JPH08245396A - Agent for anticholesterol - Google Patents

Abstract

PURPOSE: To obtain an agent for anticholesterol of mammal and poultry excluding Primates and Rodentia, containing salts of L-ascorbic acid-2-phosphoric acid ester as active ingredients and stable in feeds and drinking water. CONSTITUTION: This agent-contains salts such as sodium, potassium, calcium or magnesium of L-ascorbic acid-2-phosphoric acid ester as active ingredients. The effective dose of the compound is 0.01-0.5mmmol based on 1kg feed or 1l drinking water so as to prevent breakage of egg shell of poultry and improve egg quality and 0.003-0.03mmmol/day based on 1kg weight of poultry in the case of anticholesterol agents for animals or health medicines.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an anticholesterol drug for mammals and poultry other than primates and rodents, which contains a salt of L-ascorbic acid-2-phosphate ester as an active ingredient. It is about.

[0002]

2. Description of the Related Art Damage caused by breakage of eggshells has reached 5% or more of production in the egg industry. On the other hand, L
-Ascorbic acid has the effect of preventing damage due to increased thickness of eggshells in poultry, improving egg production, egg weight, etc.,
C. F. Nockels and others [Poultry Science 5
2, 1862-1867 (1973)] and many other results have been reported. However, ascorbic acid is extremely unstable and is particularly unstable in an aqueous solution, and is easily oxidized by metals such as copper contained in the feed, and in the above report, L-ascorbic acid in the feed was 1300 ppm. Even if the above ingredients are added, the purpose of preventing damage to eggshell of chicken eggs cannot be achieved.

Further, since excessive cholesterol intake from food may contribute to hyperlipidemia in animals and humans, control of cholesterol in livestock has been an important issue for livestock production. Therefore, many cholesterol control techniques have been studied.

For example, an example of reducing the cholesterol content of poultry meat by heat treatment [Sharma et al., J. Food
Sci. Technol. , 19 , 5, 212 to 2
14 (1982)], an attempt to suppress cholesterol deposition in beef by donating unsaturated fatty acids to cattle [Weiyangt et al., J. Am. Food Sci. , 41 , 6, 14
21-1425 (1976)], a report that feeding grass to cows reduces the amount of cholesterol in the bone marrow compared to feeding cereals [Kunsman et al., J. Chem. Food S
ci. , 46 , 6,1785-1786 (198
1)], an attempt to suppress cholesterol content by controlling feeding of young pigs [J. Nutr. 115 ,
8, 1016 to 1024 (1985)], an example in which pigs are fed with a diet rich in minerals to produce cholesterol with suppressed cholesterol content [Nikkei Keizai Shimbun, January 30, 1986, 5th].
Page] etc. For pets such as dogs and cats, in recent years, hypercholesterolemia, which is thought to be due to overnutrition, is considered to be the cause of dog-cat disease, and at the same time, the physiological metabolism of dogs and cats also serves as a model for human diseases. Much research has been done on cholesterol metabolism and methods of lowering it. For example, when dogs were fed with eggs as a substitute for soybean protein, cholesterol in the blood significantly increased, and in particular, HDL cholesterol increased (Nutr Rep I).
nat, 301, 163-170, 1984). Also,
An example of intramuscular injection of adrenaline in dogs that reduces blood cholesterol (Kyoto Prefectural University Academic Report, 34, 31-3)
6, 1983) and the like have been reported. However, these conventional techniques have a problem that an expensive drug has to be administered, and there is a problem that the cholesterol content in meat of livestock animals cannot be stably and sufficiently reduced because of a large variation.

[0005]

In view of the above circumstances, the present inventors have conducted extensive research into veterinary drugs that are stable and prevent damage to the eggshell with a small amount, and as a result, L-ascorbic acid-2 was obtained.
-It is extremely stable even when salts of phosphates such as sodium, potassium, calcium and magnesium salts are added to poultry feed or drinking water, and feed 1k
addition of 0.01 to 0.5 mmol per liter of drinking water to prevent damage to the eggshells of poultry, and to show sufficient effects for improving egg production such as increase in egg production and egg white protein. In addition, the present invention was completed, recognizing that the compound in the present invention is also effective as an anticholesterol agent or a health drug for animals including poultry, and completed the present invention.

