KR20030097164A - An animal fee additive comprising δ-aminolevulinic acid - Google Patents

Abstract

The present invention relates to a livestock feed additive containing deltaaminolevulinic acid. By adding deltaaminolevulinic acid to a conventional livestock feed, it enhances the autoimmunity of the livestock and improves the feed efficiency. Increasing daily weight gain and feed efficiency increase the levels of iron, hemoglobin, erythrocytes and leukocytes in the blood, and effectively prevent and treat diarrhea caused by Escherichia coli, which shows high incidence in weaning pigs. Increasing the flow rate of cows and reducing somatic cells in milk can improve the grade of milk, and when added to poultry feed, improves the survival rate of laying hens and maximizes autoimmunity against various diseases to increase productivity of laying hens. Very effective in livestock and feed industry A.

Description

An animal fee additive comprising δ-aminolevulinic acid

The present invention relates to a livestock feed additive containing deltaaminolevulinic acid. More specifically, the present invention is a livestock feed additive having the effect of improving the metabolism of animals, enhance the autoimmunity and anti-stress effect and feed efficiency by containing delta aminolevulinic acid which is a metabolite of transformed microorganism It is about.

Heme biosynthesis in higher organisms is synthesized by four cytoplasmic enzymes and four mitochodrial enzymes. Synthesis of ALA (5-aminolevulinic acid) is the first limiting step of heme synthesis and condensation of succinylCoA and glycine by ALAS. Progress through. (C4 pathway). Biosynthesis of ALA differs significantly between erythroid cells and non-erythroid cells, especially heme synthesis in non-erythroid cells. It is decided by. In the hepatic gallbladder, about 20% of heme is converted to bile pigment (bilirubin) and about 80% to hemoprotein (Grandchamp et al., 1981). Heme has also been shown to play an important role in intracellular trafficking of thyroperoxidase, which is important for the synthesis of thyroid hormones. About 65% of the heme synthesized in the liver (mon erythroid cell) is used for the synthesis of cytochrome P450 and about 15% is catalase and peroxidase. ), Hemoproteins such as phosphodiesterase, nitric oxide synthase, tryptophan pyrrolase, guanylate cyclase do. Heme-containing proteins play an important role in many life phenomena such as aerobic respiration, energy production, oxidative metabolism, growth and differentiation (Badway et al., 1980; Pinnix IB et al., 1994 ).

The effects of the synthesis of heme in vivo can be largely explained from two perspectives. First, it can be expected to improve the metabolic rate in vivo through the activation of erythroid cells and maturation into RBCs. Through this, the use of feed, the absorption rate and the metabolic rate can be expected to increase the physiological effects such as oxygen transport, metabolism and nutrient transport of the living body can be expected. have. From this, it is possible to keep the livestock in a healthy state overall and improve the disease resistance and growth rate through the activation of metabolism. Similar effects have resulted in the commercialization of heme iron from slaughter blood in order to increase the absorption of iron with general livestock feed and nutritional supplements. Second, the effect of heme on non-erythroid cells due to intracellular uptake of ALA is considered to have a more direct effect on the treatment and prevention of disease (Wagener, et al. , 1997).

The addition of small amounts of antibiotics to animal feed in the 1950s has been reported to improve unit growth and feed efficiency. Antibiotics are commonly used as feed additives, but the mechanism of action of these antibiotics on improving growth and feed conversion costs is not fully understood. Common terms for this class of feed additives are growth promoters, and Virginia mycin, tyrosine, flavomycin, and avoparcin are widely used as growth promoters.

Resistance of pathogenic bacteria to antibiotics is increasing rapidly in both humans and livestock. This makes it difficult to treat humans with bacterial infections and requires the development of a new class of antibiotics. Experts estimate that accelerated resistance to various antibiotics may be responsible for the widespread use of antibiotics in animal feed. Because of this, Sweden has banned the use of all antibiotics as growth promoters in animal feed and Denmark has banned the use of certain antibiotics, such as avoparsin. In other countries, the use of antibiotics in livestock is under pressure from consumer and health care organizations. In order to eliminate these shortcomings, the feed industry has been interested in developing natural products with improved livestock resistance, feed efficiency and growth promoting effects. For example, chitosan, beta glucan and the like are natural feed additives widely used in the livestock industry.

