HK1095490A - Composition for regulating animal growth, method of manufacture and use thereof - Google Patents

Description

Composition for regulating animal growth, its preparation method and application

The present application is a divisional application entitled "composition for regulating animal growth, method of preparation and use thereof", filed 12/2001 by the present applicant under application number 01820603.4 (international application number PCT/EP 2001/014628).

Technical Field

The present invention relates to a cysteamine-containing composition for regulating growth of animals including, but not limited to, pigs, rabbits, quails, sheep, cattle, and chickens. The invention also relates to a preparation method of the composition, an animal feed additive and an animal feed, and application of the composition in preparing the animal feed additive and the animal feed.

Technical Field

Growth hormone has long been shown to play an important role in regulating the growth process of animals. For example, the use of growth hormone in meat producing animals will increase their body weight, including the growth of muscle mass. However, there are a number of disadvantages associated with the direct use of growth hormone in these animals to increase their meat production. First, growth hormones from different animals have little homology, and different animals (e.g., mammals) respond only to specific growth hormones of a particular type. Although suitable exogenous growth hormones are usually isolated from the pituitary gland, it is difficult and uneconomical to prepare a sufficient amount of suitable exogenous growth hormone to meet the requirements of large scale use. Although exogenous growth hormones can now be prepared by recombinant DNA techniques, the production of exogenous growth hormones by this method is still rather expensive. Second, the administration of exogenous growth hormone to livestock is usually by direct injection, which is necessarily quite expensive and difficult for a large farm. Third, it is difficult to control the dosage administered to produce precisely the desired effect, and excessive amounts of exogenous growth hormone may be harmful to the animal. Fourth, the residues of these exogenous growth hormones can enter the meat product and eventually enter the human body by consumption. Although some scientists are still concerned about the negative side effects of these exogenous growth hormones on humans, intensive research is needed in this regard.

Cysteamine is a component of coenzyme a and acts as a physiological regulator. Cysteamine has been used as a feed additive to promote growth of meat producing animals. US patent No. 4,711,897 discloses an animal feeding method and a feed composition containing cysteamine. However, cysteamine has proven to be a rather sensitive and unstable compound under normal room temperature conditions. For example, cysteamine is readily oxidized when exposed to air or elevated temperatures. Cysteamine is highly hygroscopic. In addition, cysteamine tastes bad when taken directly orally. In addition, ingestion of cysteamine directly will produce unpleasant gastric side effects. For these reasons, the use of cysteamine has for a long time been limited to direct injection of cysteamine-containing solutions into meat producing animals. And effective and large-scale application of cysteamine to promote growth of livestock is considered impractical.

Accordingly, there remains a need for a composition that can regulate and/or promote the growth of animals, particularly livestock.

It is therefore an object of the present invention to provide the above, or at least to provide the public with a useful alternative composition. Preferably, the composition is safe to administer and easy to formulate with a wide variety of animal feeds.

Summary of The Invention

According to a first aspect of the present invention there may be provided a method of preparing a composition for regulating the growth of an animal, the method comprising the steps of: preparing cysteamine or a salt thereof, and reacting the cysteamine or a salt thereof with cyclodextrin or a derivative thereof in a reactor. Preferably, this mixing process can be carried out under the protection of inert substances. The method may comprise heating the cysteamine or its salt and the cyclodextrin or its derivative mixed for a certain time at a temperature of about 25-40 ℃. The method may further comprise stirring the cysteamine or salt thereof and the cyclodextrin or derivative thereof to form a first mixture. Preferably, the method may comprise drying the first mixture at about 40-50 ℃, preferably in vacuo. The method further includes grinding and/or sieving the first mixture (e.g., 40 mesh, i.e., 40 holes per square inch of the mesh) to form a second mixture. Although a 40-mesh screen may be used, screens of different mesh sizes may be used depending on the particle size of the desired composition. The second mixture is then mixed with at least one of a filler, a disintegrant, and a binder to form a third mixture, which may be pelletized. A coating material made of an ingredient selected from the group consisting of cellulose acetate phthalate, polyethylene terephthalate, ethyl acetate, isopropyl acetate is then applied to the granules.

Preferably, the composition may contain 1-95 wt% of said predetermined amount of cysteamine or a salt thereof. More preferably, the composition may further comprise 75 wt% of said predetermined amount of cysteamine or a salt thereof.

Advantageously, the diameter of the granular form of the composition may be between 0.28 and 0.90 mm.

According to a second aspect of the present invention there is provided a composition prepared according to the above method.

In accordance with a third aspect of the present invention there is provided a composition for regulating animal growth, the composition comprising 1 to 95 wt% cysteamine or a salt thereof, and an inclusion compound host material composition, wherein the inclusion compound host material composition comprises a stabilizer selected from the group consisting of cyclodextrin or a derivative thereof.

