KR100428702B1 - Feed additive compositions for animals comprising polyethoxylated alpha tocopherol ester derivatives - Google Patents

Abstract

The present invention relates to a feed additive composition for animals containing a polyethoxylated alpha tocopherol ester derivative of the formula (1) as an active ingredient:

[Formula 1]

Where

R is CH ₃ OCH ₂ CH ₂ (OCH ₂ CH ₂ ) n, where n is an integer from 2 to 400.

When feeding the animal feed additive composition of the present invention to livestock, it is possible to maximize the effect of the meat improver, weight gain effect and feed requirements, it can be used as a source of vitamin E in all feeds.

Description

Feed additive compositions for animals comprising polyethoxylated alpha tocopherol ester derivatives

The present invention relates to a feed additive composition for animals containing a polyethoxylated alpha tocopherol ester derivative of the following formula 1 and a method for preparing the same:

Where

R is CH ₃ OCH ₂ CH ₂ (OCH ₂ CH ₂ ) n, where n is an integer from 2 to 400.

Vitamin E (DL-alpha-tocopherol) represented by the following Chemical Formula 2 is widely used as an antioxidant in living organisms, and recently, the field of clinical application is expanding, and the demand for this is increasing:

Vitamin E is a compound having a hydroxy group in the benzene ring, which is physically insoluble in water, and because vitamin E itself is generally oxidized, it is not only chemically unstable but also an oxidation product of tocopherol quinone. Does not have the biological activity of vitamin E. Therefore, in order to prevent the oxidation of vitamin E is converted to more stabilized derivatives, such derivatives include tocopherol acetate, palmitate tocopherol, succinate tocopherol and the like. They have advantages of storage and transport because of their relatively high stability compared to vitamin E itself, and are effective for the manufacture of substitutes for vitamin E because of their acceptable stability for pharmacological purposes.

In addition, in the case of oral administration, the vitamin E ester compounds described above are completely hydrolyzed upon contact with pancreatic enzymes and intestinal enzymes when absorbed through the intestinal tract in vivo, and are absorbed in vivo in the form of tocopherols.

For this reason, vitamin E substitutes are widely used in all feedstocks, and tocopherol acetate is widely used as a source of vitamin E in pig feed, and it is widely known that it is effective as a meat improver of pork.

In order to be used as an animal feed additive for supplying vitamin E, the active compounds must be prepared in a liquid phase by dissolving in water or an organic solvent and diluting them, or by adsorbing to a solid excipient that can be used as a feed additive. . However, since the physical properties of the above active compounds are viscous liquids, they cannot be used by themselves in the feed manufacturing process to which a small amount is added, or they are difficult to use.

Accordingly, the inventors have found that the polyethoxylated alpha tocopherol ester derivatives used in the present invention have high solubility in water, are not oxidized well, are chemically stable, and are useful as a source of vitamin E. Focusing on the development of the animal feed additive composition to complete the present invention.

Accordingly, it is an object of the present invention to provide an animal feed additive composition comprising the derivative of Formula 1.

Another object of the present invention is to provide a method for preparing the animal feed additive composition for obtaining a solid or liquid formulation by dissolving or adsorbing the derivative of Formula 1 as an active ingredient in an excipient.

Animal feed additive composition of the present invention contains a polyethoxylated alpha tocopherol ester derivative of the formula (1) as an active ingredient:

[Formula 1]

Where

R is CH ₃ OCH ₂ CH ₂ (OCH ₂ CH ₂ ) n, where n is an integer from 2 to 400.

Preferred groups in the compound of Formula 1 are those having a group of R where n is an integer from 2 to 50.

Animal feed additive composition according to the invention can be formulated in the form of a solid or liquid by dissolving or adsorbing the derivative of Formula 1 in the excipient.

Excipients used for formulation include adsorbents, inorganic or organic media or vegetable oils. Adsorbents include zeosil, sugar, cellulose, powdered milk, bone meal, coarse flour, corncob, starch or skim steel. Inorganic or organic media also include water or ethanol, sodium chloride, calcium carbonate, bicarbonate, aluminum oxide, silica, alumina, precipitated or colloidal silicon dioxide or phosphate used as solvent. Soybean oil, castor oil, cottonseed oil, palm oil etc. are mentioned as vegetable oil.

Referring to the preparation of specific polyethoxylated alpha tocopherol ester derivatives are as follows. Liquid formulations include DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 6) -ethanol / water; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -ethanol / water; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -ethanol / water solution; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate in solid form (n = 6) -corn cob; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -corn cob; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -corn cob; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 6) -degreasing steel; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -degreasing steel; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -degreasing steel.

The preparations according to the invention are suitable for animal feed additives for the supply of vitamin E, and are particularly preferred as feed additives for livestock and fish feed additives.

