TW310274B

TW310274B -

Info

Publication number: TW310274B
Application number: TW83105327A
Authority: TW
Original assignee: Allan L Goldstein; Mirela O Fagarasan
Priority date: 1994-06-10
Filing date: 1994-06-11
Publication date: 1997-07-11

Description

經濟部中喪揉準局貞工消费合作社印製 310274 五、發明说明（1 ) I阻背i 祖關申齔盡_2^交U-i 本案為1993年10月7日申誧之待審美鼷申請案第 08/132.859號之部分延鑛申請案。發明霞蓝- 本發明係關於哺乳類之敗血病休克之療法。背景技術之. . .KM . 胸腺素a i ( T a t )是一種由胸腺衍生得之胜肽’據報導含28個胺基酸。Τα t之胺基酸序列資訊揭示於美國第 4,079, 127號專利案（併述於此Μ供參考）° Τα i是免疫糸統調理劑，前此已報導可用於治療肺癌、 B型肝炎和C型肝炎等。敗血病休克是感染廣泛獼漫身鱷多區的情況’感染常經血液由一組嫌敗播至另一组纗，引起廣泛傷害。敗血病休克見於多種醫事病情*含（η感染由子宮和_卵管败播開引起腹膜炎；（2)腸破裂引起的腹_炎*偶爾因腸病或傷口引起；（3 >因單純感染敗布引起全身感染；（4 )特別由氣性壞疽桿菌造成的全身壊疽感染；（5)感染由腎或尿路散布入血。因其它理由故由明床親黏知敗血病体克相當重要，此情況常導致死亡。 _然敗血病体克是略微常見的臨床規象，相U懺轉及病理變化仍未充分了解。舉例言之，雖言治療细菌性感染，許多病人仍持續惡化，可能歸咎於系統血管阻力低之低血壓，轚功能不全，成人呼吸瞽迫症候群，嚴重凝血病變， -4- 本纸張尺度適用中國國家標準（€阳}八4规格（210父297公釐） 83. 3.10,000 (請先《讀背Λ之注意事項其镇寫本頁) 訂線- 310274 A7 B7五、發明説明（2 ) 經濟部中央樣準局貝工消费合作社印製和蜃重代謝功能不良的睡床後果。如此，業界迫切需敗血病休克的有效療法。發明概述· 根據本發明晡乳類之敗血病休克之療法包含對該等哺乳類投予敗血病休克治療有效量之Τα 出乎意外地發現胸腺素α d可有效治療或預防敗血病体克或敗血病。此種發現出人翥表歸因於初次試驗畤預期Tot i對敗血病休克並無活性。 ”胸腺素α λ”及”Τα ι/’等語意指具美圔第4.079, 137號專利案（參見上文）揭示之胺基酸序列之胜肽。哺乳類敗血病休克與嚅乳類«發生一系列"敗血病症狀 ”有Μ。敗血病症狀典型地始於哺乳類寄主之细菌性感染，结果導致放出细菌性毒素，蒂進内毒素，活化寄主防衛糸統（即血漿蛋白系統）及细胞防衛系統，含内數细胞、巨噬细胞、軍核细胞，和嘈中性细胞；放出發炎前媒介物含细胞動素（cytokinesi、脂質代謝產物、蛋白解_、毒性氧產物、氧化氮和粘著蛋白質。根據本發明之一態樣，有效量Ται投予一镅髑降低血中自由基澹度，綾此治療或預防個體之數·血病休克，或妨礙镯體之敗血病症狀的進展。發現Ται可降低血中自由基溻度嫌乎如S0D (超氣化物變異卿，乃可消除自由基之酵素）般多。酋敗血病休克治療或預防有效量之Toti投予晡乳類時，哺乳類艚内綑菌誘生致命病理媒介物的血中禳度降低 -5- 本紙張尺度適用中國國家標準（CNS ) A4规格（210X297公兼） 83.3.10,000 (請先聞讀背面之注$項再填寫本頁) •t 訂 -線』經濟部中央標準局貝工消费合作社印製 Α7 Β7 五、發明説明（3 ) 發現Tcti會阻_晡乳類之敗血病症狀。敗血病時血中脂霣逢氧化反*[蝤加（丙二醮二醒之《莫耳數）’但投予 Τα ^時返回正常或約略正常。敗血病也降低麩胱甘肽 (glutathione)之循瓌血中濃度。但投予Ται使循壤挺狀甘肽濃度返回正常或近乎正常° , 如前記，敗血病時投予Ται降低血中通氧化物®度及血中麩胱甘肽濃度。敗血病時投予1*0^也降低细胞cGMP瀨度，並降低花生四烯酸代謝產物如Tx^®2和6_嗣基_PGFia ’ PAF及畑胞動素如IL-1«和THF-a血中濃度。不欲受任何理論所限’威信降低哺乳類之由细菌誘生的致命性病理媒介物血中濃度可降低哺乳類之感染量’其又有助於阻礙敗血病症狀·及預防與治療敗血病体克。如此根據本發明提供於哺乳類治療與預防敗血病休克之方法。本發明方法包含對哺乳類投予敗血病休克治療有效最，敗血病休克預防有效量及敗血病症狀進展妨礙有效量之 T a 1 ° 根據本發明之較佳具黼例’有效量之Toti投予個體而治療或預防個«之敗血病休克，或妨礙個體之敗血病休克之進展。此等具«例中，儷鱺宜為人體。根據本發明之較佳具嫌例，含Τα i之組合物可Μ習知方式配方供Μ任何癫當途徑投葯。缠當投葯途徑含唯非值限於經口、直腸、Λ、局部、陰道及腸外（含皮下、肌肉、靜脈和皮内）投葯。特佳具髓例採用經口或腸外投葯•而 Μ腸外投葯為更佳具髓例。唯須了解較佳途徑可因接受者 -6- 本紙張尺度適用中國钃家橾準（CNS > Α4规格（210Χ297公釐） 83. 3.10,000 (請先閲讀背面之注意事項再填寫本頁) 訂- 綉五、發明説明（4 ) Α7 Β7 經濟部中央標準局貝工消费合作社印装情況、年齡及類別而異。雖非必要，但於較佳具黼例中* Tat係圼醫_配方之部份投予。本發明之K方包括Toti*同一種或多種《蕖可接受性載爾和視需要可達同其它治療成分。載Μ為：可接受 ”意指與配方其它成分相容而對接受者無害。配方包含蘧供纆口、直腸、鼻、局部（含頰和舌下）、陰道或腸外（含皮下、肌肉、靜脈和皮内）投葯。配方可圼方便的單位劑型*例如錠劑和持鑲釋放型膠囊，旦可_任何逋當齧_方法製備。此等方法包含唯非饉限於將Τα 1與組成一種或多種附鼸成分之載劑組合在一起。一般而言*配方係經由將Τα ^與液艚載劑或细分固«載劑或二者均勻、緻密組合，及然後若有所需成形產物而製備。缠供口服之本發明«方可呈分立單位，如各含預定# Ται之腰囊、葯包或錠_ ;散爾或粒_ ;於水液或非水液之溶液爾或懸浮液劑；或油/水液體乳液劑或水/油液«乳液劑等。錠劑可藉打錠或棋製視需要可埋同一種或多種附鼷成分製造。在製錠之製法係於應當機器壓縉自由流動型Τα 1如粉末或顆粒，視需要可混Μ黏结劑、潤滑劑，惰性稀釋劑、保藏劑、界面活性劑或勻敗劑。換製錠之製法係於缠當櫬器横製Μ惰性稀釋液瀦澜的粉狀化合物。錠_視需要可包衣或刻痕，可配方成鍰慢或Μ控制方式釋放活性成分。 -7- 本紙張尺度逋用中國國家橾準（CNS ) Α4规格（210Χ297公釐〉 83. 3.10,000 (請先閲讀背面之注意事項再填寫本頁) 訂線 Α7 Β7 3!〇274 五、發明说明（5 ) 缠供局部投葯配方含口含錠，内含TaiMfll味基劑，通常蔗糖和阿拉伯膠或西黄蕃膠；耱衣錠含ΐαι於惰性基劑，如明膠和甘油，或蔗耱與阿拉伯膠；及漱口水，含Τα, 於逋當液體載劑。蘧供局部投葯於皮虜之fi方呈砍齋、乳營膠漿和, 包括了〇«1和靨藥可接受性載謂；或可採含成分之經皮貼布〇直腸投葯配方可呈含*當基_包括例如可可脂或水楊酸鷗之栓劑。逋供纆鼻投葯之配方其中載劑為固驩，含粒經例如於由約20至約500微米範之粗粉，其以鼻粉方式投葯，亦即粉末容器靠近鼻子，經典道快速吸入。其中載劑為液體的壩當K方例如鼻啧霧劑或鼻滴劑，含活性成分之水或油溶液。壤供陰道投药之配方可呈塞_、乳蕾、膠漿、糊劑、發泡劃或«霧繭配方内含癰當載劑與Τα 遺供腰外投葯之Κ方包含水和非水無菌注射溶液劑，其視需要可含抗氧化劑，嫌銜劑•抑菌黼和使配方與接受者血液等張的溶霣；及水及非水無菌懸浮液蹋•其含懸浮_ 及《稠劑。配方可呈軍劑董或多劑量容器包装，例如密封安瓯及小瓶，且可Μ凍乾雔存*僅需恰於用前加入無菌液 «載劑如注射用水。即席瘸製的注射溶液劑和懸浮液_可由前述類別之無菌粉末、顆粒和錠麵製。唯須了解除Μ上特別«述的成分外，本發明配方可含各 -8- ----------ΙΨ- (請先Η讀背面之注$項再填寫本頁) 趣濟部中央棣準局貝工消費合作社印製 --打------線-7"----„---7---^--：-- 本紙張尺度適用中國國家橾率（CNS > Α4规格（210X297公釐） 83. 3.10,000 A7 B7 經濟部中央橾準局員工消费合作社印裝五、發明说明（6 ) 該配方類別相闞的其它應當成分，例如遽供口服者可含雉味劑。本發明組合物之投葯劑量為敗血病休克治療或則血病休克預防有效量之Τα，，可於由約〇.4薄克至約4奄克Τα 公斤接受者體重（《g/kg)，較佳由約1至約4ag/kg。單一劑量可每日投予病人，每〖3 —次或多次，例如每日二或三次 .及可每遇一或數日，例如二、三、四、五、六或t日/ 埋。本發明_用於天然Τα ^，及具天然Τα 胺基酸序列的合成Tcxi和重組Ται，胺基酸序列大體類似者*或其觴縮序列形，及其具大鱷類似ται之生鱷活性且具取代、刪失、延長、替換或Μ其它方式修改序列的生物活性類Μ物。根據本發明之一個具艚例，Τα 1可與治療有效璗之另一種治療敗血病休克有用的物質併用，後者例如抗生素*或針對内毒素上抗原之抗艚（多株或單株）°當然其它物霣之可接受性劑量範園將依其性霣而定（亦即可接受的劑量範圓將依是否投予其它物霣而定> ° Τα 1與另一種可用於預防或治療敗血病体克之物質"一併”投葯•如此處定義含設計投予Tot t及其它物質姶個體之計劃（無論其它物質輿Ται是分闢或一起投葯）’故同時個«存在有所需劑量之ται及其它物質。根據本發明任何缠當計劃皆可用Μ ” 一併”投予Τα 另一棰預防或治療敗血病体克有用的物質。單獨Τα 1或Tex i併同另一種預防或治療敗血病体克有用 -9- (請先聞讀背面之注意事項再填寫本頁) 碌· 訂線本紙張尺度逍用中國國家樑準（CNS > A4规格（210X297公釐） 83. 3.10,000 A7 B7五、發明説明（7 ) 經濟部中央橾準局貝工消費合作社印製的物質之遽當劑最可每日投予一至三次或以上。精確劑量將依接受者年聆、情況及其它因素而定。下列霣例懂為舉例性而非限制性者。 S_J@I___L 合成Τα t係由Alpha 1生醫公司（馬里蘭州20817貝色大 Two Deeocracy Center, 6903 Rock ledge Drive, S t e . 12 00 )提供。Tot i係藉固相胜呔合成製備。瑞士韋斯特小鼠（四至六遇龄，20至25克）分成兩組：内毒素組小鼠（急性處理腹内注射内毒素60ng/kg)及以三次注射100微克Tot X處理的内毒素小鼠（投予内毒素後5分鐘，2及4小時）。下表I和Π所示结果指示投予内毒素後投予三次Τα 1可埔高接受内毒素處理小联的存活率達1 00¾。下表ffi — VI所示結果顯示T ct 1分別對小蹴血中丙二醢二醛濃度、麩胱甘肽濃度、臞cGMP濃度、血清TNF- α濃度、及血濟THF-α和[L - 漉度之影響。