TWI323158B - Feed for fish and use thereof - Google Patents

Description

U23158 A7 五、發明説明（1 ) 發明領域 本發明有關用於飼養水產動物且特別是養殖魚類之半 胱胺或其相似物組成物及/或含半胱胺組成物的用途。本 發明亦有關於飼養魚類的方法、用於魚類之飼料材料、以 及製備此飼料材料的方法。 發明背景 在調節動物的生長方面，生長激素長久以來已經扮演 著重要的角色。例如，在產肉動物施予生長激素將增加其 包括肌肉量的體重。然而，在這些動物中直接使用生長激 素來增加肉產量有許多缺點。第一，來自於不同動物的生 長激素少有同質性，且不同的動物只會對某些特定種類的 生長激素作出反應。由於合適的外源性生長激素通常萃取 | 自腦下垂體’所以準備足量之合適外源性生長激素來用於 大規模的應用是相當困難且不經濟。雖然外成生長激素目 前可利用基因重組技術製備，以此種方式製造的外成生長 激素依然相當昂貴。第二’對飼養動物施予外源性生長激 素通常以直接注射實施，其必然昂貴且在一個如養牛場的 大農場對於一個提供者而言難以施行。在養殖場的魚類， 施打外源性生長激素則更加困難，因為在一般環境下捕捉 以及li測個別的魚體以及注射適量的生長激素實際上不可 能。第三，控制施藥的劑量以產生精確的預期效果是相當 困難的，而過量的外成生長激素很可能會對動物有害。第 四，這些殘留的外成生長激素可能會經由肌肉的生成以及 本纸張尺度適用中國國家標準（CNS) A4規格（210X 297公釐）U23158 A7 V. INSTRUCTION DESCRIPTION OF THE INVENTION (1) Field of the Invention The present invention relates to the use of cysteamine or a similar composition thereof and/or a cysteamine-containing composition for feeding aquatic animals, particularly farmed fish. The present invention also relates to a method of raising fish, a feed material for fish, and a method of preparing the same. BACKGROUND OF THE INVENTION Growth hormone has long played an important role in regulating the growth of animals. For example, administration of growth hormone in a meat-producing animal will increase its body weight including muscle mass. However, the direct use of growth hormone in these animals to increase meat yield has many disadvantages. First, growth hormones from different animals are less homogenous, and different animals only respond to certain types of growth hormone. Since suitable exogenous growth hormone is usually extracted from the pituitary gland, it is quite difficult and uneconomical to prepare a sufficient amount of suitable exogenous growth hormone for large-scale application. Although exogenous growth hormone is currently produced by genetic recombination techniques, exogenous growth hormone produced in this manner is still quite expensive. The second 'administration of exogenous growth hormone to the breeding animals is usually carried out by direct injection, which is necessarily expensive and difficult to perform for a provider on a large farm such as a cattle farm. In fish in the farm, it is more difficult to apply exogenous growth hormone, because it is practically impossible to capture and measure individual fish in the general environment and to inject appropriate amounts of growth hormone. Third, it is quite difficult to control the dosage of the application to produce a precise desired effect, and an excess of exogenous growth hormone is likely to be harmful to the animal. Fourth, these residual exotrophic hormones may be produced through muscle production and the Chinese National Standard (CNS) A4 specification (210X 297 mm) on this paper scale.

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-4 - 丄： 五、發明説明（2 隨著食用而傳遞至人類。儘管一些科學家所關心這些外源 性生長激素對人類負面影響仍然需要進一步的相關研究。 有鑑於人口快速成長，包含海產，特別是魚類的各型 食品需求持續增加。最近根據聯合國的估計指出，目前的 海產供應量必須增加七倍才能符合全世界對於海產的需求 。：^成全世界漁獲量遞減的主要原因是過度捕獵以及魚類 棲息地的破壞。然、而，許多魚種的飼養產量由於一些因素 受到挑戰或有其妨礙。這些困難包括了合適品種的筛選及 供應’铜養魚類的生長率及飼料換肉率的增力口，飼料成本 的控制，生殖週期的管理以及疾病的預防。 為了在飼養環境中飼養魚類以便於其體重可快速增加 ’對魚類料外源性生長激素為—種常見的方法。然而， 如以上解釋，對於魚類料外成生長激素若非不可能也非 常困難。 另一種方式是藉由交又育種來強化有益的特性以生產 所欲的魚類品種。然而，這些特性通常浮現的相當緩慢且 無法預料。儘管應用交叉育種，魚類的基因組通常仍然不 包含人類所欲的之預期效果的基因。 還有另外可取代傳統筛選及育種的方法，是使用現代 基因工程來產生能快速成長的基因轉瘦魚。特別是基因 轉殖魚可以經由運用分子生物學鐘別、離析以及構成對應 於所欲之特性的基因，同時轉瘦基因至魚類品種而產生。 基於此種現代技術，新的不存在於魚類基因組中的特性能 夠由不相關的物種中被轉殖出來’賦予新的而且有益的性 請 先 閱 讀 背 之- 注 意- 事- 項 再 填_ 寫 本 頁-4 - 丄: V. Description of the invention (2) transmitted to humans as it is consumed. Although some scientists are concerned that the negative effects of these exogenous growth hormones on humans still require further research. In view of the rapid population growth, including seafood, In particular, the demand for various types of fish continues to increase. According to United Nations estimates, the current supply of seafood must be increased by seven times to meet the world’s demand for seafood. The main reason for the decline in catches worldwide is over-hunting and The destruction of fish habitats. However, the feeding yield of many fish species is challenged or hindered by a number of factors, including the screening of suitable varieties and the supply of 'brown fish growth rate and feed rate. Enhancement port, control of feed cost, management of reproductive cycle and prevention of disease. In order to raise fish in the breeding environment so that its body weight can be rapidly increased, 'the common method of exogenous growth hormone for fish is a common method. However, As explained above, it is very difficult if the growth hormone of the fish material is not impossible. Another way is to strengthen the beneficial properties by cross-breeding to produce the desired fish species. However, these characteristics usually appear to be quite slow and unpredictable. Despite the cross-breeding, the fish genome usually does not contain humans. Genes that have the desired effect. There is another alternative to traditional screening and breeding, using modern genetic engineering to produce fast-growing genes that turn to lean fish. In particular, genetically modified fish can use molecular biology. Clocks, segregation, and genes that make up the desired characteristics, while transfecting lean genes into fish species. Based on this modern technology, new properties that do not exist in the fish genome can be transferred from unrelated species. Colonize 'to give new and beneficial sex, please read the back first - Note - Things - Item Refill _ Write this page