Preparation of the formulation of the alpha-tocopherol ester derivative of formula (1) is preferably carried out by dissolving a soluble (carrying) medium in the alpha-tocopherol ester derivative of formula (1) in the case of liquid phase, and in a suitable solvent in the case of solid phase. Alpha-tocopherol ester derivatives and excipients are added, followed by heating as necessary and evaporation of the solvent. At this time, the alpha-tocopherol ester derivative and the excipient are mixed in a ratio of 3: 2 to 1:99 so that the concentration of the alpha-tocopherol ester derivative formulation is 60% to 1% (w / w).

Suitable solvents for formulation preparation (solid) are water as well as inert organic solvents such as alcohols (methanol or ethanol), ethers, hydrocarbons (toluene, benzene and xylene).

The concentration of the active compound in the feed when added to the animal feed using the formulation is usually 1.0 to 500 ppm (based on vitamin E) and preferably 10 to 200 ppm based on the total weight of the feed.

As already mentioned, the active substance can be used as a source of vitamin E for humans and animals and is particularly suitable for animals and fish. Animals of interest include: cattle, horses, pigs, sheep, goats, cats, dogs, mammals such as camels, animals with hair such as mink and chinchillas, animals in zoos and laboratory animals such as mice and rats; Birds such as geese, chickens, turkeys, ducks, pigeons, and laboratory birds such as parrots and macaws; Fish such as carp, trout, salmon, tenches and eel, ornamental fish and aquarium fish; Reptiles such as crocodiles and snakes.

The present invention will be described with reference to Examples, but the present invention is not limited to these Examples.

Example 1 Preparation of DL-alpha-tocopheryl-ω-methylpolyethyleneglycoryl-succinate (n = 6) -ethanol / water liquid

60 g of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 6, average molecular weight: 863) is dissolved in 40 g of 95% ethanol to give 60 g (w / w) of 100 g of the title compound. .

Example 2. Preparation of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -ethanol / water liquid

60 g of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11, average molecular weight: 1063) was dissolved in 40 g of 95% ethanol to give 60 g (w / w) of 100 g of the title compound. do.

Example 3. Preparation of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -ethanol / water liquid

60 g of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44, average molecular weight: 2153) was dissolved in 40 g of 95% ethanol to give 60 g (w / w) of 100 g of the title compound. do.

Example 4. Preparation of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 6) -corn cob formulation

60 g of DL-alpha-tocopheryl-ω-methyl polyethyleneglycolyl-succinate (n = 6, average molecular weight: 863) was dissolved in 100 ml of methylene dichloride, and 240 g of corncob was added to the solution, followed by 30 minutes at room temperature. Stir for 1 hour. The mixture was distilled off under reduced pressure to afford 20 g (w / w) of 300 g of the title compound as a solid.

Example 5 DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -corn cob formulation

Instead of the tocopherol derivative (n = 6) of Example 4, 300 g of the title compound is obtained using 60 g of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11, average molecular weight: 1063). .

Example 6. Preparation of DL-alpha-tocopheryl-ω-methylpolyethyleneglycoryl-succinate (n = 44) -corn cob formulation

Instead of the tocopherol derivative (n = 6) of Example 4, 300 g of the title compound is obtained using 60 g of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44, average molecular weight: 2153). .

Example 7 DL-alpha-tocopheryl-ω-methylpolyethyleneglycoryl-succinate (n = 6) -degreasing steel formulation preparation

Instead of 240 g of corncob of Example 4, 240 g of skim steel is used to obtain 300 g of the title compound.

Example 8 DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -degreasing steel formulation preparation

DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate instead of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 6, average molecular weight: 863) of Example 4 n = 11, average molecular weight: 1063) and 300 g of the title compound were obtained using 240 g of degreasing steel instead of corncob.

Example 9 DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -degreasing steel formulation preparation

DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (Example 4 instead of DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 6, average molecular weight: 863) n = 44, average molecular weight: 2153) 300 g of the title compound were obtained using 60 g of degreasing steel instead of corncob.

Experimental Example 1. Evaluation of the effect on the growth and carcass quality of finishing pigs

Efficacy test group to investigate the effect of the compound of formula 1 (n = 11) compared to the standard control compound tocopherol (n = 11) as the ethanol / water solution of Example 2 on the growth and carcass quality of the finishing pig when administered with feed Body weight, feed intake, weight gain per day, feed requirement (feed intake / weight gain, lower efficiency were better) and carcass rating were compared.

The total number of test animals was 160 (5 / pen), average weight 78 ± 2 Kg (50 heads) 1 repetition, 74 ± 2 Kg (50 heads) 2 repetition, 70 ± 2 Kg (50 heads) Three repetitions, the male and female ratio was adjusted to the same ratio so that there is no difference between treatments, the experiment was carried out using ternary hybrid pigs.