致命内毒素劑最和Τα i後墦士韋斯特小鼠之存活率小鼠存活數 0小時 2 4小時 4 8小時 7 2小時 7 111 7 7 7 7 實驗組別内毒素60ng/kg 内毒素60ag/kg + Τ α 1 1 00 u g 3 x 10- 本紙》：尺度適用中國11家橾準（〇灿）八4规格（210父297公釐） 83. 3.10,000 (锖先w讀背面之注$項再填寫本頁) -訂線 S10274 五、發明説明（8 ) Τα Μ致命劑量内毒素處理小鼠之存活率之膨響小鼠存活敝實驗組別 0小時 24小時 48小時 72小時 7日14日内毒素60mg/kg 内毒素60mg/kg + T α 1 1 Ο Ο ϋ g 3 ; Ο 8 复JL小鼠Μ致命劑量内毒素處理後Τα 1對血中過氧化酶禳度之影響實驗組別丙二醢二醛血中濃度（η Mo 1 MD A > 對照 1 7 . 5 土 1 . 2 内毒素 6〇Bg/kg 38 . 2 ± 2 . 9 内毒素 60ig/kg 16.9 ± 1.36 a X 100*全血樣（0.5¾升）係於投予内毒素後1小時採尾血而得。 .於Μ致命劑董内毒素處理小鼠Τα 1對麩胱甘肽濃度的影響 (請先聞讀背面之注$項再填寫本頁) 訂線經濟部中央標準局負工消费合作社印製實驗組別對照内毒素6〇Bg/kg 内毒素60ng/kg ^Τα χ 100 w g/老鼠 RBC GSH(m bo 1 es/n 1 细胞） 1 . 25土 0·09 0 . 61 ± 0.05 1 . 1 2 ± 0 . 1 2 -11 本紙張尺度適用中國國家樑準（CNS > A4规格（210 X 297公釐） 83. 3.10,000 310274 A7 B7 五、發明説明（9 *總紅血球麩脒甘肽（其中98X係圼堪原形（GSH))係韉酵素 "環形方法”澜定。於Μ致命謂量内骞素處理小鼠Τα 1對CGMP腦禳度之彩響實驗組別臞皮霣環肜GMP (ooal/ig蛋白質對照 1 0 . 1 土 0.2 内毒素60ig/kg腹内注射 30.7±4.1 内毒素60ig/kg腹内注射 14.6 土 1.2 + T a 1 100/ug Μ致命劑量内毒素處理小鼠之血清TNF-a禳度實驗組別 TNF-a (pg/nl ) 1小時 3小時 5小時内毒素 60ag/kg 1098 ± 106 783± 38 623 ±51 内毒素 eOBg/kg + Ta^eSStS? 4 26 ± 3 7 297±27 (讀先W讀背面之注意事項再填寫本頁) 訂經濟部中央梂準局負工消费合作社印裝表—ML «使用SOD和Τα α前處理而保護不因内毒素誘生致命之小鼠之血濟TNF-α和IL-la濺度* 前處理 TNF-ot(pg/el) IL-Ια (pg/nl) 無 4462土 123 1137± 123 S0D(3.3x 104« /kg) 63 ± 5.1 5 3 ± 3.1 Tai lOOitg/小鼠 285 ±23·6 109±71 X投予内毒素前30分鐘小鼠K SOD (超氧化物歧化_)前處理投予内毒素後1小時採血測定TNF-a和IL_la濃度。 -12- 本紙張尺度適用中國國家橾準（CNS > A4规格（210X297公釐） 83. 3.10,000 五、發明説明（10 ) 使用如簧例1之相同材料與方法，研究Τα ^對内毒素致命性之保護效果的時間與劑量闞係。結果示於下表VI。由表VI可見，内毒素處理後即刻，2及4小時給喿或内毒素《理後2，4和6小時給萘時，Τα ^對内毒素毒性具保護效果。有效保護劑最為l〇〇Wg Ται投予三次。弃VI 給予致命内毒素劑量和Ta i後瑞士聿斯特小鼠之存活性情形活小鼠數目實驗姐別 0小時24小時48小時72小時96小降I.20小時 4 内毒素 SO mg/kg 8 4 4 4 4 内毒素 SO mg/kg 8 8 8 8 — 8 + T α 1 100 w ε. 3χ Τ ot t係在内毒素後即刻，2及4小時投予 8 ---------- (請先Μ讀背面之注$項再填寫本頁吣訂内襄素 60 mg/kg 8 8 8 + Taj 100 fig, 3x; Τα ^係在内毒素後2、4及6小時投予線經濟部中央橾準局負工消費合作社印製Printed by the Ministry of Economic Affairs of the Ministry of Economic Affairs, Zhengong Consumer Cooperative 310310 V. Description of the invention (1) I resisted the ancestors of the ancestors of the ancestors _2 ^ 交 Ui This case was an application for the application of the Aesthetic Appeal on October 7, 1993 Case No. 08 / 132.859 part of the application for mine extension. Invention Xia Lan-This invention relates to the treatment of septic shock in mammals. BACKGROUND OF THE INVENTION KM Thymosin a i (T a t) is a peptide derived from the thymus. It is reported to contain 28 amino acids. The amino acid sequence information of Τα t is disclosed in US Patent No. 4,079, 127 (and described here for reference) ° Τα i is an immunological system conditioning agent, which has been reported to be used for the treatment of lung cancer, hepatitis B and Hepatitis C, etc. Septic shock is a condition in which a wide range of crocodilian crocodiles are infected. Infection often passes through the blood from one group to another group, causing widespread injury. Septic shock is seen in various medical conditions * Contains (η infection is caused by the uterine and _ fallopian tube opening caused by peritonitis; (2) abdominal rupture caused by intestinal rupture * occasionally due to bowel disease or wound; Systemic infection caused by infection and dissemination; (4) systemic infection caused by gas gangrene bacillus; (5) infection spread from the kidney or urinary tract into the blood. For other reasons, it is known that the septicemia body is equivalent to the bed Importantly, this situation often leads to death. _Blood septicemia is a slightly common clinical rule, and the changes and pathological changes are still not fully understood. For example, despite the treatment of bacterial infections, many patients continue to deteriorate , May be attributed to the low blood pressure of the system's low vascular resistance, dysfunction, adult respiratory syndrome, severe coagulopathy, -4- this paper scale is applicable to the Chinese national standard (€ yang) 84 specifications (210 father 297 mm ) 83. 3.10,000 (please read “Notes on reading Λ and write this page first) Ordering line-310274 A7 B7 V. Description of invention (2) Printed and weighed by the Beige Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs Bed with poor metabolic function Therefore, there is an urgent need for an effective treatment for septic shock in the industry. SUMMARY OF THE INVENTION The treatment of septic shock in milk according to the present invention includes the administration of an effective amount of Tα to septic shock treatment for these mammals. It was found that thymosin α d can effectively treat or prevent septicemia or septicemia. This finding was attributed to the initial test because it was expected that Tot i was not active against septic shock. ”Thymosin α λ The terms "" and "Τα ι / 'mean peptides with the amino acid sequence disclosed in US Patent No. 