1330532 九、發明說明 【發明所屬之技術領域】 本發明爲有關一種生產對治療各種疾病有效的蚯蚓乾 燥粉末的方法，該方法不會降低蚯蚓原有的藥理作用，並 可以去除附著於消化道內、體表的污物。 【先前技術】 自古以來主要在東洋各國中，蚯蚓被應用作爲各種疾 病的預防劑、治療劑，目前已知有膀胱結石縮小劑及排出 促進劑、黃疸治療劑、分娩促進劑、强壯劑、育毛劑、强 精劑、解熱劑、痙攣治療劑、血液迂迴促進劑、半身不遂 治療劑、間接鎭痛劑、排尿劑、支氣管哮喘劑、高血壓治 療劑等用途。 但是，以蚯蚓活體爲原料製備口服給藥的藥物製劑時 ，必須去除殘留在蚯蚓消化道內的消化物、附著於體表的 污物等，迄今爲止，已有提出了多種以此爲目的的方法。 直至目前，提出了以下方法，例如，將蚯蚓活體浸泡 在鈉鹽或鉀鹽等鹼鹽的水溶液中，排泄出消化道內的糞土 後，濕式粉碎，將得到的懸濁液真空冷凍乾燥，來生產作 爲糖尿病治療劑、抗高血脂劑或血壓調節劑有效的蚯蚓乾 燥粉末的方法（JP1-47718A、 JP1-47719A、 JP1-47720A 及JP 1 -26 863 9A);將蚯蚓活體在維持於6〜26°C的酸性 水溶液中浸泡〇. 1〜5小時’去除蚯蚓消化道內的糞土後 磨碎，對磨碎物進行脫氣，然後進行階段性升溫，同時真 -5- 1330532 空乾燥以生產血栓病患者治療藥物的方法（JP3-72427A) 等。 然而’蚯蚓活體在鹼鹽水溶液或酸水溶液中長時間浸 泡，會造成蚯蚓的體力下降，其結果爲，由於活體內所含 的蛋白質發生變性’酶作用下降，從而使所得蚯蚓粉末的 藥理作用變差。 【發明內容】 本發明的目的在於，提供一種在保持良好藥理作用的 狀態下，生產蚯蚓乾燥粉末的方法，該方法不會降低蚯蚓 體力’且可有效率地從蚯蚓活體排泄殘留在其消化道內的 消化物或附著於體表的污物。 本發明人等爲了有效使殘留在蚯蚓活體消化道內的消 化物排泄出來，而不損失蚯蚓的體力，進行反覆深入硏究 的結果發現：先對活蚯蚓進行加工，通過在明亮處放置及 再與有機酸接觸，製造蚯蚓不喜歡的環境，在該條件下培 育蚯蚓一定時間，蚯蚓爲了適應所述環境，排泄出消化道 內的消化物，由於所述排泄物覆蓋全身，所以去除附著於 體表的污物即排泄物就可以得到去除雜質的活體，基於該 發現完成本發明。 即，本發明提供一種蚯蚓乾燥粉末之製造方法，該方 法包括，將活蚯蚓在明亮處放置10〜50小時後，用不織 布等吸附去除附著於體表的污物，再與有機酸接觸，然後 用水迅速稀釋調整pH至2〜5，在該條件下保持3〜180 -6- 1330532 分鐘後，經水洗，磨碎，將該磨碎物在-18 °C〜-35 °C下冷 凍20〜240小時，再在真空下進行冷凍乾燥，同時進行脫 氣。 以下，將對本發明的方法進行詳細說明。 本發明方法中，採用活蚯蚓作爲原料，所述活蚯蚓， 可以任意選自例如粉正蝴（Lumbricus rubellus)、陸正 虫引(Lumbricus terrestris )、赤子愛勝虫引(Eisenia foetida)、背闇異唇蝴（Allolobophora caliginosa)、八 道住木蝴（Dendrobaena octaedra ) 、Allolobophora japonica Michaelsen (學名） 、Drawida hattamimizu1330532 IX. INSTRUCTIONS OF THE INVENTION [Technical Field to Which the Invention Is Alonged] The present invention relates to a method for producing a dry powder which is effective for treating various diseases, which does not reduce the original pharmacological action and can be removed from the digestive tract. The dirt on the surface. [Prior Art] Since ancient times, it has been used as a prophylactic and therapeutic agent for various diseases in the Toyo countries. Currently, there are known bladder stone reduction agents and discharge enhancers, jaundice therapeutic agents, birth promoters, strong agents, and hair growth. Agent, strong essence agent, antipyretic agent, sputum therapeutic agent, blood bypass agent, hemiplegia treatment agent, indirect analgesic agent, urination agent, bronchial asthma agent, hypertension therapeutic agent and the like. However, when preparing a pharmaceutical preparation for oral administration using a living body as a raw material, it is necessary to remove the digested matter remaining in the digestive tract of the sputum, the dirt adhering to the surface of the body, and the like. method. Up to now, the following methods have been proposed. For example, the living body is immersed in an aqueous solution of an alkali salt such as a sodium salt or a potassium salt, excreted in the digested earth, wet pulverized, and the obtained suspension is vacuum-dried. A method for producing a dry powder of sputum effective as a therapeutic agent for diabetes, an antihyperlipidemic agent or a blood pressure regulating agent (JP1-47718A, JP1-47719A, JP1-47720A, and