1. Experimental method

After weighing the subject's shaft, feed is fed for one week, followed by a week of purifying the struggle, then weighed again, and then fed test feeds.

In the case of the test feed, only the basic food and the vitamin-mineral mixture prepared with the energy protein of the hog test feed are purchased separately, but the vitamin E is purchased with the existing vitamin preparation. Compound 1 is supplied separately and used in feed formulations. Feed and water were allowed to be freely consumed, followed by a total of six weeks of specification testing, and body weight and feed requirements were measured every three weeks. Slaughter and graded at the end of the test.

2. Test result

Effectiveness test results in pigs (n = 15 two) density Weight (kg) Weight gain per day (kg / day) Feed Intake (kg) Feed requirement 0 weeks 3 weeks 6 Weeks 0 to 3 3 to 6 0-6 weeks 0 to 3 3 to 6 0-6 weeks 0 to 3 3 to 6 0-6 weeks Tocopherol Acetate 10 ppm 73.9 91.3 106.0 0.83 0.70 0.76 43.3 47.3 90.6 2.51 3.24 2.83 Tocopherol Acetate 90 ppm 71.7 88.2 103.4 0.79 0.73 0.76 42.2 48.0 90.2 2.58 3.18 2.85 Formula 110 ppm 70.8 88.9 104.8 0.86 0.76 0.81 43.4 49.2 92.6 2.42 3.20 2.73 Formula 190 ppm 71.5 90.2 106.8 0.89 0.79 0.84 45.7 52.5 98.2 2.45 3.19 2.78

Conductor rating result (n = 15 two, average value) Dosing method Live weight (kg) Conductor weight (kg) Conductor weight ratio (%) Back fat (mm) Conductor rating (%) A B C Tocopherol Acetate 104.3 79.0 75.9 19.5 48.9 42.2 8.9 Formula 1 106.3 80.1 75.4 18.5 53.3 42.2 4.4

The compound of the present invention can be used as a source of vitamin E in animal feed as can be seen in the above experimental example, and in particular, the effect of the meat improver of pork is superior to the conventionally widely used tocopherol acetate in pig feed, and when using tocopherol acetate It can be used as a source of vitamin E in all feeds because it can maximize the weight gain effect and feed requirements that were not expected.

Claims (8)

Animal feed additive composition comprising a polyethoxylated alpha tocopherol ester derivative of the formula (1) as an active ingredient: [Formula 1] Where R is CH ₃ OCH ₂ CH ₂ (OCH ₂ CH ₂ ) n, where n is an integer from 2 to 400. The compound of formula 1 wherein the compound of formula 1 is DL-alpha-tocopheryl-ω-methyl polyethyleneglycolyl-succinate (n = 6), DL-alpha-tocopheryl-ω-methyl polyethyleneglycoryl-succinate The composition selected from the group consisting of Nate (n = 11) and DL-alpha-tocopheryl-ω-methyl polyethyleneglycolyl-succinate (n = 44). The composition according to claim 1, wherein the derivative of formula 1 is in a solid or liquid formulation. 4. The liquid formulation of claim 3, wherein the liquid formulation comprises DL-alpha-tocopheryl-ω-methylpolyethyleneglycoryl-succinate (n = 6) -ethanol / water; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -ethanol / water; And DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -ethanol / water, wherein the solid dosage form is DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl. Succinate (n = 6) -corn cob; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -corn cob; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -corn cob; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 6) -degreasing steel; DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 11) -degreasing steel; And DL-alpha-tocopheryl-ω-methylpolyethyleneglycolyl-succinate (n = 44) -degreasing steel. 4. A composition according to claim 3, containing 1.0 to 60% by weight of solid or liquid formulation. A method for preparing the animal feed additive composition of claim 1, wherein the polyethoxylated alpha tocopherol ester derivative of Formula 1 is dissolved or adsorbed in an excipient to obtain a solid or liquid formulation. [Formula 1] Where R is CH ₃ OCH ₂ CH ₂ (OCH ₂ CH ₂ ) n, where n is an integer from 2 to 400. 7. The method of claim 6, wherein the excipient is selected from the group consisting of adsorbents, inorganic or organic media and vegetable oils. 8. The excipient according to claim 7, wherein the excipients are zeosil, sugar, cellulose, powdered milk, meat bone meal, coarse flour, corncob, starch, skim steel, water, ethanol, sodium chloride, calcium carbonate, bicarbonate, oxidation Aluminum, silica, alumina, precipitated or colloidal silicon dioxide, phosphate, soybean oil, castor oil, cottonseed oil and palm oil.