TW200920391A - Multi-target post-receptor action used in pharmaceutical composition for depression treatment - Google Patents
Multi-target post-receptor action used in pharmaceutical composition for depression treatment Download PDFInfo
- Publication number
- TW200920391A TW200920391A TW96143310A TW96143310A TW200920391A TW 200920391 A TW200920391 A TW 200920391A TW 96143310 A TW96143310 A TW 96143310A TW 96143310 A TW96143310 A TW 96143310A TW 200920391 A TW200920391 A TW 200920391A
- Authority
- TW
- Taiwan
- Prior art keywords
- group
- pharmaceutical composition
- weight
- composition
- parts
- Prior art date
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
200920391 九、發明說明： •【發明所屬之技術領域】 =明係關於―叙包含以人參皁戒灿.及甘草酸及 鬱症的藥物m ϋ錄標受體後_機_於治療憂 θ種能避免引起強°區吐等副作用的治療憂 #症的口服藥物或保健食品。 ’、 【先前技術】 憂鬱症是-種常見的疾病，據統計在―般人口中大約有 过㈣過憂#症，雜巾約有職左右經 歷過憂鬱症（張春興著：《現代心理學》）。世界衛生植織 (WHO)提供的資料：憂#症在全世界的發病率約爲Μ， 目前全球約有3.4億精神㈣患者，而且這個數字仍成上升趨 勢，调查發現在今後2〇年，憂營症將會上升爲全球第二大常 見疾病。 現有技術中，抗憂鬱藥物以百憂解、赛洛特、左洛 ⑻RI、麵、NDRI等類的5_HT、顺、da再攝取抑制劑） 爲主’其作關制是通過增加人體神經介質内$ 分含量以緩解憂鬱症狀。 4成 但是，已問市的抗憂營藥物都有不同程度的副作用 如：增加自殺率、頭痛、頭暈、暈眩、失眠、嗜睡、耳鳴、 口乾、厭食、食慾增加、體重上升、血壓上升、腸胃不適、 反胃、嗔心“區吐、消化不良、腹篇、便秘、下肢痛、 出療、顫抖、痙攣、多汗、水腫、性慾降低、性無能等。近 200920391 年來百憂解4抗憂營藥物已成爲社會嚴重關注的問題，美國 食品暨藥物管理局（FoodandDrugAdministraiion FDA)更於 2〇〇4年要求樂雜市場上主要的32種抗憂鬱藥物重新標示 /、田!作用和纟告的部分，並對醫護人員強調這些藥物可能增 加孩童及青少年自殺的機率。其中，赛洛特更是早在1996年 就被發現存在有安全隱患，自篇年開始已陸續從市場上召 =。20〇4年6月，美國组約州總檢察長指控英國葛蘭素史克 公司爲了獲取利潤，欺騙性隱瞒了服用賽洛特與“增加青少年 自殺傾向及行爲的風險，，之間有關聯的研究報告。在這種背景 下’如何研發新—代副作用低又能有鴨抗憂 已成爲全球醫藥界所關注㈣題。 樂物 *近年來，國際醫藥界的科學家們在題症致病機理的研 九方面出現了新的突破，發現除了以5-HT、NE、DA的再攝 m式治療雜症之外’更可以採取獨受體後作用機 、方式治療憂，並且由於受體後作用機制調節類藥物 埶里晋拉（R〇lipram)的問世而成爲醫藥界抗憂營藥物的研發 扣;;羅列普拉是四型磷酸二酯酶（ρ1ι〇_—彻阳“， 物侧’臨賴驗表明它财明顯的 $於服用羅列普拉會出現強舰吐，故被迫終止研^缺 的部開拓了新—代「受體後作用機制抗抑#藥物」 悉心=之故’ 人鑑W知技術情產生之缺失，乃經 「多^與棟索’亚一本鐵而不捨之精神，終構思出本案之 ^讀後侧機_於治療㈣症的藥物組 卜马本案之簡要說明。 Λ 200920391 【發明内容】 為了克服現有技術的不足，本發明的目的在於提俾—电 匕3以人參皂甙Rg卜RM、甘草酸及大棗cAMp 在 =多純受體後_機儀於治療抑#症的口服藥物或保ς ^口 ’特別是不料起強純吐物作_新技術方案。 本發明藥物的解決方案是經吾人潛心研究探索的結 ^現代醫學治療憂鬱症的病理及藥理學理論，特別是於人 受體後作關制抗憂_轉研究，、_大4的動物實^二 明：人參息武含有腺芽酸活化_ (aden細cydase，ac)二 激翁，並含有cAMP麟酸二醋酶（CApD)的抑制成份；甘 草酸（甘草次酸）是cAMP_二_ (CApD)強抑制劑。 人茶皂武、甘草酸（甘草次酸）二者配伍，協同作用，可以 進-步提高eAMP的_度和雜，而eAMp的濃度和活性 增強，則可增加去甲腎上腺素（職_咖啤ne)等神經 遞質的合祕_，職職性神、㈣翻子（kain^ived 職伽phic factor, BDNF)的表達，抑制下視丘_腦下垂體-腎 上腺軸（hypothalamic-pituitary-adrenal axis，ΗΡΑ軸）的亢進 和糖皮質激素的分泌，從而達到顯著的抗憂鬱功能。另外， 大棗CAMP亦可以提高人體cAMp的表達，從而起到抗憂鬱 作用’將大棗中含量極微（約萬分之一）的大棗cAMp萃取 並純化成含1 %大棗cAMP的大棗萃取物進行抗試驗性抑鬱作 用動物試驗的結果顯示，具有明顯的抗試驗性抑鬱功能，但 僅以一般例如用水加溫萃取而未進一步純化提高其萃取物大 棗cAMP濃度的大棗萃取物，雖然含有微量的大棗cAMp卻 不具有明顯的抗試驗性抑#功能，爲了進一步增強本發明的 200920391 :憂=效甘―、人參娜甘草酸三者配 明人參、甘草、去參—i τ巳充y刀證 的H明二者配安全性’發明人研究及實驗 的萃取物和目若僅以—般㈣的煎煮方式萃取所得 著的抗真治療憂鬱症的抗憂雜物相比不具備顯 提古墓，但再採取例如上柱層析的純化方式進一步 =:的濃度’再加上甘草酸或甘草次酸等原 猶酬沒有顯著的抗憂_ 4 人提^Ah及大棗不會發生賴嗯吐等副作用，故發明 制P 武％1、RM及甘草酸和大裘cAMP為原料， =====於治療憂的口服藥物或保 濃戶=!卒取物中人參皂武¥、rm及大棗翁 列上含甘草酸或甘草次酸等原料製成不會引起強 相翻的新技術方案輯料知技術 天0 200920391200920391 IX. Description of invention: • [Technical field to which the invention belongs] = Ming Department on the narration of ginseng saponin and glycyrrhizic acid and depression drug m ϋ recorded receptor _ machine _ in the treatment of θ An oral or health food that avoids the treatment of side effects such as strong vomiting. ', 【Prior Art】 Depression is a common disease. According to statistics, there are about (4) over-health in the general population, and the diaper has experienced depression in about a job (Zhang Chunxing: Modern Psychology) . According to the information provided by the World Health Organization (WHO): the incidence of sorrow # worldwide is about Μ, there are about 340 million mentally (four) patients worldwide, and this number is still on the rise, the survey found that in the next two years, The worry camp will rise to become the second most common disease in the world. In the prior art, the antidepressant drugs are mainly based on Prozac, Celote, Zolo (8) RI, face, NDRI, etc. 5_HT, cis, da reuptake inhibitors. The amount of $ is to relieve the symptoms of depression. 40% However, the anti-AIDS camp drugs that have been asked have different degrees of side effects such as increased suicide rate, headache, dizziness, dizziness, insomnia, lethargy, tinnitus, dry mouth, anorexia, increased appetite, weight gain, and increased blood pressure. Gastrointestinal discomfort, nausea, phlegm, vomiting, indigestion, abdominal, constipation, lower extremity pain, treatment, tremor, phlegm, sweating, edema, loss of sexual desire, sexual incompetence, etc. Near 200920391, Prozac 4 The slogan drug has become a serious concern in the society. The Food and Drug Administration (FDA) has requested the main 32 anti-depressant drugs in the market to be re-marked/fielded and reported in 2.4 years. Part of it, and stressing that these drugs may increase the chances of suicide among children and adolescents. Among them, Selot was found to have potential safety hazards as early as 1996, and has been calling from the market since the beginning of the year. In June 2004, the US Attorney General of the State Department accused the British GlaxoSmithKline of deceptively concealing the use of Celote and "increasing the youth" in order to obtain profits. Some studies report an association between the risk of killing tendencies and behavior ,,. In this context, 'how to develop new-generation side effects are low and ducks can be worried. It has become the focus of the global medical community (4). Musical Materials* In recent years, scientists in the international medical community have made new breakthroughs in the research and development of the disease mechanism of the disease. It has been found that in addition to the re-exposure of 5-HT, NE, and DA, the treatment of the disease is more It can be treated with a single receptor and after-effect machine, and it can be used as a research and development deduction for anti-worry drugs in the pharmaceutical industry due to the release of the drug-restricting mechanism R〇lipram. It is a type IV phosphodiesterase (ρ1ι〇_—Chuyang”, and the side of the object indicates that it is obvious that it will be forced to spit out when taking Luo Lipu, so it is forced to terminate the research. The new-generation "receptor post-action mechanism anti-suppressed #drug" carefully = the reason of the people's knowledge of the lack of technical sentiment, is the "multi-^ and Dongsuo" Ya, a spirit of perseverance, the final concept A brief description of the case of the drug group in the treatment of (4) disease. Λ 200920391 [Summary of the Invention] In order to overcome the deficiencies of the prior art, the object of the present invention is to extract 匕 匕 以 以 以 以 以 以Rg Bu RM, glycyrrhizic acid and jujube cAMp after = multi-pure receptor Anti-drug oral medication or Baozheng ^ mouth 'especially unexpectedly strong pure spit for _ new technology program. The solution of the drug of the invention is the pathology and pharmacology of modern medical treatment of depression caused by our research Theory, especially after the human receptors, to control the anti-worry _ transfer study, _ big 4 animal real ^ two Ming: ginseng Xiwu contains adenosine activation _ (aden fine cydase, ac) two stimuli, and Containing inhibitory component of cAMP linonic acid diacetate (CApD); glycyrrhizic acid (glycyrrhetinic acid) is a strong inhibitor of cAMP_二_(CApD). The combination of human tea soap and glycyrrhizic acid (glycyrrhetinic acid) synergy Function, can further improve the eAMP _ degree and impurities, and the concentration and activity of eAMp is enhanced, it can increase the secret of neurotransmitters such as norepinephrine (professional _ _ _ _ beer ne), (4) The expression of the scorpion (kain^ived gamph factor, BDNF) inhibits the hyperthyroidism-hyperhalal-pituitary-adrenal axis (ΗΡΑaxis) and the secretion of glucocorticoids Significant anti-depressant function. In addition, jujube CAMP can also improve human cAM The expression of p, which plays an anti-depressant role, extracts and purifies jujube cAMp with a very small amount (about 1 in 10,000) in jujube into jujube extract containing 1% jujube cAMP for anti-depressant animals. The results of the test showed that there was a significant anti-experimental depression function, but only the jujube extract which was generally extracted with water and heated without further purification to increase the concentration of jujube cAMP in the extract, although containing a trace amount of jujube cAMp, It has obvious anti-testing and anti-function, in order to further enhance the 200920391 of the present invention: worrying about the effect of Gan--, ginseng-na-glycyrrhizic acid, ginseng, licorice, and ginseng-i τ巳The safety of the 'inventor's research and experimental extracts and the purpose of extracting only the anti-suppressor anti-worry artifacts obtained by the decoction method of the general (four) decoction does not have the obvious tomb, but then Take, for example, the purification method of the upper column chromatography further =: the concentration 'plus the glycyrrhizic acid or glycyrrhetinic acid and other original weights have no significant anti-worry _ 4 people mention ^ Ah and jujube will not occur 赖 吐 吐 and other side effects , so the invention of P 武%1, R M and glycyrrhizic acid and scorpion cAMP as raw materials, ===== Oral drugs or preserved households in the treatment of sorrow =! The ginseng saponin ¥, rm and jujube in the strokes contain glycyrrhizic acid or licorice A new technical solution made of raw materials such as acid will not cause strong phase turnover. Technology Day 0 200920391