4.079, 137 (see above). Mammal septic shock and dairy« A series of " "Septicemia symptoms" have M. Symptoms of septicemia typically start from a bacterial infection of the mammalian host, resulting in the release of bacterial toxins, endotoxins, and activation of the host defense system (ie, the plasma protein system) and the cell defense system , Containing internal number cells, macrophages, military nucleus cells, and noisy neutrophils; pre-inflammatory mediators containing cytokines (cytokinesi, lipid metabolites, proteolysis, toxic oxygen products, nitric oxide and viscous) According to one aspect of the present invention, an effective amount of Tαι administered to an americium reduces the free radicals in the blood, and this treatment or prevention of the number of individuals · hemorrhagic shock, or obstructs the symptoms of septicemia of the bracelet Progress. It is found that Ται can reduce the degree of free radicals in the blood as much as S0D (super gasification mutation, which is an enzyme that can eliminate free radicals). Toti septic shock treatment or preventive effective amount of Toti administered to milk During the period, the blood concentration of the deadly pathological vector induced by the bacillus in mammals is reduced -5- This paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 public) 83.3.10,000 (please read the back side first Note $ item and then fill out this page) • t order-line 』Printed Α7 Β7 by the Beigong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs V. Invention description (3) It was found that Tcti would block the symptoms of septicemia from milk. Fat in the blood during septicemia 霣餣 oxidative reaction * [蝤加 (Bermal awakening of the "mol number") 'but returned to normal or approximately normal when administered Τα ^. Septicemia also reduces the concentration of glutathione in the blood. However, the administration of Ται returned to the normal or nearly normal concentration of glyphosate along the soil. As mentioned above, the administration of Ται in the case of septicemia reduced the level of blood oxide and the concentration of glutathione in the blood. In the case of septicemia, the administration of 1 * 0 ^ also reduces the cellular cGMP level, and reduces arachidonic acid metabolites such as Tx ^ ®2 and 6_ 圣基 _PGFia 'PAF and 畑 motif such as IL-1 «and THF-a blood concentration. Without wishing to be bound by any theory, 'Prestige to reduce the blood concentration of mammalian lethal pathological agents induced by bacteria can reduce the amount of infection of mammals'. It also helps to prevent the symptoms of septicemia and prevent and treat septicemia. G. Thus, according to the present invention, a method for treating and preventing septic shock in mammals is provided. The method of the present invention includes administering septic shock therapy to mammals most effectively. The effective amount of septic shock prevention and the effective amount of septicemia hindering the effective amount of T a 1 ° According to the preferred embodiment of the present invention, the effective amount of Toti is administered to an individual to treat or prevent a septic shock, or hinder the progress of the individual's septic shock. In these examples, Liyang should be a human body. According to a preferred example of the present invention, the composition containing Tα i can be formulated in a conventional manner for administration in any epilepsy route. The tangdang administration route contains only non-limiting oral, rectal, Λ, topical, vaginal and parenteral (including subcutaneous, intramuscular, intravenous and intradermal) administration. The best medullary cases are administered orally or parenterally. Μ parenteral administration is the better medullary case. Only need to understand the better way can be accepted by the recipient-6- This paper standard is applicable to China's National Standards (CNS > A4 specifications (210Χ297mm) 83. 3.10,000 (please read the precautions on the back before filling this page ) Order-Embroidery V. Description of Invention (4) Α7 Β7 The printing status, age and type of the Beigong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs vary. Although not necessary, but in the best case * Tat Department of Medical_ Part of the formulation is administered. The K side of the present invention includes Toti * with one or more "acceptability of chervil and other therapeutic ingredients as needed." M is: acceptable "means to be compatible with other ingredients of the formulation The content is harmless to the recipient. The formula includes oral, rectal, nasal, topical (including buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous and intradermal) administration. The formula is convenient Unit dosage forms * such as lozenges and hold-release capsules are prepared by any method. These methods include, but are not limited to, combining Tα 1 with the carrier that constitutes one or more of the attached mule ingredients. Generally speaking, the formula is based on the combination of Tα ^ and liquid Or subdivided solid «carrier or both uniform, dense combination, and then prepared if the desired shaped product. The present invention wrapped for oral administration« can be presented as discrete units, such as waist bag, medicine containing predetermined # Ται Bags or tablets _; Saner or granules _; solution or suspension in aqueous or non-aqueous liquid; or oil / water liquid emulsion or water / oil «emulsion, etc. Tablets can be borrowed from tablets or Chess can be manufactured by burying one or more attached ingredients as needed. The method of making ingots is based on machine-pressing free-flowing Tα 1 such as powder or granules, and can be mixed with M binder, lubricant and inert diluent as needed. , Preservatives, surfactants or leveling agents. The method of changing the ingot is to produce a powdered compound with an inert diluent entangled in a horizontal container. The ingot can be coated or scored if necessary, and can be formulated into The active ingredient is released by slow or controlled mode. -7- This paper uses the Chinese National Standard (CNS) Α4 specification (210Χ297mm) 83. 3.10,000 (please read the precautions on the back before filling this page) Threading Α7 Β7 3! 〇274 V. Description of the invention (5) Wrapped for local administration formula containing mouth Contains tablets containing TaiMfll flavor base, usually sucrose and gum arabic or sage gum; gelatin tablets containing lαι in an inert base, such as gelatin and glycerin, or sucrose and gum arabic; and mouthwash, containing Tα, Yu Dang is a liquid carrier. The fi for the local administration to Piru is Chai Zhai, Ruying Glue, and includes 〇1 and the acceptance statement of the acceptability of the drug; or transdermal with ingredients can be taken. The patch rectal formulation can be presented as a suppository containing * dang base, including, for example, cocoa butter or gull salicylate. The formulation for nasal administration in which the carrier is Guhuan, the granules contains, for example, from about 20 to Coarse powder with a range of about 500 microns, which is administered as a nasal powder, that is, the powder container is close to the nose, the classic way is rapid inhalation. Where the carrier is a liquid, such as nasal aerosol or nasal drops, water or oil solution containing the active ingredient. The formula for the vaginal administration of the soil can be in the form of plugs, breast buds, glue, paste, foaming pads or «mist cocoon formula containing carbuncle as a carrier and Tα. The K side for the external administration of the waist contains water and non-aqueous Sterile injectable solutions, which may contain antioxidants, suspect agents, bacteriostats, and dissolving formulas that make the formulation equal to the blood of the recipient, as needed; and water and non-aqueous sterile suspensions. • It contains suspension_ and "thick Agent. The formulations can be packaged in military agents or multi-dose containers, such as sealed Anou and vials, and can be freeze-dried and stored * just add sterile liquid just before use «Carrier such as water for injection. Injectable solutions and suspensions made by impotence can be made from sterile powders, granules and pasta of the aforementioned category. With the exception of removing the special ingredients mentioned on Μ, the formula of the present invention may contain each -8- ---------- ΙΨ- (please read the note $ item on the back before filling in this page) Printed by Beigong Consumer Cooperative of the Central Bureau of Economic Affairs of the Ministry of Economic Affairs--Dao ------ Line-7 " ---- „--- 7 --- ^-:-This paper standard is applicable to the Chinese National Standard Rate (CNS > Α4 specification (210X297mm) 83. 