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1323158 A71323158 A7

請 先 閲 讀 背 S 之~ 注 意- 事、 項 再 填_ 寫 本 頁 五、發明説明（4 ) 因此，對於飼養環境中的魚類可增進體重和降低死亡 率的化合物及/或方法仍存在著需求。較佳地，該方法是 安全，能被輕易施用以及不昂貴地施行，而且對環境友善 本發明的目的就是滿足上述問題，或者至少提供大眾 一種有效的選擇。 發明摘要 依據對於本發明的第一觀點，提供了用於飼養魚類以 增加其體重的含半胱胺組成物。 依據對於本發明的第二觀點，提供了餵食飼養環境申 魚類的含半胱胺組成物以降低因疾病和負面生長環境所導 致的死亡率。 較佳地，該含半胱胺組成物能藉由一最終狀態的飼料 來餵飼魚類。然而，含半胱胺組成物亦可以其他適合的， 即自主的飼料來餵飼魚類。 適當地，該組成物大體上可由1至95重量％之的具有 NH2-CH2-CH2-SH化學式的半胱胺或其鹽類化合物。該組成 物可包含1至80重量％的載體。亦作為一安定劑的載體可選 自包括環狀糊精或其衍生物所構成的組群。該組成物大體 上可包含30重量％的半胱胺或其鹽類化合物。該組成物可 包含10重量％的載體。該組成物可包含選自膨鬆劑崩解 劑或對該組成物提供外覆層之材料所構成之組群的組份。 該外覆層之材料在室溫條件中可為固態。該外覆層之材料 A7 發明説明 可在魚的腸内才可溶解。該外覆層在其組成物中可表現出 多層的結構。該外覆層可適合在在pH為1.5至3.5時保持不 溶°該最終飼料可包含飼料濃縮劑/或飼料補充物。該最 铜料可包含選自油菜籽、大豆、魚粉、小麥甦皮、小麥 草粉、礦物質、維他命及結著劑所構成組群之合適的基礎 飼料。該最終飼料大體上可包含3〇至15〇ppm的半胱胺。該 最終铜料大體上可包含100至5 OOppm的組成物。該最終飼 料在乾燥狀態下大體上可包含33至165ppm的半胱胺。該最 終飼料在乾燥狀態下大體上可包含丨1()至550ppm的組成物 依據本發明的第三觀點，提供一種飼養魚類的方法， 其包含了以合適的基礎铜料（如前述）來混合含半胱胺組成 物（如則述），以及由此混合產生的最終飼料飼養魚類的步 驟。 較佳地，該混合可包含直接以該基礎飼料與該組成物 混合。任擇地，該混合可包含製備一含有該含半胱胺組成 物的預混合物，以及隨後以基礎飼料與該預混合物材料混 合以形成最终飼料的步驟。該預混合物材料可藉由混合該 組成物與一合適的食物原料來製備。作為中間混合物之預 混合物的用途為促進混合以便於該組成物能更平均地分布 於該最終飼料中。該預混合物材料可具有1至25重量％之該 組成物的量。較佳地，該預混合物材料可具有1〇至2〇重量 %之該化合物的量。 依據本發明的第四觀點，係提供一種飼養魚類的方法 本紙張尺度適用中國國家標準（CNS) A4規格（210X297公爱） 請 閲 讀 背 面 之_ 注 項 再 填- 寫 1323158 A7 B7 五、發明説明（6 ) ，其包含一每日個別以含半胱胺或其鹽類化合物或如上述 之含半胱胺組成物，較佳經由一飼料來飼養魚類的步驟。 當魚在其平均體重相當或少於500g的發育階段時，該魚適 合以含30至60ppm的半胱或其鹽類化合物、或含100至 200ppm之含半胱胺組成物的飼料來傲飼。當魚在其平均體 重大於500g的發育階段時，該魚適合以含60至150ppm的半 胱或其鹽類化合物、或含200至500ppm之含半胱胺組成物 的飼料來餵飼。 根據本發明的第五觀點，提供一種包含了含半胱胺組 成物的魚飼料。該組成物大體上可包含1至95重量％之具有 NH2-CH2-CH2-SH化學式的半胱胺或其鹽類混合物。該載體 可選自環狀糊精或其衍生物所構成之組群。 依據本發明的第六觀點，提供了 一種製備上述魚飼料 的方法，其包含了一將含半胱胺組成物與該基礎飼料材料 混合的步驟。 發明詳述 本發明是基於半胱胺或其鹽類化合物、及/或含半胱 胺組成物的論證，其當由如魚類的水產動物所攝取時具有 至少增加其體重的活性。在此發現之前，並未暗示或有效 顯示半胱胺可對魚類有此活性。 對於哺乳動物已經發現類似的情形，魚類生長激素的 分泌被啟動了。魚類的生長激素釋放抑制激素（SS)的構造 經發現和哺乳動物的類似，同時該生長激素釋放抑制激素 本紙張尺度適用中國國家標準（CNS) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁)Please read the back S first ~ Note - things, items refill _ write this page 5, invention description (4) Therefore, there is still a need for compounds and / or methods that can increase body weight and reduce mortality in fish in the environment . Preferably, the method is safe, can be easily applied and inexpensively performed, and is environmentally friendly. The object of the present invention is to satisfy the above problems, or at least to provide the public with an effective choice. SUMMARY OF THE INVENTION In accordance with a first aspect of the present invention, a cysteamine-containing composition for feeding fish to increase its body weight is provided. According to a second aspect of the present invention, a cysteamine-containing composition for feeding fish in a feeding environment is provided to reduce mortality caused by disease and a negative growth environment. Preferably, the cysteamine-containing composition is capable of feeding the fish by a feed in a final state. However, the cysteamine-containing composition can also be fed to other suitable, i.e., autonomous feeds. Suitably, the composition may be substantially from 1 to 95% by weight of a cysteamine having a chemical formula of NH2-CH2-CH2-SH or a salt thereof. The composition may comprise from 1 to 80% by weight of the carrier. A carrier which is also a stabilizer may be selected from the group consisting of cyclodextrin or a derivative thereof. The composition may substantially contain 30% by weight of cysteamine or a salt thereof. The composition may comprise 10% by weight of a carrier. The composition may comprise a component selected from the group consisting of a leavening agent disintegrating agent or a material that provides an outer coating to the composition. The material of the outer cover layer may be solid at room temperature. Material of the outer cover A7 Description of the invention It can be dissolved in the intestines of fish. The overcoat layer may exhibit a multi-layered structure in its composition. The outer cover may be adapted to remain insoluble at a pH of from 1.5 to 3.5. The final feed may comprise a feed concentrate/feed supplement. The most copper material may comprise a suitable base feed selected from the group consisting of rapeseed, soybean, fish meal, wheat soy, wheat flour, minerals, vitamins and binding agents. The final feed may generally comprise from 3 to 15 ppm of cysteamine. The final copper material may generally comprise from 100 to 500 ppm of the composition. The final feed may generally comprise from 33 to 165 ppm of cysteamine in the dry state. The final feed may generally comprise a composition of from 1 (1) to 550 ppm in a dry state. According to a third aspect of the present invention, there is provided a method of raising fish comprising mixing with a suitable base copper material (as described above) A step comprising a cysteamine composition (as described above) and a final feed resulting from the mixing of the fish. Preferably, the mixing may comprise mixing the composition directly with the base feed. Optionally, the mixing may comprise the step of preparing a premix comprising the cysteamine-containing composition, and subsequently mixing the base feed with the premix material to form a final feed. The premix material can be prepared by mixing the composition with a suitable food material. The use of the premix as an intermediate mixture is to promote mixing so that the composition can be more evenly distributed in the final feed. The premix material may have from 1 to 25% by weight of the amount of the composition. Preferably, the premix material may have an amount of from 1 to 2% by weight of the compound. According to a fourth aspect of the present invention, a method for feeding fish is provided. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 public interest). Please read the back _ Note Refill - write 1323158 A7 B7 V. Invention Description (6) comprising the step of individually feeding the fish with a cysteamine or a salt thereof or a cysteamine-containing composition as described above, preferably via a feed. When the fish is at a developmental stage where the average body weight is equal to or less than 500 g, the fish is suitable for feeding with 30 to 60 ppm of cyste or a salt thereof, or a feed containing 100 to 200 ppm of a cysteamine-containing composition. . When the fish is in its developmental stage of an average body weight of 500 g, the fish is suitably fed with 60 to 150 ppm of cysteine or a salt thereof, or a feed containing 200 to 500 ppm of a cysteamine-containing composition. According to a fifth aspect of the invention, there is provided a fish feed comprising a cysteamine-containing composition. The composition may generally comprise from 1 to 95% by weight of a cysteamine having a chemical formula of NH2-CH2-CH2-SH or a mixture thereof. The vector may be selected from the group consisting of cyclodextrin or a derivative thereof. According to a sixth aspect of the present invention, there is provided a method of preparing the above fish feed comprising the step of mixing a cysteamine-containing composition with the base feed material. DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the demonstration of cysteamine or a salt thereof, and/or a cysteamine-containing composition which has an activity of at least increasing its body weight when ingested by an aquatic animal such as a fish. Prior to this discovery, it was not suggested or effectively shown that cysteamine can be active in fish. A similar situation has been found in mammals, and secretion of fish growth hormone has been initiated. The structure of the fish's growth hormone-releasing hormone (SS) has been found to be similar to that of mammals, and the growth hormone-releasing hormone is applied to the Chinese National Standard (CNS) A4 specification (210X297 mm) on the paper scale (please read the back) Please fill out this page again)