藥物標的 機制— 1. 啟動cAMP依賴的絡氨酸經化 酶，增加NE合成 2. 攝酸化突觸蛋白，增加NE釋放 1.啟動cAMP依賴的酪氨酸羥化 酶，增加NE合成 2·ί粦酸化突觸蛋白，增加NE釋放； 酸 _ 降 3:口 解’挺同cAMP利用度而發揮作用。提scAMp利用度而發揮作用； 4. 啟動AC，增加cAMP的濃度和活 性； 5. 通過提高ATP促使cAMP的生成； 6. 促進笨丙酸透過血腦屏障，促進 NE、DA的合成和下調ΗΡΑ軸； 7. 通過直接上調腦細胞中BDNF和 ΝΤ-3的表達，抗應激反應。 不良反應 會引起強烈嘔吐等副作用 純植物製劑’而且原料均可藥食兼 用，長期服用副作用低、安全性高 本發明藥物與習知的受體後作用機制的抗憂鬱藥物羅列 普拉不同之處，在於既可以同樣的通過多靶標受體後作用機 制達到抗憂鬱侧’又能避免如服用羅列綠後所引起的強 烈嘔吐等副作用。 由於甘草酸在人體内轉化爲甘草次酸的轉化率幾乎達到 100%，而脂溶性比甘草酸強的甘草次酸能夠透過血腦屏障進 入腦内，故甘草酸抑制CAPD起到抗憂鬱功效是通過體内轉 化爲甘草次酸來進行的，因此，可以用甘草酸或甘草次酸為 原料加工製成本發明的藥物組合物。 本發明係揭露一種多靶標受體後作用機制用於治療抑鬱 症的藥物組合物，它是由包括含有人參皂甙Rgl、Rbl及甘草 酸或甘草次酸等原料所製成。 較佳者，本發明之藥物組合物，是由包括含有人參皂甙 200920391 (Rgl+Rbl)合計2〜％重量份與甘草酸或甘草次酸3〜奶重 量份的原料所製成。 較佳者’本發明之藥物組合物，是由包括含有人參專武 (Rgl+Rbl)合計4〜13重量份與甘草酸或甘草次酸5〜16重 量份的原料所製成。 根據本發明之另—概念，本發鶴揭露—種乡輕標受體 後作用機細於治療抑驗的藥物組合物，它是由包括含有 人荼矣戒Rgl、Rbl及甘草酸或甘草次酸及大棗eAMp等原 料所製成。 較佳者，本發明之藥物組合物，是由包括含有人參息武 jRgl+Rbl)合§十2〜26重量份與甘草酸或甘草次酸3〜48重 量伤及大棗cAMP0.002〜〇·5重量份的原料所製成。 較it者本杳明之藥物組合物，是由包括含有人參息武 胃(Rgl+Rbl)合計4〜13重量份與甘草酸或甘草次酸5〜16重 量伤及大棗cAMPO.Ol〜〇.1重量份的原料所製成。 ^較佳者，本發明之藥物組合物包括可以含有藥學上可接 受的載體或添加劑，可以製成錠劑、膠囊劑、散劑、片劑、 粕背丨/谷液劑、微囊劑、混懸劑、乳劑、顆粒劑、滴丸劑、 丸劑等任何藥劑學上所公知的口服藥物劑型。 一較佳者，所述的藥物組合物可用來製成用於治療抑鬱症 的藥物、保健食品和營養劑。 本發明說明書和申請專利範圍中所述之用於治療憂鬱症 的口服藥物’是貫現本發明目的的核心内容，在本發明公開 ^ ’本領域的技術人員彳以根據中醫理論或是侧現代藥理 學理淪，對上述藥物進行常規的加減化裁或是用功效作用相 200920391 同的其他中藥有效成分（如遠志甙、柴胡甙、甘草香豆素等） 替代。這種常規的加減化裁和用作用機理相似或相同的其他 CAPD抑制劑、AC啟動劑的中藥或是相應的有效成分來替 代，均屬於本領域技術和研究人員的一般性技術活動，故其 都在本發明的保護範圍之内。 本發明得藉參閱如附圖示及詳細說明而獲較佳瞭解。 【實施方式】 以下將結合附圖和實施例進一步說明本發明。本發明主 要是採用本領域技術人員習知的方法結合本發明的特徵製備 本發明所述_物。以下實施例健是爲了朗，並非限定 本發明。 為了完成本發明的目的，本發明特別提出下列技術方案。 本發明係揭露-種多練受體後作用機制 抑 症的藥物組合物，它是由包括含有人參 酸或甘草次酸等原料所製成。 甘单 方案一： 物組合物。 < 體後作職儀於治療㈣症的藥 方案二： 合計2〜26重量份與甘草酸 加工製成本發明的藥物組合 以含有人參息武（Rgl+RM) 或甘草次酸3〜48重量份的原料， 物。 200920391 方案三： 以δ有人參皂武（Rgl+Rbl )合計4〜13重量份與甘草酸 或甘草次酸5〜Ιό重量份的原料，加工製成本發明的藥物組合 物。 方案四： 以含有人參皂甙Rgl、Rbl、甘草酸或甘草次酸及大棗 cAMP等原料，加工製成本發明錄標受體後仙機制用於 治療憂鬱症的藥物組合物。 方案五： 以含有人參皂甙（Rgl+Rbl)合計2〜26重量份、甘草酸 或甘草次酸3〜48重量份及大棗cAMP 〇 〇〇2〜〇 5重量份的原 料，加工製成本發明的藥物組合物。 方案六： 以含有人參皂武（Rgl+RM)合計4〜n重量份、甘草酸 或甘草次酸5〜16重量份及大棗cAMP 0.01〜0.1重量份的 料，加工製成本發明的藥物組合物。 ’、 方案七： 本發明之藥驗合物包括可时㈣學上可接受 或添加劑’可以製雜劑、膠囊劑、散劑、片劑、粉劑、々 ㈣、微囊劑、混_、乳劑、顆粒劑、滴丸劑、丸劑等ς 12 i 200920391 何藥劑學上所公知的口服藥物劑型。 方案八 方法一 ^ 了几成本發明的目的，特提出以下藥物的製作方法。 取含有人參4叙gl、RM及甘草酸的 物為原科’或直接採用已製備成的含有人參息武 ΠίΓΓ域甘草魏的補，加工製成本㈣多革巴標受 體後作關_於治療錄症的藥物組合物 方法. 將含有人參I武（Rgl+Rbl)合計2〜26重量份與甘草酸 或甘草次酸3〜48重|份的馬4立4· A1 更里知的原枓，加工製成本發明的藥物組合 有人4 4戒（Rg1+RM)合計4〜丨3重量份與甘草酸 或甘草次酸5〜16重量份的周祖士 里里⑽蘭’加卫製成本發_藥物組合 方法四： 自人參及甘草及大棗巾萃取含有人參皂❹gl、The mechanism of drug labeling - 1. Initiate cAMP-dependent tyrosine oxidase, increase NE synthesis 2. Acquire acid synaptic protein, increase NE release 1. Activate cAMP-dependent tyrosine hydroxylase, increase NE synthesis 2 · ί Acidification of synaptic proteins, increased NE release; acid _ drop 3: oral solution 'same as cAMP utilization. Promote the utilization of scAMp; 4. Start AC, increase the concentration and activity of cAMP; 5. Promote the production of cAMP by increasing ATP; 6. Promote the diffusion of streptopropionic acid through the blood-brain barrier and promote the synthesis and down-regulation of NE and DA. Axis; 7. Anti-stress response by directly up-regulating the expression of BDNF and ΝΤ-3 in brain cells. Adverse reactions can cause strong vomiting and other side effects of pure botanical preparations' and raw materials can be used for both medicine and food, long-term use of low side effects, high safety. The anti-depressant drug Roleta is different from the anti-depressant drug of the present invention. In the same way, the anti-depression side can be achieved through the action mechanism of the multi-target receptor, and the side effects such as strong vomiting caused by taking the column green can be avoided. Since the conversion rate of glycyrrhizic acid into glycyrrhetinic acid in the human body is almost 100%, and the glycyrrhetinic acid which is more fat-soluble than glycyrrhizic acid can enter the brain through the blood-brain barrier, glycyrrhizic acid inhibits CAPD and has anti-depression effect. It is carried out by in vivo conversion to glycyrrhetinic acid, and therefore, the pharmaceutical composition of the present invention can be produced by processing with glycyrrhizic acid or glycyrrhetinic acid as a raw material. The present invention discloses a pharmaceutical composition for treating depression in a multi-target receptor post-action mechanism, which is prepared by including a raw material containing ginsenoside Rgl, Rbl, and glycyrrhizic acid or glycyrrhetinic acid. Preferably, the pharmaceutical composition of the present invention is prepared from a raw material comprising 2 to % by weight of total ginsenoside 200920391 (Rgl + Rbl) and 3 parts by weight of glycyrrhizic acid or glycyrrhetinic acid. Preferably, the pharmaceutical composition of the present invention is prepared from a raw material comprising 4 to 13 parts by weight of total ginseng (Rgl + Rbl) and 5 to 16 parts by weight of glycyrrhizic acid or glycyrrhetinic acid. According to another concept of the present invention, the present invention discloses a pharmaceutical composition which is finer than a therapeutic inhibitor, and which comprises a human sputum ring Rgl, Rbl and glycyrrhizic acid or licorice It is made from raw materials such as acid and jujube eAMp. Preferably, the pharmaceutical composition of the present invention is composed of ginseng-containing jRgl+Rbl) §10 2 to 26 parts by weight with glycyrrhizic acid or glycyrrhetinic acid 3 to 48 weights and jujube cAMP0.002~〇 • 5 parts by weight of the raw material. Compared with the pharmaceutical composition of the present invention, it comprises 4 to 13 parts by weight of total ginseng-containing stomach (Rgl+Rbl) and 5 to 16 weights of glycyrrhizic acid or glycyrrhetinic acid and jujube cAMPO.Ol~〇. 1 part by weight of the raw material. Preferably, the pharmaceutical composition of the present invention comprises a pharmaceutically acceptable carrier or additive, which can be used as a tablet, a capsule, a powder, a tablet, a sputum/cold solution, a microcapsule, and a mixture. Any of the pharmaceutically acceptable oral pharmaceutical dosage forms such as suspensions, emulsions, granules, pills, pills, and the like. Preferably, the pharmaceutical composition is useful for the manufacture of a medicament for the treatment of depression, a health food and a nutraceutical. The oral drug for treating depression as described in the specification and the scope of the present application is the core content of the present invention, and is disclosed in the present invention by a person skilled in the art according to the theory of Chinese medicine or the side modern Pharmacology, the conventional addition or subtraction of the above drugs or the use of other effective Chinese ingredients (such as Polygalaceae, Bupleurum, licorice coumarin, etc.). Such conventional addition and subtraction and replacement with other CAPD inhibitors, AC initiators, or corresponding active ingredients having similar or identical mechanism of action are common technical activities of those skilled in the art, and therefore All are within the scope of the invention. The invention will be better understood by reference to the drawings and the detailed description. [Embodiment] Hereinafter, the present invention will be further described with reference to the accompanying drawings and embodiments. The present invention is primarily directed to the preparation of the present invention by methods known to those skilled in the art in conjunction with the features of the present invention. The following examples are intended to be illustrative and not limiting. In order to accomplish the object of the present invention, the present invention particularly proposes the following technical solutions. The present invention discloses a pharmaceutical composition for inhibiting the action mechanism of a receptor, which is prepared by including a raw material containing ginseng or glycyrrhetinic acid. Gandan Scheme 1: Composition of matter. < Pharmacology for treating (4) after treatment: 2 to 26 parts by weight combined with glycyrrhizic acid to prepare a pharmaceutical combination of the present invention to contain 3 to 48 weight of ginseng (Rgl + RM) or glycyrrhetinic acid Parts of raw materials, things. 200920391 Scheme 3: The pharmaceutical composition of the present invention is processed by using 4 to 13 parts by weight of a total of δ ginseng (Rgl + Rbl) and a raw material of 5 parts by weight of glycyrrhizic acid or glycyrrhetinic acid. Scheme 4: A pharmaceutical composition for treating depression is processed by using a raw material containing ginsenoside Rgl, Rbl, glycyrrhizic acid or glycyrrhetinic acid and jujube cAMP. Scheme 5: The present invention is processed by using 2 to 26 parts by weight of total ginsenosides (Rgl + Rbl), 3 to 48 parts by weight of glycyrrhizic acid or glycyrrhetinic acid, and 5 parts by weight of jujube cAMP 2 2 to 5 parts by weight. Pharmaceutical composition. Scheme 6: The pharmaceutical composition of the present invention is processed by using 4 to n parts by weight of ginsenoside (Rgl + RM), 5 to 16 parts by weight of glycyrrhizic acid or glycyrrhetinic acid, and 0.01 to 0.1 parts by weight of jujube cAMP. Things. ', Scheme 7: The drug composition of the present invention includes a time- (4) academically acceptable or additive' can be used as a dopant, a capsule, a powder, a tablet, a powder, a bismuth (four), a microcapsule, a mixed _, an emulsion, Granules, pills, pills, etc. i 12 i 200920391 Oral pharmaceutical dosage forms well known in pharmacy. Scheme 8 Method 1 ^ The purpose of the invention is to propose the following methods for the preparation of the following drugs. Take the ginseng 4 gl, RM and glycyrrhizic acid as the original ' or directly use the prepared ginseng-containing martial arts ΓΓ 甘 甘 甘 甘 甘 魏 的 , , , , , , , , , , , , , , ( ( 于 于 于 于A pharmaceutical composition method for treating a disease. A total of 2 to 26 parts by weight of ginseng I (Rgl + Rbl) and 3 to 48 parts by weight of glycyrrhizic acid or glycyrrhetinic acid are used.枓, processed into the pharmaceutical composition of the present invention 4 4 ring (Rg1 + RM) total 4 ~ 丨 3 parts by weight with glycyrrhizic acid or glycyrrhetinic acid 5 to 16 parts by weight of the ancestral celestine (10) blue ' 卫 卫 _ _ Drug combination method four: from ginseng and licorice and jujube towel extraction containing ginsenoside gl,