Pig diarrhea caused by Escherichia coli is mainly caused in young pigs, and the incidence rate is high, and once diarrhea is treated, even if treated, it remains as atrophy, and the economic damage to pig farms is very great. E. coli diarrhea occurs mainly through the infection of Escherichia coli. Escherichia coli, which causes diarrhea, is different from non-pathogenic Escherichia coli. Escherichia coli is infected through the oral cavity of pigs, attaches to the small intestine mucosa, proliferates, produces enteric toxins, and changes the osmotic pressure in the intestine, causing diarrhea. Pigs infected with E. coli and diarrhea show dehydration due to loss of water, and in severe cases die. Vaccines are used worldwide to prevent E. coli diarrhea, and this method is still the most widely used. Prevention of E. coli by vaccine is achieved by inoculating a mother pig before delivery, making antibodies to the mother's body, and then delivering the antibody to the piglets through colostrum after delivery. Recently, oral feed additives using dry powder of yolk containing specific antibodies have been reported for the purpose of effective prevention and treatment of Escherichia coli diarrhea causing such diarrhea.

In order to improve the economic feasibility required for price competitiveness and quality improvement of eggs and to improve the quality stability of food hygiene, feed additives having safe functionality in domestic and overseas laying industry are required. In the laying hen industry, livestock is gradually increasing in size, and dense breeding is getting higher in limited space considering economics. For this reason, it is important to improve the feed efficiency and productivity of livestock by means of dense breeding. Poor productivity can be more problematic due to several factors, such as nutritional imbalances, nutritional efficiency imbalances, and breeding conditions such as environmental conditions. In addition, the use of drugs, which are a problem for the food hygiene of consumers, should gradually reduce their use due to residues, and eventually, the development of safe substitutes as foods is necessary.

Instead of administering conventional medicines, these natural materials substitutes enhance natural immunity to improve disease defense and promote maximum absorption along with nutrients from feeds that are consumed, thus reducing the mortality of laying hens. The scattering rate can be improved.

In view of the above, the present inventors have confirmed that deltaaminolevulinic acid improves feed efficiency by promoting autoimmunity by increasing macrophages and increasing iron in blood, and adding the deltaaminolevulinic acid to the feed of weaning piglets. It can increase and increase the daily weight gain and feed efficiency by raising the feed by a certain amount, and effectively prevent and treat diarrhea caused by Escherichia coli, which increases the levels of iron, hemoglobin, erythrocytes and leukocytes in blood and shows high incidence in weaning piglets. After confirming, it is confirmed that the milk feed is increased by increasing the flow rate of cows and reducing the somatic cells in the milk to improve the grade of the milk.In addition, it is added to the poultry feed to improve the survival rate of laying hens and to various diseases. Spawning by maximizing autoimmunity against By the increase of the productivity confirmed and completed the present invention.

Accordingly, it is an object of the present invention to provide a livestock feed additive containing deltaaminolevulinic acid.

The object of the present invention is to confirm that deltaaminolevulinic acid improves feed efficiency by promoting autoimmunity by increasing macrophages and increasing blood iron, and adding the deltaaminolevulinic acid to the feed of weaning pigs by a predetermined amount. By raising the feed per day to increase the daily weight gain and feed efficiency to increase the levels of iron, hemoglobin, red blood cells and leukocytes in the blood and confirmed that it can effectively prevent and treat diarrhea caused by Escherichia coli, which shows a high incidence in weaning pigs. It is confirmed that it increases milk flow rate and decreases somatic cells in milk to improve milk grade by adding to the feed of cows, and improves the survival rate of laying hens and raises the autoimmunity against various diseases by adding to the poultry feed. Increased productivity of laying hens by maximizing Check was achieved by.

Hereinafter, the configuration of the present invention.

1 is a graph showing the proliferation effect of macrophages by adding deltaaminolevulinic acid to the medium of macrophages.

Figure 2 is a graph showing the results of measuring the flow rate of cows after breeding for 4 weeks by adding 10 ppm deltaaminolevulinic acid to the cow's feed.

Figure 3 is a graph showing the results of measuring the flow rate of cows after breeding for 4 weeks by adding 1.0 ppm of deltaaminolevulinic acid to the cow's feed.

Figure 4 is a graph showing the results of measuring the flow rate of cows after breeding for 4 weeks by adding 0.1 ppm of deltaaminolevulinic acid to the cow's feed.

5 is a graph showing the results of measuring somatic changes in milk after 4 weeks of breeding by adding 10 ppm of deltaaminolevulinic acid to cow's feed.