訂— 9 五、發明説明（7 ) (SS)亦抑制了魚類生長激素的釋放。已知生長激素調節了 魚類的代謝以及營養吸收且導致生長及其體重的增加。研 究顯不生長激素促進蛋白質合成且促進魚類體中正向的氮 平衡。 魚類的生長激素受體（GHR)廣泛的分佈於不同的組織 ，如肝臟、腦、生殖腺、支氣管、小腸以及腎臟。在生殖 腺中，生長激素及生長激素受體調整了類固醇的濃度，導 致***及卵子發育的促進。生長激素以及生長激素受體在 支氣管、小腸及腎臟所扮演的角色，是控制魚類體内的滲 透壓。一般相信小腸中生長激素的增加能影響營養的吸收 ，同時增加在循環中胺基酸的濃度，導致飼料換肉率的增 加。同時也發現生長激素受體的集中程度在魚類體内的其 他組織中大約為在肝臟中的3至6%。然而，生長激素與生 長激素受體的鍵結活性在肝臟中和其他組織中是一樣的。 如同所說明的，魚類的生長激素促進了生長同時調節 制滲透壓，且這些由胰島素生長因子（IGF1)居中完成。在 本發明中，半胱胺及/或者含半胱胺組成物的機制其目的 為耗盡魚類的生長激素釋放抑制激素，以便生長激素的濃 度能增加以促進生長。須注意的是，該生長激素係由魚體 内產生，而非外源生長激素。 心相彳5半耽胺具有扮演生長促進因子的生理活性。 天然的半胱胺是辅酶A的一部份（已知也是c〇A_SH或c〇A) ，是泛酸的輔酶形態。在代謝過程中，輔酶A扮演著作為 一 11硫酿基或與辅酶A之二氛硫酿基連結之二氫硫醢基變 本Μ張尺度適用中國國家標準（CNs) A4規格（210X297公爱·） 10 五、發明説明（8 ) 體的擔體。實驗顯示在其他如豬、牛、禽類、山羊以及兔 子等溫血動物顯示半胱胺可減少生長激素釋放抑制激素。 在獲得本發月期間，非預期地發現半脱胺對於魚類同樣也 可抑制生長激素釋放抑制激素。先前相信半胱胺對於生長 激素释放抑制激素的抑制只對哺乳動物及禽類有效。生長 激素釋放抑制激素的抑制增加了魚類血液中生長激素的濃 度，同時提高了各種其他生長促進因子，包含了類騰島素 生長因子（IGF-I)以及騰島素。如同解釋的，生長激素相信 可直接促進各種組織生理上的發展。 隨著這些不同之生長促進因子的增加，魚類的消化代 謝率明顯地上升了。已知魚類的一般蛋白質合成率相對地 上升，而因此魚類的體重因此而上升得更快速。 各種試驗經導引證明了施予含有含半胱胺組成物之飲 食（或飼料）增進了魚類生長以及體重，其中一個實驗詳細 敘述如後》 實驗 背景資料 實驗經發表以證明魚類以含半胱胺組成物餵飼的效果 ’其詳細敘述於後。用於本實驗之魚品種為已知的團頭妨 。有兩組實驗組及兩組控制組的魚類。每組有4〇至41隻魚 。每一組飼養在分離的水槽中。每一只水槽的容量大約為 0.26M3。水槽配備自動溫度控制系統，水溫維持在攝氏25 至26度之間。水槽亦配備了循環系統，藉此以新鮮的河水 A7 B7Order - 9 V. Inventive Note (7) (SS) also inhibits the release of fish growth hormone. Growth hormone is known to regulate fish metabolism and nutrient absorption and leads to growth and an increase in body weight. Studies have shown that growth hormone promotes protein synthesis and promotes a positive nitrogen balance in fish. The fish's growth hormone receptor (GHR) is widely distributed in different tissues such as the liver, brain, gonads, bronchi, small intestine, and kidney. In the genital gland, growth hormone and growth hormone receptors regulate the concentration of steroids, leading to the promotion of sperm and egg development. The role of growth hormone and growth hormone receptors in the bronchi, small intestine, and kidneys is to control the osmotic pressure in fish. It is generally believed that an increase in growth hormone in the small intestine can affect the absorption of nutrients, while increasing the concentration of amino acids in the circulation, resulting in an increase in feed rate. It has also been found that the concentration of growth hormone receptors is approximately 3 to 6% in the liver in other tissues of the fish. However, the binding activity of growth hormone to growth hormone receptor is the same in the liver as in other tissues. As illustrated, fish growth hormone promotes growth while regulating osmotic pressure, and these are centered by insulin growth factor (IGF1). In the present invention, the mechanism of cysteamine and/or cysteamine-containing composition is aimed at depleting the growth hormone releasing hormone of fish so that the concentration of growth hormone can be increased to promote growth. It should be noted that this growth hormone is produced by fish rather than by exogenous growth hormone. The heart phase 彳5-haloxime has physiological activity as a growth promoting factor. Natural cysteamine is part of coenzyme A (known to be c〇A_SH or c〇A) and is a coenzyme form of pantothenic acid. In the metabolic process, Coenzyme A plays the role of a 11 sulfur-based or disulfide-based disulfide-based variant of Coenzyme A. The Chinese Standard (CNs) A4 specification (210X297 public) ·) 10 V. Description of invention (8) Body support. Experiments have shown that in other warm-blooded animals such as pigs, cattle, poultry, goats, and rabbits, cysteamine can reduce growth hormone releasing inhibitory hormone. Unexpectedly, during the current month of the month, hemi-deamination also inhibits growth hormone releasing inhibitory hormones for fish. It has previously been believed that the inhibition of growth hormone releasing hormone by cysteamine is only effective for mammals and birds. Inhibition of growth hormone-suppressing hormone increases the concentration of growth hormone in the blood of fish, while increasing various other growth-promoting factors, including the TNT-I and T. As explained, growth hormone is believed to directly promote the physiological development of various tissues. As these different growth-promoting factors increase, the fish's digestion rate increases significantly. It is known that the general protein synthesis rate of fish is relatively increased, and thus the body weight of fish is thus increased more rapidly. Various tests have been shown to promote the growth of fish and body weight in a diet (or feed) containing a cysteamine-containing composition. One of the experiments is described in detail later. Experimental background data experiments have been published to prove that fish contain cysteine. The effect of feeding the amine composition is described in detail below. The fish species used in this experiment are known group heads. There were two groups of experimental groups and two groups of fish in the control group. There are 4 to 41 fish in each group. Each group is housed in a separate sink. The capacity of each sink is approximately 0.26M3. The sink is equipped with an automatic temperature control system that maintains a water temperature between 25 and 26 degrees Celsius. The sink is also equipped with a circulation system for fresh river water A7 B7

1323158 五、發明説明（9 ) 來取代水槽内的水以保持水的新鮮。 材料 A. 含半胱胺組成物 用於本實驗之含半胱胺組成物包含30重量％的半耽胺 、20重量°/❶的包含殼體材料以及包覆材料、26重量％的填 充劑、23_9重量％的碎裂劑及結著劑以及〇‘ 1重量％的香料 和香味劑。對於一可行之含半胱胺組成物的特定需求將進 一步在稍後的敘述中說明。 B. 預混合材料 預混合材料係一含有含半胱胺組成物的中間混合物。 該預混合材料促進隨後與基礎飼料材料的混合。用於製備 預混合材料的組份可選自一適合食品材料所構成之組群， 其包括胺基酸、鹽類、磷以及玉米粉。該預混合材料包含 從10至20重量％的含半胱胺組成物，隨然1至25重量％之一 較寬的可行範圍亦被使用。 C. 基礎飼料 用於實驗中之基礎飼料包含大約20重量％的油菜軒、 15重量°/〇的大豆、15重量％的魚粉、1〇重量％的麵皮、19 重量％的麥粉、5重量％的礦物質、〇_5重量％的結著劑以及 0.5重量％的維生素。然而，亦可使用其他適合的組份。 D. 最終飼料 完全相同的最終飼料種類A1及A2用於飼養該等二實 驗組（組I及II)的魚。該最終飼料種類幻及八2係由混合適量 之含有含半胱胺組成物與該基礎飼料所製備❶特別是，該 本紙張尺度適用中國國家標準（CNS> A4規格（210X 297公釐〉 請 先 閲 面 之 注 意· 事_ 項 再 填_ 寫 本 頁1323158 V. Description of invention (9) to replace the water in the sink to keep the water fresh. Material A. Cysteamine-Containing Composition The cysteamine-containing composition used in this experiment contained 30% by weight of samaramine, 20% by weight of ruthenium containing shell material and coating material, and 26% by weight of filler. 23-9 wt% of a fragmenting agent and a binder and 1% by weight of a fragrance and a fragrance. The specific need for a viable cysteamine-containing composition will be further described in the following description. B. Premixed material The premixed material is an intermediate mixture containing a cysteamine-containing composition. The premixed material promotes subsequent mixing with the base feed material. The component used to prepare the premixed material may be selected from the group consisting of a suitable food material comprising an amino acid, a salt, phosphorus, and corn flour. The premixed material comprises from 10 to 20% by weight of a cysteamine-containing composition, and a wide range of from 1 to 25% by weight is also used. C. Basic feed The basic feed used in the experiment contains about 20% by weight of rapeseed, 15 weight%/〇 of soybean, 15% by weight of fish meal, 1% by weight of dough, 19% by weight of wheat flour, and 5 weight. % mineral, 〇 5% by weight of the binder and 0.5% by weight of the vitamin. However, other suitable components can also be used. D. Final Feed The identical final feed types, A1 and A2, were used to raise the fish of the two experimental groups (Groups I and II). The final feed type is imaginary and the 8th series is prepared by mixing an appropriate amount of a cysteamine-containing composition with the base feed. In particular, the paper scale is applicable to the Chinese national standard (CNS> A4 specification (210X 297 mm) Note on the first reading · Things _ Item refill _ Write this page