Advantageously, the stabilizer may substantially comprise cyclodextrin or a derivative thereof.

Preferably, the composition may contain 1-75 wt% of cysteamine or a salt thereof, and more preferably, the composition may contain 1-40 wt% of cysteamine or a salt thereof.

Preferably, the composition may contain 1-60 wt% of the clathrate host material composition. More preferably, the composition may contain 10-40 wt% of the clathrate host material composition.

Suitably, the stabilizing agent in the inclusion compound host material composition may be selected from the group comprising beta-cyclodextrin (beta-CD), methyl-beta-cyclodextrin (M-beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), hydroxyethyl-beta-cyclodextrin (HE-beta-CD), poly-cyclodextrin, ethyl-beta-cyclodextrin (E-beta-CD) and branched cyclodextrin.

Suitably, the composition may comprise at least one of a filler, a disintegrant, a binder, a flavouring agent and a coating material. The coating material may comprise 1-20 wt% of the composition. Preferably, the coating material may comprise 1-15 wt% of the composition. The coating material may be an enteric coating. The coating material may be selected from the group comprising cellulose acetate phthalate, starch acetate phthalate, methyl cellulose phthalate, glucose or fructose derivatives of phthalic acid, acrylic and methacrylic acid copolymers, polymethyl vinyl ether, partially esterified substances of maleic anhydride copolymers, takh and formaldehyde gelatin.

Preferably, the composition may contain a filler, which may be selected from the group comprising powder-like cellulose, starch and calcium sulphate. In particular, the composition may contain from 1 to 90% by weight of filler. More particularly, the composition may contain from 1 to 60% by weight of filler.

Preferably, the composition may contain 5-50 wt% of a binder and a disintegrant, which may be selected from the group consisting of hydroxypropyl starch, microbial alginate, microcrystalline cellulose and starch. In particular, the composition may contain 15-35 wt% of a binder and a disintegrant.

Advantageously, the composition may contain 0.05 to 0.3 wt% of flavouring and odorants to enhance the flavour of the present formulation.

Suitably, the composition may be formed into granules, each of which may contain at least one or more layers of coating material. Specifically, in each granule, the cysteamine or its salt is isolated from the surrounding environment by the inclusion compound host material. The diameter of each particle of the composition may be between 0.28 and 0.90 mm.

Advantageously, each particle of the composition may be encapsulated by an enteric coating material.

According to a fourth aspect of the present invention there is provided an animal feed additive comprising the above composition.

According to a fifth aspect of the present invention there is provided an animal feed comprising the above composition. Suitably, the animal feed may contain 250-700mg/kg of the above composition.

According to a sixth aspect of the present invention there is provided the use of a composition as described above for the formulation of an animal feed additive.

According to a seventh aspect of the present invention there is provided the use of a composition as described above for the formulation of an animal feed.

According to an eighth aspect of the present invention there is provided a method of preparing an animal feed, the method comprising the step of mixing the above composition with a basal feed (or foodstuff).

Detailed Description

The present invention is based on the demonstration that when a composition containing cysteamine is ingested by livestock, the composition has activity of increasing body weight of livestock. Prior to this finding, there was no suggestion or sufficient evidence that large-scale administration of a cysteamine-containing composition to an animal might have such activity to effectively and safely increase the weight of the animal. The present invention also provides a method for preparing a cysteamine-containing composition and its use in raising animals by mixing it with basal feed (or food). The present invention can be applied by directly mixing the cysteamine-containing composition with an appropriate basal feed. The present invention can also be carried out by first mixing a premix made of the cysteamine-containing composition and other ingredients, and then mixing the premix with an appropriate basal feed to prepare a final feed. Basal feed refers to a food that is normally fed to an animal. Different animals require different basal feeds. For example, quail basal feeds typically include primarily cereal feeds.

It is generally believed that cysteamine, which is physiologically active, acts as a growth stimulator. Natural cysteamine is a component of coenzyme A (also known as CoA-SH or CoA), a coenzyme form of pantothenic acid. In the course of metabolism, coenzyme A acts as a carrier for dimercapto or a variant of the mercapto group linked to the mercapto group of coenzyme A. Animal experiments, such as swine, poultry, goats, rabbits and fish, have shown that cysteamine can deplete somatostatin (SS) in organisms, especially in the median raised nerve terminals and the pericentral nuclear nerve cells. This increases the levels of growth hormone in the blood of the animal, as well as the levels of various other growth stimulating factors including insulin-like growth factor I (IGF-I), insulin, triiodothyronine (T3), thyroxine (T4) and β -endorphin (β -END).

With the increase of various growth promoting factors, the digestive metabolism rate of the animals is correspondingly increased. It will be appreciated that the overall protein synthesis rate of the animal will also be increased thereby.

The physiological regulation of cysteamine is detailed below:

(i) cysteamine can enhance somatostatin metabolism and transport, and promote somatostatin degradation by affecting the vesicles that store somatostatin.