Rb卜甘 13 200920391 草酸及大棗CAMP的萃取物為原料，或直接採用已製備成的 含有人參皂Rgl、RM、甘草酸或甘草次酸及大棗cAMp的原 料，加工製成本發明多靶標受體後作用機制用於治療憂鬱症 的藥物組合物。 方法五： 將含有人參皂甙（Rgl+Rbl)合計2〜26重量份、甘草酸 或甘草次酸3〜48重量份及大棗cAMp 〇 〇〇2〜〇 5重量份的原 料，加工製成本發明的藥物組合物。 方法六： 將含有人參皂甙（Rgl+RM)合計4〜13重量份、甘草酸 或甘草次酸5〜16重量份及大棗」重量份的原 料，加工製成本發明的藥物組合物。 、 方法七： 本發明所述的藥物組合物包括可时有S學上可接受的 —體或添加劑’可以製成錠劑、膠囊劑、散劑、片劑、粉劑、 ，液:]微囊劑、混懸劑、乳劑、顆粒劑、滴丸劑、丸劑等 壬何藥劑學上所公知的口服藥物劑型。 方法八： 14 200920391 具體貫施例 以下將結合附圖和具體實施案例進一步說明本發明。 實施例1 請參閱第一圖，爲製備本發明實施例1藥物的方法流程 不思圖。在第一圖中，先將20kg的人參破碎後用70%乙醇溶 液加溫萃取，經上柱層析分離純化、乾燥，得含120 g人參皂 甙（Rgl+Rbl)的人參萃取物0.8kg;接著，再將1〇kg的甘 草破碎後常溫浸泡12小時，以水提醇沈法萃取、濃縮乾燥， 得含甘草酸200 g的甘草萃取物2 kg ;之後，將上述方法得到 的人參萃取物150 g及甘草萃取物2〇〇 g粉碎混合均勻後，得Rb Bugan 13 200920391 The extract of oxalic acid and jujube CAMP is used as raw material, or the prepared raw material containing ginseng soap Rgl, RM, glycyrrhizic acid or glycyrrhetinic acid and jujube cAMp is directly processed to form the multi-target subject of the present invention. A post-body mechanism of action is used to treat a pharmaceutical composition for depression. Method 5: The raw material containing ginsenoside (Rgl+Rbl) total 2~26 parts by weight, glycyrrhizic acid or glycyrrhetinic acid 3~48 parts by weight, and jujube cAMp 〇〇〇2~〇5 parts by weight, is processed into the present invention. Pharmaceutical composition. Method 6: A raw material containing 4 to 13 parts by weight of ginsenoside (Rgl + RM), 5 to 16 parts by weight of glycyrrhizic acid or glycyrrhetinic acid, and parts by weight of jujube are processed to prepare a pharmaceutical composition of the present invention. Method 7: The pharmaceutical composition of the present invention comprises a s-acceptable body or an additive, which can be used as a tablet, a capsule, a powder, a tablet, a powder, a liquid: a microcapsule Oral pharmaceutical dosage forms well known in the art, suspensions, emulsions, granules, pills, pills, and the like. Method 8: 14 200920391 DETAILED DESCRIPTION OF THE INVENTION The present invention will be further described below in conjunction with the drawings and specific embodiments. Example 1 Referring to the first figure, the flow of the method for preparing the drug of Example 1 of the present invention is not considered. In the first figure, 20kg of ginseng is firstly crushed and then extracted with 70% ethanol solution, and separated and purified by upper column chromatography, and dried to obtain 0.8 kg of ginseng extract containing 120 g of ginsenoside (Rgl + Rbl); Then, 1 〇kg of licorice was crushed and immersed at room temperature for 12 hours, extracted by water extraction and alcohol precipitation, and concentrated and dried to obtain 2 kg of licorice extract containing 200 g of glycyrrhizic acid; then, the ginseng extract obtained by the above method was obtained. 150 g and licorice extract 2〇〇g pulverized and mixed evenly,
35〇 g (含22.5 g人參皂甙Rgl+Rbi及2〇 g甘草酸）本發明 方案一的藥物組合物Q 實施例2 請參閱第二圖，爲製備本發明實施例2藥物的方法流程 示意圖。在第二圖中，將已製備成純度爲96%的甘草次酸3.96 g及實施例1所得的人參萃取物2〇〇 g粉碎混合均勻後，得 203.96g (含30g人參皂甙Rgl+Rbl及3.4甘草次酸）本發 明方案二的藥物組合物。 實施例3 請參閱第三圖’爲製備本發明實施例3藥物的方法流程 示意圖。在第三圖中，將已製備成的3.4g純度爲90〇/〇的人參 皂甙Rg卜7.8 g純度爲90%的人參皂甙Rbl及36.8 g純度爲 95%的甘卓酸粉碎混合均勻後，得48 g (含10 g人參息戒· 15 20092039135 〇 g (containing 22.5 g of ginsenoside Rgl + Rbi and 2 〇 g glycyrrhizic acid) The pharmaceutical composition Q of the first embodiment of the present invention. Example 2 Referring to the second figure, a schematic flow chart of a method for preparing the drug of Example 2 of the present invention. In the second figure, 3.96 g of glycyrrhetinic acid prepared to have a purity of 96% and 2 g of the ginseng extract obtained in Example 1 were pulverized and mixed uniformly to obtain 203.96 g (containing 30 g of ginsenoside Rgl+Rbl and 3.4 Glycyrrhetinic acid) The pharmaceutical composition of the second aspect of the invention. Embodiment 3 Please refer to the third figure' for a schematic flow chart of a method for preparing the drug of Example 3 of the present invention. In the third figure, 3.4 g of ginsenoside Rg, having a purity of 90 〇/〇, 7.8 g of ginsenoside Rbl having a purity of 90%, and 36.8 g of gansolic acid having a purity of 95% are pulverized and mixed uniformly. Get 48 g (including 10 g ginseng ring · 15 200920391
Rgl+Rbl及35g甘草酸）本發明方案三的藥物組合物。 實施例4 請參閱第_，爲製備本發明實施例4藥物的方法流程 示意圖。在第四圖中，將1Gkg的大棗破碎後加水常溫浸泡， 再以水提醇沈法萃取獲得大棗萃取液，再用大孔樹脂〇1； 2、 ME-2兩柱先後連續上柱吸附分離、乾燥，得含大棗cAMp 〇 3 g的大棗萃取物30 g作為原料供製備本發明藥物。 接著，將實施例1得到的人參萃取物15〇 g、甘草萃取物 200 g及前述大棗萃取物3 g粉碎混合均勻後，得353 g (含 22.5 g人參皂甙Rgi+Rbl、20g甘草酸及0 03 g大棗cAMP) 本發明方案四的藥物組合物。 實施例5 睛參閱第五圖，爲製備本發明實施例5藥物的方法流程 示意圖。在第五圖中’將實施例1得到的人參萃取物15〇 g 及甘草萃取物200 g及實施例4得到的大棗萃取物0.5 g粉碎 混合均勻後’得350.5 g (含22.5 g人參皂甙Rgl+Rbl、20 g 甘草酸及O.OOSg大棗cAMP)本發明方案五的藥物組合物。 實施例6 請參閱第六圖，爲製備本發明實施例6藥物的方法流程 示意圖。在第六圖中，將已製備成的6.8 g純度爲90%的人參 皂甙Rg卜15.6 g純度爲90%的人參皂甙RM、26 g純度爲 96%的甘草次酸及實施例4得到的大棗萃取物1〇 g粉碎混合 16 200920391 均勻後’件58.4 g (含20 g人炎台4 舻月士击A 、 參皂甙％1+RM、2Sg甘草次 ^及§大棗撕）本翻方“_物組合物。 實驗例—實關！對小鼠絲 1.1實驗動物 〜警 ICR小鼠，雄性，體重22 學實驗動物科學部提供。 §’二級，北京首都醫科大 1.2實驗藥品 1 :北京歐納爾生物工程技術有限公司提供。 η實驗儀ί (賽樂特）：中美天津史克制財限公司産品。 1.3實驗儀器：秒錶。 1.4劑量設計 /^#]t ： 8〇mg/kg/d^#]* ^ 40mg/kg/d^^ 劑置.20mg/kg/d。 1.5實驗方法及結果 1.5.1分組給藥 =每組1G隻：①實施例ι大劑量組⑽ ②實fΠ ㈤， 潘雨、、a知例1小劑置組（2〇mg/kg，ΡΟ，給藥7d); β a /Tj (3 mg/kg ’ PO ’ 給藥 7ί〇;⑤生理鹽水組（p〇)。 束後一;人給藥後1小時進行懸尾實驗。 1.5.2實驗方法 的木(距尾尖1 用谬布枯在高山臺面5 cm 山統計^里分鐘，記錄後5分鐘内小鼠的不動時間。 17 200920391 實驗資料用x±幼表示’實驗結果用SPSS 11.5統計軟體 進行方差分析。 實驗結果 實驗結果請參閱表1。 表1、實施例1對小鼠不動時間的 組別 動物數（隻） 不動日奔間(秒） 生理鹽水組（模型組） 帕羅西汀組 實施例1大劑量組 實施例1中劑量組 實施例1小劑量組 註：與模型組比較* p<0 05 **p<001 結論： 113.22±21.18 75.33±22.91* 54.67±26.38** 72.68士 27.06* 95_26 土 49.91Rgl + Rbl and 35 g glycyrrhizic acid) The pharmaceutical composition of the third embodiment of the present invention. Example 4 Referring to Figure _, a schematic diagram of a process for preparing a medicament of Example 4 of the present invention. In the fourth figure, 1Gkg of jujube is crushed, soaked in water at room temperature, and then extracted with water and alcohol precipitation to obtain jujube extract, and then macroporous resin 〇1; 2. ME-2 two columns successively on the column Adsorption separation and drying gave 30 g of jujube extract containing jujube cAMp 〇 3 g as a raw material for preparing the medicament of the present invention. Next, 15 g of the ginseng extract obtained in Example 1, 200 g of the licorice extract and 3 g of the jujube extract described above were pulverized and mixed to obtain 353 g (containing 22.5 g of ginsenoside Rgi+Rbl, 20 g of glycyrrhizic acid and 0 03 g jujube cAMP) The pharmaceutical composition of the fourth aspect of the invention. Example 5 The eye Fig. 5 is a schematic view showing the flow of a method for preparing the drug of Example 5 of the present invention. In the fifth figure, '15 ng of ginseng extract obtained in Example 1 and 200 g of licorice extract and 0.5 g of jujube extract obtained in Example 4 were pulverized and mixed uniformly to obtain 350.5 g (containing 22.5 g of ginsenoside). Rgl+Rbl, 20 g glycyrrhizic acid and O.OOSg jujube cAMP) The pharmaceutical composition of the fifth aspect of the invention. Example 6 Please refer to the sixth drawing, which is a schematic flow chart of a method for preparing the drug of Example 6 of the present invention. In the sixth figure, 6.8 g of ginsenoside Rg having a purity of 90%, 15.6 g of ginsenoside RM having a purity of 90%, 26 g of glycyrrhetinic acid having a purity of 96%, and the large amount obtained in Example 4 were prepared. Jujube extract 1〇g crushed and mixed 16 200920391 Even after 'parts 58.4 g (including 20 g human Yantai 4 舻月士士A, ginseng 甙%1+RM, 2Sg licorice ^ and § jujube tear) "_ composition. Experimental example - real off! On the mouse silk 1.1 experimental animal ~ police ICR mouse, male, weight 22 experimental animal science department. § 'Secondary, Beijing Capital Medical University 1.2 experimental drugs 1: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd. ηExperimental Instrument ί (Selite): Sino-US Tianjin Shike System Financial Co., Ltd. 1.3 Experimental Instrument: Stopwatch. 1.4 Dose Design /^#]t : 8〇mg/ Kg / d ^ #] * ^ 40mg / kg / d ^ ^ agent set. 20mg / kg / d. 1.5 experimental methods and results 1.5.1 group administration = 1G per group only: 1 example ι high dose group (10) 2实fΠ (5), Pan Yu,, a know the case 1 small group (2 〇 mg / kg, sputum, 7d); β a / Tj (3 mg / kg ' PO ' administration 7 〇 〇; 5 saline Group (p〇) After the bundle, the suspension experiment was carried out 1 hour after the administration. 1.5.2 The wood of the experimental method (from the tip of the tail 1 with the sputum on the alpine table 5 cm in the mountain count ^ minutes, recorded within 5 minutes after the mouse 17 200920391 Experimental data expressed by x± young 'Experimental results were analyzed by SPSS 11.5 statistical software for variance analysis. Experimental results The experimental results are shown in Table 1. Table 1, Example 1 The number of animals in the group with no movement time in mice ( Only) No moving day (seconds) Saline group (model group) Paroxetine group Example 1 High dose group Example 1 Medium dose group Example 1 Low dose group Note: Compared with model group * p<0 05 ** p<001 Conclusion: 113.22±21.18 75.33±22.91* 54.67±26.38** 72.68士27.06* 95_26 土49.91
/ 10 10 10 10 10 很據以上實驗 J Μ有出本發明貫施例1大、中 和帕羅西汀組均可減少小鼠懸德 '、 皮細以⑽w 心尾賴獨時間，且與生理鹽 JC、、且（模型組）相比有 1 H ^ 貝者性差呉攸而可以推斷本發明實 把例1具有抗實驗轉鬱魏。 愤月貫 鼠利血平誘導體溫下降的影響 實驗例2實施例1對小 2.1實驗動物 北京首都醫科大 収小鼠，雄性，體重22.0±2g，二級 學實驗動物科學部提供。 2.2實驗藥品 實施例1:北京歐納爾 帕羅西汀（賽樂特）： 生物工程技術有限公司提供。 中美天津妓㈣有限公司產 18 200920391 利血平：廣東邦民制藥廠有限公司。 2.3實驗儀器 GM222型電子溫度計，秒錶。 2.4劑量設計 ΓΛ 貫施例1大劑量：8〇 mg/kg/d、中劑量：40 mg/kg/d及 劑量：20 mg/kg/d。 ^ 2.5實驗方法及結果 2.5.1分組給藥 將小鼠隨機分組’每組1〇隻：①實施例1大劑量組（8〇 mg/kg，PO ’給藥州；②實施例丨中劑量組⑽^ 〇 給藥7d);③實施例丨小劑量組（2〇mg/kg，ρ〇，給藥π); ④帕羅西〉丁組（3 mg/kg，ρ〇，給藥);⑤生理鹽水組（。 2.5.2實驗方法 。/ 10 10 10 10 10 According to the above experiment J, there are cases in which the large, medium and paroxetine groups of the present invention can reduce the mice's dangling', the skin is fine (10) w, and the physiological time is JC, and (model group) have 1 H ^ Bayerity difference, and it can be inferred that the present invention has an anti-experimental effect. The effect of stagnation and resuscitation on the decrease of body temperature induced by reserpine blood. Experimental Example 2 Example 1 Small 2.1 Experimental animals The Beijing Capital Medical University received mice, male, weighing 22.0±2g, provided by the Department of Secondary Laboratory Animal Science. 2.2 Experimental Drugs Example 1: Beijing O'Neill Paroxetine (Selite): Provided by Bioengineering Technology Co., Ltd. Sino-US Tianjin Hao (four) Co., Ltd. 18 200920391 Li Xueping: Guangdong Bangmin Pharmaceutical Factory Co., Ltd. 2.3 experimental instrument GM222 type electronic thermometer, stopwatch. 2.4 Dose design ΓΛ Example 1 large dose: 8 〇 mg / kg / d, medium dose: 40 mg / kg / d and dose: 20 mg / kg / d. ^ 2.5 Experimental methods and results 2.5.1 group administration randomization of mice '1 group per group only: 1 Example 1 large dose group (8 〇 mg / kg, PO 'administered state; 2 example 丨 mid-dose Group (10) ^ 〇 administration 7d); 3 examples 丨 small dose group (2 〇 mg / kg, ρ 〇, administration π); 4 Paroxet butyl group (3 mg / kg, ρ 〇, administration) ; 5 saline group (. 2.5.2 experimental methods.