[0006] That is, the present invention provides a veterinary drug which is extremely stable in feed or drinking water and has an anti-cholesterol action having ascorbic acid activity.
In the present invention, the term “animal” refers to an animal targeted by veterinary drugs, that is, domestic animals, poultry and other so-called useful animals, which are targeted for poultry and anticholesterol agents. Further, the subject animals of this invention are limited to mammals and poultry except primates and rodents.

As mentioned above, the effective dose of the compound is to prevent damage to eggshells of poultry and to improve egg quality.
The active ingredient of the present invention is added in an amount of 0.
In the case of an anticholesterol agent or a health drug for animals, it is sufficient to administer 0.003 to 0.03 mmol / day / kg body weight of poultry. As an administration method, an active ingredient can be mixed with talc, a surfactant and the like to prepare a compounding agent once and then added to feed and drinking water, or it can be administered as an injection. It can also be used in combination with other antibacterial agents for animals, antiprotozoal agents, antihistamine agents, and antiphlogistic agents.

[0008]

The present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Example 1 (Anti-cholesterol effect on pigs) In order to confirm the anti-cholesterol effect of salts of L-ascorbic acid-2-phosphate ester on pigs, the following experiment was conducted to confirm the effect. 20 + 20 23-day-old boars of Landrace x Yorkshire breed (L-ascorbic acid-2-phosphate sodium salt-added group + non-added group) were used in total of 40 heads. The pigs were bred with the same commercial feed containing no added vitamin C until 23 days of age excluding the lactation period and the weaning period.

The L-ascorbic acid-2-phosphate sodium salt, which is the active ingredient of the present invention, is administered by adding it to the feed, avoiding injections, etc., in order to ensure that it is taken up without giving extra stress to the animal. However, the trace amount of sodium L-ascorbic acid-2-phosphate was added to the feed by the following commonly used trace additive administration method so as to mix uniformly. L-ascorbine in corn 75% (below% by weight), soybean flour (CP 45%) 20%, calcium phosphate 1.5%, and a proper amount of inorganic mixture, yeast, comprehensive vitamin mixture excluding ascorbic acid, and antibiotic mixture. Acid 1-phosphate sodium salt 1% was added and sufficiently stirred, and heat-molded by a normal pelletizer machine, and dried to obtain a high-concentration L-ascorbic acid-2-phosphate sodium salt-containing feed. did.

Separately from this, sodium L-ascorbic acid-2-phosphate is not contained, but normal L-
Sodium ascorbate at about 0.5 molar concentration
% Feed was prepared with the same composition as above. That is, 75% corn (% is the weight percentage below), soybean flour (CP45
%) 20%, calcium phosphate 1.5%, sodium L-ascorbate 0.5% and an appropriate amount of an inorganic substance mixture, yeast, a comprehensive vitamin mixture excluding ascorbic acid, an antibiotic mixture, and a well-stirred one It was heat-molded with a pelletizer machine and dried to obtain an additive-free general feed. The feed was heat-formed and dried to improve the feed efficiency, reduce bacteria in the feed, and reduce dust in the barn. The condition was the maximum temperature of the product in the pelletizer, about 7 degrees Celsius.
The temperature was 0 ° C., and the drying condition was 50 ° C. for 20 minutes, and then left at room temperature.

[0012] The test section, the test section, weight 1k per day
The above-mentioned high-concentration L-ascorbic acid-2-phosphate sodium salt-containing feed was orally administered once daily every morning so that about 0.02 mmol of L-ascorbic acid-2-phosphate sodium salt was orally administered per g. Was added. Body weight is measured once a week and high concentration L-ascorbic acid-
The addition amount of the sodium 2-phosphate ester-containing feed was adjusted. On the other hand, the control group was raised only with the above-mentioned non-additive general feed. 60 days after the start of the test, blood was collected from each pig and glucose, protein content, creatinine, GPT, GOT, L in the blood were maintained.
DH and total cholesterol were measured by a usual biochemical analysis method. As a result, the average value of total cholesterol in blood of pigs administered with L-ascorbic acid-2-phosphate sodium salt was significantly lower than that of the control group by 25% on average. Further, the average value of LDH was significantly lower than that of the control group by 27% on average. No significant difference was observed in other measurement items. As a result, it was confirmed that the administration of L-ascorbic acid-2-phosphate magnesium salt has an anticholesterol effect on pigs having L-ascorbic acid synthesizing ability. It had no effect.