(ii) Cysteamine can alter the structure and conformation of somatostatin by affecting dimercapto bonds formed at positions 3 and 14 of SS-14 and positions 17 and 18 of SS-28. This is important for modulating biological and immunological activities in the physiology of animals.

(iii) Cysteamine can modulate somatostatin receptors and reduce the affinity for gastric mucosal cell receptors in animals fed with a cysteamine-containing composition. Cysteamine is a component capable of forming coenzyme a, which depletes somatostatin in animal tissues and organs and in the animal blood stream. Cysteamine may also promote the synthesis and release of endogenous growth hormones, regulate the production of neuroendocrine hormones, and potentiate basal, peak, and total levels of various growth hormones.

The novel cysteamine-containing composition prepared according to the present invention comprises two main ingredients, namely 1-95 wt% cysteamine (or a salt thereof, such as cysteamine hydrochloride or a pharmaceutically acceptable other acid addition salt thereof) and 1-80 wt% of a carrier, such as a clathrate host material.The chemical formula of cysteamine is HSCH₂CH₂NH₂. The term "cysteamine" appearing hereinafter refers to a compound of cysteamine and/or its salt. Cysteamine and its salts are well known in the chemical literature.

The common chemical formula of the cysteine salt is C2H7NS.X, wherein X can be hydrochloric acid, phosphoric acid, hydrogen tartrate, salicylate, etc. The cysteamine used preferably meets pharmaceutically acceptable standards and wherein the carbon, hydrogen, nitrogen and sulphur content is about 31.14 wt%, 9.15 wt%, 18.16 wt% and 41.56 wt%, respectively. Although a practicable content of cysteamine in the cysteamine-containing composition is between 1 and 95 wt%, a preferred range of cysteamine that may be used is 1 to 75 wt%, and a more preferred range is 1 to 40 wt%. Cysteamine is one of the main active components of a cysteamine-containing composition. However, it has been proved that if the cysteamine content of the cysteamine-containing composition exceeds 95 wt%, it will be difficult to mix the composition with basal feed, and the effect of the composition in regulating animal growth will be hindered.

Clathrate host material compositions comprise predominantly cyclodextrins and/or derivatives thereof selected from the group comprising methyl-beta-cyclodextrin (M-beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), hydroxyethyl-beta-cyclodextrin (HE-beta-CD), polycyclodextrin, ethyl-beta-cyclodextrin (E-beta-CD) and branched cyclodextrins. The general chemical formula of cyclodextrin is (C)₆O₅H₉)_n·(C₆O₅H₉)₂The molecular structural formula is as follows:

wherein α -CD n ═ 4; β -CD n ═ 5; gamma-CD n ═ 6

(Cyclodextrin is a cyclic oligomer of alpha-D-glucopyranose.)

It is noteworthy that beta-CD type cyclodextrin is preferred because its intramolecular diameter is about 6 to 8 , which makes it particularly suitable as a candidate for preparing an inclusion compound host material comprising a cysteamine composition involving application of an inclusion process. The term "cyclodextrin" appearing hereinafter refers to cyclodextrin and/or its derivatives. Any cyclodextrin derivative can be used as long as it has the properties of stabilizing and protecting cysteamine from degradation. For example, any one of the above-mentioned cyclodextrins or derivatives thereof may be used.

While the inclusion compound host material composition in the cysteamine-containing composition may be present in a practicable amount ranging from 1 to 80 wt%, inclusion compound host material compositions having a preferred practicable range of 1 to 60 wt%, and a more preferred practicable range of 1 to 40 wt% may also be used. The actual amount of clathrate host material composition used is determined by the actual amount of cysteamine used in preparing the cysteamine-containing composition.

The cysteamine-containing composition may contain 1-90 wt% of filler, although the preferred practicable range of filler used is 1-60 wt%, with a more preferred practicable range of 1-40 wt%. The actual amount will be determined by the actual amount of cysteamine and the clathrate host material composition used. The filler may be selected from the group consisting of powdered cellulose, starch, and calcium sulfate (e.g., CaSO)₄.2H₂O). It should be noted that if the content of the filler in the cysteamine-containing composition exceeds 90 wt%, the content of the main active ingredient will be reduced and the cysteamine-containing composition will fail in regulating the growth of animals fed with the feed mixed with the composition.

The cysteamine-containing composition may also contain 5-50 wt% of a disintegrant and a binder, although a preferred workable range is 10-40 wt%, and a more preferred workable range is 15-35 wt%. The actual amount will be determined by the actual amounts of cysteamine, the clathrate host material composition, and other ingredients used. The binder and disintegrant may be selected from the group comprising hydroxypropyl starch, microbial alginate, microcrystalline cellulose and starch. It has been demonstrated that if the content of disintegrant and binder in the composition is below 5 wt%, the resulting granules of this composition lack the desired hardness. In addition, the manufacture of such compositions would become difficult. If the content of disintegrant and binder is higher than 50 wt%, the resulting composition will be too hard, especially if the binder is the majority of its mixture with the disintegrant. This can cause the composition to be poorly absorbed by the animal's intestine.