第8天給藥後1小時測定小鼠肛溫，然後經腹腔注射 ，於注射利血平後4小時再測定小鼠肛溫。每 二則溫時溫度計插人小氣肛門崎度及時間均. ·5.3統計學處理 致 實驗資料用1±切表示 進行方差分析。 2.5.4實驗結果 ’實驗結果用SPSS 11.5統計軟體 實驗結果請參閱表2。 19 200920391 隻) 10 10 10 10 10 P<0.01 _^溫下降值（°c) 3.65±0.77 2.38±0.69** 1.85±1.01** 2.05士 1.03** 2.35±0.69** 生理鹽水組（模型組） 帕羅西汀組 實施例1大劑量組 實施例1中劑量組 實施例1小劑晉鈿 註：與模型組比較*p<〇 〇5 結論： 她丨Ϊ據以上實驗’可以看出本發明實施例1大、中、小三 帕羅西汀組均可明顯減少利血平誘導的體溫下 關，=_；抗實驗性㈣作用可能與影響單胺遞質含量有 關攸而可以推斷本發明實施例1具有抗實驗性抑鬱功能。 貫驗ϊ j 3 Μ施例2對小鼠懸尾實驗的影響 3.1實驗動物 ICR小鼠，雄性，體重22 0±2 學實驗動物科學部提供。 、及m都糾大 3·2實驗藥品 貝=例2·北京歐納_生物I程技術有限公司提供。 u ’西/T (赛樂特）：中美天津史克制藥有限公司産品。 3.3實驗儀器 秒錶。 3.4劑量設計 、例2大劑嚴· 80 mg/kg/d、中劑量：40 mg/kg/d及小 20 200920391 劑量：20 mg/kg/d。 3.5實驗方法及結果 3.5.1分組給藥 將小鼠隨機分組，每組1〇隻：①實施例2大劑量組（8〇 mg/kg ’ PO ’給藥7d);②實施例2中劑量組（40 mg/kg，p〇， 給藥7d);③實施例2小劑量組（2〇 mg/kg，p〇，給藥7d); ④帕羅西汀組（3 mg/kg，PO，給藥7d);⑤生理鹽水組（p〇 )。 最後一次給藥後1小時進行懸尾實驗。 3.5.2實驗方法 將小鼠尾（距尾尖1 0„!處）用膠布粘在高山臺面5 cm 的木條上懸吊6分鐘，記錄後5分鐘削、鼠的不動時間。 3.5.3統計學處理 實驗資料用文⑽表示，實驗結果用SPSS 11.5統計軟體 進行方差分析。 3.5.4實驗結果 貫驗結果請參閱表3。 表3、實施例2對小鼠不動時間的影響 組別 動物數（隻） 不動時間（秒） 生理鹽水組（模型組） 10 113.22±21.18 帕羅西汀組 10 75.33±22.91* 實施例2大劑量組 10 93.27±36.42 實施例2申劑量組 10 76.21±28.36* 實施例2小劑量組 10 107.79±32.56 註：與模型組比較*p<〇,〇5 ** P<0.01 結論： 21 200920391 羅西小3看出本發明實施例2㈣量組和帕 Λ , J鼠心尾後的不動時間，且與生理鹽水組 2 具有抗實驗 實驗例4實施例 4-1貫驗動物 2對小鼠利血平誘導體溫下降的影響 g，二級，北京首都醫科大 ICR小鼠，雄性’體重22.0±2 學實驗動物科學部提供。 4.2實驗藥品 貫鈀例2.北尔歐納爾生物工程技術有限公司提供。 帕羅西叮（賽樂特）：中美天津史克制藥有限公司產品。 利血平.廣東邦民制藥廠有限公司。 4.3實驗儀器 GM222型電子溫度計，秒錶。 4.4劑量設計 實施例2大劑量：80 mg/kg/d、中劑量：4〇瓜獅/d及小 劑量：20 mg/kg/d。 4.5實驗方法及結果 4.5.1分組給藥 將小鼠隨機分組，每組10隻：①實施例2大劑量組（8〇 mg/kg ’ PO，給藥7d);②實施例2中劑量組（4〇 mg/kg，p〇， 給藥7d);③實施例2小劑量組（20 mg/kg，p〇，給藥7d); ④帕羅西汀組（3 mg/kg ’ PO，給藥7d);⑤生理鹽水組（p〇)。 4.5.2實驗方法 22 200920391 利血平f 藥後1小測定小鼠肛溫’錢經腹腔注射 ^、"吨g’於注射利血平後4小時再測定小鼠肛溫。每 -人4皿b溫度計插入小鼠肛⑽深度及時間均一致。 4.5.3統計學處理 他喊示，實驗結果綱1U統計軟體 4·5.4實驗結果 實驗結果請參閱表4。 免4、貫施例^j、鼠利血平誘導體溫下降的影鐵 j且別 生理鹽水組（模型組） 帕羅西丁組 實施例2大劑量組 實施例2中劑量組 動物數（隻） 10 10 10 10 10 體溫下降值（°c) 3.65±〇.77 2.38土0.69** 2.93±0.74* 2.31±0.82** 3,21±0.71 !施例詈組 ^ -------- °主.與模型組比較*ρ<〇 〇5**ρ<〇 〇ι 結論： 羅西根f以上實驗’可崎出本發明實闕2巾魅組和帕 A /7、病可明顯減少利血平料的體溫 =:作用可能與影響單胺遞質含量有關，從二:; 柄明實施例2具有抗實驗性抑#功能。 a驗例5貫施例3對小氣懸尾實驗的影響 5· 1實驗動物 CR· J、鼠’雄性’體重22 0±2g，二級，北京首都醫科大 23 f-The anus temperature of the mice was measured 1 hour after the administration on the 8th day, and then the intra anal temperature was measured 4 hours after the injection of reserpine by intraperitoneal injection. Each of the two temperature-time thermometers was inserted into the small anus and the time was average. · 5.3 Statistical processing The experimental data was expressed by 1 ± cut for analysis of variance. 2.5.4 Experimental results 'Experimental results using SPSS 11.5 statistical software The experimental results are shown in Table 2. 19 200920391 only) 10 10 10 10 10 P<0.01 _^temperature drop value (°c) 3.65±0.77 2.38±0.69** 1.85±1.01** 2.05士1.03** 2.35±0.69** saline group (model group) ) Paroxetine group Example 1 High dose group Example 1 Medium dose group Example 1 Small dose Jinxi Note: Compared with model group *p<〇〇5 Conclusion: She can see the implementation of the present invention according to the above experiment Example 1 The large, medium and small paroxetine groups can significantly reduce the blood temperature induced by reserpine, = _; anti-experimental (four) effect may be related to the influence of monoamine transmitter content, and it can be inferred that embodiment 1 of the present invention has Anti-experimental depression. The effect of Example 2 on the tail suspension experiment of mice 3.1 Experimental animals ICR mice, male, weighing 22 0 ± 2 were provided by the Department of Experimental Animal Science. And m are rectified 3·2 experimental drugs Bei = example 2 · Beijing Ou Na _ biological I Cheng Technology Co., Ltd. provided. u ‘West/T (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products. 3.3 Experimental instrument Stopwatch. 3.4 Dose design, Example 2 large dose strict · 80 mg / kg / d, medium dose: 40 mg / kg / d and small 20 200920391 dose: 20 mg / kg / d. 3.5 Experimental methods and results 3.5.1 group administration The mice were randomly divided into groups of 1 group: 1 Example 2 large dose group (8 〇mg/kg 'PO 'administered for 7 days); 2 Example 2 dose Group (40 mg/kg, p〇, 7d); 3 Example 2 low-dose group (2〇mg/kg, p〇, 7d); 4 paroxetine group (3 mg/kg, PO, given Drug 7d); 5 saline group (p〇). A tail suspension experiment was performed 1 hour after the last administration. 3.5.2 Experimental method The tail of the mouse (1 0 „! from the tip of the tail) was suspended with a tape on a 5 cm wooden strip on a mountain table for 6 minutes, and the movement time of the mouse was cut 5 minutes after the recording. The experimental data of statistical processing were expressed by the text (10), and the experimental results were analyzed by SPSS 11.5 statistical software for variance analysis. 3.5.4 The results of the experimental results are shown in Table 3. Table 3, Example 2 Effect on immobility time of mice Group animals Number (only) Immobility time (seconds) Saline group (model group) 10 113.22±21.18 Paroxetine group 10 75.33±22.91* Example 2 Large dose group 10 93.27±36.42 Example 2 Application dose group 10 76.21±28.36* Implementation Example 2 Low-dose group 10 107.79±32.56 Note: Compared with the model group *p<〇,〇5 **P<0.01 Conclusion: 21 200920391 Rosie Xiao 3 sees the embodiment 2 (four) of the present invention and the Pai, J rats The immobile time after the end of the heart, and with the saline group 2 has anti-experimental experimental example 4 Example 4-1 test animal 2 on the retinal-induced hypothermia decline in mice g, secondary, Beijing Capital Medical University ICR small Rat, male 'body weight 22.0±2 4.2 Experimental drug palladium case 2. Provided by Beier O'Neill Bioengineering Technology Co., Ltd. Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. Li Xueping. Guangdong Bangmin System Pharmaceutical Co., Ltd. 4.3 Experimental Instrument GM222 Electronic Thermometer, Stopwatch 4.4 Dose Design Example 2 Large dose: 80 mg/kg/d, medium dose: 4 〇 lion/d and small dose: 20 mg/kg/d 4.5 Experimental Methods and Results 4.5.1 Group Administration The mice were randomly divided into groups of 10: 1 Example 2 large dose group (8〇mg/kg 'PO, 7d administration); 2 Example 2 dose Group (4〇mg/kg, p〇, 7d); 3 Example 2 low dose group (20 mg/kg, p〇, 7d); 4 paroxetine group (3 mg/kg 'PO, given Drug 7d); 5 saline group (p〇). 4.5.2 Experimental method 22 200920391 Reserpine f drug 1 small measurement of mouse anal temperature 'money by intraperitoneal injection ^, " ton g' infusion of reserpine After 4 hours, the anus temperature of the mice was measured again. The temperature of each mouse was inserted into the anus (10) and the time was consistent. 4.5.3 Statistical analysis He shouted, the results of the experiment 1U statistical software 4·5.4 Experimental results The experimental results are shown in Table 4. Free 4, the application of the method ^j, the mouse reserpine induced temperature drop of the shadow iron j and other saline group (model group) paroxetine group Example 2 high dose group implementation Example 2 Number of animals in the dose group (only) 10 10 10 10 10 Body temperature drop value (°c) 3.65±〇.77 2.38 soil 0.69** 2.93±0.74* 2.31±0.82** 3,21±0.71 ! Group ^ -------- ° Main. Compared with the model group *ρ<〇〇5**ρ<〇〇ι Conclusion: Rosiegen f above the experiment 'can be found out of the present invention 2 Pa A / 7, disease can significantly reduce the body temperature of reserpine =: the effect may be related to the influence of monoamine transmitter content, from two:; handle example 2 has anti-experimental inhibition # function. a test example 5 the effect of the application of the third example on the small gas suspension experiment 5 · 1 experimental animal CR · J, mouse 'male' body weight 22 0 ± 2g, two, Beijing Capital Medical University 23 f-