Figure 6 is a graph showing the results of measuring somatic changes in milk after 4 weeks of breeding by adding 1.0 ppm of deltaaminolevulinic acid to cow feed.

Figure 7 is a graph showing the results of measuring somatic changes in milk after 4 weeks of breeding by adding 0.1 ppm of deltaaminolevulinic acid to the cow's feed.

The present invention comprises the steps of adding deltaaminolevulinic acid to the macrophage medium to determine the effect on the macrophage proliferation; Confirming that iron is increased after feeding and feeding deltaaminolevulinic acid to mice; Measuring daily gain and feed efficiency by adding 0.1-10 ppm of deltaaminolevulinic acid to the feed of weaned piglets; Measuring the contents of erythrocytes, leukocytes, lymphocytes, iron and hemoglobin in the blood of weaning piglets by adding 0.1-10 ppm of deltaaminolevulinic acid to the feed of weaning piglets; Measuring the scattering rate by adding 0.1-10 ppm of the deltaaminolevulinic acid to the feed of the poultry; Measuring mortality by adding 0.1-10 ppm of the deltaaminolevulinic acid to the feed of poultry; Measuring the weight of the egg by adding 0.1 to 10 ppm of the deltaaminolevulinic acid to the feed of the poultry; Measuring blue quality and egg quality by adding 0.1-10 ppm of deltaaminolevulinic acid to the feed of poultry; Measuring the flow rate of cows by raising 0.1-10 ppm of the deltaaminolevulinic acid to the cow's feed; It is composed of the step of measuring the somatic changes in milk by raising 0.1-10 ppm of the deltaaminolevulinic acid to the cow's feed.

Deltaaminolevulinic acid of the present invention may be added to the feed in the form of powder, liquid or fermentation product containing deltaaminolevulinic acid.

The following examples are intended to illustrate the present invention in detail, but the following examples are only for illustrating the present invention and are not intended to limit the scope of the invention.

Example 1 Effect of Delta-Aminolevulinic Acid on Macrophage Proliferation

Various effects of deltaaminolevulinic acid (ALA) were added to the medium of macrophage to investigate the effect on the proliferation of macrophages. ALA was added to the cell culture medium at a concentration of 1.0 uM to 0.1 pM, and the number of cells 1 and 3 days after the addition was counted by hematocrit. As a result, all the concentrations of added ALA showed a macrophage proliferation effect compared to the control. This result is considered to be a factor that increases the immunity of the animal by the increase of macrophages by ALA added to the feed.

Example 2 Effect of Delta Amino Acid on Blood Iron Increase

Forty-four week-old mice were acclimated for one week and then bred for two weeks with 0.1, 1.0 and 10 ppm of ALA added to the feed. Blood was collected after breeding and the results of analysis of free iron and total iron in blood are shown in Table 1. As shown in Table 1, it was found that iron iron was significantly increased by the addition of ALA, and this result was confirmed to improve the feed efficiency by accelerating oxygen delivery.

ALA increases blood iron effect Iron type Control 0.1 ppm 1.0 ppm 10 ppm Fe ²⁺ (μg / g) 24 ± 2 29 ± 2 32 ± 3 28 ± 2 Total iron (㎍ / g) 121 ± 13 160 ± 20 164 ± 21 143 ± 17

Example 3: Weight gain and feed efficiency of weaning piglets by feeding of deltaaminolevulinic acid

Each control and test were divided into 140 heads of 20 weaning pigs on the 20th day of life, and ALA was added in 0.1, 1.0, 2, and 10 ppm of feed. Table 3 shows the results of daily weight gain, daily feed intake, and feed efficiency of each test plot during breeding. As shown in Table 3, the weight gain and feed intake increased by the addition of ALA. These results demonstrate that ALA has the effect of enhancing the growth of weaning piglets when used as feed additive.

Until 10 days of breeding, the weight gain was slightly lower than that of antibiotics, but the feed intake and feed efficiency were higher than those of antibiotics, and the weight gain was significantly increased by adding ALA to the conventional diets. It was. These results suggest that the combination of antibiotics and ALA increases the function of antibiotics as growth promoters.

The daily weight gain, daily feed intake and feed efficiency were higher than those of the antibiotic treatment group after 20 days of ALA treatment. Especially, the antibiotic growth rate was higher by simultaneously treating antibiotics and ALA.