The cysteamine-containing composition may also contain 0.05-0.3 wt% of flavoring agents and flavoring agents, which may be flavoring essences.

The cysteamine-containing composition may also contain 1-20 wt% of a coating material. Although a preferred workable range is 1-15 wt%, a more preferred workable range is 2-10 wt%. The actual amount will be determined by the actual amounts of cysteamine, the clathrate host material composition, and other ingredients used. The coating material is preferably an enteric coating which can be decomposed in an alkaline environment, such as the intestinal tract. The coating material may be selected from the group comprising cellulose acetate phthalate, starch acetate phthalate, methyl cellulose phthalate, glucose or fructose derivatives of phthalic acid, acrylic and methacrylic acid copolymers, polymethyl vinyl ether, partially esterified substances of maleic anhydride copolymers, takh and formaldehyde gelatin. It has been demonstrated that if the content of the coating material is less than 1 wt%, the coating material as a protective layer may not completely surround the composition particles. The cysteamine-containing composition may thus be degraded before being absorbed by the gut into the blood stream. On the other hand, if the content of the coating material is more than 15 wt%, the active ingredient in the composition may not be effectively released from the composition. Therefore, the intended growth regulating effect will not be obtained. In any case, animal feeds containing 250 to 700mg/kg of the composition have proven effective and can increase body weight when fed to animals.

The cysteamine-containing composition produced according to the present invention is in the form of small granules, each granule having a preferred diameter of substantially 0.28-0.90 mm. These particles are prepared by applying an enteric encapsulation process. The method involves the application of a macromolecular substance having inclusion properties. Substances that can be used are the inclusion compound host materials described above (mainly including cyclodextrins). The inclusion compound main body material is a macromolecular substance and is used as a molecular capsule to include cysteamine molecules, so that the cysteamine in the composition is isolated from ambient light, heat, air and moisture and is protected. Thus the stability of cysteamine is preserved. The inclusion compound host material used in the enteric encapsulation process is preferably a cyclic polysaccharide compound containing 6 to 12 glucose molecules, which compound can be obtained by reacting cyclodextrin glycosyltransferase with starch in the presence of bacillus. Many studies using acute, subacute and chronic toxicity tests have shown that macromolecular substances are not toxic. After the enteric encapsulation process, each particle may be coated with at least one, and preferably multiple layers of the coating materials described above. A more detailed description of one embodiment of a method for preparing a cysteamine-containing composition according to the present invention is provided below.

In a jacketed reactor with attached polytetrafluoroethylene and equipped with a polytetrafluoroethylene-coated stirrer, nitrogen in air was added mainly to 4080 g of 75 wt% cysteamine hydrochloride solution in alcohol. The purity, melting point and combustion residue of cysteamine are preferably 98% or more, 66 to 70 ℃, 0.05% or less, respectively. 1200 grams of beta-cyclodextrin (quality of beta-cyclodextrin meets the requirements of food additives. specifically, the dry basis purity is higher than 98%, the weight loss after drying is less than 10.0%, the combustion residue is less than 0.2%, the content of heavy metals is less than 10ppm, and the arsenic content is less than 2ppm) are then added into the reactor under the protection of nitrogen gas. The mixture was then heated at 40 ℃ for 3 hours. The heating is then stopped and stirring is continued for two hours, and the resulting product is ground and dried under vacuum at 40-50 ℃ and sieved through a mesh screen (e.g., 40 mesh). All parts of the equipment that may come into contact with the ingredients in the composition are preferably made of stainless steel.

In a tank mixer, under dry environmental protection, 4200 g (on a dry basis) of cysteamine subjected to the above inclusion procedure, 2600 g of filler and 1200 g of disintegrant and 1700 g of binder were added. These ingredients were mixed well, added with an appropriate amount of anhydrous ethanol, and then mixed therewith. The resulting mixture exhibited a soft mass with moderate hardness, allowing it to be pelletized with a light hand. The resulting spherical mixture can be separated by light contact. After the mixture is granulated by the granulator under nitrogen, the granules thus formed are immediately introduced into a fluid bed dryer and then dried at 40-50 ℃ in a substantially vacuum atmosphere.

Then an enteric coating material was prepared by a method having the following formulation: 8.0 g of cellulose acetate phthalate, 2.4ml of polyethylene terephthalate, 33.0ml of ethyl acetate and 33.6ml of isopropyl acetate. The granules obtained in the above are uniformly coated with at least one, preferably more, layers of the enteric coating materials described above under nitrogen. The enteric coating material is soluble only in alkaline environments. This prevents premature release of cysteamine from the composition while still in the stomach of the animal. Cysteamine has an undesirable irritating effect on the gastric mucosa of animals.