Example 2 (Anti-cholesterol effect on cattle) In order to confirm the anti-cholesterol effect of the salts of L-ascorbic acid-2-phosphate ester on cattle, the following experiment was conducted to confirm the effect. 25 + 25 Holstein 53 day old bulls
A total of 40 heads (L-ascorbic acid-2-phosphate calcium addition group + non-addition group) were used. As this cow, a cow that had been bred with the same commercial feed containing no vitamin C added until 53 days of age except the lactation period and the weaning period was used.

The L-ascorbic acid-2-phosphate calcium, which is the active ingredient of the present invention, is administered by adding it to the feed, avoiding injections, etc., in order to ensure that it is taken up without giving extra stress to cattle. Although a little L
-The calcium ascorbate-2-phosphate was added to the feed by the following commonly used trace additive administration method so that calcium ascorbic acid-2-phosphate was uniformly mixed. 30% bran (% by weight below), 20% barley flour, 44% rice bran, 5 soybean meal
%, Salt 0.5%, and a proper amount of inorganic substance mixture and a total vitamin mixture excluding ascorbic acid, 1% of L-ascorbic acid-2-phosphate calcium, and sufficiently stirred, a normal pelleter machine Was heat-molded and dried to obtain a high-concentration L-ascorbic acid-2-phosphate calcium-containing feed.

Separately from this, a feed containing no ordinary calcium L-ascorbate-2-phosphate and containing normal calcium L-ascorbate was prepared with the same composition as described above. That is, 30% bran (% by weight below), 20% barley flour, 44% rice bran, 5% soybean meal, 0.5% salt,
L-calcium ascorbate 0.5%, inorganic sodium phosphate 0.25% and an appropriate amount of inorganic mixture, a comprehensive vitamin mixture excluding ascorbic acid were added and well stirred, and then heat-molded by a normal pelletizer machine. Was dried to obtain L-ascorbic acid-2-phosphate calcium-free general feed. The feed was heat-molded and dried to improve the feed efficiency and to reduce various bacteria in the feed. The condition was that the maximum temperature of the product in the pelleter was about 75 degrees Celsius and the drying condition was 50 degrees. After performing minutes, it was left in a room temperature environment.

[0016] The test section, the test section, weight 1k per day
The above high-concentration L-ascorbic acid-2-phosphate calcium-containing feed was orally administered once daily every morning so that approximately 0.02 mmol of L-ascorbic acid-2-phosphate calcium per g was orally administered. Was added. Body weight is measured once a week and high concentration L-ascorbic acid-
The addition amount of the feed containing calcium 2-phosphate was adjusted. On the other hand, the control group was bred only with the above L-ascorbic acid-2-phosphate calcium-free feed. 90 days from the start of the test after breeding for 90 days in this state
After each day, blood was collected from each cow and the total cholesterol in the blood was measured by the usual enzyme method. As a result, the value of total cholesterol in the blood of cattle fed with a feed containing L-ascorbic acid-2-phosphate calcium potassium salt was 17 compared with that of the control group on average.
% Was significantly lower. As a result, L-ascorbic acid-2-
It has been confirmed that calcium phosphate potassium phosphate has an anticholesterol effect on cattle, but normal L-
Calcium ascorbate had no effect.

Example 3 (Test of anticholesterol effect of salts of L-ascorbic acid-2-phosphate ester) In order to confirm the anticholesterol effect of salts of L-ascorbic acid-2-phosphate ester on dogs, An experiment was conducted to confirm the effect.
Purebred Beagle dogs with an average weight of 8.71 kg, 6 females and 6 males
A total of 12 heads, 3 males and 3 females, were divided into 2 groups, a test group and a control group (1 group 3 males and 3 females).
0.02 mmol of L-ascorbic acid-2-phosphate magnesium ester was orally administered per kg, and the control group was fed without receiving L-ascorbic acid-2-phosphate magnesium salt. The feed is L-ascorbic acid,
A test feed for dogs in which L-ascorbic acid-2-phosphate magnesium and L-ascorbic acid derivatives were not detected was used.

Twelve weeks after the start date of the test (the start date of L-ascorbic acid-2-phosphate magnesium ester administration), blood was collected from each dog and glucose, protein content, creatinine, GPT, GOT, LDH in the blood, Total cholesterol was measured by conventional biochemical analysis methods. As a result, the average value of total cholesterol in blood of dogs to which L-ascorbic acid-2-phosphate magnesium salt was administered was significantly lower than that of the control group by 17% on average. Further, the average value of LDH was significantly lower by 23% than that of the control group. No significant difference was observed in other measurement items. As a result, L-ascorbic acid-
It was confirmed that administration of 2-phosphate magnesium salt has an anticholesterol effect on dogs having L-ascorbic acid synthesizing ability.

