wherein R is CH3OCH2CH2 (OCH2CH2) n, where n is an integer of 2-400, and to a process for preparing the same.

BACKGROUND ART Vitamin E (DL-alpha-tocopherol) represented by the following formula 2 is widely used as an antioxidant in a living body, its clinically applied fields are extended, and its need tends to be increased.

Vitamin E is a compound having a hydroxyl group on a benzene ring, and has a characteristic of liposolubility that is not dissolved in water. Generally, since Vitamin E itself is easily oxidized, it is chemically unstable. Moreover, tocopherol quinone, an oxidation product, does not have a biological activity of Vitamin E. Therefore, to prevent

oxidation of vitamin E, the more stabilized derivatives of vitamin E can be prepared synthetically. Such derivatives include tocopherol acetate, tocopherol palmitat, tocopherol succinate, etc. These derivatives have advantages in storage and transportation, since they have relatively higher stability than Vitamin itself. Also, they are effective substitutes of Vitamin E, since they have a permissible stability for pharmacological purpose.

Furthermore, in case of oral administration, when the above-mentioned Vitamin E ester compounds are absorbed via in vivo intestinal tracts, they contact with pancreatic enzyme or intestinal enzyme, and are completely hydrolyzed to be absorbed in the form of tocopherol in vivo.

Therefore, Vitamin E substitutes are widely used in all feed for the whole livestock.

Particularly, it is known that tocopherol acetate is widely used as a source providing Vitamin E in feed for pigs and has an effect as an agent improving the pork's flesh.

In order that the above active compounds are used as a feed additive for providing Vitamin E, they must be prepared in a liquid phase by dissolving them in water or an organic solvent and diluting the solution, or be prepared in a solid phase by absorbing. them on a solid excipient that may be used as a feed additive. However, since a physical property of the above active compounds is viscous liquid, the compounds can not be used as such in the process for preparing feed that they must be added by a small portion. Even if the compounds are used, there are many problems.

DISCLOSURE OF THE INVENTION The present inventors have found that the polyethoxylated alpha tocopherol ester derivatives used in the present invention have a high solubility-in-water, are hard to be oxidized, have a chemical stability, and are useful as a source providing Vitamin E.

Based on these findings, they have developed a feed additive composition for animals.

Therefore, they have completed the present invention.

The object of the present invention is to provide a feed additive composition for animals comprising a derivative of the above formula 1.

Another object of the present invention is to provide a process for preparing the above feed additive composition for animals by dissolving or absorbing a derivative of the above formula 1 in an excipient to obtain a solid phase formulation or a liquid phase formulation.

The feed additive composition for animals of the present invention contains polyethoxylated alpha tocopherol ester derivatives of the following formula 1 as an effective ingredient: wherein R is CH30CH2CH2 (OCH2CH2) n, where n is an integer of 2-400.

Among the above compounds of formula l, the compounds that have the definition of R, wherein n is an integer of 2-50, are preferable.

The feed additive composition for animals in accordance with the present invention may be formulated in the form of a solid or liquid phase by dissolving or absorbing the derivative of the above formula 1 in an excipient.

The excipient used for formulation includes an absorbent, an inorganic or organic medium or a vegetable oil. The absorbent includes zeosil, sugar, cellulose, powdered milk, meat meal and powdered bones, rough and fine cereal powder, corncob, starch or defatted bran.

In addition, the inorganic or organic medium includes water or ethanol used as a solvent, sodium chloride, calcium carbonate, bicarbonate, aluminum oxide, silica, alumina, precipitated or colloid silicon dioxide or phosphate. The vegetable oil includes soybean oil, castor oil, cotton-seed oil, palm oil, etc.

Specific formulations of polyethoxylated alpha tocopherol ester derivatives are mentioned as follows: as a liquid formulation, DL-alpha-tocopheryl-o)-methylpolyethyleneglycolyl- succinate (n=6)-ethanol/water ; DL-alpha-tocopheryl--methylpolyethyleneglycolyl- succinate (n=ll)-ethanol/water ; and DL-alpha-tocopheryl--methylpolyethyleneglycolyl- succinate (n=44)-ethanol/water ; and as a solid formulation, DL-alpha-tocopheryl-co- methylpolyethyleneglycolyl-succinate (n=6)-corncorb ; DL-alpha-tocopheryl-a)- methylpolyethyleneglycolyl-succinate (n=l l)-corncorb ; DL-alpha-tocopheryl-c)- methylpolyethyleneglycolyl-succinate (n=44)-corncorb ; DL-alpha-tocopheryl-- methylpolyethyleneglycolyl-succinate (n=6)-defatted bran; DL-alpha-tocopheryl-co- methylpolyethyleneglycolyl-succinate (n=ll)-defatted bran; and DL-alpha-tocopheryl-- methylpolyethyleneglycolyl-succinate (n=44)-defatted bran.