The resulting cysteamine composition containing granules are then thoroughly dried in a substantially vacuum desiccator at 40-50 ℃. Then, all the solvent was removed. The resulting granules were then cooled to room temperature and the microcapsules were mixed with appropriate amounts of flavoring and flavor agents using a cantilever twin screw blender. The cysteamine-containing composition is a microcapsule which contains cysteamine hydrochloride and cyclodextrin inside and enteric coating material outside.

The resulting composition will appear as small granules (or micro-particles), have a smooth surface, be very fluid, and be easily mixed with a variety of animal feeds. The diameter of each particle of the composition is preferably 0.28 to 0.90 mm. The composition also has high stability. It has been found that the properties of the composition remain unchanged when sealed in plastic bags and stored for one year in cool, dark and dry places. They meet the requirements of feed additives.

The above-described composition having a specific structure has many advantages in function over the use of cysteamine alone. First, the activity of the cysteamine contained in the composition is protected after its formation. This is important for feed additives, for example the composition may be stored for a considerable period of time before use. Second, the composition does not produce any visible gastric side effects on the animals fed with it. Third, the activity of the composition is not only preserved upon storage, but more importantly, its protection is maintained until the composition reaches the animal's intestinal tract. Fourth, the composition is easily and economically fed to livestock on a large scale because it is easily mixed with any basal feed. And no additional procedures or injections are required.

Many experiments have been conducted to demonstrate the effect of adding a cysteamine-containing composition to the diet of various types of livestock.

Example 1

The cysteamine-containing composition used in this experiment comprised 30 wt% cysteamine, 20 wt% inclusion compound host material composition and coating material, 26 wt% filler, 23.9 wt% disintegrant and binder, 0.1 wt% flavoring agent and flavoring agent. It should be noted that the compositions in this experiment comprise 12-17 wt% of the inclusion host material composition and 1-5 wt% of the coating material, wherein the inclusion host material composition comprises mainly cyclodextrin.

The experimental animals were 35-day-old piglets at weaning. The experimental group and the control group were 80 weaned piglets each. The experimental group of piglets was fed with 500mg/kg of basal feed containing the cysteamine composition. The control group of piglets was fed the same basal diet but without the cysteamine composition. The experimental time was 28 days.

As a result:

the record shows that the average daily weight gain of each piglet in the experimental group is 512 g, while that in the control group is 456 g. The average daily gain of each piglet in the experimental group is calculated to be 12.28 percent higher than that of the control group.

Example 2

The cysteamine-containing composition used in this experiment was the same as that used in experiment one.

The experimental animals were 50 to 90 day-old growing pigs. The experimental group and the control group were 100 growing pigs each. The pigs were fed with 700mg/kg basal feed containing the cysteamine composition. The control group of pigs were fed the same basal diet but without the cysteamine composition. The experimental time was 95 days.

As a result:

the record showed that each pig in the experimental group gained an average weight of 842 g per day, while the control group gained 747 g per day. The weight gain of each pig in the experimental group is calculated to be 12.72 percent higher than that of the control group.

Example 3

The cysteamine-containing composition used in this experiment was the same as that used in experiment one.

The experimental animals were New Zealand rabbits. The experimental group consisted of 29 rabbits, and the control group consisted of 14 rabbits. All rabbits were 55 days in size. Rabbits were fed with 300mg/kg basal diet containing the cysteamine composition. The control group of rabbits was fed the same basal diet, but without the cysteamine composition. All other conditions were consistent for both groups of rabbits. The experimental time was 66 days.

As a result:

the record showed that during the experiment, the average daily weight gain per rabbit was 1061.8 grams in the experimental group versus 840.1 grams in the control group. The average daily weight gain of each rabbit in the experimental group was 26.4% higher than that in the control group.

Example 4

The cysteamine-containing composition used in this experiment was the same as that used in experiment one.

The experimental animal is the second filial generation (F) of lamb (including New Zealand fine wool sheep (male parent) X local production sheep (female parent)₂)). The experimental group and the control group were 14 lambs each. All lambs are inThe experiments were all three months old at the beginning. The experimental group of lambs was fed 250mg/kg of basal feed containing the cysteamine composition, while the control group of lambs was fed the same feed, but without the cysteamine composition. All other conditions were consistent for both groups of lambs. The experimental time was 56 days.

As a result:

the record showed that the average daily weight gain per lamb in the experimental group was 70.8 kg during the experimental period. The average daily weight gain of each lamb in the experimental group is higher than that of the control group by 15.08 percent.

Example 5

The cysteamine-containing composition used in this experiment was the same as that used in experiment one.

