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Title:
FEED ADDITIVE COMPOSITIONS FOR ANIMALS COMPRISING POLYETHOXYLATED ASCORBIC ACID DERIVATIVES
Document Type and Number:
WIPO Patent Application WO/2003/011048
Kind Code:
A1
Abstract:
The present invention relates to a feed additive composition for animals which comprises a polyethoxylated ascorbic acid derivative of formula (I) as an effective ingredient. When the feed additives are mixed in feed for livestock or fish, level of ascorbic acid in blood is not only homogeneously maintained, but also high in tissues. Therefore, useful effects such as reduction of mortality by heat stress and reduction of broken and soft egg production may be obtained in poultry.

Inventors:
CHUNG BONG-YOUL (KR)
PARK BONG-JUN (KR)
KIM YOUNG-KEUN (KR)
Application Number:
PCT/KR2002/001083
Publication Date:
February 13, 2003
Filing Date:
June 07, 2002
Export Citation:
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Assignee:
LG LIFE SCIENCES LTD (KR)
CHUNG BONG-YOUL (KR)
PARK BONG-JUN (KR)
KIM YOUNG-KEUN (KR)
International Classes:
A23K1/16; (IPC1-7): A23K1/16
Domestic Patent References:
WO1999050258A11999-10-07
Foreign References:
US5221673A1993-06-22
US4749577A1988-06-07
US5558889A1996-09-24
Attorney, Agent or Firm:
Choi, Kyu-pal (Kangnam-ku Seoul 135-080, KR)
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Claims:
Claims
1. A feed additive composition for animals which comprises a polyethoxylated ascorbic acid derivative of the following formula (I) as an effective ingredient: wherein, R is hydrogen or lower alkyl having 110 carbon atoms, and n is an integer of 2400.
2. The composition of Claim 1, which contains the derivative of formula 1 in the form of a solid or liquid formulation.
3. The composition of Claim 2, wherein the solid formulation is selected from the group consisting of 30PEG350 monomethyletherascorbic acidstarch, 30PEG350 monomethyletherascorbic acidcorncorb, 30PEG350 monomethyletherascorbic acidsilica, 30PEG350 monomethyletherascorbic aciddefatted bran, 30PEG550 monomethyletherascorbic acidstarch, 30PEG550 monomethyletherascorbic acid corncorb, 3OPEG550 monomethyletherascorbic acidsilica and 3OPEG550 monomethyletherascorbic aciddefatted bran; and the liquid formulation is selected from the group consisting of 3OPEG350 monomethyletherascorbic acidaqueous solution, 30PEG350 monomethyletherascorbic acidethanol, 3OPEG550 monomethyletherascorbic acidaqueous solution and 3OPEG550 monomethylether ascorbic acidethanol (where, PEG refers to polyethylene glycol).
4. The composition of Claim 2, wherein the solid or liquid formulation is contained in an amount of 1.0 to 60 % by weight.
5. The composition of Claim 2, wherein the solid or liquid formulation is contained in an amount of 10 to 30 % by weight.
6. A process for preparing the feed additive composition for animals of Claim 1, characterized in that a polyethoxylated ascorbic acid derivative of the following formula (I) is dissolved or absorbed in an excipient to obtain a solid or liquid formulation: wherein, R is hydrogen or lower alkyl having 110 carbon atoms, and n is an integer of 2400.
7. The process of Claim 6, wherein the excipient is one or more selected from the group consisting of zeosil, sugar, cellulose, powdered milk, meat meal and powdered bones, rough and fine cereal powder, corncob, starch, defatted bran, water, ethanol, sodium chloride, calcium carbonate, bicarbonate, aluminum oxide, silica, alumina, precipitated or colloid silicon dioxide, and phosphate.
Description:
Feed additive compositions for animals comprising polyethoxylated ascorbic acid derivatives TECHNICAL FIELD The present invention relates to feed additive compositions for animals comprising a polyethoxylated ascorbic acid derivative of formula (I) and to a process for preparing the same: wherein, R is hydrogen or lower alkyl having 1-10 carbon atoms, and n is an integer of 2-400.

BACKGROUND ART It is well known in the art, that ascorbic acid (Vitamin C) and the salts thereof are employed in animal food and additives for animal feed. However, since there is a disadvantage that ascorbic acid itself is easily oxidized in a status of aqueous solution by temperature and oxygen, it cannot be used in feed additives for animals. In addition,. when animal feeds with ascorbic acid added are produced and stored, ascorbic acid is significantly decomposed. Consequently, its effectiveness is lowered due to such a loss.