JP 1 -26 863 9A); Soak 〇 in an acidic aqueous solution at ~26 ° C. 1~5 hours' After removing the faeces in the digestive tract, grind it, degas the ground material, and then gradually increase the temperature, while the true -5 - 1330532 air drying A method for producing a therapeutic drug for a patient with thrombosis (JP3-72427A) and the like. However, when the living body is immersed in an alkali salt aqueous solution or an aqueous acid solution for a long time, the physical strength of the cockroach is lowered, and as a result, the enzyme activity of the protein contained in the living body is degraded, so that the pharmacological action of the obtained bismuth powder is changed. difference. SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing a dry powder of yttrium in a state in which a good pharmacological action is maintained, which does not reduce the body strength and can be efficiently excreted from the sputum living body in its digestive tract. Digestion inside or dirt attached to the body surface. In order to effectively excrete the digested material remaining in the digestive tract of the sputum, without losing the physical strength of the sputum, the inventors found that the sputum was processed first, and then placed in a bright place and then placed in a bright place. Contact with an organic acid to create an environment that is not liked by cockroaches, and cultivate for a certain period of time under the conditions, in order to adapt to the environment, excrete the digestive material in the digestive tract, and remove the adhering body because the excrement covers the whole body The present invention was completed based on the findings that the soil of the watch, that is, the excrement, was able to obtain a living body from which impurities were removed. That is, the present invention provides a method for producing a mash dry powder, which comprises, after placing the live cockroaches in a bright place for 10 to 50 hours, adsorbing and removing the dirt adhering to the body surface with a non-woven fabric or the like, and then contacting the organic acid, and then Dilute with water to adjust the pH to 2~5. After maintaining for 3~180 -6- 1330532 minutes under this condition, wash with water, grind, and freeze the ground product at -18 °C~-35 °C. After 240 hours, freeze-drying was carried out under vacuum while degassing. Hereinafter, the method of the present invention will be described in detail. In the method of the present invention, living cockroaches are used as raw materials, and the living cockroaches can be arbitrarily selected from, for example, Lumbricus rubellus, Lumbricus terrestris, Eisenia foetida, and back darkness. Allolobophora caliginosa, Dendrobaena octaedra, Allolobophora japonica Michaelsen (scientific name), Drawida hattamimizu