3.10,000 A7 B7 Printed by the Central Consumer ’s Bureau of the Ministry of Economic Affairs Employee Consumer Cooperative V. Description of the invention (6) Other ingredients that should be included in the formula category, such as unavailable The oral administration may contain pheasant. The dosage of the composition of the present invention is the effective amount of Tα for the treatment of septic shock or the prevention of septic shock, which can be from about 0.4 gram to about 4 gram Tα kg The weight of the recipient ("g / kg), preferably from about 1 to about 4ag / kg. A single dose can be administered to the patient daily, every three or more times, such as two or three times a day. One or several days, such as two, three, four, five, six or t days / buried. The present invention is for natural Tα ^, and synthetic Tcxi and recombinant Tαι with natural Tα amino acid sequence, the amino acid sequence is roughly Similar * or Constricted sequence shape, and its biologically active M species with crocodile-like crocodile activity similar to ται, and with substitution, deletion, elongation, substitution, or other ways to modify the sequence. According to an example of the present invention, Τα 1 Can be used in combination with another therapeutically effective substance for the treatment of septic shock, such as antibiotics * or anti-pigs (multi-strain or single-strain) against antigens on endotoxin. Of course, the acceptable dose range of other substances It will depend on its sex (that is, the acceptable dosage range will depend on whether it is administered to other substances)> Τα 1 and another substance that can be used to prevent or treat septicemia. Medicines • As defined here, a plan containing an individual designed to administer Tot t and other substances (regardless of whether other substances and Tαι are divided or administered together) ', so at the same time «there is a required dose of ται and other substances. According to this Any invented plan can be used to administer Tα to another substance that is useful for preventing or treating septicemia. Tα1 or Texi alone and another substance for preventing or treating septicemia can be useful-9- (Please first Read the precautions on the back and then fill out this page) Lu · The book size of the line book is easy to use. China National Standards (CNS> A4 specifications (210X297mm) 83. 3.10,000 A7 B7 V. Invention description (7) Economy The most effective dose of the substance printed by the Ministry of Central Bureau of Industry and Commerce Beigong Consumer Cooperative is one to three or more times per day. The precise dosage will depend on the recipient ’s annual listening, circumstances and other factors. The following examples are examples S_J @ I ___ L synthetic Tα t is provided by Alpha 1 Biomedical Company (Two Deeocracy Center, 6903 Rock ledge Drive, S te. 12 00). Tot i is prepared by solid phase Sheng Xing synthesis. Swiss West mice (4 to 6 years of age, 20 to 25 grams) were divided into two groups: endotoxin group mice (acute treatment with intraperitoneal injection of endotoxin 60ng / kg) and endotoxin treated with three injections of 100 micrograms Tot X Mice (5 minutes, 2 and 4 hours after endotoxin administration). The results shown in the following Tables I and Π indicate that the endotoxin administration after three administrations of Tα 1 can achieve endotoxin-treated Xiaolian with a survival rate of 100 00. The results shown in the following table ffi — VI show that T ct 1 shows the concentration of malondialdehyde in small blood, glutathione concentration, cGMP concentration, serum TNF-α concentration, and blood THF-α and [L -The influence of luo. Deadly endotoxin agent and the survival rate of the West West mice after Tα i Number of mice survived 0 hours 2 4 hours 4 8 hours 7 2 hours 7 111 7 7 7 7 Endotoxin 60ng / kg endotoxin in the experimental group 60ag / kg + Τ α 1 1 00 ug 3 x 10- This paper ": The standard is suitable for 11 Chinese standard (〇 Can) 8 4 specifications (210 father 297 mm) 83. 3.10,000 (read the back first (Note $ item and fill in this page again)-Line S10274 V. Description of the invention (8) Survival rate of mice with lethal endotoxin treated with Τα Μ Survival mice Survival test group 0 hours 24 hours 48 hours 72 hours 7 Endotoxin 60mg / kg Endotoxin 60mg / kg + T α 1 1 Ο Ο ϋ g 3 on the 14th day; Ο 8 The effect of Tα 1 on the level of peroxidase in the blood after the lethal dose of endotoxin in JL mice Blood concentration of alleldialdehyde (η Mo 1 MD A > Control 17.5 ± 1.2 Endotoxin 6〇Bg / kg 38.2 ± 2. 9 Endotoxin 60ig / kg 16.9 ± 1.36 a X A 100 * whole blood sample (0.5¾ liter) was obtained after tail blood was collected 1 hour after endotoxin administration. The effect of treatment of mouse Tα 1 on the concentration of glutathione with the lethal agent Dong Endotoxin (Please listen first Read the note $ item on the back and fill in this page) The line of the Ministry of Economic Affairs Central Standards Bureau Consumer Labor Cooperative Printed the experimental group control Endotoxin 6〇Bg / kg Endotoxin 60ng / kg ^ Τα χ 100 wg / RBC GSH rat m bo 1 es / n 1 cell) 1. 25 soil 0 · 09 0. 61 ± 0.05 1. 1 2 ± 0. 1 2 -11 This paper scale is applicable to the Chinese National Liang Zhun (CNS & A4 specifications (210 X 297 Mm) 83. 