However, it is known in the art, that the above polyethoxylated ascorbic acid derivatives are present in the form of ascorbic acid protected against oxidative degradation and heat

degradation, have an excellent heat stability in aqueous solution, and have an excellent effect of eliminating radicals and inhibiting against tyrosinase [Ref. : WO 99/50258, KR Patent Application No. 99-8784 (Patent Laid-Open No. 2000-60467) ]. Upon taking these derivatives, ascorbic acid is released in host organism.

DISCLOSURE OF THE INVENTION The present inventors have conducted extensive researches and experiments, and discovered that the polyethoxylated ascorbic acid derivatives of the above formula (I) are useful as an ascorbic acid source, since they are easily released in organisms. In this regard, the present inventors further discovered that these derivatives are suitable as feed additives for animals.

Therefore, the object of the present invention is to provide a feed additive composition for animals comprising a derivative of the above formula (I) as an effective ingredient.

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 (I) in an excipient to obtain a solid formulation or a liquid formulation.

Specifically, the feed additive composition for animals of the present invention contains a polyethoxylated ascorbic acid derivative of the following formula (I) as an effective ingredient:

wherein, R is hydrogen or lower alkyl having 1-10 carbon atoms, and n is an integer of 2-400.

Since the physical property of the above active compounds is viscous liquid, they cannot be available in preparing feeds that the compounds should be added in a small amount. In order to use the compounds as feed additives for animals providing ascorbic acid, they should be formulated in a liquid phase by dissolving them in water, an organic solvent, and the like to be diluted, or in a solid phase by absorbing them on a solid excipient.

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 (I) in an excipient.

The excipient used for formulation includes an absorbent, or an inorganic or organic medium. 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.

Specific formulations of the polyethoxylated ascorbic acid derivatives are mentioned as follows: as a liquid formulation, 3-0-PEG350 monomethylether-ascorbic acid-aqueous solution, 3-0-PEG350 monomethylether-ascorbic acid-ethanol, 3-0-PEG550 monomethylether-ascorbic acid-aqueous solution, 3-0-PEG550 monomethylether-ascorbic acid-ethanol; as a solid formulation, 3-0-PEG350 monomethylether-ascorbic acid-starch, 3- 0-PEG350 monomethylether-ascorbic acid-corncorb, 3-0-PEG350 monomethylether- ascorbic acid-silica, 3-0-PEG350 monomethylether-ascorbic acid-defatted bran, 3-O- PEG550 monomethylether-ascorbic acid-starch, 3-0-PEG550 monomethylether-ascorbic acid-corncorb, 3-0-PEG550 monomethylether-ascorbic acid-silica, 3-0-PEG550

monomethylether-ascorbic acid-defatted bran (where, PEG refers to polyethylene glycol).

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 ascorbic acid.

Preferably, the process for preparing the liquid formulation of the ascorbic acid derivatives of formula (I) is dissolving a soluble (carrying) medium in ascorbic acid derivatives of formula (I). The process for preparing the solid formulation is adding the ascorbic acid derivative of formula 1 and an excipient to a suitable solvent, if necessary, heating the mixture and then evaporating the solvent. At this time, the ascorbic acid derivative and the excipient are able to be mixed in a ratio of 3: 2 to 1: 99, so that the concentration of the formulation is 60% to 1% (w/w) and more preferably, 10% to 30% (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 animal, the concentration of the active compound in the feed is usually from about 0.01 to 1000ppm and preferably from 10 to 500ppm on the basis of active ascorbic acid.

As mentioned hereinbefore, the active materials may be used as a source providing Vitamin C for the human body, animals, and most suitably for animals and fish. The livestock that 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 3-O-PEG3so monomethylether-ascorbic acid-aqueous solution 100g of the title formulation [60% (w/w) ] is obtained by dissolving 60g of 3-0-PEG350 monomethylether-ascorbic acid (average molecular weight 508) in 40g of water.

Example 2: Preparation of 3-0-PEG350 monomethylether-ascorbic acid-corncorb formulation 60g of 3-0-PEG350 monomethylether-ascorbic acid (average molecular weight: 508) 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 is obtained by vaporization of methylene dichloride under reduced pressure.

Example 3: Preparation of 3-0-PEG550 monomethylether-ascorbic acid-aqueous solution 100g of the title formulation [60% (w/w) ] is obtained by using 60g of 3-0-PEG550 monomethylether-ascorbic acid (average molecular weight: 708) instead of 3-0-PEG monomethylether-ascorbic acid in Example 1.

Example 4: Preparation of 3-0-PEG550 monomethylether-ascorbic acid-corncorb formulation 300g of the title formulation [20% (w/w) ] is obtained by using 60g of 3-0-PEG550

monomethylether-ascorbic acid instead of 3-0-PEG350 monomethylether-ascorbic acid in Example 2.

Example 5: Preparation of 3-0-PEG350 monomethylether-ascorbic acid-defatted bran formulation 300g of the title formulation [20% (w/w) ] is obtained by using 240g of defatted bran instead of 240g of corncorb in Example 2.