Hatai (學名）、Pheretima divergens Michaelsen (學名） 、Pheretima communissima (學名）、Pheretima agrestis (學名）、Pheretima sieboldi Horst (學名）'Pheretima hilgendorfi (學名）、Pontodrilus matsushimensis lizuka (學名）、絲虫丘虫引(Tubifex hattai Nomura )、 Limnodrilus gotoi Hatai = L. Socialis Stephenson 等一般 統稱爲蚯蚓的環節動物門寡毛綱類生物。 本發明方法中，先將活蚯蚓在明亮處放置特定的時間 。即，從養殖床中取出活蚯蚓，轉移到托盤般的平箱中， 在陽光下或夜間在電照明下保持明亮放置1 〇〜5 0小時。 這時平箱內的收納量設置爲形成30〜60mm，優選40〜 50mm厚的量。由於ί丘蚓具有夜行性，放置在明亮處，會 發揮自我防禦的本能，爲了阻斷光，防止水分蒸發而附著 的污物來覆蓋體表，所以反覆數次通過適當的方法去除這 1330532 些污物，最後從腸道內排泄出固體物質或體液來覆蓋體表 。於是，在這期間內，在平箱中，大量的活蚯蚓呈相互疊 在一起的狀態，各個蚯蚓爲了確保暗處而鑽入其他蚯蚓的 身體之下，相互接觸，通過摩擦，將覆蓋於體表的污物、 排泄物擦落。於是，例如用不織布等覆蓋在活蚯蚓上，擦 落的污物、排泄物就能夠被其吸附，不費力即可去除。Hatai (scientific name), Pheretima divergens Michaelsen (scientific name), Pheretima communissima (scientific name), Pheretima agrestis (scientific name), Pheretima sieboldi Horst (scientific name) 'Pheretima hilgendorfi (scientific name), Pontodrilus matsushimensis lizuka (scientific name), silkworm worm ( Tubifex hattai Nomura ), Limnodrilus gotoi Hatai = L. Socialis Stephenson, etc. are generally referred to as 蚯蚓 蚯蚓 环节 门 寡 寡 。 。 。. In the method of the present invention, the live cockroaches are first placed in a bright place for a specific period of time. That is, remove the live cockroaches from the culture bed, transfer them to a tray-like flat box, and keep them bright for 1 〇 to 50 hours under sunlight or at night under electric lighting. At this time, the storage amount in the flat case is set to be 30 to 60 mm, preferably 40 to 50 mm thick. Because ί丘蚓 has a nocturnal nature, it is placed in a bright place, and it exerts its own self-defense instinct. In order to block the light and prevent the dirt from evaporating, it covers the body surface. Therefore, the 1330532 is removed by appropriate methods several times. Contaminants, and finally excrete solid or body fluids from the intestines to cover the body surface. Therefore, during this period, in the flat box, a large number of live rafts are stacked on each other, and each scorpion penetrates into other squat bodies in order to ensure the darkness, and contacts each other, and rubs them to cover the body. The dirt and excrement of the watch are wiped off. Then, for example, it is covered with a non-woven fabric or the like, and the dirt and excrement that is rubbed off can be adsorbed by the living tissue, and can be removed without much effort.
本發明方法中，將這樣去除污物或排泄物的活蚯蚓水 洗後，與有機酸接觸，急速形成讓活蚯蚓產生不適感的生 活環境。與該有機酸的接觸，既可以將有機酸粉末直接撒 在活蚯蚓上，也可噴灑高濃度的有機酸水溶液。 這時使用的有機酸，可以列舉例如乙酸、蘋果酸、檸 檬酸、乳酸、丙二酸、琥珀酸等。所述物質既可單獨使用 ’也可2種以上混合使用。特佳之有機酸例如是檸檬酸。 這樣的情况下，如果活蚯蚓長時間與有機酸粉末或高 濃度的有機酸水溶液接觸，就會死亡，或者失去生活能力 ’而不能排泄出消化道內的消化物，所以活蚯蚓與有機酸 的接觸要儘量快，通常在30秒以內，優選在20秒以內就 必須用水稀釋有機酸，調整pH至2〜5的範圍。所述的 用水稀釋必須迅速進行。時間過長將引起蚯蚓死亡，因此 必須充分注意。 在本發明的方法中，利用有機酸的殺菌作用，暫時對 活蚯蚓進行殺菌’然後，通過冷凍真空乾燥進一步殺菌， 能夠確實更保證殺菌效果。 在本發明的方法中，將夜行性的活蚯蚓放置在難以行 -8- 1330532 動的生活環境下即明亮處，然後，將該活蚯蚓放入迅速產 生不適感的生活環境下，活蚯蚓由於自我保護本能釋放出 污物、排泄物等固體物質或體液以改善生活環境，自動地 進行淨化。 有機酸具有殺菌性，所以在本發明的方法中，如上所 述’利用有機酸，發揮排泄殘留在消化道內的消化物的作 用，同時能夠殺滅水洗無法去除的雜菌。 爲了發揮所述的身體保護機能，必須存在水分，由於 活蚯蚓的組織的6 5 %是水分，所以用於發揮所述身體保 護機能的時間尙且有些寬餘，但是如果活蚯蚓死亡，就一 無所得，所以將活蚯蚓放置在促使其產生不適感的生活環 境下的時間必須慎重控制》所述時間受條件控制，通常在 3〜180分鐘範圍內。 將活蚯蚓放置在與有機酸接觸而促使其產生不適感的 生活環境下，不僅將殘留在消化道內的消化物排出，還將 含有產生惡臭的氨和對人體有毒的砷的體液排出，氨幾乎 被完全去除。 