3.10,000 310274 A7 B7 V. Description of the invention (9 * total red blood cell bran amidine glycosides (of which 98X is the original form (GSH)) series of zymotic enzymes " ring method "Lan Ding. The amount of endothelin-treated mice Tα 1 to the CGMP brain color test group 鞞皮霣霜膜 GMP (ooal / ig protein control 10. 1 soil 0.2 Endotoxin 60ig / kg intraperitoneal injection 30.7 ± 4.1 Toxin 60ig / kg intraperitoneal injection of 14.6 soil 1.2 + Ta 1 100 / ug Μ lethal dose of endotoxin-treated mice serum TNF-a test group TNF-a (pg / nl) 1 hour 3 hours 5 hours Toxin 60ag / kg 1098 ± 106 783 ± 38 623 ± 51 Endotoxin eOBg / kg + Ta ^ eSStS? 4 26 ± 3 7 297 ± 27 (read the precautions on the back side and fill in this page) order economy Printed form of the Ministry of Industry, Ministry of Industry, Consumer Cooperatives-ML «Pretreatment of SOD and Ταα to protect the blood from TNF-α and IL-la splashes of fatal mice induced by endotoxin * Pretreatment of TNF -ot (pg / el) IL-Ια (pg / nl) No 4462 ± 123 1137 ± 123 S0D (3.3x 104 «/ kg) 63 ± 5.1 5 3 ± 3.1 Tai lOOitg / mouse 285 ± 23 · 6 109 ± 71 X Pre-treatment of mouse K SOD (superoxide disproportionation) 30 minutes before endotoxin administration Blood was collected 1 hour after endotoxin administration to determine TNF-a and IL_la concentrations. -12- This paper scale is applicable to the Chinese National Standard (CNS> A4 specification (210X297mm) 83. 3.10,000 V. Description of the invention (10) Using the same materials and methods as spring example 1, study Τα ^ Internal The time and dosage of the lethal protective effect of toxins are shown in Table VI below. From Table VI, it can be seen that immediately after endotoxin treatment, 2 or 4 hours will be given or endotoxin will be given after 2, 4 and 6 hours. When naphthalene is used, Τα ^ has a protective effect on endotoxin toxicity. The effective protective agent is administered three times at the most 100Wg Ται. Discard VI Give a lethal endotoxin dose and the viability of Swiss Kestrel mice after giving Tai Number of experimental sisters 0 hours 24 hours 48 hours 72 hours 96 small drops I. 20 hours 4 Endotoxin SO mg / kg 8 4 4 4 4 Endotoxin SO mg / kg 8 8 8 8 — 8 + T α 1 100 w ε . 3χ Τ ot t is administered immediately after endotoxin, 2 and 4 hours to administer 8 ---------- (please read the note $ on the back first and then fill in this page to subscribe to endoxin 60 mg / kg 8 8 8 + Taj 100 fig, 3x; Τα ^ is printed at 2, 4, and 6 hours after endotoxin by the Ministry of Economic Affairs, Central Bureau of Preservation and Consumer Cooperatives

I 毒鬵 60 mg/kg 8 8 5 5 'a, 10 /xg, 3x; .… 3L係在内毒素後即刻，2及4小時投予使用如實例1和2之相同材料與方法，研^Ται封1L_la ，THF-ct ，PAG，Tx々2W6-嗣基- PGF'a等内薄累誘使致命之病理媒質的影響。结果示於下表B -VI ° 13- 本紙張尺度逋用中國鬮家橾率（CNS ) Α4规格（210x297公釐） 83. 3.10,000 A7 B7 310274 五、發明説明（11 由表IX -XIV可見Tot Γ可降低投予致命劑量内毒素後之 IL-la ，TNF-α 血清溻度及 PAF’ Tx/32 和 6-酮基- PGhaA 漿濃度。I Poison 60 mg / kg 8 8 5 5 'a, 10 / xg, 3x;... 3L is administered immediately after endotoxin, and administered with the same materials and methods as in Examples 1 and 2 for 2 and 4 hours. Ται 封 1L_la, THF-ct, PAG, Tx々2W6- 劣基 -PGF'a and other internal thinness induce the effects of lethal pathological media. The results are shown in the following table B -VI ° 13- This paper uses the Chinese family rate (CNS) A4 specifications (210x297 mm) 83. 3.10,000 A7 B7 310274 V. Description of the invention (11 from Table IX -XIV It can be seen that Tot Γ can reduce the concentration of IL-la, TNF-α serum and PAF 'Tx / 32 and 6-keto-PGhaA slurry after the lethal dose of endotoxin.

轰JDL 竇酴驵别 ILji：La_p_g_ZjLLLltJft..濃.,.度_丄 1小<睦,._ 14i .M_ 内毒素 60^g/kg 49 2 ± 45.2 550 ± 37.1 内毒素 6〇Bg/kg+ 8 3 ± 7.1 165 ± 13.7 嫌後即刻投予 T a 1 1 0 0 w 8 鬣重直1 内毒素60ng/kg 内毒素6 0 b g / k g _ 隨後即刻投予 T a 1 1 0 0 w gBoom JDL Dou 酴鈵别 ILji: La_p_g_ZjLLLltJft .. Concent.,. Degree_ 丄 1 小 & Mu, ._ 14i .M_ Endotoxin 60 ^ g / kg 49 2 ± 45.2 550 ± 37.1 Endotoxin 6〇Bg / kg + 8 3 ± 7.1 165 ± 13.7 Immediately after the administration of T a 1 1 0 0 w 8 Hyalurosis 1 Endotoxin 60ng / kg Endotoxin 6 0 bg / kg _ Immediately afterwards administration of T a 1 1 0 0 wg