-12 - 1323158 A7 ________B7_ 五、發明説明（10 ) 最終飼料種類A1及A2係經配製以包含大約200ppm的含半 胱胺組成物或3 0至60ppm的半胱胺β然而，一最終飼料實 際上可含有一 1〇〇至2〇〇ppm的含半胱胺或30至60ppm的半 肤胺的可行範圍。實際上，這些含半胱胺組成物或半胱胺 濃度之範圍的飼料係特別適合於體重相當於或少於5〇〇g的 魚。用於體重大於500g的魚，最終飼料較佳地包含200至 500ppm的含半胱胺組成物或6〇至I50ppm的半胱胺》微量的 飼料濃縮物及/或飼料補充物亦可包括於其中以增進該最 終飼料之營養價值的平衡。 實際上，當不使用預混合物時，該含半胱胺組成物可 直接與一基礎飼料混合。 該二控制組（組I及II)係以不添加該含半胱胺組成物之 完全相同的最終飼料種類Β1及B2餵飼。 最終飼料種類Al、A2以及Β 1、B2之間唯一的差異在 於前者包含所欲量的含半胱胺組成物。 方法 該實驗於2〇〇1年10月17日至2〇〇1年11月17日之間實施 。四組魚的個別體重在實驗前後測量。亦紀錄實驗期間魚 死亡的數目。亦紀錄四組魚所攝取的飼料量。 結果及討論 表1總結該實驗的結果。 本紙張尺度適用中國國家標準（CNS) A4規格（210X297公爱） 請 先 閲 讀 背 面 之- 注 意- 事--12 - 1323158 A7 ________B7_ V. INSTRUCTIONS (10) The final feed types A1 and A2 are formulated to contain approximately 200 ppm of cysteamine-containing composition or 30 to 60 ppm of cysteamine beta. However, a final feed actually It may contain from 1 to 2 ppm of cysteamine or from 30 to 60 ppm of hepatosamine. In fact, these feed lines containing a range of cysteamine compositions or cysteamine concentrations are particularly suitable for fish having a body weight of equal to or less than 5 g. For fish weighing more than 500g, the final feed preferably comprises from 200 to 500 ppm of cysteamine-containing composition or from 6 to 110 ppm of cysteamine. A small amount of feed concentrate and/or feed supplement may also be included therein. To improve the balance of the nutritional value of the final feed. In fact, when the premix is not used, the cysteamine-containing composition can be directly mixed with a base feed. The two control groups (Groups I and II) were fed with the exact same final feed types Β1 and B2 without the addition of the cysteamine-containing composition. The only difference between the final feed types Al, A2 and Β 1, B2 is that the former contains the desired amount of cysteamine-containing composition. Method The experiment was carried out between October 17, 2001 and November 17, 2001. The individual weights of the four groups of fish were measured before and after the experiment. The number of fish deaths during the experiment was also recorded. The amount of feed taken by the four groups of fish was also recorded. Results and Discussion Table 1 summarizes the results of this experiment. This paper scale applies to the Chinese National Standard (CNS) A4 specification (210X297 public). Please read the back side first - Note - Things -

訂 -13 - 1323158 A7 B7 五、發明説明（11 ) 飼料種類 A1 A2 Β1 B2 魚組 組1(試驗） 組Π(控制） 組Π(控制） 實驗前 曰期 2001年10月 5曰 2001年10月 5曰 2001 年 10 月5曰 2001年10月 5曰 魚數目 41 40 40 41 總重(g) 289.7 183.2 207.6 223.1 每隻魚平均 重量(g) 7.06 4.58 5.19 5.44 實驗後 曰期 2001年11月 17日 2001年11月 17日 2001 年 11 月17曰 2001年11月 17日 魚數目 41 40 39 41 總重(g) 558.9 403.0 419.9 381.5 每隻魚平均 重量(g) 13.6 10.10. 10.77 9.3 飼料攝取量 630.2 582.3 594.6 595.0 總重增加(g) 269.2 219.8 212.3 222.4 飼料轉換效 率 2.34 2.65 2.80 2.68 死魚數目 0 0 3 (每隻7.5g) 3 存活率(％) 100 100 92.5 92.7 (請先閱讀背面之注意事項再填寫本頁)Order-13 - 1323158 A7 B7 V. INSTRUCTIONS (11) Feed type A1 A2 Β1 B2 Fish group 1 (test) Group Π (control) Group Π (control) Pre-experimental period 2001 October 2001 曰 2001 10 Month 5曰 October 5, 2001 October 2001 5 Number of squid 41 40 40 41 Total weight (g) 289.7 183.2 207.6 223.1 Average weight of each fish (g) 7.06 4.58 5.19 5.44 Post-experiment flood season November 2001 17th November 17, 2001 November 17, 2001 November 17, 2001 Number of fish 41 40 39 41 Total weight (g) 558.9 403.0 419.9 381.5 Average weight of each fish (g) 13.6 10.10. 10.77 9.3 Feed intake Amount 630.2 582.3 594.6 595.0 Total weight increase (g) 269.2 219.8 212.3 222.4 Feed conversion efficiency 2.34 2.65 2.80 2.68 Number of dead fish 0 0 3 (7.5g each) 3 Survival rate (%) 100 100 92.5 92.7 (Please read the back Please fill out this page again)