200920391 學貫驗動物科學部提供。 5.2實驗藥品 實施例3 :北京歐納爾生物工程技術有限公司提供。 帕羅西汀（赛樂特）：中美天津史克制藥有限公司産品。 5·3實驗儀器： 秒錶。 5.4劑量設計 貫施例3大劑量：80 mg/kg/d、中劑量：4〇 劑量：20mg/kg/d。 g 5.5實驗方法及結果 5.5.1分纟且給藥 將小鼠隨機分組，每組10隻：①實施例3大劑量組（8〇 ’ PO ’給藥7d);②實施例3中劑量組（4〇 ， =藥7d);③實施例3小劑量組（2〇mg/kg，p〇，給藥 =帕羅西汀組（3 mg/kg ’ p〇 ’給藥7d);⑤生理鹽水組（⑼。 最後一次給藥後1小時進行懸尾實驗。 5·5·2實驗方法 將小鼠尾（距尾尖1 cm處）用膠布粘在高山臺面$ 的木條上1;巾6分鐘，記錄後5分鐘内小I的不動 111 5·5·3統計學處理 曰 實驗資料用：Ϋ±奶表示，實驗結果用 進行方差分析。 5·5·4實驗結果 實驗結果請參閱表5 SPSS11.5統計軟體 24 200920391 生理鹽水組（模型組） 10 帕羅西汀組 10 實施例3大劑量組 10 實施例3令劑量組 10 實施例3小劑量组 -—：_______ 10 註··與模型組比較*P<〇.〇5 * * P<0.01 結論： 表5、實200920391 Provided by the Department of Animal Science. 5.2 Experimental Drugs Example 3: Provided by Beijing O'Neill Bioengineering Technology Co., Ltd. Paroxetine (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products. 5. 3 experimental instruments: stopwatch. 5.4 Dosage design Example 3 large dose: 80 mg / kg / d, medium dose: 4 〇 dose: 20 mg / kg / d. g 5.5 Experimental methods and results 5.5.1 minutes and administration of mice Randomly grouped mice, each group of 10: 1 Example 3 large dose group (8 〇 'PO 'dose 7d); 2 Example 3 dose group (4〇, = drug 7d); 3 Example 3 low-dose group (2〇mg/kg, p〇, administration = paroxetine group (3 mg/kg 'p〇' administration 7d); 5 saline group ((9). The tail suspension experiment was performed 1 hour after the last administration. 5.5.2 Experimental method The mouse tail (1 cm from the tip of the tail) was glued to the wooden strip of the alpine tabletop $1; towel 6 minutes In the 5 minutes after recording, the small I does not move. 111 5·5·3 Statistical processing 曰 Experimental data: Ϋ±milk, the experimental results are analyzed by variance. 5.·5·4 Experimental results See Table 5 SPSS11 .5 Statistical Software 24 200920391 Normal saline group (model group) 10 Paroxetine group 10 Example 3 Large dose group 10 Example 3 Order dose group 10 Example 3 Low dose group -::_______ 10 Note ··Compared with the model group *P<〇.〇5 * * P<0.01 Conclusion: Table 5, real
動物數(隻） 不動時間（秒) 113.22±21.18 75.33±22.91 * 70.37±28.14* 76.26±23.81* 90.40土3] .32 =據以上實驗’可以看出本發嘴施例3大、 和帕羅西汀組均可減少小鼠 、'、 t (姑組)相比有顯著性差異，從而可以推斷本發明每 施例3具有抗實驗性抑鬱功能。 X貝 只驗例6 f施例;3對小鼠利血平誘導體溫下降的景增 6.1實驗動物 v θ 北京首都醫科大 ICR小鼠’雄性’體重22 〇士2 g，二級， 學實驗動物科學部提供。 6.2實驗藥品 貫軛例3:北京歐納爾生物工程技術有限公司提供。 帕羅西/X (賽樂特）：中美天津史克制藥有限公司産品。 利血平：廣東邦民制藥廠有限公司。 生⑽ 6.3實驗儀器 GM222型電子溫度計，秒錶。 6.4劑量設計 200920391 8〇mg/kg/d’ 中劑量：4〇mg/kg/d 及小 實施例3大劑量 劑量：20 mg/kg/d 〇 6.5實驗方法及結果 6.5.1分組給藥 將小鼠隨機分組’每組10隻：①實施例3大劑量組（8〇 mg/kg，PO，給藥7d);②實施例3中劑量組（明_咏，p〇， 給藥7d);③實施例3小劑量組⑽，p〇，給藥如 ④帕羅西、;T組（3 mg/kg ’ PO ’給藥7d);⑤生理鹽水組⑻）。 6.5.2實驗方法 在第8天給藥後！小時測定㈣肛溫，然後經腹腔注射 私平2 mg/kg，概射利血平後4小時再測定小氣肛溫。每 -人測溫時溫度計插入小鼠肛門的深度及時間均一致。 6.5.3統計學處理 實驗資料用文表示，實驗結果用SPSS 11.5統計軟體 進行方差分析。 ' 6.5.4實驗結果 實驗結果請參閱表6。 表6、實施例3小鼠利血平誘導體溫下降的影響 組別 動物數__體溫I值(°〇 生理鹽水組（模型組） 帕羅西丨丁組 貫施例3大劑量組 實施例3中劑量組 實施例3小劑量組 3.65±〇.77 2.38±〇.69** 2.18±〇.92** 2·36±〇.83** 2·97±〇·67* 10 10 10 10 10 註：與模型組比較*Ρ<〇.〇5**Ρ<0·01 26 200920391 結論： 根據以上實驗，可以看出本發明實施例3大、中、小劑 量組和帕羅西>丁組均可明顯減少利血平誘導的體溫下降，表 明其抗實驗性抑鬱作用可能與影響單胺遞質含量有關，從而 可以推斷本發明實施例3具有抗實驗性抑鬱功能。 貫驗例7實施例4對大鼠嗅球損毁實驗的影響 7-1實驗動物 嗅球毁彳貝模型.健康Wistar雄性大氣，二級，體重330士2〇 g，購於北京維通利華實驗動物技術有限公司（合格證編號 SCXK (京）2002-0003 )。 7.2試劑與藥品 實施例4由歐納爾生物工程技術有限公司提供（批號： 060313)，帕羅西汀爲中美天津史克制藥有限公司産品（批 號：04050011)，以上藥物用〇.5%羧曱基纖維素納（CMC Na) 配製後供灌胃使用，注射用青黴素納爲華北制藥股份有限公 司産品（批號：S0511204);去曱腎上腺素（NE)及5_經色 私：（5-HT) ^示準品爲Sigma公司産品；其他試劑均爲市隹。 7.3儀器 Ω 自製開野實驗箱，避暗實驗箱，大鼠腦立體定位儀，高 效液相色譜儀，DFM-96型10管放射免疫γ計數器。 7.4實驗方法 7.4.1動物分組與給藥方法 大鼠隨機分6組，假手術組、模型對照組、實施例4高 劑量組（60 mg/kg/d)、實施例4中劑量組（30 mg/kg/d)、實 27 200920391 方也例4低劑里組（mg/kg/d)、帕羅西汀組（2 mg/kg/d)。受 试藥與陽性藥用〇.5%羧甲基纖維素納（CMC-Na)配製。每 天一次灌胃給藥。 7·4·2模型製備方法 大鼠用水合氯醛麻醉，麻醉後從大鼠前囟門前1 cm至前 囪後1 cm正中線處切開，暴露顱骨。在距離前囪前8 mm、 正中線兩側2mm處分別開骨窗，直徑約2mm。用特製電烙 r 鐵垂直插入顱内2秒’破壞嗅球，用止血賴填充骨窗縫合 皮膚，術後母4天以腹腔注射（intraperit〇neai，正）給與青黴 素鈉4〇,000單位/Kg ’並連續給與受試藥物％天。 7.5觀測指標 7.5.1開野實驗 開野實驗箱域藍色膠合板聽合金框_成〇 m X i m =111)才目底劃分爲25個方格（每個20 cm x 20 cm)，沿 =爲外周格，其餘爲中央格。將動物放人正 數察;：：::，爪一^^ 7.5.2被動回避實，驗一避暗法 實驗箱内由明、暗兩宕έ 士、 入，暗室隔柵與電擊儀蝴、、· ^巾财—個通道供大鼠出 進入暗室則遭電擊。訓練時，L/純板。如大鼠 適應5分鐘，然後將隔板抽出觀察;：二向洞:放入明室中 入暗室時間（觸電潛伏期），此爲學=5己錄大鼠百次進 試^ _錢電5分顯察 ：24 測 此爲記憶成績。 人纘入暗至的時間， 200920391 7.6統計學處理 貫驗資料用切表示’實驗結果用SPSS 11.5統計軟體 進行方差分析。 7·7貫驗結果 7/U開野實驗結果請參閱見表7。 表7、嗅球毁損模型大鼠開野實驗結果Number of animals (only) Immobile time (seconds) 113.22±21.18 75.33±22.91 * 70.37±28.14* 76.26±23.81* 90.40 soil 3] .32 = According to the above experiment, it can be seen that the mouth of the mouth is 3 large, and paroxetine The group can reduce the significant difference in the mice, ', t (group), so that it can be inferred that each of the examples 3 of the present invention has an anti-experimental depression function. X shell only case 6 f example; 3 pairs of mice reserpine induced body temperature decline Jing Zeng 6.1 experimental animals v θ Beijing Capital Medical ICR mice 'male' weight 22 Gentleman 2 g, secondary, experimental Provided by the Department of Animal Science. 6.2 Experimental Drugs Example 3: Beijing O'Neill Bioengineering Technology Co., Ltd. Parosi / X (Selite): Sino-US Tianjin Shike Pharmaceutical Co., Ltd. products. Reserpine: Guangdong Bangmin Pharmaceutical Factory Co., Ltd. Health (10) 6.3 Experimental Instrument GM222 type electronic thermometer, stopwatch. 6.4 Dose design 200920391 8〇mg/kg/d' Medium dose: 4〇mg/kg/d and small Example 3 Large dose: 20 mg/kg/d 〇6.5 Experimental methods and results 6.5.1 Group administration Mice were randomized into '10 per group: 1 high dose group of Example 3 (8 〇mg/kg, PO, 7d); 2 dose group of Example 3 (bright 咏, p〇, 7d) 3 Example 3 Small dose group (10), p〇, administration such as 4 Paroxet; Group T (3 mg/kg 'PO 'administered for 7 days); 5 saline group (8)). 6.5.2 Experimental method After administration on the 8th day! Hourly measured (four) rectal temperature, and then intraperitoneal injection of 2 mg / kg, after the injection of blood level 4 hours and then determine the small air anus temperature. The depth and time of insertion of the thermometer into the anus of the mouse were consistent when the temperature was measured. 6.5.3 Statistical processing The experimental data were expressed in texts, and the experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance. ' 6.5.4 Experimental results Refer to Table 6 for the experimental results. Table 6, Example 3 The effect of reserpine induced hypothermia on the number of animals in the group __ Body temperature I value (° 〇 saline group (model group) Paroxetine group Example 3 Large dose group example 3 medium dose group Example 3 low dose group 3.65±〇.77 2.38±〇.69** 2.18±〇.92** 2·36±〇.83** 2·97±〇·67* 10 10 10 10 10 Note: Comparison with model group *Ρ<〇.〇5**Ρ<0·01 26 200920391 Conclusion: According to the above experiment, it can be seen that Example 3 of the present invention has large, medium and small dose groups and Parosi> Ding group can significantly reduce the decrease of body temperature induced by reserpine, indicating that its anti-experimental depression may be related to the influence of monoamine transmitter content, so it can be inferred that Example 3 of the present invention has anti-experimental depression function. Example 4 Effect on Rat Olfactory Ball Damage Experiment 7-1 Experimental Animal Olfactory Ball Destruction Mussel Model. Healthy Wistar Male Atmosphere, Grade II, Weight 330 ± 2〇g, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. Certificate No. SCXK (Beijing) 2002-0003. 7.2 Reagents and Pharmaceuticals Example 4 by Onal Bioengineering Technology Co., Ltd. Provided (batch number: 060313), paroxetine is the product of Sino-US Tianjin Shike Pharmaceutical Co., Ltd. (batch number: 04050011), the above drugs are prepared with 5% carboxymethyl cellulose (CMC Na) for intragastric administration, injection Penicillin was used as the product of Huabei Pharmaceutical Co., Ltd. (batch number: S0511204); norepinephrine (NE) and 5_经色私:(5-HT) ^ indicates that the product is Sigma product; other reagents are market 7.3 Instrument Ω Self-made open field experiment box, dark test chamber, rat brain stereotaxic instrument, high performance liquid chromatography, DFM-96 10-tube radioimmuno γ counter. 