以往，由於將洗淨的活蚯蚓直接進行磨碎冷凍，因此 無法去除氨，在後續的冷凍真空乾燥過程中去除氨，但因 爲不能完全去除氨’產品質量參差不齊，使得產品的品質 管理出現困難。並且，在冷凍真空乾燥過程中，爲了去除 氨時’則容易損傷該過程中的裝置，必須進行繁瑣的維護 ，運行成本增加，無法避免成本方面的不利。而且，活蚯 蚓的氨含量隨季節變動，即使少量殘留也會引起胃炎，所 -9- 1330532 以出現製品的品質管理難的問題，但是根據本發明方法， 在進行冷凍真空乾燥前幾乎完全去除氨，即使微量殘留的 量也可以通過冷凍真空乾燥而完全地去除，所以具有能夠 生產均勻品質的產品的優點。 其次，將實質上完全去除了污物的蚯蚓活體用純水洗 淨後，磨碎形成液狀至糊狀的磨碎物。所述磨碎採用例如 勻漿機、混合機、高速攪拌機、混砂機、加壓型細胞破壞 裝置，通常在1〜25 °C，優選在2〜15 °C溫度下進行。接 著將所述磨碎物放入不銹鋼盤中，乾燥，這時，蚯蚓活體 所含的酶不作用於活細胞而對死細胞瞬間作用，並發熱、 腐敗產生强腐敗性的氣體，所以爲了防止所述情况，必須 迅速置於-1 8 °C至-3 5 °C的溫度下，採用能夠抑制酶作用的 冷凍真空乾燥。 爲了不損失蚯蚓原有的藥理作用進行粉末化，必須迅 速冷凍，但是另一方面過短時間內冷凍，則使與作爲蚯蚓 糊主要成分的蛋白質同時存在的雜質形成斑點狀的不冷凍 部分，無法分離，所以不建議過度迅速冷凍。因此，冷凍 在-18°C〜-35°C低溫下進行20〜240小時，較佳爲進行50 〜1 7 0小時。 冷凍真空乾燥時，選擇在去除水分的同時也去除雜質 的條件是極爲重要的。因此，在50Pa以下的壓力下，-60 °C至+ 90°C的溫度中，使溫度階段性上升，較佳爲控制在 10〜60小時的範圍內。 例如，如上所述，磨碎物需要在· 1 8 °c至-3 5 °c的溫度 -10- 1330532 • 下冷凍20〜240小時，然後，使溫度在-60 °C〜+ 90 °C之間 • ，壓力在4〜80Pa之間，分多階段變化，冷凍真空乾燥 ' 1 〇〜6 0小時，能夠得到無菌狀態的淡黃色蚯蚓乾燥粉末 • 。這時，通過真空抽吸進行脫氣。 ' 在本發明方法中，通過選擇乾燥條件，能夠明顯縮短 - 以往冷凍乾燥所需的1 〇〇小時或1 〇〇小時以上的時間。 這樣所得的蚯蚓乾燥粉末根據蚯蚓的種類、採集地點 I 、採集時間會有一些變動，粉末100g中，含有精氨酸70 〜120mg、賴氨酸 110〜150mg、組氨酸35〜60mg、苯丙 氨酸55〜80mg、酪氨酸50〜75mg、亮氨酸100〜150mg 、異亮氨酸60〜90mg、蛋氨酸25〜40mg、纈氨酸7 0〜 105mg、丙氨酸85〜135mg、甘氨酸75〜105mg、脯氨酸 60〜85mg、谷氨酸210〜3 00mg、絲氨酸80〜1 10mg、蘇 氨酸 75〜1 1 Omg、天冬氨酸 150〜220mg、色氨酸 15〜 3 〇 m g及胱氨酸2 0〜3 5 m g。 【實施方式】 以下，將以實施例對本發明的具體實施方式進行說明 實施例1 將活的粉正蝴（Lumbricus rubellus) 30kg放入平箱 中’平鋪成約5cm厚，在螢光燈照射下保持24小時，用 不織布覆蓋在活蚯蚓上，使體表上分離的污物、排泄物吸 -11 - 1330532 ' 附在不織布上，去除後進行水洗。再均勻地撒入檸檬酸粉 • 末2 5 Og ’過1 5秒後加入3 0升純水稀釋。剛加入水後的 ' pH爲2.25，完全稀釋後的PH爲2.74。 • 再將浸泡在所述稀釋檸檬酸中的蚯蚓在20 °C下放置 60分鐘’蚯蚓爲了緩解對於其本身來講不適的生活環境 ' ，體液隨著消化道內的消化物排出體外，同時造成惡臭的 氨和對人體有害的砷也一起排泄出來。 φ 以往，由於必須在pH 3〜6·5的檸檬酸水溶液中至少 浸泡1小時左右，蚯蚓變得虛弱，損失多，所以這樣迅速 與高濃度的檸檬酸接觸的結果，蚯蚓沒有變虛弱，且能夠 幾乎完全去除氨。 然後從髒的檸檬酸水溶液中取出活蚯蚓，水洗後，用 勻漿機在下進行磨碎，調製成蚯蚓糊。再將所述蚯 蚓糊轉移至不銹鋼盤上，瞬間驟冷至-30 °C，在該溫度下 維持5 0小時慢慢冷凍。 # 如此，冷凍的蚯蚓糊在-35°C下緩慢減壓至50Pa並保 持3小時後，溫度升溫至20°C，在40Pa的壓力下保持12 小時，再升溫至4(TC，在35Pa壓力下保持25小時，最 後升溫至80°C，在20Pa壓力下保持5小時，進行冷凍真 ' 空乾燥。通過所述處理得到含水量8質量％的淡黃色蚯蚓 乾燥粉末。這樣得到的乾燥粉末的氨基酸含量如表1所示 實施例2In the method of the present invention, after the active cockroach which removes the dirt or excrement is washed with water, it is brought into contact with the organic acid to rapidly form a living environment in which the living cockroaches are uncomfortable. In contact with the organic acid, the organic acid powder can be directly sprinkled on the living crucible or sprayed with a high concentration of an aqueous organic acid solution. The organic acid to be used at this time may, for example, be acetic acid, malic acid, citric acid, lactic acid, malonic acid or succinic acid. These may be used singly or in combination of two or more kinds. A particularly preferred organic acid is, for example, citric acid. Under such circumstances, if the live cockroach is in contact with an organic acid powder or a high concentration of an organic acid aqueous solution for a long time, it will die or lose its ability to live', and cannot excrete the digestive material in the digestive tract, so it is active and