•訂_ .P, 在控制組（I)中，三隻魚在實驗中死亡，二隻體重相似 的備用魚加入以取代兩隻死魚。在控制組π中，三隻魚在 實驗中死亡，三隻體重相似的備用魚加入以取代全部三隻 死魚。 如表1所示，兩試驗組（組I及II)之魚的總體重在實驗前 後分別為 472.9g[=289.7+183.2]及 961.9g[=558_9+403.0]° 因 本紙張尺度適用中國國家標準（CNS) A4規格（210X297公釐） 14 1323158 A7 _____B7___ 五、發明説明（12 ) 此總體重增加489_0g，換算約增加103%的總體重。兩控制 組（組I及II)之魚的總體重在實驗前後分別為 430.7g[207_6+223_l]及 801_4g[419.9+381.5]。因此總體重増 加370.7g，換算僅約增加86%的總體重。 兩試驗組（組I及II)之魚的平均體重在實驗前後分別為 5.84g及11.88g。因此平均體重增加6.03g，換算大約増加 103%的總體重。兩控制組（組I及π)之魚的平均體重在實驗 前後分別為5.32g及10.02g。因此平均體重增加4.70g，換算 僅約增加88%的總體重。此顯示在試驗組的魚在增加體重 方面成長至少快了 15% » 因此’可以推論以含半胱胺組成物的詞料飯飼的魚可 明顯地生長較快速。 亦發現二試驗組的魚其飼料轉換效率為2.34及2.65。 二控制組的魚其飼料轉換效率為2.80及2.68。相對較低的 飼料轉換效率暗示產生一個單位的體重需要較少量的飼料 。明顯的是，試驗組的魚在轉換飼料成為其體重為較有效 率的。 因此’可以推論以含有含半胱胺組成物的飼料餵飼的 魚可較有效率地轉換並吸收飼料成為其體重，以及本發明 之含半胱胺組成物可加其體重。 需注意的是水槽狀態一般對於水產工業係相似的。不 過，相較於野生動物該狀態相對較擁擠。因此，在水產養 殖中的一些魚類在此一環境死於疾病或過度擁擠並不稀奇 。然而，在二試驗組中的魚在實驗期間並無死亡，但是在 本紙張尺度適用中國國家標準（CNS) Α4規格（210X 297公釐） (請先閲讀背面之注意事項再填寫本頁)• Order _.P, in the control group (I), three fish died in the experiment, and two spare fish of similar weight were added to replace the two dead fish. In the control group π, three fish died in the experiment, and three spare fish of similar weight were added to replace all three dead fish. As shown in Table 1, the total weight of the fish in the two test groups (Groups I and II) was 472.9 g [= 289.7 + 183.2] and 961.9 g [= 558_9 + 403.0] before and after the experiment, respectively. Standard (CNS) A4 specification (210X297 mm) 14 1323158 A7 _____B7___ V. Description of invention (12) This total weight is increased by 489_0g, and the conversion is increased by about 103% of the total weight. The total weight of the fish in the two control groups (Groups I and II) was 430.7 g [207_6 + 223_l] and 801_4 g [419.9 + 381.5] before and after the experiment. Therefore, the overall weight is increased by 370.7g, and the conversion is only about 86% of the total weight. The average body weight of the fish in the two test groups (Groups I and II) was 5.84 g and 11.88 g before and after the experiment. Therefore, the average weight gain is 6.03g, which translates to an overall weight of 103%. The average body weight of the fish in the two control groups (Group I and π) was 5.32 g and 10.02 g, respectively, before and after the experiment. Therefore, the average weight gain is 4.70g, and the conversion is only about 88% of the total weight. This shows that the fish in the test group grew at least 15% faster in gaining weight. Therefore, it can be inferred that the fish fed with the cysteamine-containing composition can grow significantly faster. The feed conversion efficiency of the fish in the two test groups was also found to be 2.34 and 2.65. The feed conversion efficiency of the fish in the second control group was 2.80 and 2.68. Relatively low feed conversion efficiencies suggest that a unit of weight requires a smaller amount of feed. It is obvious that the test group of fish is more effective in converting the feed into its body weight. Therefore, it can be inferred that the fish fed with the feed containing the cysteamine-containing composition can efficiently convert and absorb the feed to its body weight, and the cysteamine-containing composition of the present invention can add its body weight. It should be noted that the state of the sink is generally similar to that of the aquaculture industry. However, this state is relatively crowded compared to wild animals. Therefore, it is not uncommon for some fish in aquaculture to die of disease or overcrowding in this environment. However, the fish in the two test groups did not die during the experiment, but the Chinese National Standard (CNS) Α4 specification (210X 297 mm) was applied to this paper scale (please read the notes on the back and fill out this page)

.訂· .Ρ, 15 1323158 A7.Book · .Ρ, 15 1323158 A7

丄 JO 五、發明說明（Η 构精、乙基石-環狀糊精（E-^S-CD)以及支鏈環狀糊精。環 狀糊精的化學通式為（c6〇5H9)n . (C605H9)2，且其結構式如 下。丄JO V. Description of the invention (Η 精, ethyl stone-cyclodextrin (E-^S-CD) and branched cyclodextrin. The chemical formula of cyclodextrin is (c6〇5H9)n. (C605H9) 2, and its structural formula is as follows.

(請先閲讀背面之注意事項再填寫本頁) 其中 a -CD n=4 KD n=5 ; 7 -CD n=6。 (%狀糊精係α _D-葡哌喃醣的環狀寡聚物。） 訂— 值得注意的是，環狀糊精的/5-CD型在用途上係較佳 的因為其为子内控約6-8A，使之成爲一特別適合之候選 物來作爲用於該半胱胺組成物之製備，這涉及使用一包含 製程的包覆化合物基質材料。在此所用之「環狀糊精」術 «吾忍指環狀糊精及/或其衍生物。具有安定並保護半胱胺 使之免於分解之任何環狀糊精的衍生物皆可使用。例如， 上述該等環狀糊精組群的任一或其衍生物皆可使用。當含 半胱胺組成物中包覆化合物基質材料的有效量範圍在1至 80重量％時，較佳的有效範圍為1至6〇重量％，且更佳為j 至40重量％之有效範圍的包覆化合物基質材料亦可使用。 所用之包覆化合物基質實際量將取決於在製備含半胱胺組 成物中所用的半胱胺。該含半胱胺組成物亦可包含1至 重量％的填充劑，然而較佳有效量的範圍為1至6〇重量0/〇，(Please read the notes on the back and then fill out this page) where a -CD n=4 KD n=5 ; 7 -CD n=6. (The cyclic oligo of the % dextrins α _D-glucopyranose.) Order - It is worth noting that the /5-CD type of cyclodextrin is preferred for its use because it is a sub-internal control Approximately 6-8A makes it a particularly suitable candidate for use in the preparation of the cysteamine composition, which involves the use of a coating compound matrix material comprising a process. "Cyclodextrin" used herein refers to cyclodextrin and/or its derivatives. Any derivative of cyclodextrin which has stability and protects cysteamine from decomposition can be used. For example, any of the above-mentioned cyclodextrin groups or derivatives thereof can be used. When the effective amount of the coating compound matrix material in the cysteamine-containing composition is in the range of 1 to 80% by weight, the effective range is preferably from 1 to 6 % by weight, and more preferably from J to 40% by weight. The coated compound matrix material can also be used. The actual amount of coating compound matrix used will depend on the cysteamine used in the preparation of the cysteamine-containing composition. The cysteamine-containing composition may also comprise from 1 to 5% by weight of filler, although a preferred effective amount ranges from 1 to 6 Torr and 0/〇.