The formulations in accordance with the present invention are suitable for a feed additive for animals, more preferably, a feed additive for livestock and a feed additive for fish, providing Vitamin E.

Preferably, the process for preparing the formulation of alpha-tocopherol ester derivatives of formula 1 comprises dissolving a soluble (carrying) medium in alpha-tocopherol ester derivatives of formula 1 in case of being a liquid phase; or adding alpha-tocopherol ester derivative of formula 1 and an excipient to a suitable solvent, if necessary, heating the mixture and evaporating 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 formulation of alpha-tocopherol ester derivative is 60% to 1% (w/w).

The suitable solvent used for preparing the formulation (solid) is an inert organic solvent,

for example, alcohol (methanol or ethanol), ether, hydrocarbon (toluene, benzene and xylene) as well as water.

When the above formulation is added to a feed for animals, the concentration of the active compound in the feed is usually 1. 0 to 500 ppm (on the basis of Vitamin E), and, preferably, 10 to 200 ppm, based upon the total weight of the feed.

As mentioned above, the active materials may be used as a source providing Vitamin E for the human body and animals, and, most suitably, for animals and fish. The livestock to which may be applied are the following animals: mammals such as cattle, horse, pig, sheep, goat, cat, dog, and camel; animals with fur such as mink and chinchilla; animals that live in a zoological garden; laboratory animals such as mouse and rat; birds such as goose, fowl, turkey, duck, and pigeon; laboratory birds such as parrot and macaw; fish such as carp, trout, salmon, tench and eel; ornament fish; aquatic fish; and reptiles such as crocodile and snake.

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is explained in detail by means of the following examples, but it is not limited to them.

Example 1. Preparation of DL-alpha-tocopheryl-cl)-methylpolyethyleneglycolyl-succinate (n=6)-ethanol/water liquid 60g of DL-alpha-tocopheryl-co-methylpolyethyleneglycolyl-succinate (n=6, average molecular weight: 863) is dissolved in 40g of 95% ethanol to obtain 100g of the title formulation [60% (w/w)].

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

60g of DL-alpha-tocopheryl--methylpolyethyleneglycolyl-succinate (n=l l, average molecular weight: 1063) is dissolved in 40g of 95% ethanol to obtain 100g of the title formulation [60% (w/w)].

Example 3. Preparation of DL-alpha-tocopheryl--methylpolyethyleneglycolyl-succinate (n=44)-ethanol/water liquid 60g of DL-alpha-tocopheryl-co-methylpolyethyleneglycolyl-succinate (n=44, average molecular weight: 2153) is dissolved in 40g of 95% ethanol to obtain 100g of the title formulation [60% (w/w)].

Example 4. Preparation of DL-alpha-tocopheryl--methylpolyethyleneglycolyl-succinate (n=6)-corncorb formulation 60g of DL-alpha-tocopheryl-co-methylpolyethyleneglycolyl-succinate (n=6, average molecular weight: 863) is dissolved in 100ml of methylene dichloride. 240g of corncorb is introduced into the resulting solution, and stirred for 30 minutes to 1 hour at room temperature. 300g of the title formulation in solid phase [20% (w/w)] is obtained by vaporization of methylene dichloride under reduced pressure.

Example 5. Preparation of DL-alpha-tocopheryl-z-methylpolyethyleneglycolyl-succinate (n=ll)-corncorb formulation 300g of the title formulation is obtained by using 60g of DL-alpha-tocopheryl-- methylpolyethyleneglycolyl-succinate (n=ll, average molecular weight: 1063) instead of the tocopherol derivative (n=6) in Example 4.

Example 6. Preparation of DL-alpha-tocopheryl-a)-methylpolyethyleneglycolyl-succinate (n=44)-corncorb formulation

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

Example 7. Preparation of DL-alpha-tocopheryl--methylpolyethyleneglycolyl-succinate (n=6)-defatted bran formulation 300g of the title formulation is obtained by using 240g of defatted bran instead of 240g of corncorb in Example 4.