The experimental animal is a weaned piglet and is a descendant of a big white pig and a long white pig. The experiment was carried out on a philippine Esconde farm for 28 days from 24 days 4 to 21 days 5 in 2000. The experimental group and the control group were 80 weaned piglets each. All weaned piglets were 35 days old and the initial weight per piglet was 8.6 kg. The experimental group of piglets was fed with 500ppm of a basal feed containing a cysteamine composition. The control group of piglets was fed the same feed but without the cysteamine composition. All other conditions were consistent for the two groups of weaned piglets. The following table is the nutritional content of the daily basal diet:

table 1: content of basic feed

Total energy M.E (metabolic energy)	3250 kcal/kg
		Crude protein	20wt％
Calcium carbonate	0.95wt％
		Phosphorus (P)	0.54wt％
Coarse fiber	＜3wt％
		Amino acids: lysine	1.40wt％
Amino acids: methionine and cysteine	0.77wt％

As a result:

the records after the experiment show that the average weight of the control group of piglets is 21.4 kg, namely the weight of the control group of piglets increases 456 g per day. While the average weight of the piglets in the experimental group was 23 kg, i.e. the weight gain was 512 g per day. The weight gain of the piglets in the experimental group is calculated to be 12.28 percent higher than that of the piglets in the control group.

The feed conversion efficiency of the piglets in the experimental group was 1.37 and that in the control group was 1.41. A feed conversion efficiency of 1.37 means that 1.37 feed needs to be consumed per 1 kg of body weight gain. That is, the feed conversion efficiency of the piglets in the experimental group was 2.13% higher than that of the control group.

Notably, piglets in the experimental group reduced feed consumption by 432 grams. Therefore 80 piglets were tested to reduce the total feed consumption by 34.56 kg.

Example 6

The cysteamine-containing composition used in this experiment was the same as that used in experiment one.

The experimental animals are piglets which are being fattened, are about 35 to 90 days in size, and are offspring of large white pigs and long white pigs. The experiment was performed on a philippine Rocky farm for 95 days. The experimental group and the control group were 100 pigs each. At the beginning of the experiment, the average weight of pigs in the experimental group is 23.3 kg, and the average weight of pigs in the control group is 23.6 kg. The experimental group of piglets was fed 700ppm of a basal feed containing a cysteamine composition. The control pigs were fed the same feed but without the cysteamine composition. All other conditions were consistent for both pigs. The following table shows the daily basal feed contents:

table 2: content of basic feed

	Growing food	Processed food
			Total energy M.E (metabolic energy)	3150 kcal/kg	3100 kcal/kg
Crude protein	18％	16％
			Calcium carbonate	0.85％	0.75％
Phosphorus (P)	0.52％	0.50％
			Coarse fiber	＜4.0	＜5.0
Amino acids: lysine	1.2％	1.09％
			Amino acids: methionine and cysteine	0.65％	0.60％

As a result:

the records after the experiment show that the average weight of the pigs in the control group is 94.6 kg, namely the weight of the pigs increases 747 g per day. The average weight of the pigs in the experimental group is 103.9 kg, namely 842 g of weight is increased per day. The weight increase of the pigs in the experimental group is calculated to be 12.72 percent higher than that of the pigs in the control group.

The feed conversion efficiency of the experimental group was 2.36 and that of the control group was 2.66. That is, the feed conversion efficiency of the pigs in the experimental group was 1.13% higher than that of the control group.

Notably, the experimental group of pigs reduced the consumption of feed by 24.81 kg. Therefore, the total feed consumption of 100 experimental pigs was reduced by 2,418 kg.

Example 7

The cysteamine-containing composition used in this experiment was the same as that used in experiment one.

The experiment is carried out in the physiology and biochemistry laboratory of Nanjing agriculture university, and the time is from 12 months and 5 days to 12 months and 28 days in 2000. The experimental animal is quail. 160 quails with the size of 15 days are applied. The experiments were started when quails reached a size of 17 days and ended when they reached a size of 38 days.

Quails were randomly divided into 8 groups. Three types of foods were formulated with different amounts of the cysteamine-containing composition. The food mainly comprises cereal basal feed. All groups of quails have unrestricted access to their respective diets and have their respective food consumption. Quail diet and average body weight before and after the experiment are summarized in table 3.

Table 3: effect of cysteamine-containing composition on growth of quail

Group of	Quail age when fed with cysteine-containing food	Basal feed (basal feed: cereal) with varying amounts of cysteine-containing composition	Average quail body weight in grams before test	Average quail weight after test, g
					1	--	0ppm	60.34±7.56	177.35±18.32
2	--	0ppm	59.86±8.01	173.53±12.76
					3	17-38	200ppm	59.22±8.38	*153.42±14.94
4	17-38	300ppm	58.03±7.26	179.45±15.45
					5	24-38	200ppm	59.99±8.35	*194.08±17.93
6	24-38	300ppm	58.72±9.65	*210.06±24.71
					7	31-38	200ppm	59.26±7.78	167.64±18.55
8	31-38	300ppm	60.86±9.05	168.57±17.97

Groups 1 and 2 are controls. Their diet contained basal feed, mainly cereal, and no cysteamine-containing composition. Groups 3 to 8 are experimental groups. Their diets contained the same basal feed, but with different amounts of the cysteamine-containing composition added as shown in column 3.