17 - A7 一 - _ B7 ^_ 五、發明説明（15 ) (請先閲讀背面之注意事項再填寫本頁) 且更佳有效量範圍為1至40重量〇/〇的填充劑亦可用於該組 成物中。實際用量將取決於半胱胺以及包覆化合物基質的 實際用量。該填充劑選自經粉末化之纖維素、澱粉以及硫 酸鈣（如CaS〇4 · 2H2〇)所構成的組群。需注意若該填充劑 在含半胱胺組成物中的量超過9〇重量％，主要有效組份的 將因而降低，且含半胱胺組成物將變得無效。該含半胱胺 組成物亦可包含5至50重量％的碎裂劑以及結著劑，然而較 佳為10至40重量％的有效範圍，以及更佳為15至35重量％ 的有效範圍亦可使用。其實際用量將取決於所用的半胱胺 、包覆化合物基質材料以及其他組份。該結著劑以及碎裂 劑可選自羥丙基澱粉、微生物藻酸鹽、微晶化纖雉素及澱 粉。經確認的是若該組成物中碎裂劑及結著劑的量少於5 重量％，所產生之該組成物的顆粒將缺乏所需的硬度。此 外，該組成物的製造將變的非常的困難。然而，若該碎裂 劑以及結著劑多於50重量％，產生的組成物將有過度的硬 度，此特別在若該碎裂劑以及結著劑之混合物中其結著劑 表現大部分時。此將造成該組成物在魚的腸道難以吸收。 該含半胱胺組成物亦可包含〇.〇5至〇.3重量％之可為香精的 香味以及氣味劑。該含半胱胺組成物亦可包含i至2〇重量0/〇 的包覆材料，然而較佳的可行範圍為1至15重量％，更佳的 可行範圍為2至10重量％。其實際含量取決於半胱胺酸、包 覆化合物基質材料以及其他組份的實際量。該等包覆材料 在一般室溫為固狀且較佳在如腸内之驗性環境可溶解者。 該等包覆材料可選自纖維素醋酸態酞酸酯、激粉醋酸敌酸 本紙張尺度適用中國國家標準（CNS) A4規格（210X297公爱） 18 五、發明説明（16 (請先閲讀背面之注意^-項再填寫本頁) 知、甲基纖維素酞酸酯、源自酞酸之葡萄糖或果糖衍生物 、丙稀與甲基丙烯共聚物、聚曱基乙烯酯、馬來酐共聚物 的部分酯化物質、takh以及甲醛明膠所構成的組群。該等 包覆材料可在pH為1.5至3.5的酸性環境下仍為不溶。已確 疋的疋’若包覆材料的含料少於1重量％’組成物的顆粒不 月b藉由作為保s蔓層的包覆材料所完全包覆。該含半耽胺組 成物因此在由小腸吸收進入動物或本文所描述之水產養殖 魚類的血流之前就會分解《另一方面，若該包覆材料的含 量超過15重量％，該組成物中的有效組份將無法有效地從 該組成物中釋出。因此無法獲得預期的生長調節。無論如 何，已確認的是在用於增加所飼養之水產養殖魚類的體重 時，包含100至500ppm之該組成物（或30至75ppm半胱胺酸） 的飼料是有效的。 用於本發明所述之含半胱胺組成物係為每個具有大體 上車乂佳為0 ·28至0_9Omm直徑的小顆粒形式。這些顆粒係利 用微膠囊化法製備。該方法涉及利用具有包覆特性之巨大 分子的物質。可利用的物質之一為前述之包覆化合物基質 材料（其主要包含環狀糊精）。該包覆化合物基質材料係作 為包入半胱胺酸分子之分子膠囊的巨大分子物質，藉此保 護組成物中的半胱胺酸並隔離環境中的光、熱、空氣以及 水分。半胱胺的安定性因此得以保留。用於微膠囊化法之 包覆化合物基質材料較佳為具有6至12個葡萄糖分子的環 狀多糖化合物，該環狀多醣係藉由在芽胞桿菌屬 之存在下令環狀糊精糖轉移酶與澱粉反應而產生。以魚性 本紙張尺度適用中國國家標準（CNS) A4規格（210X297公釐） 19 1323158 A7 「 们 _ 五、發明説明（17 ) ' --- 、亞急性以及慢性毒性試驗的不同研究顯示這些巨大分子 ㈣是無毒的。隨後之微膠囊化步驟，每-顆粒可包覆至 彡一層且較佳為多層之上述的包覆材料。以下提供製備如 树明之含半歧組成物的方法，[㈣實施例詳述之 纟種不同的使用急性、亞急性與慢性毒性試驗之研究 [顯示該巨分子材料是無毒的。在該微膠囊化方法之後， 顆粒可被包覆以至少-層且較佳為數層的上述包覆材 _。下面提供_種減本㈣心製備半胱㈣成物之方 法之一實例的更為詳細之說明。 纟主要為氮氣的大氣環境τ，在—㈣四氣乙稀連結 Α配備有-個聚四氟乙稀塗覆授拌器之有套反應器中添加 4G8_75重量％之溶於乙醇中的含半胱胺氫氣酸溶液。所 用的含半胱胺之純度、熔點與燃燒殘留物較佳分別為98% 4更高、66至7(TC以及〇.()5重量％或更低。接著同樣在氮 氣之保護下，將120(^的/5-環糊精加至該反應器中。（沒_ 環糊精之品質係依據食物添加劑之要求。特別地乾燥基 礎純度係超過98%;乾燥之重量損失係低於1〇 〇%;燃燒殘 留物係低於0.2%;重金屬之含量係低於1〇ppm;砷含量係 低於2Ppmp該混合物接著於4(rc加熱歷時3小時。接著終 止加熱，且持續攪拌兩小時，由此所産生的產物在經過一 40至50 C之溫度真空乾燥後，予以研磨處理並篩析通經一 個網篩（例如4 0 -篩孔）。可能會與該組成物之組份相接觸的 所有儀器部件，較佳地應為不銹鋼所製成。在一乾燥環境 本紙張尺度翻中國國家標準（CNS) A4規格（21QX297公釐)~ '—~' -20 -17 - A7 一 - _ B7 ^_ V. INSTRUCTIONS (15 ) (Please read the note on the back and fill out this page) and a better effective amount of filler from 1 to 40 weight 〇 / 亦可 can also be used for this In the composition. The actual amount will depend on the actual amount of cysteamine and the coating compound matrix. The filler is selected from the group consisting of powdered cellulose, starch, and calcium sulphate (e.g., CaS〇4·2H2〇). It is to be noted that if the amount of the filler in the cysteamine-containing composition exceeds 9% by weight, the main effective component will be lowered, and the cysteamine-containing composition will become ineffective. The cysteamine-containing composition may also contain 5 to 50% by weight of a fragmenting agent and an anchoring agent, but preferably an effective range of 10 to 40% by weight, and more preferably 15 to 35% by weight of the effective range. be usable. The actual amount used will depend on the cysteamine used, the coating compound matrix material, and other components. The binder and the fragmenting agent may be selected from the group consisting of hydroxypropyl starch, microbial alginate, microcrystalline fibroin, and starch. It has been confirmed that if the amount of the fragmentation agent and the binder in the composition is less than 5% by weight, the particles of the composition produced will lack the desired hardness. In addition, the manufacture of the composition will become extremely difficult. However, if the fragmentation agent and the binder are more than 50% by weight, the resulting composition will have an excessive hardness, especially if the binder is mostly present in the mixture of the breaker and the binder. . This will cause the composition to be difficult to absorb in the intestines of the fish. The cysteamine-containing composition may also comprise from 〇5 to 0.3% by weight of a fragrance which is a fragrance and an odorant. The cysteamine-containing composition may also comprise a coating material of from 0 to 2 Å by weight, although a preferred range is from 1 to 15% by weight, more preferably from 2 to 10% by weight. The actual amount depends on the actual amount of cysteine, the matrix material of the coating compound, and other components. The coating materials are generally solid at room temperature and are preferably soluble in an intestine environment such as the intestine. The coating material may be selected from the group consisting of cellulose acetate phthalate, and the powder of acetic acid. The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 publicity). 18 V. Invention description (16 (please read the back first) Note ^-item and fill in this page) Know, methyl cellulose phthalate, glucose or fructose derivatives derived from citric acid, copolymers of propylene and methacrylic acid, poly(ryryl vinyl ester), maleic anhydride copolymerization a group consisting of a partially esterified material, takh, and formaldehyde gelatin. The coating materials are still insoluble in an acidic environment having a pH of 1.5 to 3.5. Less than 1% by weight of the composition of the particles is not completely covered by the coating material as a sap layer. The semiquinone-containing composition is thus absorbed into the animal from the small intestine or the aquaculture described herein. The blood flow of the fish is decomposed before. On the other hand, if the content of the coating material exceeds 15% by weight, the effective component in the composition cannot be effectively released from the composition. Growth regulation. Anyway, confirmed It is effective to use a feed containing 100 to 500 ppm of the composition (or 30 to 75 ppm of cysteine) when used to increase the body weight of the aquaculture fish to be reared. The composition is in the form of small particles each having a diameter substantially from 0. 28 to 0_9 mm. These particles are prepared by microencapsulation. The method involves the use of a substance having a large molecular weight of coating properties. One of the substances is the aforementioned coating compound matrix material (which mainly contains a cyclic dextrin). The coating compound matrix material serves as a macromolecular substance of a molecular capsule encapsulating a cysteine molecule, thereby protecting the composition. The cysteine in the environment and the light, heat, air and moisture in the environment. The stability of the cysteamine is thus retained. The coated compound matrix material used for the microencapsulation method preferably has 6 to 12 glucoses. a cyclic polysaccharide compound of a molecule produced by reacting a cyclic dextrin transferase with starch in the presence of a genus of the genus Bacillus. National Standard (CNS) A4 Specification (210X297 mm) 19 1323158 A7 "We_5, Invention Description (17) ' ---, subacute and chronic toxicity tests showed that these giant molecules (4) are non-toxic. In the microencapsulation step, each particle may be coated onto one layer and preferably a plurality of layers of the above-mentioned coating material. The following provides a method for preparing a semi-discriminate composition such as Shuming, [(4) different details of the examples A study using acute, subacute and chronic toxicity tests [showing that the macromolecular material is non-toxic. After the microencapsulation process, the particles may be coated with at least a layer and preferably several layers of the above cladding material. A more detailed description of one example of a method for reducing the content of the cysteous (four) protein is provided below.纟 is mainly the atmospheric environment of nitrogen, τ, in the set of reactors equipped with a PTFE coated applicator in the (four) four ethylene sulphur joints, adding 4G8_75% by weight of the soluble half in ethanol Cystamine hydrogen acid solution. The purity, melting point and combustion residue of the cysteamine to be used are preferably 98% 4 higher, 66 to 7 (TC and 5. () 5% by weight or less, respectively. Then, under the protection of nitrogen, 120 (^/5-cyclodextrin is added to the reactor. (No _ cyclodextrin quality is based on the requirements of food additives. In particular, the dry basis purity is over 98%; the dry weight loss is less than 1 〇〇%; combustion residue is less than 0.2%; heavy metal content is less than 1〇ppm; arsenic content is less than 2Ppmp. The mixture is then heated at 4 (rc heating for 3 hours. Then the heating is terminated and stirring is continued for two hours) The product thus produced is subjected to a vacuum drying at a temperature of 40 to 50 C, then ground and sieved through a mesh screen (for example, a 40-mesh opening), possibly with a component of the composition. All instrument parts in contact should preferably be made of stainless steel. In a dry environment, the paper size is changed to the Chinese National Standard (CNS) A4 specification (21QX297 mm)~ '-~' -20 -