Example 8. Preparation of DL-alpha-tocopheryl-co-methylpolyethyleneglycolyl-succinate (n=ll)-defatted bran formulation 300g of the title formulation is obtained by using 60g of DL-alpha-tocopheryl-co- methylpolyethyleneglycolyl-succinate (n=11, average molecular weight: 1063) and 240g of defatted bran instead of DL-alpha-tocopheryl-o-methylenepolyethyleneglycolyl-succinat e (n=6, average molecular weight: 863) and corncorb in Example 4.

Example 9. Preparation of DL-alpha-tocopheryl--methylpolyethyleneglycolyl-succinate (n=44)-defatted bran formulation 300g of the title formulation is obtained by using 60g of DL-alpha-tocopheryl-co- methylpolyethyleneglycolyl-succinate (n=44, average molecular weight: 2153) and 240g of defatted bran instead of DL-alpha-tocopheryl--methylenepolyethyleneglycolyl- succinate (n=6, average molecular weight: 863) and corncorb in Example 4.

Experimental Example 1: Measuring an effect on the pig's growth performance and meat quality

Compared with tocopherol acetate as the standard control compound, the compound (n=ll) of formula 1 was prepared in an ethanol/water liquid as Example 2, and the formulation was provided with pig, together with the feed. In order to measure an effect on the pig's growth and meat quality, body weight, feed intake, daily gain, feed conversion rate (feed intake/body weight gain; the lower the value, the better the efficency), and carcass grade of the effective test group were measured and compared.

A total of 160 pigs were used in the above experiment (5 pigs/pen). Average body weights of the animals were as follows: 78 2 kg (50 pigs) by 1 replication, 74 2 kg (50 pigs) by 2 replication, 70 2 Kg (50 pigs) by 3 replication. Equal numbers of male and female were used without any difference between treatments. The above experiment was carried out by using three way cross hybrid pigs.

1. Experiment Method The body weights of the pigs were measured, and the acclimation procedure against fighting one another was introduced for one week, with providing them with the feed.

Then, the body weight of the livestock was measured again, and the test feed was provided to them.

Basic feed adjusted to energy protein of a test feed for pigs and the mixture of vitamins and minerals were separately purchased as the test feed, and a conventional vitamin preparation was purchased as Vitamin E. The compound of formula 1 was separately provided. The animals were freely intaking the feed and water. The experiment was carried out for 6 weeks, the body weights and feed conversion rate were measured every three weeks.

After completing the experiment, the animals were slaughtered and graded.

2. Experiment Result [Table 1] Result of measuring effectiveness in pigs Concentration Body weight (kg) Daily gain Feed Intake (kg) Feed Conversion (ppm)(kg/day) rate 0 3 6 0-3 3-6 0-6 0-3 3-6 0-6 0-3 3-6 1 0-6 wk wk wk wk wk wk wk wk wk wk wk wk Tocopherol 10 73.9 91.3 106. 0 0.83 0. 70 0. 76 43.3 47.3 90.6 2. 51 3. 24 2. 83 acetate 90 71.7 88.2 103.4 0.79 0.73 0.76 42.2 48.0 90.2 2.58 3.18 2.85 Compound 10 70.8 88. 9 104. 8 0.86 0.76 0.81 43.4 49. 2 92. 6 2. 42 3.20 2.73 (1) 90 71.5 90. 2 106. 8 0. 89 0.79 0.84 45.7 52. 5 98. 2 2. 45 3. 19 2.78 [Table 2]

Results of estimating carcass grade (n=15 pigs, average value) Live body Carcass Ratio of BFT (Back fat Carcass grade weight (kg) weight (kg) carcass thickness) (mm) (%) weight (%) ABC DL-a-104.3 79.0 75.9 19.5 48.9 42. 2 8.9 Tocopherol acetate Compound (1) 106.3 80. 1 75. 4 18.5 53. 3 42. 2 4 4

INDUSTRIAL AVAILABILITY As shown in the above Experimental Example, the compound of the present invention may be used as a source providing vitamin E in feed for animals. Especially, in case of the feed for pigs, the present compound has a more excellent effect on improving the meat quality than DL-a-tocopherol acetate which has been widely used. In addition, the present compound may maximize increments of the body weight and feed conversion ratio which could not be expected by using tocopherol acetate. Therefore, the present compound may be used as a source providing vitamin E in feed for all species.