Results and discussion:

comparing the average quail body weight of groups 5 and 6 with groups 1 and 2, it was shown that the feed containing the cysteamine composition was fed by diet with a 10.65% to 19.7% weight gain at 24 days of quail size. More particularly, quail weight gain was higher in group 6 than in group 5. This can be explained by the fact that the quail diet in group 6 contains a high content of the cysteamine-containing composition.

Comparing the average quail body weights of groups 7 and 8 with groups 1 and 2, it was shown that the presence of the cysteamine-containing composition did not contribute to the increase in quail body weight of groups 7 and 8. Comparing the average quail body weight of groups 3 and 4 with groups 1 and 2, it was shown that the presence of the cysteamine-containing composition did not contribute to the increase in quail body weight of groups 3 and 4.

The effect of the cysteamine-containing composition on quails in different groups is explained as follows. The active growth period of quails is quite short. The cysteamine-containing composition plays a role in increasing the weight of animals mainly in the growth phase. The administration of the cysteamine-containing composition starting at a premature stage of quail development (e.g., before 17 days) does not contribute to weight gain. For this reason, quails in groups 1, 2 and groups 3, 4 were similar in body weight before and after the experiment. Likewise, administration of the cysteamine-containing composition starting at a too late stage of quail development (e.g., after 31 days) does not contribute to weight gain. Preferably, the cysteamine-containing composition should be administered from the beginning of the middle to the end of the growth of the animal. Groups 3 and 4 were given cysteamine-containing compositions beginning at a premature stage of development. This may cause a reduction in the level of growth receptors, resulting in a cysteamine-containing composition that is unable to increase the weight of the animal.

The contents of each of the references discussed above, including the priority applications and references cited herein, are hereby incorporated by reference in their entirety. It should be noted that numerous variations, modifications, and further embodiments are possible, and accordingly, all variations, modifications, and further embodiments are to be regarded as being included within the present invention and should be understood by those skilled in the art.

Claims (53)

1. A method of preparing a composition for regulating animal growth comprising the steps of: preparing a cyclodextrin or a salt thereof, and mixing the cyclodextrin and/or the salt thereof with a stabilizer and/or a coating material, such that the composition comprises (i)1-95 wt% of the cysteamine and/or the salt thereof, and (ii)1-60 wt% of the stabilizer and/or 1-20 wt% of the coating material, wherein the stabilizer and/or the coating material stabilizes and protects the cysteamine from degradation, and/or minimizes side effects of the cysteamine and/or the salt thereof on an administered animal.

2. The method according to claim 1, wherein the animal is a multi-gastric animal.

3. The method of claim 1, wherein the animal is a livestock animal.

4. The method according to claim 1, wherein the animal is a pig, rabbit, quail, sheep or chicken.

5. The method according to claim 1, said stabilizer being selected from the group consisting of cyclodextrins, derivatives thereof, and combinations thereof.

6. The method, according to claim 1, wherein the mixing of the cysteamine or its salt with the stabilizer or its derivative is carried out under protection of an inert substance.

7. The method, according to claim 1, comprising heating the cysteamine or salt thereof and the stabilizer while mixing for a period of time at a temperature of about 25-40 ℃.

8. The method, according to claim 1, comprising agitating the cysteamine or salt thereof with the stabilizer to form a first mixture.

9. The method of claim 8, comprising screening the first mixture through a mesh screen to form the second mixture.

10. A process according to claim 9, comprising the step of drying the second mixture at 40-50 ℃.

11. The method according to claim 10, comprising the step of mixing the second mixture with at least one of a filler, a disintegrant, and a binder to form a third mixture.

12. A method according to claim 11, including the step of agglomerating the third mixture into particles.

13. The method of claim 12, comprising: a coating material consisting of an ingredient selected from the group consisting of cellulose acetate phthalate, polyethylene terephthalate, ethyl acetate and isopropyl acetate is applied to the granules.

14. The method, according to claim 1, wherein said composition comprises 1-75 wt% of said cysteamine or salt thereof.

15. A method according to claim 60, wherein said composition is in the form of granules having a diameter of between 0.28 and 0.90 mm.

16. A composition prepared according to the method of claim 1.

17. A composition for regulating animal growth comprising

(i)1-95 wt% of the cysteamine and/or salt thereof, and

(ii)1-60 wt% clathrate host material composition and/or 1-20 wt% coating material to stabilize and protect the cysteamine or derivative thereof from degradation and/or minimize side effects of the cysteamine and/or derivative thereof on an administered animal.