、^— (請先閲讀背面一足注^^-項#填寫本頁), ^— (Please read the first one on the back ^^-item# fill this page)

五、發明説明（18 ) 之保護下’於一個槽式混合器中加入4200g(乾重）之經進行 過上述包含製程的含半胱胺、2600g的填料以及1200g的碎 裂劑與1700g的結著劑。該等組份接著經徹底混合，一適量 之無水乙醇可加入並與之混合《所產生的混合物呈現一具 有中度硬度之軟質料，藉此可以手掌輕握而將之塑形爲一 個球體。經塑形成球體之該産生之混合物可接著利用一輕 觸而令其散開。該混合物在氮氣保護下以一個造粒機予以 切粒後，所產生之小顆粒被立即地送至一流體床乾燥器， 並接著在一實質真空之環境内，以4〇i5〇〇c之溫度下將之 乾燥。腸溶性包覆材料接而藉由一個利用下列配方之方法 來製備：8g的纖維素醋酸醜酸酯、2.4ml的聚乙二醇對苯二 甲酸醋、33.Oml的乙酸乙酯與33.6ml的乙酸異丙酯。上述 所得之該形成的顆粒，在氮氣的保護下係均一地以至少一 層、但較佳為多層的上述腸溶性包覆材料包覆。換言之， 在每一該組成物之生成顆粒的包覆材料係以一多層結構存 在著。該腸溶性包覆材料係為僅能在一鹼性環境下溶解的 。這可防止當該組成物仍存於該動物胃十時，半胱胺過早 地自該組成物中逸出。半胱胺可不利地刺激動物的胃之胃 黏膜。本案半胱胺組成物所產生之顆粒接著在一實質真空 乾燥器中，以40t至5(TC之溫度經乾燥完全。於是，所有 的溶劑被移除。所産生之顆粒接著冷卻至室溫，利用一個 懸臂式雙螺旋混合器將微膠囊與一適量之調味劑和氣味劑 混合。該半胱胺組成物係為一種内部具有含半胱胺氫氣酸 與環狀糊精，且其外部以該腸溶性材料包覆的微膠囊。 1323158 A7 ---- B7___ 五、發明説明（I9 ) 生成之組成物會呈現具有平滑外表、良好流動性質且易與 各種動物飼料相混合的小顆粒（或微粒）形狀。該組成物之 每一顆粒的直徑較佳為0.28至〇.9〇m„^該組成物亦具有優 良的安定性。已發現當該組成物以密封塑膠袋包裝，並儲 存於一涼爽、黑暗與乾燥的地方歷時一年之後，其特性維 持不變。因此，該組成物符合作爲一飼料添加劑之要求。 具有上述之特定構成之組成物具有許多超過含半胱胺本身 之功能性優點。首先，包覆於該組成物中的含半胱胺活性 在經製造之後仍可維持著❶這是重要的，因為諸如該組成 物的飼料添加劑在使用之前可儲存一段相當長之時間。第 二，該組成物不會對經該組成物餵食的動物引起任何顯著 的胃副作用。第三，該組成物的活性不僅在貯存期間維持 著，更重要的是可以維持至該組成物抵達魚的小腸時。第 四，該組成物可以一大規模基礎且有成本效率的方式容易 地施用至水產養殖魚類，因爲它可容易地與任—種基本飼 料相混合。根本不需要分開的操作程序或注射。 上述揭示之的各參考文獻的内容，國際申請案 PCT/EP01/14628以及中國大陸專利申請案第〇〇132ι〇7 2號 ，包括在此引述的參考文獻在此全部併入參考。須注竞許 多變化、修飾以及進一步的具體實施係為可能的，因^所 有變化以及具體實施係視為本發明之範圍内。 本纸張尺度適用中國國家標準（CNS) A4規格（210 X 297公釐）5. Under the protection of invention (18), 4200 g (dry weight) of a cysteamine, 2600 g of filler and 1200 g of a fragmenting agent and 1700 g of a knot containing the above-mentioned inclusion process were added to a tank mixer. Attention. The components are then thoroughly mixed and an appropriate amount of absolute ethanol can be added and mixed. The resulting mixture exhibits a moderately soft material which can be shaped into a sphere by gently gripping the palm of the hand. The resulting mixture of plastic shaped spheres can then be spread out with a touch. After the mixture is pelletized by a granulator under the protection of nitrogen, the small particles produced are immediately sent to a fluid bed dryer, and then in a substantially vacuum environment, 4 〇i5〇〇c Dry at temperature. The enteric coating material was prepared by a method using the following formulation: 8 g of cellulose acetate valerate, 2.4 ml of polyethylene glycol terephthalate, 33.0 ml of ethyl acetate and 33.6 ml. Isopropyl acetate. The pellets obtained as described above are uniformly coated with at least one layer, but preferably a plurality of layers of the enteric coating material under the protection of nitrogen. In other words, the coating material forming the particles in each of the compositions is present in a multi-layered structure. The enteric coating material is soluble only in an alkaline environment. This prevents cysteamine from escaping prematurely from the composition when the composition is still present in the stomach of the animal. Cysteamine can adversely irritate the gastric mucosa of an animal's stomach. The granules produced by the cysteamine composition of the present invention are then dried in a substantially vacuum desiccator at 40 to 5 (the temperature of TC is completely dried. Thus, all the solvent is removed. The resulting granules are then cooled to room temperature, The microcapsules are mixed with an appropriate amount of flavoring agent and odorant using a cantilever double helix mixer. The cysteamine composition is an inner portion having a cysteamine-containing hydrogen acid and a cyclodextrin, and the exterior thereof is Microcapsules coated with enteric materials. 1323158 A7 ---- B7___ V. INSTRUCTIONS (I9) The resulting composition will exhibit small particles (or particles) that have a smooth appearance, good flow properties, and are easily mixed with various animal feeds. The shape of each of the particles of the composition is preferably from 0.28 to 〇.9〇m. The composition also has excellent stability. It has been found that the composition is packaged in a sealed plastic bag and stored in a The cool, dark and dry place lasts for one year and its properties remain unchanged. Therefore, the composition meets the requirements as a feed additive. The composition having the specific composition described above has many super Functional advantage of containing cysteamine itself. First, it is important that the cysteamine-containing activity encapsulated in the composition maintains hydrazine after manufacture because feed additives such as the composition are used before use. It can be stored for a considerable period of time. Second, the composition does not cause any significant gastric side effects on the animals fed the composition. Third, the activity of the composition is not only maintained during storage, but more importantly It can be maintained until the composition reaches the small intestine of the fish. Fourth, the composition can be easily applied to aquaculture fish in a large-scale, cost-effective manner because it can be easily mixed with any basic feed. No separate operating procedures or injections are required at all. The contents of the above-referenced publications, the International Application No. PCT/EP01/14628, and the Chinese Patent Application No. 136, the entire disclosure of which is incorporated herein by reference. The literature is hereby incorporated by reference in its entirety. It is possible to note that many variations, modifications, and further implementations are possible, since all changes and Department deemed within the scope of the invention. The present paper scale applicable Chinese National Standard (CNS) A4 size (210 X 297 mm)