7.4 Experimental method 7.4.1 Animal grouping and drug delivery Methods Rats were randomly divided into 6 groups: sham operation group, model control group, high dose group of Example 4 (60 mg/kg/d), and medium dose group of Example 4 (30 mg/kg/d), real 27 200920391 square. Also in Example 4, the low dose group (mg/kg/d) and the paroxetine group (2 mg/kg/d) were prepared with the test drug and the positive medicinal 〇.5% carboxymethylcellulose sodium (CMC-Na). Rats were administered once a day. 7.4.1 Preparation of the model. Rats were anesthetized with chloral hydrate. After anesthesia, 1 cm before the front of the rat. The posterior midline of the 1 cm was cut open to expose the skull. The bone window was opened 8 mm from the front of the anterior humerus and 2 mm on both sides of the median line. The diameter was about 2 mm. The iron was inserted into the skull vertically for 2 seconds to destroy the olfactory bulb. The skin was sutured with a hemostatic sputum-filled bone window. After 4 days of postoperative mothers, intraperitoneal injection (intraperit〇neai, positive) was given to penicillin sodium 4〇,000 units/Kg′ and the test drug was continuously administered for 1 day. 7.5 Observation Index 7.5.1 Open field experiment Open field experiment box blue plywood listening alloy frame _ Cheng 〇 m X im =111) The bottom of the field is divided into 25 squares (each 20 cm x 20 cm), along = For the outer perimeter, the rest is the central grid. The animals are placed in positive numbers;::::, claws one ^^ 7.5.2 passively avoiding the reality, the test of a dark method in the experimental box by the light and dark two gentlemen, into, dark room grille and electric shock instrument, , · · towel money - a channel for rats to enter the dark room was shocked. L/pure board during training. If the rat is acclimated for 5 minutes, then the separator is taken out for observation;: Two-way hole: into the dark room into the dark room time (electric shock latency), this is the learning = 5 recorded rats a hundred times into the test ^ _ Qian 5 Sub-discovery: 24 This is a memory score. The time when people broke into darkness, 200920391 7.6 Statistical processing The perceptual data were cut and expressed. 'Experimental results were analyzed by SPSS 11.5 statistical software for analysis of variance. 7. 7 results of the test 7 / U open field test results see see Table 7. Table 7. Results of open field experiment in rat model of olfactory bulb destruction
動物數水平運動 _(跨格次數) 垂直運動 (直立次數） 貫施例4大劑量組 11 隻 49.18127.68 ** 10.91±6.91 ** 實施例4中劑量組 11 隻 54.55±23.01 13·45±5·72* 實施例4小劑量組 11 隻 61.82±21.43 15.18+4.47 帕羅西ί丁組 11 隻 55.36125.96 * 14.36±5.55 模型組 11 隻 79.55±24.33 19.09+8.53 假手術組 11 隻 45.36±26.84 ** 10.45±6.19** 註：與模型組比較*Ρ〈〇.〇5**ρ<〇·〇ιAnimal number horizontal movement _ (cross-frame number) vertical movement (upright number) Example 4 large dose group 11 only 49.18127.68 ** 10.91±6.91 ** Example 4 medium dose group 11 only 54.55±23.01 13·45± 5·72* Example 4 low-dose group 11 only 61.82±21.43 15.18+4.47 paroxetine group 11 only 55.36125.96 * 14.36±5.55 model group 11 only 79.55±24.33 19.09+8.53 sham operation group 11 only 45.36± 26.84 ** 10.45±6.19** Note: Compared with the model group *Ρ<〇.〇5**ρ<〇·〇ι
7.7.2避暗實驗結果請參閱表8。 表8、嗅球毀損模型大鼠避暗實驗結果 動物數 第一天潛伏期(S) 第-天潛伏期(S) 實施例4大劑量組 11隻 187.00+87.59 * 289.82128.59 * 實施例4中劑量組 11隻 191.71±72.95 * 288.82+37.09 * 實施例4小劑量組 11隻 152.44±76.81 271.18 土 38.61 帕羅西汀組 11隻 181.87190.54 * 265.00±65.39 模型組 11隻 111.21±82.93 236.88+74.17 假手術組 11隻 211.46±82.1〇 ** 292.82il4.37* 註：與模型組比較*P<0.05 ** PcO.Ol 29 200920391 結論· 實驗例7結果顯示：實施例4大劑量組可明顯改善嗅球 毀損所造成的大鼠水平及垂直運動增加，實施例4中劑量組 對嗅球毀損模型大鼠的垂直運動增加也有明顯改善作用。另 外，實施例4大、中劑量組對嗅球毀損所造成的大鼠學習及 記憶功能減退也有明顯改善作用。 實驗例8實施例4對大鼠不可預測長期應激實驗的影響 8.1實驗動物 3 不可預測性長期應激模型··健康Wistar雄性大鼠，二級， 體重240〜270 g，購於北京維通利華實驗動物技術有限公司 (合格證編號SCXK (京）2002-0003 )。 8.2試劑與藥品 實施例4由歐納爾生物工程技術有限公司提供（批號： 060313) ’帕羅西>丁爲中美天津史克制藥有限公司産品（批 號：04050011)’以上藥物用〇.5〇/0羧曱基纖維素納（CMC_Na) 配製後供灌胃使用，注射用青黴素鈉爲華北制藥股份有限公 司産品（批號：S0511204);去甲腎上腺素（NE)及5-經色 胺（5-HT)標準品爲Sigma公司産品；其他試劑均爲市售。 8.3儀器 自製開野實驗箱’避暗實驗箱，大鼠腦立體定位儀，高 效液相色譜儀，DFM-96型1〇管放射免疫丫計數器。 8.4實驗方法 8.4.1動物分組與給藥方法 大氣隨機分6、組’假手術紅、翻對照組、實施例4高 30 200920391 劑量組（60 mg/kg/d)、實施例4中劑量組（3〇 mg/kg/d)、實 1 4低劑量組（15 mg/kg/d )、帕羅西汀組（2 mg/kg/d )。受 試藥與陽性藥用0.5%羧曱基纖維素納（CMC_Na)配製。每 天一次灌胃給藥。 8·4.2模型製備方法 不可預測性長期應激模型：空白對照組正常飲食飲水， 不給任何刺激。其他五組，每籠飼養1隻，並接受24天不可 預^的應激刺激’包括：3次24小時禁食，3次24小時斷水， 人24小日守潮濕墊料（鼠盒中加水200 ml)，3次通宵照明， ^次4 C冷水游泳5分鐘，3次45。(：烤箱熱烘5分鐘，3次】 刀鐘夾尾’及3次30分鐘高速水平振邊；。每天隨機給予一種 刺激，共刺激24天，每種刺激不得連續給予。每天一次灌胃 給藥，共24天。 8·5觀測指標 8·5·1開野實驗：同上。 8.5.2被動回避實驗：同上。 8·5.3大鼠強迫游泳 末次給藥後實驗分兩天進行。第一天預試15分鐘，玻璃 缸内裝25 C溫水，水深25 cm。24小時後，進行正式實驗， 給藥後1小時，將大鼠放入缸中，觀察並記錄5分鐘不動時 間。 8·5·4體重測試 比較各組動物實驗前後體重的增加值。 8·5·5飲篇糖水量測試： 比較各種動物蔗糖攝入量。讓各組大鼠飲用1%的蔗糖水 31 200920391 (定時爲1小時），應激前、應激後3周各測一次飲水旦. 鼠在禁食禁水14小時後，將1%的蔗糖水放人籠中代 的飲用水。稱量記錄大鼠飲縣糖水〗小時前後她重的差 值計算每次的歸水個量。比較各組每—㈣試中糖水攝 入量的差異。 8·5·6高效液相一電化學檢测法 測定大鼠大腦皮質中ΝΕ及5-ΗΤ含量。7.7.2 See Table 8 for the results of the darkening test. Table 8, olfactory bulb damage model rat darkness test results Animal number first day latency (S) Day-day latency (S) Example 4 high dose group 11 187.00 + 87.59 * 289.82128.59 * Example 4 medium dose group 11 only 191.71±72.95 * 288.82+37.09 * Example 4 low dose group 11 152.44±76.81 271.18 soil 38.61 paroxetine group 11 181.87190.54 * 265.00±65.39 model group 11 only 111.21±82.93 236.88+74.17 sham operation group 11 Only 211.46±82.1〇** 292.82il4.37* Note: Compared with the model group *P<0.05 ** PcO.Ol 29 200920391 Conclusion · Experimental example 7 results show that the high dose group of Example 4 can significantly improve the damage caused by the olfactory bulb The horizontal and vertical movements of the rats increased, and the dose group in Example 4 also significantly improved the vertical movement of the rat model of olfactory bulb destruction. In addition, the large and medium dose groups of Example 4 also significantly improved the learning and memory function of rats caused by olfactory bulb damage. Experimental Example 8 Effect of Example 4 on Unpredictable Long-Term Stress Test in Rats 8.1 Experimental Animals 3 Unpredictable Long-Term Stress Model·· Healthy Wistar Male Rats, Grade II, Weight 240~270 g, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. (Certificate No. SCXK (Beijing) 2002-0003). 8.2 Reagents and Drugs Example 4 is provided by Onar Bioengineering Technology Co., Ltd. (batch number: 060313) 'Parosi> Ding is the product of Sino-US Tianjin Shike Pharmaceutical Co., Ltd. (batch number: 04050011) 'The above drugs are used. 5〇/0 carboxymethyl cellulose (CMC_Na) is formulated for intragastric administration. Penicillin sodium for injection is product of Huabei Pharmaceutical Co., Ltd. (batch number: S0511204); norepinephrine (NE) and 5-color The amine (5-HT) standard is a product of Sigma; other reagents are commercially available. 8.3 Instruments Self-made open field experiment box 'Darkness test box, rat brain stereo locator, high performance liquid chromatograph, DFM-96 type 1 tube radioimmunoassay counter. 8.4 Experimental methods 8.4.1 Animal grouping and administration methods Atmospheric randomization 6, group 'sham surgery red, turning control group, example 4 high 30 200920391 dose group (60 mg / kg / d), example 4 medium dose group (3〇mg/kg/d), real 1 4 low dose group (15 mg/kg/d), paroxetine group (2 mg/kg/d). The test substance was formulated with a positive pharmaceutical 0.5% carboxymethyl cellulose (CMC_Na). Administered once a day. 8.4.2 Model preparation method Unpredictable long-term stress model: The blank control group received normal drinking water without any stimulation. The other five groups, one in each cage, and received 24 days of unpredictable stress stimulation' included: 3 times 24 hours fasting, 3 times 24 hours water cut, 24 hours of wet dwelling in the mouse box Add water 200 ml), 3 times overnight lighting, ^ 4 C cold water swimming for 5 minutes, 3 times 45. (: oven oven for 5 minutes, 3 times) knife and knife tail 'and 3 times 30 minutes high-speed horizontal vibration edge;. Randomly give a stimulus every day for 24 days, each stimulation should not be given continuously. Medicine, a total of 24 days. 8·5 observation index 8. 5·1 open field experiment: the same as above. 8.5.2 passive avoidance experiment: the same as above. 8. 5.3 rats forced swimming after the last dose of the experiment was carried out in two days. 15 minutes pre-test, 25 C warm water in a glass jar, water depth 25 cm. After 24 hours, a formal experiment was carried out, and 1 hour after the administration, the rats were placed in a cylinder, and the immobility time was observed and recorded for 5 minutes. ·5.4 weight test to compare the weight gain of each group of animals before and after the experiment. 8·5·5 drink syrup volume test: Compare the sucrose intake of various animals. Let each group of rats drink 1% sucrose water 31 200920391 ( The time was 1 hour), and the drinking water was measured before stress and 3 weeks after stress. After 14 hours of fasting and water ban, the rats were put 1% sucrose water in the drinking water of the cage. The weighing record was large. Rat drinking county syrup 〗 〖 hours before and after her weight difference calculated each time the amount of water returned. Compare each group - (four) The difference in the amount of syrup intake was tested. 8·5·6 High Performance Liquid Phase-Electrochemical Detection Method The content of strontium and 5-quinone in rat cerebral cortex was determined.