18. A composition according to claim 17, wherein the clathrate host material composition is or includes a stabilizer.

19. The composition according to claim 18, wherein the stabilizing agent is selected from the group consisting of cyclodextrins, derivatives thereof, and combinations thereof.

20. The composition, according to claim 18, which comprises said cysteamine and/or its derivative in a major amount.

21. The composition, according to claim 17, comprising 1-75 wt% cysteamine or a salt thereof.

22. The composition, according to claim 21, comprising 1-40wt cysteamine or a salt thereof.

23. A composition according to claim 17, comprising 10 to 40 wt% of the clathrate host material composition.

24. The composition according to claim 18, wherein the stabilizer is selected from the group comprising β -cyclodextrin (-CD), methyl- β -cyclodextrin (M- β -CD), hydroxypropyl- β -cyclodextrin (HP- β -CD), hydroxyethyl- β -cyclodextrin (HE- β -CD), poly-cyclodextrin, ethyl- β -cyclodextrin (E- β -CD), and branched cyclodextrin.

25. A composition according to claim 17, comprising at least one of a filler, a disintegrant, a binder, a flavoring, and a flavouring agent.

26. A composition according to claim 17, comprising 1-20 wt% of said coating material.

27. The composition according to claim 17, wherein said coating material is enteric.

28. The composition according to claim 17, said coating material being selected from the group comprising cellulose acetate phthalate, starch acetate phthalate, methyl cellulose phthalate, glucose or fructose derivatives of phthalic acid, copolymers of acrylic and methacrylic acid, polymethyl vinyl ether, partially esterified substances of maleic anhydride copolymers and formaldehyde gelatin.

29. A composition according to claim 25, containing from 1 to 90% by weight of said filler.

30. The composition according to claim 25, wherein the filler is selected from the group comprising powder-like cellulose, starch and calcium sulphate.

31. A composition according to claim 29, containing from 1 to 60% by weight of said filler.

32. A composition according to claim 25, comprising 5-50% by weight of said binder and said disintegrant.

33. A composition according to claim 32, comprising 15-35% by weight of said binder and said disintegrant.

34. The composition according to claim 25, wherein the binder and the disintegrant are selected from the group comprising hydroxypropyl starch, microbial alginate, microcrystalline cellulose and starch.

35. A composition according to claim 25, comprising 0.05 to 0.3% by weight of flavouring and odorant to enhance the flavour of said composition.

36. A composition according to claim 17, wherein said composition is formed into granules, each granule containing at least one layer of said coating material.

37. The composition of claim 17, which forms a granule, wherein the cysteamine or salt thereof is isolated from the surrounding environment by the clathrate host material composition and/or the coating material.

38. A composition according to claim 36 or 37, wherein each particle of the composition has a diameter size of from 0.28 to 0.90 mm.

39. A composition according to claim 17, said composition being encapsulated by said coating material.

40. The composition according to claim 17, which is suitable for increasing the body weight of an animal when orally administered to the animal.

41. A composition according to claim 17 which is adapted to increase the feed conversion rate when administered orally to an animal.

42. An animal feed additive comprising the composition for regulating animal growth of claim 17.

43. An animal feed comprising the composition for regulating animal growth of claim 17 or the animal feed additive of claim 42.

44. The animal feed according to claim 43, comprising 250-700mg/kg of said composition for regulating animal growth or 75-210mg of said cysteamine or a salt thereof.

45. Use of the composition for regulating animal growth of claim 16 or 17 for the preparation of an animal feed additive for regulating animal growth.

46. Use of the composition for regulating animal growth of claim 16 or 17 for the preparation of an animal feed for regulating animal growth.

47. The use according to claim 46, wherein said animal feed contains 250-700mg/kg of said composition or 75-210ppm of said cysteamine or a salt thereof.

48. Use of the animal feed of claim 42 for modulating growth, increasing weight gain and/or increasing feed conversion rate in an animal.

49. A method of preparing an animal feed comprising the step of mixing the composition for regulating the growth of an animal of claim 16 or 17 with a basal feed.

50. A method of regulating animal growth, increasing animal weight, or increasing feed conversion efficiency comprising the step of orally administering to a target animal a composition of claim 16 or 17.

51. A method of modulating the growth of an animal comprising orally administering the composition of claim 16 or 17 through an animal feed.

52. The method according to claim 51, wherein said animal feed comprises 250-700mg/kg of said composition or 75-210ppm of said cysteamine or a salt thereof.

53. Use of a composition for modulating the growth of an animal, wherein said composition comprises (i) 1-95% cysteamine or a salt thereof, (ii) a clathrate host material composition comprising a stabilizer, and (iii) a coating material, wherein said clathrate host material composition and said coating material are a stabilizer and a protective agent that protects said cysteamine or a salt thereof from environmental effects.