表II *_MJ8_fi!L 1χΛ^.2丄.β^Ιλ,,ΙΛΙΛ M ML度丄 m'l Lili見仏見 3小時内毒素 6〇Bg/kg 1442 ± 1 03 2937 土 258 912 土 105 695 土 65 内毒素 60mg/kg+ 910土 85 1 92 1 土 1 85 530 ± 47 391 ± 260 嫌後即刻投予 Tai lOOwg 14- 本紙張尺度適用中國國家橾率（CNS ) A4规格（210X297公釐） (請先聞讀背面之注$項再填寫本頁) ^ P_Afκ / m. 1(血继灌庖）. 2 小時. 3小時 78± 6 279 ± 17 127± 13 55± 3 48± 3 136± 9 68 土 4 32 ± 2 -訂線經濟部中央標準局貝工消費合作社印製 83. 3.10,000 五、發明説明（ 12 實驗組.J1L 内毒素60mg/kg 内毒素6〇Bg/kg+ 随後即刻投予 Τ α 1 1 Ο Ο μ g 鬣..肢1別_ 内毒素60ng/kg 内毒素60mg/kg+ 随後即刻投予 Τ α 1 1 0 0 w g A7 B7 表JLL丄 jrlMUmm 341±31 1141± 112 897 ±75 224± 1 9 745±62 341±33 14—、直 811 ± 7 205 ± 19 EM .Lb.又ZjlLL(血浦滬度）_ H 5小時 938 783 66 2 508 567 429 (血潼濃度」 1小時 3小勝 5小時内毒素60nig/kg 938 662 567 内毒素 60mg/kg·»· 783 508 429 經濟部中央揉準局貝工消費合作社印製随後即刻投予 Τ α η 1 0 0 α g 使用大鼠（史伯格-拉利，雄性*各200-225克）之敗血病休克横式，研究單獮胸腺素αι和併同抗生素之影響。Μ 15 (請先聞讀背面之注意事項再填寫本頁)Table II * _MJ8_fi! L 1χΛ ^ .2 丄. Β ^ Ιλ ,, ΙΛΙΛ M ML degree 丄 m'l Lili see 3 hours endotoxin 6〇Bg / kg 1442 ± 1 03 2937 soil 258 912 soil 105 695 soil 65 Endotoxin 60mg / kg + 910 ± 85 1 92 1 ± 1 85 530 ± 47 391 ± 260 Immediately afterwards, it is administered to Tai lOOwg 14- This paper scale is applicable to China National Atomic Rate (CNS) A4 specification (210X297mm) (please Read the note $ item on the back first and then fill out this page) ^ P_Afκ / m. 1 (blood irrigating). 2 hours. 3 hours 78 ± 6 279 ± 17 127 ± 13 55 ± 3 48 ± 3 136 ± 9 68 Tu 4 32 ± 2-Printed by Beihang Consumer Cooperative of Central Bureau of Standards, Ministry of Economics 83. 3.10,000 V. Description of the invention (12 experimental group. J1L Endotoxin 60mg / kg Endotoxin 6〇Bg / kg + Then cast immediately To T α 1 1 Ο Ο μ g Hyena: Limb 1 part_ Endotoxin 60ng / kg Endotoxin 60mg / kg + Immediately administered to T α 1 1 0 0 wg A7 B7 Table JLL 丄 jrlMUmm 341 ± 31 1141 ± 112 897 ± 75 224 ± 1 9 745 ± 62 341 ± 33 14-, straight 811 ± 7 205 ± 19 EM .Lb. And ZjlLL (blood pump) _ H 5 hours 938 783 66 2 508 567 429 (blood concentration '' 1 hour 3 small wins 5 hours endotoxin 60nig / kg 938 662 567 Endotoxin 60mg / kg · 783 508 429 Printed by the Ministry of Economic Affairs, Central Bureau of Industry and Economics, Beigong Consumer Cooperative, and then immediately administered to T α η 1 0 0 α g Rats (Sberg-La Lee, male * each 200-225 grams) of septic shock horizontal, to study the effects of monothymic thymosin αι and concurrent antibiotics. Μ 15 (Please read the precautions on the back before filling this page)

本紙張尺度適用中國國家梯準（CNS ) Α4规格（210X297公釐） 83. 3.10,000 A7 B7五、發明説明（13 ) 經濟部中央標準局負工消费合作社印製下述方式對大鼠誘發腹膜炎。腹膜作1公分切開，暴露出肓腸。K 4 - 0鍵線於小臈嵌合處壇繃，於盲臈周圃緊緊结紮|生成無生活力組孅區同時仍保持腸子的連讀。K16號針頭在盲腸的腸系膜對側表面剌穿一口，擠出小量糞便。肓腸重新置回腹腔，前側腹壁及皮Λ Μ手術鏠線«閉。各頭動物給予大劑量生理鹽水U5ml / kg)供水化且任其恢復隔夜。表XV结果顯示Τα i可提高大鼠存活率。敗血病休克、抗生素•和胸腺素〇(1後史伯格-拉利大鼠之存活率奮驗姐別 0小時 2 4小時 48小時 72小時腹膜炎+抗生素大鼠 10 1 1 0 腹膜炎+抗生素* 1 0 8 6 6 +胸腺素α 1 lBg/大鼠 X 3** * gentanicin sulfate, loig /大鼠 X 誘發腹膜炎後0小時，2小時及4小時下表XVI至XIX所示結果顯示Τα :分別對大鼠畑胞動素濃度，血中丙二釀二醛濾度，麩胱甘肽濃度及花生四烯酸代謝產物濃度之影響。 -16- 本紙張尺度逋用中國國家橾準（CNS ) Α4规格（210Χ297公釐） 83. 3.10,000 (請先閲讀背面之注意事項再填寫本頁) -訂線 310274 五、發明説明（14) 經濟部中央標準局負工消费合作社印裝於大鼠敗血實驗胤.1 對照敗血病休克大敗血病体克大 +如前述T ot i 於大鼠敗血病mm 對照敗血病体克大敗血病休克大 +如前述T a i 於大鼠敗血tmJoiL 對照敗血病体克大敗血病休克大 +如前述Τ α 1This paper scale is applicable to China National Standard (CNS) Α4 specification (210X297mm) 83. 3.10,000 A7 B7 V. Description of invention (13) Printed by the Ministry of Economic Affairs Central Standards Bureau Negative Work Consumer Cooperative in the following way peritonitis. The peritoneum was cut 1 cm to expose the gut. The K 4-0 key line is stretched at the altar of the Xiaomao fitting place and tightly tied at the blind Zhoupu | Create a vitality group while still maintaining the continuous reading of the intestines. K16 needle pierced the surface of the mesentery on the opposite side of the cecum to squeeze out a small amount of feces. The gut was placed back into the abdominal cavity, and the anterior abdominal wall and the skin were closed. Each animal was given a large dose of normal saline (U5ml / kg) for water supply and allowed to recover overnight. Table XV results show that Tα i can improve the survival rate of rats. Septic shock, antibiotics, and thymosin. (1 Survival rate of post-Sberg-Larley rats 0. 24 hours 4 hours 48 hours 72 hours peritonitis + antibiotics rat 10 1 1 0 peritonitis + antibiotics * 1 0 8 6 6 + thymosin α 1 lBg / rat X 3 ** * gentanicin sulfate, loig / rat X 0 hours, 2 hours, and 4 hours after peritonitis-induced results shown in the following tables XVI to XIX show Tα: The effects on rat cytokinin concentration, blood malondialdehyde filtration, glutathione concentration, and arachidonic acid metabolite concentration in rats. -16- This paper scale uses the Chinese National Standard (CNS) ) Α4 specification (210Χ297 mm) 83. 3.10,000 (please read the notes on the back before filling in this page) -Reservation line 310274 V. Description of invention (14) Printed by the Ministry of Economic Affairs Central Standards Bureau Cooperative Consumer Cooperative Rat septicemia experiment. 1 Control septic shock shock major septicemia body + as described above T ot i in rat septicemia mm Control septic body shock major septicemia shock + as described above T ai in rat septicemia tmJoiL control septicemia body septicemia shock shock + as before Τ α 1