Weight gain and feed efficiency of weaning pigs by ALA Processing period Item Control ALA0.1 ppm ALA1 ppm ALA2 ppm ALA10 ppm ALA + Antibiotics Antibiotic-free group Antibiotic treatment group ^a) 0-10 days Integral weight gain (g) 140 220 165 182 170 175 253 Daily feed intake (g) 258 329 284 325 295 304 344 Feed efficiency 0.54 0.67 0.55 0.56 0.58 0.58 0.74 10-20 days Integral weight gain (g) 249 268 278 313 342 340 374 Daily feed intake (g) 378 403 385 418 411 415 421 Feed efficiency 0.66 0.67 0.68 0.75 0.83 0.82 0.89

A) Addition of apramycin + oxyetetracycline (100 g / ton)

Example 4 Changes in the Content of Weaned Piglets in Blood by Feeding Deltaaminolevulinic Acid

In the same experiment as in Example 3, blood was collected after feeding ALA to weaning pigs for 20 days, and then red blood cells (HCT; hematocrit), red blood cells (RBC; red blood cells), white blood cells (WBC; white blood cells) and lymphocytes ( lymphocytes) are shown in Table 3. HCT, RBC and WBC were slightly increased and lymphocytes were significantly increased by ALA addition.

Changes in the Blood Content of Weaning Piglets by ALA Feeding Item Control ALA0.1 ppm ALA1 ppm ALA2 ppm ALA10 ppm ALA + Antibiotic Treatment ^a SE Antibiotic-free group Antibiotic treatment group ^a) HCT (%) 29.75 ^c 30.85 ^b 30.21 32.09 ^ab 32.29 ^a 32.45 32.60 ^a 0.61 RBC (× 10 ⁶ / min) 5.17 ^b 5.44 ^ab 5.24 5.33 ^ab 5.52 ^a 5.54 5.60 ^a 0.08 WBC (× 10 ³ / min) 21.15 ^b 22.98 ^ab 22.14 22.94 ^ab 23.34 ^a 23.65 23.67 ^a 0.84 Lymphocyte (%) 47.61 ^b 50.71 ^ab 52.35 58.35 ^ab 58.34 ^a 58.95 58.64 ^a 2.45

A) Addition of apramycin + oxyetetracycline (100 g / ton)

Example 5 Change in the Content of Weaned Piglets in Blood by Feeding Deltaaminolevulinic Acid

In the same experiment as Example 3, ALA was fed to the weaning pigs for 20 days, and then blood was collected to analyze total protein, iron, total iron-binding capacity (TIBC) and hemoglobin. One result is shown in Table 4. The addition of ALA slightly increased HCT, RBC and WBC, and the lymphocytes were significantly increased.

Changes in Serum Proteins, Iron and Hemoglobin in Weaning Piglets by ALA Feeding Item Control ALA0.1 ppm ALA1.0 ppm ALA2 ppm ALA10 ppm PE-1 + Antibiotic Treatment ^a SE Antibiotic-free group Antibiotic treatment group ^a) Total protein (g / dL) 5.24 ^b 5.36 ^b 5.48 5.84 ^ab 6.04 ^a 6.12 6.28 ^a 0.21 Iron (µg / dL) 66.25 ^c 75.21 ^b 72.5 83.74 ^a 84.23 ^a 84.20 86.23 ^a 4.15 TIBC (μg / dL) 503.30 ^a 508.00 ^c 505.40 527.25 ^b 547.85 ^ab 546.40 566.61 ^a 8.75 Hb (g / dL) 8.60 ^b 8.86 ^b 8.80 9.06 ^ab 9.67 ^a 9.60 9.40 ^a 0.14

A) Addition of apramycin + oxyetetracycline (100 g / ton)

Example 6 Comparison of Scattering Rate by Feeding Deltaaminolevulinic Acid

Scattering rate was measured by adding 10,000 concentrations of laying hens in a poultry farm in Gyeonggi-do. Table 5 shows the results of the scattering rates measured from June to September 2001. As shown in Table 5, the addition of ALA to the feed was shown to improve egg production.