organic. The contact should be as fast as possible, usually within 30 seconds, preferably within 20 seconds, and the organic acid must be diluted with water to adjust the pH to a range of 2 to 5. The dilution with water must be carried out rapidly. Excessive time will cause paralysis, so you must pay full attention. In the method of the present invention, the live mash is temporarily sterilized by the sterilizing action of the organic acid. Then, it is further sterilized by freeze vacuum drying, and the sterilizing effect can be surely ensured. In the method of the present invention, the nocturnal live cockroaches are placed in a living environment that is difficult to move -8-1332532, and then the live cockroaches are placed in a living environment that is rapidly uncomfortable, Self-protection instinct releases solid matter or body fluids such as dirt and excretion to improve the living environment and automatically purify. Since the organic acid has bactericidal properties, in the method of the present invention, the organic acid is used as described above to exert the function of excreting the digested material remaining in the digestive tract, and at the same time, it is possible to kill the bacteria which cannot be removed by washing with water. In order to exert the body protection function, moisture must be present, and since 65 % of the living tissue is water, the time for exerting the body protection function is somewhat redundant, but if the living is dead, there is no As a result, the time at which the live cockroaches are placed in a living environment that causes them to feel uncomfortable must be carefully controlled. The time is controlled by conditions, usually in the range of 3 to 180 minutes. When the living cockroaches are placed in contact with the organic acid to cause discomfort, the digestive substances remaining in the digestive tract are not only discharged, but also the body fluid containing odorous ammonia and toxic arsenic to the human body is discharged. Almost completely removed. In the past, since the washed live mash was directly ground and frozen, ammonia could not be removed, ammonia was removed during the subsequent freeze vacuum drying process, but the product quality management appeared because the quality of the product could not be completely removed. difficult. Further, in the process of freezing and vacuum drying, in order to remove ammonia, it is easy to damage the apparatus in the process, and it is necessary to perform cumbersome maintenance, increase the running cost, and fail to avoid cost disadvantage. Moreover, the ammonia content of the live cockroach varies with the season, even if a small amount of residue can cause gastritis, -9-1330532 is difficult to manage the quality of the product, but according to the method of the present invention, the ammonia is almost completely removed before the freeze vacuum drying is performed. Even if the amount of trace residual can be completely removed by freeze vacuum