8.6統計學處理 貫驗資料用1±切表示，實驗結果用81>：5!511.5統計軟體 進行方差分析。 8·7實驗結果 8.7·1大鼠飲蔗糖水量結果請參閱表9。 〜---表9、不可預測性長期應激模型大鼠飲蔗糖水量 飲蔗糖水量(g) 22.55+5.03 26.53±4.99 ** 26.97±6.93 ** 26.29±4.87 ** 19.42±4.25 29.41±3.83 ** 13隻 13隻 13隻 13隻 13隻 13隻 實施例4大劑量組 實施例4中劑量組 實施例4小劑量組 帕羅西汀組 模型組 ^白對照組 註：與模型組比較*Ρ<〇.〇5 ** ρ<〇.〇ι 8·7·2大氣體重增量結果請參閱表1〇。 32 r 200920391 實施例4大劑量組 實施例4中劑量組 實施例4小劑量組 帕羅西ί丁組 模型組 空白對照組 註：與模型組比較 8.7.3大鼠強迫游泳實驗 性長期應激模型大鼠體重增量 卑物數 體重增量(g) 13隻 13隻 13隻 13隻 13隻 13隻 86.08±10.84 96.00+11.05 ** 95.15±15.46 ** 96.85±9.30 ** 84.92112.61 120.54土 10.60 ** 不動時間結果請參閱表11。 不動時^ 數 不動時間(秒) 實施例4大劑量組 實施例4中劑量組 實施例4小劑量組 帕羅西汀組 模型組 空白對照 註：與模型組比較叩<〇.〇5，**ρ<〇Ό1 8.7.4大鼠開野實驗結果請參閱表 13隻 13隻 13隻 13 13 13 隻 隻 12 23.28±18.05 ** 18.95112.55 ** 25.20+13.60 * 31.38+19.59 39.95±17.46 26.96±12.76 * 33 200920391 可預測性長期應激模型大鼠開^實驗結果 實施例4大劑量組 14 58.31 + 15.35 * 16.54±4.24** 實施例4中劑量組 14 49.15±14.26 13.54±4.48 實施例4小劑量組 14 52.62+21.83 16.15±7.32* 帕羅西汀組 14 61.85±21.68 ** 14.69±4.2 模型組 14 39.54土 16.31 11.46±3.26 空白對照組 14 64.00±11.97 ** 16.85±3.18** 8.7.5大鼠避暗實驗結果請參閱見表13。 ——預測性長期應激模5^^暗實驗結果 實施例4大劑量組 實施例4中劑量組 實施例4小劑量組 帕羅西汀組 模型組 空白對照組 動物數$-天潛伏，、第二天潛伏期⑻ 259.22+56.51 212.76±77.27 204.85+94.99 257.46+66.92 189.25±111.99 263.38±59.68 13 隻 65.43±31.44 13 隻 58.18±18.〇 13 隻 75.98±32.22 13 隻 75.75±46.528.6 Statistical analysis The static data were expressed as 1±cut, and the experimental results were analyzed by ANOVA with 81>:5!511.5 statistical software. 8.7 Experimental results 8.7·1 The results of sucrose water consumption in rats are shown in Table 9. ~---Table 9, unpredictable long-term stress model rats sucrose water consumption sucrose water volume (g) 22.55 +5.03 26.53 ± 4.99 ** 26.97 ± 6.93 ** 26.29 ± 4.87 ** 19.42 ± 4.25 29.41 ± 3.83 * * 13 13 13 13 13 13 13 Example 4 Large dose group Example 4 Medium dose group Example 4 Low dose group Paroxetine group model group White control group Note: Compared with the model group *Ρ<〇 .〇5 ** ρ<〇.〇ι 8·7·2 The results of atmospheric weight gain are shown in Table 1〇. 32 r 200920391 Example 4 High-dose group Example 4 Medium-dose group Example 4 Low-dose group Paroxetium group model group blank control group Note: Compared with the model group 8.7.3 Experimental swimming long-term stress in rats Model rat weight gain hump number weight gain (g) 13 13 13 13 13 13 86.08 ± 10.84 96.00 +1.05 ** 95.15 ± 15.46 ** 96.85 ± 9.30 ** 84.92112.61 120.54 10.60 ** See Table 11 for the results of the inactivity time. Example 2: High dose group Example 4 Medium dose group Example 4 Low dose group Paroxetine group model group blank control Note: Compared with the model group 叩<〇.〇5, ** ρ<〇Ό1 8.7.4 Rat wild field test results Please refer to Table 13 only 13 13 13 13 13 only 12 23.28±18.05 ** 18.95112.55 ** 25.20+13.60 * 31.38+19.59 39.95±17.46 26.96± 12.76 * 33 200920391 Predictive long-term stress model rats open experiment results Example 4 high dose group 14 58.31 + 15.35 * 16.54 ± 4.24** Example 4 medium dose group 14 49.15 ± 14.26 13.54 ± 4.48 Example 4 small Dosage group 14 52.62+21.83 16.15±7.32* Paroxetine group 14 61.85±21.68 ** 14.69±4.2 Model group 14 39.54 soil 16.31 11.46±3.26 blank control group 14 64.00±11.97 ** 16.85±3.18** 8.7.5 rats See Table 13 for the results of the darkness test. - Predictive long-term stress model 5^^ dark experiment results Example 4 high dose group Example 4 medium dose group Example 4 low dose group paroxetine group model group blank control group animals $-day latency, second Day latency (8) 259.22+56.51 212.76±77.27 204.85+94.99 257.46+66.92 189.25±111.99 263.38±59.68 13 only 65.43±31.44 13 only 58.18±18.〇13 only 75.98±32.22 13 only 75.75±46.52
V 13 隻 50.01±15.7 13 隻 80.00土39.17 註：與模型組比較*ρ<〇.〇5 ** ρ<〇 〇ι U6 =鼠大腦皮質中ΝΕ及5_ΗΤ含量檢測結果請參閱見表 34 200920391 可預測性長期應激模型大鼠大腦皮質中NE及5-HT含 動物數 5-ΗΤ ΝΕ (nmol/L腦組織勻聚）（nmol/L腦組織勻漿) 230.4157±47.78554* 269.5409士58.86389** 303.4418±70.31711 * * 227.2976±28.95101** 332.7343±76.25168** 201.8688±29.80775** 227.0637士46.53838* 220.5419土38.31681** 179.3866士20.49374 57.6671±77.66958 228.1478士28.40397* 132.8598±20.84756** 量 (t) 12 12 12 12 12 12 實施例4大劑量組 實施例4中劑量組 實施例4小劑量組 帕羅西汀組 模型組 空白對照¥ 註：與模型組比較*Ρ<〇.〇5 **ρ〈〇.〇ι 結論： 口實驗例8結果顯示：實施例4中小劑量組可明顯改善不 可預，性長期應激刺激所造成的飲蔗糖水量減少及體重下 降；實施例4大巾小織組均可_增加大鼠強迫游泳實驗 Ϊ =間；實施例4大劑量組可明顯改善不可酬性長期應 1斜）所錢的域水平及垂直運械少，實施例4小劑量 性長誠賴賴造成的直運動減少也 刺激所實施例4小劑量組對不可預測性長期應激 小學習能力降低有改善作用；實施例4大中 均可明顯增加大氣大腦皮質中ΝΕ及5-ΗΤ含量。V 13 only 50.01±15.7 13 only 80.00 soil 39.17 Note: Compared with the model group *ρ<〇.〇5 ** ρ<〇〇ι U6 = detection results of ΝΕ and 5_ΗΤ in the cerebral cortex of the mouse, see see Table 34 200920391 Number of NE and 5-HT animals in the cerebral cortex of rats with predictive long-term stress model 5-ΗΤ ΝΕ (nmol/L brain tissue homogenization) (nmol/L brain tissue homogenate) 230.4157±47.78554* 269.5409士58.86389** 303.4418±70.31711 * * 227.2976±28.95101** 332.7343±76.25168** 201.8688±29.80775** 227.0637士46.53838* 220.5419土38.31681** 179.3866士20.49374 57.6671±77.66958 228.1478士28.40397* 132.8598±20.84756** Quantity (t) 12 12 12 12 12 12 Example 4 High-dose group Example 4 Medium-dose group Example 4 Low-dose group Paroxetine group model group blank control ¥ Note: Compared with the model group *Ρ<〇.〇5 **ρ〈〇.〇 Io Conclusion: The results of mouth experiment 8 show that the low-dose group in Example 4 can significantly improve the loss of sucrose water and weight loss caused by unpredictable, long-term stress stimulation; Example 4 can be increased Rat forced swimming experiment Ϊ = room The high-dose group of Example 4 can significantly improve the unrecognizable long-term 1 slant). The domain level and vertical transport of the money are small. The reduction of the direct motion caused by the low-dose long-term reliance of Example 4 also stimulates the small example 4 The dose group has an improved effect on the unpredictable long-term stress and small learning ability; in Example 4, the content of sputum and 5-strontium in the atmospheric cerebral cortex can be significantly increased.
實驗例9 f施例5對小鼠懸尾實驗的影塑 9.1藥品 H 35 200920391 號：05070384) ’以上藥物用生理鹽水配製後供灌胃使用。 9.2動物 ICR小鼠’雄性，體重20 0±1 g，二級，由北京大學醫學 部實驗動物科學部提供，動物質量合格證號SCXK (京） 2006-0008。 9.3儀器 秒錶。 9.4方法 小鼠70隻’隨機平均分成5組，NS組、帕羅西;丁缸（3 mg/kg/d)、實施例5大劑量組（80 mg/kg/d)、實施例$中劑 量組（4〇 mg/kg/d)、實施例5小劑量組（2〇 mg/kg/d)。每日 灌胃給藥一次，於第八天藥後丨小時將小鼠尾端（距尾尖 倒懸狀態，小鼠頭距底面約10 cm，懸吊6分鐘，記錄後 鐘内小鼠的累積不動時間。 ’、 分 9.5統計學處理 U·5統計軟體 實驗資料以1±见>表示，實驗結果用spss 進行單因素方差分析。 9.6結果 小鼠懸尾實驗不動時間結果請參閱表15。 36 200920391 5對小鼠懸尾實驗累積不動^間的影響 動物數(隻）劑量(mg/kg/d) 80 40 20 3 f 註：與 NS 組比較*P<〇.〇5 ** p<〇 〇1 結論. 研究結果顯示實施例5大、中、小三個劑量組及臨床有 效的抗抑鬱藥帕羅西汀均可明顯縮短小鼠懸尾累積不動時 間，表明實施例4具有一定的抗實驗性抑鬱作用。 實驗例10實施例5對小鼠強迫游泳實驗的影響 10.1藥品Experimental Example 9 f Example 5: Shadowing of a mouse tail suspension experiment 9.1 Drug H 35 200920391 No.: 05070384) The above drugs were prepared by using physiological saline and then administered to the stomach. 9.2 Animals ICR mice 'male, weighing 20 0 ± 1 g, two grades, provided by the Department of Laboratory Animal Science, Peking University Medical School, animal quality certificate number SCXK (Beijing) 2006-0008. 9.3 Instrument Stopwatch. 9.4 Methods 70 mice were randomly divided into 5 groups, NS group, Paroxet; Ding cylinder (3 mg/kg/d), Example 5 high dose group (80 mg/kg/d), Example $ The dose group (4 〇 mg/kg/d) and the low dose group of Example 5 (2 〇 mg/kg/d). The rats were intragastrically administered once a day, and the tail end of the mouse was hanged on the eighth day after the medicine (the head was suspended from the tail tip, the head of the mouse was about 10 cm from the bottom, suspended for 6 minutes, and the accumulation of the mice in the clock was recorded. No time. ', 9.5 statistical processing U·5 statistical software data is expressed as 1± see>, the experimental results were analyzed by one-way ANOVA with spss. 9.6 Results The results of the mouse tail suspension experiment time are shown in Table 15. 36 200920391 5 Effects on the accumulation of mice in the tail suspension experiment. Number of animals (only) dose (mg/kg/d) 80 40 20 3 f Note: Compared with NS group *P<〇.〇5 ** p< 〇〇1 Conclusion. The results of the study showed that the large, medium and small dose groups of Example 5 and the clinically effective antidepressant paroxetine significantly shortened the time of accumulation of mouse tail suspension, indicating that Example 4 has certain anti-experimentality. Depressive effect. Experimental Example 10 Effect of Example 5 on Forced Swimming Experiment in Mice 10.1 Drugs
不動時間(秒) 64.75±42.22** 55.41±33.83** 62.75±26.61** 53.27±20.02** 113.59±36.11 實施例5大劑量組 14 實施例5中劑量組 14 實施例5小劑量組 14 帕羅西汀組 14 NS 組 14 貫施例5由歐納爾生物工程技術有限公司提供（中試玫 大産品）；帕羅西、;丁爲中美天津史克制藥有限公司産品（抵 號：〇5〇7〇384) ’以上藥物用生理鹽水配製後供灌胃使用。 10.2動物 ICR小鼠，雄性’體重2〇 〇±1 g，二級，由北京大學醫學 部貫驗動物科學部提供，動物質量合格證號SCXK (京） 2006-0008。 10.3儀器 秒錶。 10.4方法 37 200920391 小鼠分組及給藥如同小鼠懸尾實驗。實驗各組小鼠於給 藥1小時後進行實驗，實驗前及第八天小鼠糾丨練游泳分 鐘，24小時後測試，將小鼠分別放入水深cm、直徑14 cm 的玻璃缸中，水溫25°C，觀察5分鐘記錄小鼠在水中的累積 不動時間。 10.5統計學處理 實驗資料以切表示，實驗結果用SPSS 11.5統計軟體 進行單因素方差分析。Immobility time (seconds) 64.75±42.22** 55.41±33.83** 62.75±26.61** 53.27±20.02** 113.59±36.11 Example 5 high dose group 14 Example 5 medium dose group 14 Example 5 low dose group 14 Pa Roxitin group 14 NS group 14 Example 5 is provided by O'Neill Bioengineering Technology Co., Ltd. (a pilot product); Parosi, Ding is a product of Sino-US Tianjin Shike Pharmaceutical Co., Ltd. (Rated: 〇5 〇7〇384) 'The above drugs are prepared with normal saline and used for intragastric administration. 10.2 Animals ICR mice, male 'body weight 2〇 〇 ±1 g, two grades, provided by the Department of Animal Science of Peking University Medical School, animal quality certificate number SCXK (Beijing) 2006-0008. 10.3 Instrument Stopwatch. 10.4 Methods 37 200920391 Mice were grouped and administered as a mouse tail suspension experiment. The mice in each group of the experiment were tested after 1 hour of administration. Before the experiment and on the eighth day, the mice were trained to swim for a minute, and after 24 hours, the mice were placed in a glass jar with a water depth of cm and a diameter of 14 cm. The water temperature was 25 ° C, and the cumulative time of the mice in the water was recorded for 5 minutes. 10.5 Statistical analysis The experimental data were shown as cut-off, and the experimental results were analyzed by SPSS 11.5 statistical software for one-way analysis of variance.