Comparison of scattering rate by ALA feeding term Control ALA 0.1 ppm ALA 1.0 ppm ALA 10 ppm Marisu Scattering Count Marisu Scattering Count Marisu Scattering Count Marisu Scattering Count June 180 138.5 173 137.6 181 146.5 174 144.7 In July 172 133.3 165 136.4 160 137.8 164 142.9 August 165 120.8 162 132.8 150 128.2 160 138.5 September 165 119.8 160 133.2 152 126.4 154 129.4 Average 128.1 135.2 134.7 138.9

Example 7 Comparison of Mortality by Feeding Deltaaminolevulinic Acid

The mortality of laying hens was measured by adding 10,000, 000, and 10 ppm of ALA to the feed at a weight ratio of feed. Table 6 shows the mortality rates of laying hens from June to September 2001. As shown in Table 6, the mortality of laying hens was significantly reduced by adding ALA to the feed, which may be due to the immune enhancing effect of laying hens.

Mortality comparison by ALA feeding term Control ALA addition port 0.1 ppm 1.0 ppm 10 ppm June 0.49 0.47 0.41 0.41 In July 0.47 0.42 0.38 0.36 August 0.72 0.46 0.43 0.40 September 0.71 0.61 0.52 0.48 Average 0.60 0.49 0.43 0.41

Example 8 Comparison of Weight of Eggs by Feeding Deltaaminolevulinic Acid

Amount of 1.0 ppm of ALA was added to the feed with respect to 10,000 laying hens, and 50 eggs were randomly selected while laying the hens. Table 7 shows the results of measuring the weight of the columns from June to September 2001. As shown in Table 7, the weight of eggs increased by 4.8-6.7% by adding ALA to the feed.

Weight comparison of eggs by ALA salary term Control 1.0 ppm ALA addition % Increase Marisu Egg weight (g) Marisu Egg weight (g) June 181 83 181 89 6.7 In July 172 79 160 83 4.8 August 165 74 150 78 5.1 September 165 74 152 78 5.1 Average 78 82 5.4

Example 9 Comparison of Egg Quality by Feeding Deltaaminolevulinic Acid

1.0 ppm of ALA was added to the feed at a weight ratio of 10,000 laying hens, and ten eggs were randomly selected while raising the laying hens. Table 8 shows the results of measuring the quality of the eggs from June to September 2001. As shown in Table 8, the addition of ALA to feed reduced egg yield significantly, which could be interpreted as a result of improving the commerciality by suppressing the egg blue during transportation or storage.

Comparison of Egg Quality by ALA Salary term Control 1.0 ppm ALA addition Blue ratio (%) Hough unit Blue ratio (%) Hough unit 1 week 2.2 61.1 1.7 66.6 2 weeks 2.3 60.3 1.6 63.7 3 weeks 2.5 61.2 1.6 67.5 4 Weeks 2.5 62.4 1.5 70.2 Average 2.6 61.3 1.6 67.0

Example 10 Changes in Milk Flow Rate due to Feeding Deltaaminolevulinic Acid

The flow rate was measured after the feed was added to the feed at a concentration of 0.1, 1.0 and 10 ppm by weight of cows feed. FIG. 2 shows the results of four weeks of breeding with 10 ppm ALA for feed, 1.0 ppm ALA for feed and 0.1 ppm ALA for feed.

Example 11 Changes of Somatic Cells in Milk by Feeding Deltaaminolevulinic Acid

The somatic cell count in milk was measured after adding to the feed at a concentration of 0.1, 1.0 and 10 ppm by weight of cow's feed. FIG. 5 shows the results of four weeks of breeding by adding 10 ppm ALA for feed, 1.0 ppm ALA for feed, and 0.1 ppm ALA for feed.

As described above, the animal feed additive containing deltaaminolevulinic acid of the present invention improves the metabolism of livestock and enhances autoimmunity and antistress effect, thereby increasing the feed efficiency of cows and increasing the flow rate. It improves the grade of milk by reducing somatic cells in milk, improves the survival rate of laying hens, maximizes autoimmunity against various diseases, not only increases productivity of laying hens, but also increases daily weight and feed efficiency of weaning piglets. Since iron, hemoglobin, erythrocytes and leukocytes are increased and effective in preventing and treating diarrhea caused by Escherichia coli, which shows a high incidence in weaning pigs, it is a very useful invention for livestock and feed industry.

Claims (2)

Animal feed additive, characterized in that it contains 0.1 to 10 ppm (w / w) of deltaaminolevulinic acid based on 100 of the total feed. The animal feed additive according to claim 1, wherein the deltaaminolevulinic acid is in the form of powder, liquid or fermentation product containing deltaaminolevulinic acid.