drying, there is an advantage that a product of uniform quality can be produced. Next, the living body which has substantially completely removed the dirt is washed with pure water, and then ground to form a liquid-like paste-like ground material. The grinding is carried out by, for example, a homogenizer, a mixer, a high speed mixer, a sand mixer, a pressurized cell disrupting device, usually at a temperature of 1 to 25 ° C, preferably 2 to 15 ° C. Then, the ground material is placed in a stainless steel dish and dried. At this time, the enzyme contained in the living body does not act on the living cells and acts on the dead cells instantaneously, and generates heat and spoilage to generate a highly corrosive gas, so in order to prevent the In this case, it must be rapidly placed at a temperature of -1 8 ° C to -3 5 ° C, using a freeze vacuum drying capable of inhibiting the action of the enzyme. In order to pulverize without damaging the original pharmacological action, it must be rapidly frozen. On the other hand, if it is frozen in a short period of time, the impurities which are present at the same time as the protein which is the main component of the paste form a spot-like non-freezing portion, and cannot be frozen. Separation, so it is not recommended to freeze too quickly. Therefore, the freezing is carried out at a low temperature of -18 ° C to -35 ° C for 20 to 240 hours, preferably for 50 to 170 hours. In the case of freeze vacuum drying, it is extremely important to select the conditions for removing impurities while removing moisture. Therefore, at a temperature of -50 ° C to + 90 ° C under a pressure of 50 Pa or less, the temperature is gradually increased, preferably in the range of 10 to 60 hours. For example, as described above, the ground material needs to be frozen at a temperature of -10 ° C to -3 5 ° C - 10 1330532 • for 20 to 240 hours, and then the temperature is between -60 ° C and + 90 ° C. Between •, pressure between 4 and 80 Pa, divided into multiple stages, freeze vacuum drying '1 〇 ~ 6 0 hours, able to get sterilized light yellow 蚯蚓 dry powder•. At this time, degassing was performed by vacuum suction. In the method of the present invention, by selecting the drying conditions, it is possible to significantly shorten the time required for the conventional freeze-drying of 1 hour or more. The dry powder obtained in this way has some changes depending on the type of strontium, the collection point I, and the collection time. The powder contains 100 to 120 mg of arginine, 110 to 150 mg of lysine, 35 to 60 mg of histidine, and styrene-acrylic. 