表-,XJLL 病休克棋式中Τα t對细胞動素濃度之彩響 I.lLE.a_,ijp«/,B,LJL· LLx_£ljLb^_ZjlLL 無法檢測鼠 2658 ± 197 鼠 1231 ± 129 Ug/大鼠X 3 HJULLL 体克镆式中Τα ^對脂質過氧化反應之影響 _—_______InNol ΗΡΑ)___ 無法檢測 1387土 123 689 土 53 (請先H讀背面之注$項再壤寫本頁) •-4 15 . 3 ± 1 . 3 49.1± 3 . 5 17 . 1 ± 1 . 6 18.6 ± 1.1 46.3土 3. 8 21.9 土 2 · 3 H 鼠 1·β /大歐X 3 mju.ui 病体克棋式中Τα 1對麩胱甘肽濃度之影響 RRi： GSH (a aoies/iiUffll») 1 . 38 ± 0.1 1 . 46± 0. 13 鼠 0.43 ± 0.05 0.28 ± 0.04 鼠 1.29± 0.07 1.20 ± 0.085 lug/大鼠X 3 -17 本紙張尺度逋用中國國家梯準（CNS ) A4规格（210X297公釐） 83.3.10,000 訂線 310274五、發明説明（ A7 B7 15 經濟部中央梯準局爲工消費合作社印製於大鼠敗血 aua姐別_ 對照敗血病体克敗血病休克 +如前述Τ α 下表XX和活率。敗血病体克敗血病体克 +如前述Τ α 1 w/大鼠X1LH1 敗血病体克敗血病休克 +如前述Τ α 1 Bg/大鼠X 雖已#照者在不悖鼸代換。病体克摸式中Τα 1對花生四烯酸代謝產物之影響 &:.k. e t p —iLCLE丄&/jl..LL Ixii jlLL 58 ± 3.5 89 ± 7 . 6 大鼠 1828 ± 1 45 . 3 3622 ± 295 大鼠 U32± 96 2353 ± 197 i lag /大規 x3 XX I所示结果騸證Τα Γ可提高敗血病体克大鼠存大鼠大鼠表JX在」£.太1数且_。止直 2AH ϋ小直⑴這― 10 2 2 0 10 9 9 5 复11Χ 存活大鼠黻目 m膀一 4&/上見大鼠 101 0 0 大鼠 10 8 7 3 1 3 某些較佳具體例詳细示例説明本發明，热悉本技藝本發明之範園内當可作各種修改、變化、省略與 18 本紙張尺度適用中國國家橾隼（CNS ) A4规格（210X297公釐） 83. 3.10,000 (請先H讀背面之注意事項再镇寫本頁) --f 訂- 線Table-, The color response of Τα t to cytokinin concentration in XJLL disease shock pattern I.lLE.a_, ijp «/, B, LJL·LLx_ £ ljLb ^ _ZjlLL Unable to detect rat 2658 ± 197 rat 1231 ± 129 Ug / The effect of Τα ^ on the lipid peroxidation in rat X 3 HJULLL body formula _—_______ InNol ΗΡΑ) ___ 1387 soil 123 689 soil 53 cannot be detected (please read the note on the back of H first before writing this page) • -4 15. 3 ± 1. 3 49.1 ± 3. 5 17. 1 ± 1. 6 18.6 ± 1.1 46.3 soil 3. 8 21.9 soil 2 · 3 H rat 1. β / Daou X 3 mju.ui In the formula, the effect of Tα 1 on the concentration of glutathione RRi: GSH (a aoies / iiUffll ») 1.38 ± 0.1 1.46 ± 0. 13 rat 0.43 ± 0.05 0.28 ± 0.04 rat 1.29 ± 0.07 1.20 ± 0.085 lug / Rat X 3 -17 This paper scale uses the Chinese National Standard (CNS) A4 specification (210X297 mm) 83.3.10,000 Line 310310 V. Description of the invention (A7 B7 15 Printed by the Industrial and Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Controlled by rat septicemia aua sister _ control septicemia septicemia shock + as above T α The following table XX and survival rate. Septicemia gram septicemia body + as before Τ α 1 w / rat X1L H1 septicemia body septicemia shock + As mentioned above Τ α 1 Bg / rat X Although it has been taken according to the person's substitution, the effect of Τα 1 on arachidonic acid metabolites in the patient's gram-type formula & : .k. etp —iLCLE 丄 & /jl..LL Ixii jlLL 58 ± 3.5 89 ± 7.6 rat 1828 ± 1 45 .3 3622 ± 295 rat U32 ± 96 2353 ± 197 i lag / large gauge x3 XX The results shown in I show that Tα Γ can improve the septicemia body. Rats can store JX in rats. The number is too large and _. Zhizhi 2AH ϋ Xiaozhi ⑴This ― 10 2 2 0 10 9 9 5 Complex 11Χ Surviving Rats 黻目 m 參 4 & / See Rats 101 0 0 Rats 10 8 7 3 1 3 Some of the preferred specific examples illustrate the invention in detail, and it is well understood that this technique is within the scope of the invention Various modifications, changes, omissions and 18 paper standards are applicable to the Chinese National Falcon (CNS) A4 specification (210X297 mm) 83. 3.10,000 (please read the precautions on the back before writing this page)- -f set- line

Claims

No. 83105327 Patent Application Case 丨 Amendment to Scope (84 months in 1984) g Scope of Patent Application

1. 2. 3. 5.-A combination of medicines for the progression of symptoms of mammalian septicemia that obstructs the development of septicemia bark: the composition 'includes the amount of thymosin (thymosin) α that inhibits the progression of septicemia symptoms α (T at) 〇The rodent composition for a pharmaceutical composition according to item 1 of the patent application scope. According to the first paragraph of the patent scope of the application of the pharmaceutical composition _ medicine composition. Synthesized according to the pharmaceutical composition of item 1 of the scope of patent application l ai 〇 The pharmaceutical composition α of the pharmaceutical composition according to item 1 of the patent application ranged from 0.4 to 4 mg of thymosin per kg of body weight of the recipient. It can reduce at least one of the CGMP concentration of mammalian brain, the concentration of malondialdehyde in blood and the concentration of glutathione in blood. The system is for parenteral administration. The system is for intravenous administration. The T α ϊ is the thymosin. ------------— (,,. Packing --------- order --- ---- {Line (please read the precautions on the back before filling in this page) Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs «This paper size is applicable to China. National Standard (CNS) A4 Specification (2 丨》 X 297mm )