and 100 g of DFA IV in 250 ml of hot water. In addition, blood was collected from the ridge 6 and 60 hours later, based on blood collection immediately after delivery.

  Feeding feed after delivery was TMR (hereinafter referred to as mixed feed, rough feed ratio 47.8%) including grass silage, corn silage, and mixed feed, 20 kg per day, 4 kg of mixed feed and hay were freely ingested. Table 2 below shows the contents of feed feed, the required amount, and the filling rate. The calculation conditions for the required amount are as follows: 3 days after parturition, 2 births, body weight 612 kg, milk yield 20 kg, milk fat ratio 4.0%, milk protein ratio 3.2%. NEI indicates net lactation energy, and efNDF indicates an effective neutral detergent insoluble fiber.

  The blood was centrifuged at 3,000 rpm for 10 minutes and the serum portion was stored at −30 ° C. until analysis. The analysis of calcium was performed by the OCPC method. In addition, the degree of edema was determined by palpation. The severity was 4, the moderate was 3, the mild was 2, and the normal was 1. The obtained results are shown in Table 3 and Table 4, respectively.

As is clear from the above results, the blood calcium content immediately after delivery was 7.1 to 7.3 mg / dl in each group. The blood calcium content at 6 hours did not increase in the control group, but increased in the DFA III and DFA IV groups by about 1 mg / dl immediately after delivery, 8.3 mg / dl and 8.0 mg / day, respectively. dl. However, at 60 hours, it was 8.0 mg / dl in DFA III, and no tendency to increase from 6 hours was observed in DFA IV. In none of the wards, cows with milk fever symptoms were found.

    From the above results, it was confirmed that DFA III and DFA IV increase blood calcium concentration immediately after delivery.

  The effects of DFA III and calcium and vitamin D on blood calcium levels during delivery in dairy cows were examined.

  The test cows used 5 or more Holstein calving cows from 2 or more calves. Immediately after delivery, blood was collected from the ridge, and DFA III section was orally administered by dissolving 100 g of DFA III in 250 ml of hot water. In the DFA + Ca group, 100 g of DFA III and calcium carbonate were dissolved in 200 ml of hot water, and in the DFA + Ca + VD group, DFA III and calcium carbonate were added to 100 g of each, and vitamin D10000 IU was dissolved in 200 ml of hot water and administered orally. In addition, blood was collected from the ridge at 6, 24 and 70 hours after blood collection immediately after delivery.

  Feed analysis and blood calcium content analysis were performed in the same manner as in Example 3. The obtained results are shown in Table 5 below.

  As is clear from the above results, the blood calcium concentration immediately after delivery was 6.4 to 7.4 mg / dl, and the DFA + Ca group had the lowest value. The blood calcium concentration at 6 hours increased 1.7 mg / dl in DFA III section 1.2, DFA + Ca section 2.0, and DFA + Ca + VD section compared to immediately after parturition. At 24 hours, although it decreased in the DFA III group and DFA + Ca group than in 6 hours, the DFA + Ca + VD group further increased to reach 9.3 mg / dl considered to be a normal value, and the concentration was maintained even after 70 hours. The blood calcium concentrations at 70 hours in the DFA III group and DFA + Ca group were 8.5 and 9.1 mg / dl, respectively, and an improvement in the recovery level of the DFA + Ca group was observed.

  From the above results, it was confirmed that DFA III can be used in combination with a calcium agent and further combined with vitamin D, rather than administered alone, to enhance its effect.

Claims (4)

A milk production improving agent for a postpartum feed composition for lactating cows , characterized by comprising difructose anhydride III and / or difructose anhydride IV as an active ingredient.   The agent according to claim 1, wherein the improvement in milk production is an increase in milk yield. A method for improving milk production of postpartum lactating cows , comprising orally administering an agent comprising difructose anhydride III and / or difructose anhydride IV as an active ingredient to postpartum lactating cows .   4. The method of claim 3, wherein the milk production improvement is an increase in milk yield.

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