55 to 80 mg of lysine, 50 to 75 mg of tyrosine, 100 to 150 mg of leucine, 60 to 90 mg of isoleucine, 25 to 40 mg of methionine, 7 to 105 mg of valine, 85 to 135 mg of alanine, and glycine 75. ~105mg, valine 60~85mg, glutamic acid 210~3 00mg, serine 80~1 10mg, threonine 75~1 1 Omg, aspartic acid 150~220mg, tryptophan 15~3 〇mg and Cystine 2 0~3 5 mg. [Embodiment] Hereinafter, a specific embodiment of the present invention will be described by way of examples. Example 1 A live powder of Lumbricus rubellus 30 kg is placed in a flat box and is flattened to a thickness of about 5 cm under irradiation with a fluorescent lamp. Keep it for 24 hours, cover it with a non-woven fabric on the living raft, and let the dirt and excrement separated on the body surface absorb -11 - 1330532 ' attached to the non-woven fabric, remove it and wash it. Sprinkle the citric acid powder evenly. • At the end of 2 5 Og ', after 15 seconds, add 30 liters of pure water to dilute. The pH after the addition of water was 2.25, and the pH after complete dilution was 2.74. • Place the immersion in the diluted citric acid at 20 °C for 60 minutes. “In order to alleviate the uncomfortable living environment”, the body fluid is excreted with the digestive tract in the digestive tract and causes Stinky ammonia and arsenic, which are harmful to the human body, are also excreted together. φ In the past, since it was necessary to soak for at least 1 hour in a citric acid aqueous solution having a pH of 3 to 6·5, the enthalpy became weak and the loss was large. Therefore, as a result of the rapid contact with the high-concentration citric acid, the enthalpy did not become weak, and Able to remove ammonia almost completely. Then, the live mash was taken out from the dirty aqueous citric acid solution, washed with water, and then ground with a homogenizer to prepare a paste. The crucible paste was transferred to a stainless steel pan, quenched to -30 °C in an instant, and slowly frozen at this temperature for 50 hours. # Thus, the frozen paste is slowly depressurized to 50Pa at -35 ° C for 3 hours, the temperature is raised to 20 ° C, maintained at 40 Pa for 12 hours, and then heated to 4 (TC, at 35 Pa pressure) After maintaining for 25 hours, the temperature was raised to 80 ° C, and the pressure was maintained at 20 Pa for 5 hours, and the frozen true air drying was carried out. By the treatment, a pale yellow barium dry powder having a water content of 8 mass % was obtained. The amino acid content is as shown in Table 1.
-12 - 1330532 使用陸正蝴（Lumbricus terrestris) 30kg代替實施例 1中的粉正蚓3 0kg，與實施例1完全相同進行處理，得到 淡黃色的蚯蚓乾燥粉末。由此所得的乾燥粉末的氨基酸含 量如表1所示。-12 - 1330532 Using 30 kg of Lumbricus terrestris instead of 30 kg of the powder of Example 1 was treated in exactly the same manner as in Example 1 to obtain a pale yellow dry powder. The amino acid content of the dry powder thus obtained is shown in Table 1.
氨基酸的含量單1 立 m g/ 1 0 0 g 例 實施例1 實施例2 精氨酸 1 14 72.5 賴氨酸 148 128 組氨酸 55 40 苯丙氨酸 77 62.5 酪氨酸 73 57 亮氨酸 145 119.5 異亮氨酸 87 74 蛋氨酸 3 5 33 纈氨酸 1 04 89 丙氨酸 13 1 98 甘氨酸 103 82.5 脯氨酸 83 65.5 谷氨酸 296 245.5 絲氨酸 1 05 87 蘇氨酸 1 04 8 1.5 天冬氨酸 __ 2 1 2 167 色氨酸 —^_“ A “__ 2 8 20 胱氨酸 ^----。