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Claims (1)

1323158 :、申請專利範圍 第91114532號專利申請案申請專利範圍修正本 98128 I · 一種魚類飼料，其包含有含半胱胺組成物，其中該含半 胱胺組成物實質包含1至95重量％之具有 NH^CHs-CHz-SH化學式的半胱胺或其鹽類化合物， 以及1至80重量％的作為包覆化合物基質材料之載 體，以減低半胱胺的副作用並保持半胱胺的活性。 2.如申請專利範圍第1項的魚類飼料，其中該載體係選自 包含環狀糊精或其衍生物之組群。 3. 如申請專利範圍第1項的魚類飼料，其係用於增進魚 類的生長及/或增加魚類的體重-。 4. 如申請專利範圍第1項的魚類飼料，其係用於在水產 養殖中降低魚類由於疾病或不利生存條件所致之死亡 率。 5. 6. 如申請專利範圍第3或4項的魚類飼料，其中該半胱 胺或含半胱胺組成物可經由一最終飼料飼養該魚類。 如申請專利範圍第3或4項的魚類飼料，其中該組成 物實質包含i至95重量％之具有NH2_CH2-CH2_sh化 學式的半胱胺或其鹽類化合物。 如申明專利範圍第3或4項的魚類飼料，其中該組成 物實質包含1至80重量％的一載體。 如申請專利範圍第7項的魚類飼料，其中該載體係選 自包括％狀鞠精或其衍生物的組群。 =申請專利範圍第6項的魚類飼料’其中該組成物實 貝包含30重量％的半胱胺或其鹽類化合物。 -23- 9. U23158Patent application No. 91,112, 432, the entire disclosure of which is incorporated herein by reference in its entirety, the entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire entire all all all A cysteamine having a chemical formula of NH^CHs-CHz-SH or a salt thereof, and 1 to 80% by weight of a carrier as a matrix material for a coating compound to reduce the side effects of cysteamine and maintain the activity of cysteamine. 2. The fish feed according to claim 1, wherein the carrier is selected from the group consisting of cyclodextrin or a derivative thereof. 3. If the fish feed of claim 1 is used to increase the growth of fish and/or increase the weight of the fish -. 4. Fish feed as claimed in item 1 of the patent application is used to reduce the mortality rate of fish due to disease or adverse living conditions in aquaculture. 5. 6. The fish feed according to claim 3, wherein the cysteamine or cysteamine-containing composition is capable of feeding the fish via a final feed. The fish feed according to claim 3, wherein the composition substantially comprises from i to 95% by weight of a cysteamine having a NH2_CH2-CH2_sh chemical formula or a salt thereof. A fish feed according to claim 3, wherein the composition substantially comprises from 1 to 80% by weight of a carrier. A fish feed according to item 7 of the patent application, wherein the carrier is selected from the group consisting of % quercetin or a derivative thereof. = Fish feed of claim 6 wherein the composition contains 30% by weight of cysteamine or a salt thereof. -23- 9. U23158 六、申請專利範圍 10. 如申請專利範圍第7項的魚類飼料，其中該組成物實 質包含20重量％的該載體。 11. 如申請專利範圍第3或4項的魚類飼料，其中該組成 物進一步包含選自包括膨鬆劑、填充劑、碎裂劑、結 著劑以及包覆材料之組群的組份。 12·如申請專利範圍第11項的魚類飼料，其中該包覆材料 在室溫狀態下為固狀。6. Scope of application for patents 10. The fish feed according to item 7 of the patent application, wherein the composition substantially comprises 20% by weight of the carrier. 11. The fish feed according to claim 3, wherein the composition further comprises a component selected from the group consisting of a leavening agent, a filler, a chipping agent, an anchoring agent, and a coating material. 12. The fish feed according to claim 11, wherein the covering material is solid at room temperature. 如申請專利範圍第u項的魚類飼料，其中該包覆材料 係腸衣的且在該魚類腸道為可溶的。 14·如申請專利範圍第11項的魚類飼料，其中該包覆材料 在該組成物中係表現一多層結構。 15 ·如申請專利範圍第11項的魚類飼料，其中該包覆材料 係適合在pH 1.5至3.5保持不溶的。 16·如申請專利範圍第3或4項的魚類飼料，其中該最終 飼料進一步包含飼料濃縮劑及/或飼料補充物。 17A fish feed according to claim 5, wherein the coating material is casing and is soluble in the intestinal tract of the fish. 14. The fish feed according to claim 11, wherein the covering material exhibits a multilayer structure in the composition. 15. A fish feed according to claim 11 wherein the coating material is suitable to remain insoluble at a pH of 1.5 to 3.5. 16. The fish feed according to claim 3 or 4, wherein the final feed further comprises a feed concentrate and/or a feed supplement. 17 •如申請專利範圍第3或4項的魚類飼料，其中該最終 飼料包含選自包括油菜籽、棉籽、黃豆、魚粉、小麥 麩皮、小麥草粉、礦物質、維他命及結著劑之組群之 合適的基礎飼料。 如申凊專利範圍第3或4項的魚類飼料，其中該最終 飼料實質包含30至15〇ppm的半胱胺。 如申。奮專利範圍第18項的魚類飼料，其中該最終飼料 只質包含60ppm的半胱胺。 2 〇 如申睛專利範圍第3或4項的魚類飼料，其中該最終• A fish feed according to claim 3 or 4, wherein the final feed comprises a group selected from the group consisting of rapeseed, cottonseed, soybean, fish meal, wheat bran, wheat grass powder, minerals, vitamins and binding agents. The right base feed. A fish feed according to claim 3 or 4, wherein the final feed substantially comprises 30 to 15 ppm of cysteamine. Such as Shen. The fish feed of the 18th patent range, wherein the final feed contains only 60 ppm of cysteamine. 2 鱼类 fish feed according to item 3 or 4 of the scope of the patent application, where the final -24- 1323158 六、申請專利範圍 飼料實質包含1〇〇至500ppm的該組成物6 21·如申請專利範圍第20項的魚類飼料，其中該最終飼料 實質包含200ppm的該組成物。 22. 如申請專利範圍第3或4項的魚類飼料，其中該最終 飼料在其乾無狀態貫質包含33至165ppm的半胱胺。 23. 如申請專利範圍第3或4項的魚類飼料，其中該最終 飼料在其乾餘狀癌實質包含11〇至55Oppm的該組成 物。 24. —種製備如申請專利範圍第丨或2項之魚類飼料的方 法’其包含一將該含半胱胺纽成物與一基礎飼料混合 的步驟。 25. —種用於增進魚類的生長及/或增加魚類的體重的方 法’其包含下列步驟： (i)給魚含半胱胺組成物，以增進魚類的生長及/或 增加魚類的體重；或是 (11)以一包含有含半胱胺組成物的魚類飼料來餵食魚 類， 其中該含半胱胺組成物實質包括： (a) 1至95重量％之具有NH2-CH2-CH2-SH化學式的半 胱胺或其鹽類化合物；以及 (b) 1至80重量％的一作為包覆化合物基質材料之載 體’以減低半胱胺的副作用並保持半胱胺的活性。 -25--24- 1323158 VI. Scope of Application The feed substantially comprises from 1 to 500 ppm of the composition. 6 21. The fish feed according to claim 20, wherein the final feed substantially comprises 200 ppm of the composition. 22. The fish feed according to claim 3, wherein the final feed comprises 33 to 165 ppm of cysteamine in its dry state. 23. The fish feed according to claim 3, wherein the final feed comprises from 11 to 55 ppm of the composition in the dry form of the cancer. A method of preparing a fish feed according to claim 2 or 2, which comprises the step of mixing the cysteamine-containing compound with a base feed. 25. A method for increasing the growth of fish and/or increasing the weight of a fish' comprising the steps of: (i) providing the fish with a cysteamine composition to increase the growth of the fish and/or increase the weight of the fish; Or (11) feeding the fish with a fish feed comprising a cysteamine-containing composition, wherein the cysteamine-containing composition substantially comprises: (a) 1 to 95% by weight of NH2-CH2-CH2-SH a cysteamine of the formula or a salt thereof; and (b) from 1 to 80% by weight of a carrier as a matrix material for the coating compound to reduce the side effects of cysteamine and maintain the activity of cysteamine. -25-