Example 4 (Test for anticholesterol effect of salts of L-ascorbic acid-2-phosphate ester) In order to confirm the anticholesterol effect of salts of L-ascorbic acid-2-phosphate ester on dogs, An experiment was conducted to confirm the effect.
A physiological saline solution containing 0.5% by weight of sodium L-ascorbic acid-2-phosphate was sterilized by autoclaving at 121 degrees Celsius and filtered through a membrane filter having a hole diameter of 0.45 micrometer to obtain the animal of the present invention. For injection. In addition, ascorbic acid was used as a control drug.
A physiological saline solution containing 23% and 0.11% of inorganic sodium phosphate was autoclaved at 121 degrees Celsius and filtered through a membrane filter having a hole diameter of 0.45 micrometer to prepare a solution. Two-month-old purebred beagle dogs, 8 females and 8 males, totaling 16 males and 4 males and 4 males were divided into 2 groups, a test group and a control group (4 males in 1 group, 4 females). L-ascorbic acid-2-kg / kg body weight daily
The above-mentioned injection solution of the present invention containing sodium L-ascorbic acid-2-phosphate corresponding to 0.002 mmol of sodium phosphate was intravenously injected, and the same amount of the above-mentioned control was added to the control group. The drug was intravenously injected once a day for 12 weeks. As the breeding feed during the test period, a normal breeding feed for dogs in which L-ascorbic acid, magnesium L-ascorbic acid-2-phosphate, and derivatives of L-ascorbic acid were not detected was used.

Twelve weeks after the start date of the test (the start date of intravenous injection of sodium L-ascorbate-2-phosphate ester), blood was collected from each dog and glucose, protein content, creatinine, GPT, GOT, LDH in the blood were collected. , Total cholesterol was measured by a conventional biochemical analysis method. As a result, the average value of total cholesterol in the blood of dogs to which L-ascorbic acid-2-phosphate sodium salt was administered was significantly lower than that of the control group by 25% on average. Further, the average value of LDH was significantly lower by 23% than that of the control group. No significant difference was observed in other measurement items. As a result, L-ascorbic acid-
It was confirmed that administration of 2-phosphate sodium salt has an anticholesterol effect on dogs having L-ascorbic acid synthesizing ability.

Example 5 (Anti-cholesterol effect on cats) In order to confirm the anti-cholesterol effect of salts of L-ascorbic acid-2-phosphate ester on cats, the following experiment was conducted to confirm the effect. A total of 24 12 + 12 63-day-old female cats (L-ascorbic acid-2-phosphate calcium-added group + non-added group) were used. This cat was bred with the same commercial feed without the addition of vitamin Cs until 63 days of age excluding the lactation period. As a test drug, 100 g of L-ascorbic acid-2-phosphate calcium, 400 g of dried sardine powder, 100 g of corn starch, 1 hydroxypropyl cellulose
A mixture containing 00 g and an appropriate amount of water was thoroughly stirred, and this raw material was tabletted into tablets of 700 mg each with a conventional heating tableting machine, and this was used as a test drug containing L-ascorbic acid-2-phosphate calcium salt. did. As a control drug, a mixture containing 43 g of L-ascorbic acid, 20 g of inorganic calcium phosphate, 400 g of dried powder, 100 g of corn starch, 100 g of hydroxypropyl cellulose, and an appropriate amount of water was stirred well, and one tablet of this raw material was mixed with a conventional heating tablet machine.
Tablets of 00 mg were compressed with L-ascorbic acid-2.
-It was a control drug containing no calcium phosphate.

[0022] The test section has a weight of 1k per day in the test section.
The test drug corresponding to 0.02 mmol of L-ascorbic acid-2-phosphate calcium per gram was orally administered with food, and L-ascorbic acid-2 was added to the control group.
-A control tablet containing no calcium phosphate was given in the same amount as in the test group and bred for 90 days. The feed during the test period was fed with a commercial feed without addition of vitamin C for 90 days, and after the test, blood was collected from each cat and the total cholesterol in the blood was measured by the usual enzyme method. As a result, the value of total cholesterol in blood of cats fed with the feed containing L-ascorbic acid-2-phosphate calcium salt was significantly lower than that of the control group by 13% on average. As a result, it was confirmed that L-ascorbic acid-2-phosphate calcium salt had an anticholesterol effect on cats, but normal L-ascorbic acid had no effect.