Example 6: Preparation of 3-0-PEG550 monomethylether-ascorbic acid-defatted bran formulation 300g of the title formulation [20% (w/w)] is obtained by using 60g of 3-0-PEG550 monomethylether-ascorbic acid (average molecular weight: 708) and 240g of defatted bran instead of 60g of 3-0-PEG350 monomethylether-ascorbic acid (average molecular weight: 508) and 240g of corncorb in Example 2.

Experimental Example 1: Test of efficacy in laying hens Efficacy Study in laying hen was carried out in summertime (July-August) that heat stress is the highest, by using feed that 20ppm of the compound of formula (I) (3-O- PEG350 monomethylether-ascorbic acid (average molecular weight: 508) was contained on the basis of active ascorbic acid, and the rate of broken eggs and mortality were measured. 20,800 of laying hen were used in the above experiment.

1-1. Result The result was shown in Table 1 below: [Table 1] Effect of the test substance supplementation on egg production Hen-day Broken & No. of Weekly Week Total No. egg soft egg Date Animals mortality Remarks old of eggs production production (early week) (%) (%) (%) 42 07/16-07/22 20800 111601 76.6 2.15 0.47 43 07/23-07/29 20702 109078 75.3 1.87 0.37 44 07/30-08/05 20626 107174 74.2 1.90 0.33 Feeding the 45 08/06-08/12 20558 100325 69.7 1.26 0.31 formulation 46 08/13-08/19 20495 96259 67.1 1.56 0.17 of Example 2 47 08/20-08/26 20460 97949 68.4 1.50 0.51 48 08/27-09/02 20335 100011 70.2 1.47 0.32

Experimental Example 2: Analysis of concentrations of ascorbic acid in blood and tissue concerning laying hens When the formulation for feed additive was provided, ascorbic acid level in blood and tissue (liver, kidney) of laying hens was measured, depending on time.

2-1. Feed for test The marketed middle phase-feed for laying hens, with 15%-16% of crude protein, 2, 800-2, 850 kcal/kg of metabolizable energy and 3.5% of Ca was purchased and used in the test. The formulation for feed additive (the formulation of Example 2) was added to the feed in the concentration of Oppm (control group), lOppm, 100ppm, 200ppm, and 400ppm, on the basis of ascorbic acid concentration, per 1 kg of the feed, and the resulting mixtures were used as the test feed.

2-2. Experimental design Ten of 75-week old laying hens (ISA-Brown) were divided into the whole 3 treatment groups, including the control group, and disposed in accordance with the following randomized block design: 3 replications per 1 treatment; 10 cages per 1 replication; and 2 hens per 1 cage.

2-3. Measurement of change of ascorbic acid in blood and tissue depending on time Common feed was provided the whole hen groups for one week before the experiment, and then, the hens were fasted until the next morning by empting the feed bowl in the last evening, with putting out the lights. The treated feed was provided to the hens in the next morning. Blood sampling was performed from 10 hens of each treatment at 24,48 and 72 hours after feeding. After sampling the blood from vena wing inferiors at 24 and 48 hours and from heart at 72 hours, liver and kidney were taken out to confirm distribution of ascorbic acid in tissues.

2-4. Results The results were shown in Table 2 and 3 below.

[Table 2] Analysis Result of level of ascorbic acid in blood Concentration of Ascorbic acid Level in blood (average + standard derivation), µg/m# (supply concentration), ppm 24 h 48 h 72 h 0 (Control group) 23. 23. 5 24. 27. 9 12. 0i2. 9 10 28. 2~8. 7 29. 611. 7 23. 8~19. 3 100 27. 46. 5 26. 6~10. 1 27. 422. 7 200 30. 62. 2 34. 222. 1 16. 512. 2 400 53. 224. 6 38. 625. 6 9. 364. 1 [Table 3]

Analysis Result of level of ascorbic acid in tissue Concentration of Ascorbic acid Level in tissues (average standard derivation), µg/m# (supply concentration), ppm Kidney Liver 0 (Control group) 14. 6~1. 4 28. 434. 5 10 16. 72. 6 53. 123. 9 100 26. 87. 0 26. 412. 0 200 31. 9~8. 2 42. 5~18. 0 400 30. 214. 1 55. 026. 8

INDUSTRIAL AVAILABILITY As shown from the above experiment results, the feed additives in accordance with the present invention are suitable for feed additives for animals providing ascorbic acid.

When these additives are mixed in feed for livestock or fish, level of ascorbic acid in blood is not only homogeneously maintained, but also high in tissues. Therefore, useful effects such as reduction of mortality by heat stress, reduction of broken and soft egg production may be obtained in industrial animals.