___ -^ 3 2 2 1.5 實施例3 用蘋果酸160g取代實施例1中的檸檬酸250g,與實 施例1完全相同進行遘堙，得到與實施例1所得物質幾乎Amino acid content alone 1 mg / 100 g Example 1 Example 2 Arginine 1 14 72.5 Lysine 148 128 Histidine 55 40 Phenylalanine 77 62.5 Tyrosine 73 57 Leucine 145 119.5 Isoleucine 87 74 Methionine 3 5 33 Proline 1 04 89 Alanine 13 1 98 Glycine 103 82.5 Proline 83 65.5 Glutamate 296 245.5 Serine 1 05 87 Threonine 1 04 8 1.5 Aspartame Acid __ 2 1 2 167 Tryptophan-^_" A "__ 2 8 20 Cystine ^----. ___ -^ 3 2 2 1.5 Example 3 250 g of citric acid in Example 1 was replaced with 160 g of malic acid, and hydrazine was carried out in exactly the same manner as in Example 1, to obtain almost the same as the material obtained in Example 1.
1330532 相同組成的深黃色蚯蚓乾燥粉末。 參考例 將實施例1所得的蚯蚓乾燥粉3 報的實施例所記載的方法進行處理， 使用所述精製蛋白酶0.5#g，力口 溶酶原（KABIAB公司製0.05CU) 纖溶酶活性。再根據添加和未添加精 性差異，算出纖溶酶水解活性，爲0 進行比較，使用採用上述專利公報中 蚓乾燥粉末調製的精製蛋白酶同樣求 爲0.112nm〇l/分鐘，發現根據本發明 粉末的酶活性約高1.3倍。 根據本發明方法，可以不需要任 蚯蚓自身的行爲去除污物、排泄物， 沒有氨臭等惡臭、低砷含量的優質蚯 本發明方法所得的蚯蚓乾燥粉末，與 相比，含有效價高1.2〜1.5倍的酶 浸透性大的效果。 [產業上可利用性] 通過本發明方法生產的蚯蚓乾燥 法生產的蚯蚓乾燥粉末相同，可作爲 脂症劑、糖尿病治療劑、血栓溶解劑 粉末分離有效成分，能夠用作美白劑 藥、脚癣治療藥等用途。 :按照 JP2716472B 公 調製成精製蛋白酶》 入精製人血纖維蛋白 反應，測定反應後的 製蛋白酶的情况的活 • 1 45nmol/分鐘。爲了 的以往方法所得的蚯 出纖溶酶水解活性， 方法生產的蚯蚓乾燥 何人工作業，利用活 能夠得到不含細菌、 蚓乾燥粉末》且根據 以往方法所得的物質 ，且顯示出對細胞的 粉末，與通過以往方 血壓調節劑、抗高血 等使用。從蚯蚓乾燥 、除皺劑、濕疹治療 -14-1330532 Deep yellow 蚯蚓 dry powder of the same composition. Reference Example The method described in the examples of the dry powder 3 obtained in Example 1 was treated, and the plasmin activity of the purified protease 0.5#g, lysogen (0.05 CU, manufactured by KABIAB Co., Ltd.) was used. Further, the plasmin hydrolyzing activity was calculated based on the difference between the added and the unadded precision, and the comparison was carried out for 0. The purified protease prepared by using the dry powder of the above-mentioned patent publication was also determined to be 0.112 nm /l/min, and the powder according to the present invention was found. The enzyme activity is about 1.3 times higher. According to the method of the present invention, it is possible to remove the dirt, excretion, and the high-quality odor of the odor of the arsenic, such as ammonia odor, and the bismuth dry powder obtained by the method of the present invention, and the effective price is 1.2. ~1.5 times the effect of large enzyme permeability. [Industrial Applicability] The dry powder produced by the mash drying method produced by the method of the present invention is the same as the fat-soluble agent, the diabetes therapeutic agent, and the thrombolytic agent powder, and can be used as a whitening agent and an ankle treatment. Medicine and other uses. : According to JP2716472B, a purified protease was added to the purified human fibrin reaction, and the activity of the protease after the reaction was measured to be 1 45 nmol/min. The powder obtained by the conventional method, which is obtained by the method of the present invention, which is produced by the method, can be obtained by the method of drying, and can be obtained by a conventional method, and exhibits a powder for cells. It is used with the blood pressure regulator, anti-hypertensive, etc. in the past. From dryness, wrinkle remover, eczema treatment -14-