Example 6 (Anti-cholesterol effect on chickens) In order to confirm the anti-cholesterol effect of salts of L-ascorbic acid-2-phosphate ester on broilers, the following experiment was conducted to confirm the effect. 30 male 7-day-old broilers
5 birds (L-ascorbic acid-2-phosphate magnesium ester addition group + non-addition group) were divided into 2 groups and used. This broiler was bred by the same diet for commercial chicks containing no vitamin C until 7 days of age.

[0024] The test section has a weight of 100 per day in the test section.
About 0.020 millimoles of L-ascorbic acid-2-phosphate magnesium per 0 g was orally administered to drinking water, and normal L-ascorbic acid was given to the control group without giving sodium L-ascorbic acid-2-phosphate. The same molar amount of drinking water was administered. The dose was determined by measuring the body weight of the chicken once a week and calculating the average value thereof. As for the administration method, the dose of L-ascorbic acid per day was dissolved in the water tank for administration (18 liters) for administration in the test group and the control group once a day for drinking water. During the test period, the animals were bred for 60 days with normal commercial feed, and after the test, 30 roosters were collected from each plot, a total of 60 blood samples were taken to collect blood glucose,
The protein content, creatinine and total cholesterol were measured by the usual biochemical analysis methods. Also, after blood collection, this chicken was dissected to measure the intraperitoneal fat weight. As a result, the total cholesterol in the blood of broilers administered with L-ascorbic acid-2-phosphate magnesium salt was 13% lower on average than that of the control group. In addition, the average intraperitoneal fat weight was 21% lower on average in the broilers administered with L-ascorbic acid-2-phosphate magnesium salt than in the control group. No significant difference was observed in other measurement items. As a result, L-ascorbic acid-2-
It was confirmed that the administration of phosphate magnesium salt has an anticholesterol effect and an abdominal fat weight reducing effect on chickens capable of synthesizing L-ascorbic acid, but ordinary L-ascorbic acid has no effect. It was

Reference Example 1 400 females of the 50-week-old White Leghorn breed were divided into 4 groups of 100 each, and each group was fed with the basic feed 1k shown in Table 1.
With respect to g, 0.1 mmol of L-ascorbic acid, the compound of the present invention, L-ascorbic acid-2-phosphate magnesium salt, and L-ascorbic acid-2-phosphate calcium salt were each added to L-ascorbic acid. The diet was prepared by adding 0.1 mmol in terms of acid. All the added substances were added to the basic feed 50 days before the start of feeding and stored at room temperature. However, the minerals are vitamin A: 440I. U. , Vitamin D: 501I. U. , Riboflavin: 0.22 mg, pantothenic acid: 0.46 m
g, pyridoxine: 0.29 mg, folic acid: 0.024 m
It was set to g. Collect all the eggs laid on the 50th day of feeding,
The thickness of the eggshell was measured, and the average value for each plot was calculated and shown in Table 2.

[0026]

[Table 1]

[0027]

[Table 2]

As is clear from Table 2, in the group to which the compound of the present invention was added, the thickness of the eggshell was increased by 10% or more compared to the untreated group, and was superior to the L-ascorbic acid-added group.

Reference Example 2 L-ascorbic acid-2-phosphate magnesium salt was added to 1 liter of tap water at a ratio of 0.1 mmol (3
7.9 ppm) to give poultry as drinking water.

Example 7 L-ascorbic acid-2-phosphate magnesium ester was dissolved in physiological saline to a concentration of 10% and then filled in a vial bottle. When using it, dilute it with sterile water,
The animals are injected at a dose of 0.02 mmol / kg body weight.

[0031]

[Effects of the Invention] A drug containing a salt of L-ascorbic acid-2-phosphate as an active ingredient is a cholesterol-lowering agent for poultry and mammals except primates and rodents.
Has a suppressing effect.

Claims (1)

[Claims] 1. An anticholesterol drug for mammals and poultry other than primates and rodents, which contains a salt of L-ascorbic acid-2-phosphate ester as an active ingredient.