10.6結果 小鼠強迫游泳實驗結果請參閱表16。 _参16、實施例5對小鼠強迫游泳實驗的影響 動物數(隻） 劑量(mg/kg/d) 不動時間(秒） 實施例5大劑量組 14 80 88.35士 51,64* 實施例5中劑量組 14 40 65.87±38.96** 實施例5小劑量組 14 20 88.12±38.57* 帕羅西、汀組 14 J 57.80 土38.07** NS組 14 __________132.47士 40_64 註：與 NS 組比較*P<〇.〇5 ** P<0.01 結言金. 研究結果顯示實施例5大、中、小添 抗抑營藥㈣时均可明顯输錢 及臨床有效的 間，表明卿具有一定的抗實=4::累積不動時 實驗例11 的人參殘造9公 將實施例1及實施例4萃取後收集所 * 4 38 20092039110.6 Results Refer to Table 16 for the results of forced swimming in mice. _ Ref. 16. Effect of Example 5 on forced swimming test in mice Number of animals (only) Dose (mg/kg/d) Immobility time (seconds) Example 5 High dose group 14 80 88.35 士 51, 64* Example 5 Medium dose group 14 40 65.87±38.96** Example 5 Low dose group 14 20 88.12±38.57* Paroxet, Ting group 14 J 57.80 Soil 38.07** NS group 14 __________ 132.47士40_64 Note: Compared with NS group* P<〇.〇5 ** P<0.01 Conclusion Gold. The results of the study show that the large, medium and small additions of the anti-inhibition drug (IV) in Example 5 can obviously lose money and clinically effective, indicating that Qing has certain anti-reality. =4:: When the accumulation is not moving, the ginseng residue of the experimental example 11 is 9 liters. After the extraction of the sample 1 and the example 4, the collection is carried out* 4 38 200920391
棗cAMP的殘渣混合物， 試驗。 11.1實驗動物 體重22.G±2g，二級，北京首都醫科大 ICR小鼠，雄性，體 學實驗動物科學部提供。 11.2實驗藥品 殘造混合物：北京歐納爾生物卫程技術有限公司提供。 帕羅西>7 (赛雜）：巾美天津妓制財限公司産品 11.3實驗儀器 秒錶。 11.4劑量設計 殘渣混合物大劑量·· 16〇 mg/kg/d、中劑量：8〇 mg/kg/d 及、小劑量：40 mg/kg/d。 11.5實驗方法及結果 11.5.1分組給藥 將小鼠隨機分組，每組10隻:①殘渣混合物大劑量組（16〇 mg/kg ’ PO，給藥7d);②殘渣混合物中劑量組（8〇mg/kg， PO ’給藥7d);③殘渣混合物小劑量組（40 mg/kg，p〇，於 藥7d);④帕羅西汀組（3 mg/kg，P0，給藥7d);⑤生理鹽 水組（p〇)。最後—次給藥後1小時進行懸尾實驗。 | 11.5.2實驗方法 將小鼠尾（距尾尖1 cm處）用膠布粘在高山臺面5 cm 的木條上懸吊6分鐘，記錄後5分鐘内小鼠的不動時間。 39 200920391 Η·5·3統計學處理 汽驗資料用歹土幼表示，實驗結果用SPSS 11.5統計軟體 進行方差分析。 U·5·4實驗結果 實驗結果請參閱表17。 A1?、殘渣混合物對小鼠不動時間的影響 ΓΛ 組別 生理鹽水組（模型組） 帕羅西汀組 殘渔混合物大劑量組 殘渣混合物中劑量組 S >查混合物小劑量組 註：與模型組比較* p<〇 〇5 **p<〇 〇1 結論： 動物色（隻） 10 10 10 10 10 不動時間（秒） 82.03士 43.01 38.37士20.76* 76.91±31.09 78.89±48.18 81.31 士 58.68A residue mixture of jujube cAMP, tested. 11.1 Experimental Animals Body weight 22.G ± 2g, secondary, Beijing Capital Medical University ICR mice, male, physical laboratory animal science department. 11.2 Experimental Drugs Residual Mixture: Provided by Beijing O'Neill Bio-Technology Co., Ltd. Parosi > 7 (赛杂): towel beauty Tianjin Tengquan limited company products 11.3 experimental instruments stopwatch. 11.4 Dose design Large dose of residue mixture · 16 〇 mg / kg / d, medium dose: 8 〇 mg / kg / d and small dose: 40 mg / kg / d. 11.5 Experimental methods and results 11.5.1 Group administration The mice were randomly divided into groups of 10: 1 residue mixture high dose group (16 〇mg/kg 'PO, 7d administration); 2 residue mixture medium dose group (8 〇mg/kg, PO 'administered for 7d); 3 residue mixture in low dose group (40 mg/kg, p〇 for 7d); 4 paroxetine group (3 mg/kg, P0, for 7d); Saline group (p〇). A tail suspension experiment was performed 1 hour after the last administration. 11.5.2 Experimental method The tail of the mouse (1 cm from the tip of the tail) was suspended with a tape on a 5 cm wooden strip on a mountain table for 6 minutes, and the immobility time of the mouse within 5 minutes after recording was recorded. 39 200920391 Η·5·3 Statistical Processing The steam test data was expressed in 歹土幼, and the experimental results were analyzed by SPSS 11.5 statistical software for variance analysis. U·5·4 Experimental Results Refer to Table 17 for the experimental results. A1?, the effect of residue mixture on immobility time in mice ΓΛ group saline group (model group) paroxetine group residual fish mixture large dose group residue mixture medium dose group S > check mixture small dose group Note: compared with the model group * p<〇〇5 **p<〇〇1 Conclusion: Animal color (only) 10 10 10 10 10 Immobility time (seconds) 82.03士43.01 38.37士20.76* 76.91±31.09 78.89±48.18 81.31 士58.68
=細上實驗，可赠峡奴合物大、中、小三個 !、、且可縮短小鼠懸尾後的不動時間，但與生理 型組）相比差異無顯著性，從 且（核 有抗實驗性㈣功能。❿驗混合物不具 本發侧於治療錄症的D物的應用 可以含 1. 本發明所賴用於雜讀症的卩服 有藥物學上可接受的添加劑； 、中， 2. 本發明所述的用於治療憂鬱 工製成散劑、膠囊劑、片劑、等各1 ，、为可以將其加 W寻各種習知的劑细 3·本發明所述的用於治療蚤齡 # 治療憂鬱症的保健食品。“的σ服樂物可以製用於 40 200920391 本案得由熟悉此技藝之人任施匠思而為諸般修飾，然皆 不脫如附申請範圍所欲保護者。 【圖式簡單說明】 第一圖爲製備本發明實施例1藥物的方法流程示意圖。 第二圖爲製備本發明實施例2藥物的方法流程示意圖。 第三圖爲製備本發明實施例3藥物的方法流程示意圖。 第四圖爲製備本發明實施例4藥物的方法流程示意圖。 第五圖爲製備本發明實施例5藥物的方法流程示意圖。 第六圖爲製備本發明實施例6藥物的方法流程示意圖。 【主要元件符號說明】 無 41= Fine experiment, you can give the gorge large, medium and small!, and can shorten the immobility time after the mouse tail, but compared with the physiological group), the difference is not significant, and (nuclear Anti-experimental (4) function. The application of the test mixture without the D side of the present invention may include 1. The medicinal acceptable additive for the miscellaneous reading of the present invention; 2. The invention relates to the treatment of depression, powder, capsule, tablet, etc., which can be used to find various conventional agents. 3. The invention is used for treatment.蚤龄# The health food for the treatment of depression. "The σ service can be used for 40 200920391. This case has been modified by people who are familiar with this technique, but they are all protected as intended. BRIEF DESCRIPTION OF THE DRAWINGS The first figure is a schematic flow chart of a method for preparing the drug of the embodiment 1 of the present invention. The second figure is a schematic flow chart of a method for preparing the drug of the embodiment 2 of the present invention. The third figure is a third embodiment of the present invention. Schematic diagram of the method of the drug. The fourth picture shows the preparation The method of process flowchart of a method flowchart of a method of drug out Example 4 Example 5 The picture shows a fifth medicament prepared according to the present invention. Example 6 The picture shows a sixth embodiment of the pharmaceutical preparation of the present invention. FIG. Main reference numerals 41 None DESCRIPTION
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW96143310A TW200920391A (en) | 2007-11-15 | 2007-11-15 | Multi-target post-receptor action used in pharmaceutical composition for depression treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW96143310A TW200920391A (en) | 2007-11-15 | 2007-11-15 | Multi-target post-receptor action used in pharmaceutical composition for depression treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200920391A true TW200920391A (en) | 2009-05-16 |
| TWI350172B TWI350172B (en) | 2011-10-11 |
Family
ID=44727453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW96143310A TW200920391A (en) | 2007-11-15 | 2007-11-15 | Multi-target post-receptor action used in pharmaceutical composition for depression treatment |
Country Status (1)
| Country | Link |
|---|---|
| TW (1) | TW200920391A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2625765C2 (en) * | 2012-08-15 | 2017-07-18 | ЧИЮйФэнь | Pharmaceutical composition for cyclic adenosin-phonesphate content and availability increase in organism and its production |
-
2007
- 2007-11-15 TW TW96143310A patent/TW200920391A/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2625765C2 (en) * | 2012-08-15 | 2017-07-18 | ЧИЮйФэнь | Pharmaceutical composition for cyclic adenosin-phonesphate content and availability increase in organism and its production |
Also Published As
| Publication number | Publication date |
|---|---|
| TWI350172B (en) | 2011-10-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6077305B2 (en) | Preparations containing amino acids and plants and their activity in alcohol detoxification | |
| WO2009070915A1 (en) | Pharmaceutical compositions for treating depression and anxiety | |
| TW200904461A (en) | A pharmaceutical composition for treating depression and method for preparation thereof | |
| CN110167549A (en) | The medicinal compound and nutritional supplement based on plant of snap action | |
| CN110121337A (en) | Medicinal compound and nutritional supplement | |
| CN1840166A (en) | Modern Chinese medicinal oral liquid of 'Wen Dan Tang' and preparation method thereof | |
| WO2011047576A1 (en) | Use of albiflorin for anti-depression | |
| JP5628682B2 (en) | Pharmaceutical composition for the treatment of depression | |
| WO2012068958A1 (en) | Antianxiety and sleep disorder improving use of albiflorin or metabolite thereof in | |
| WO2009070921A1 (en) | Antimelancholic medicine prepared with jujube camp materials | |
| US20230125425A1 (en) | Traditional chinese medicine extract composition with function of regulating depressive emotion and preparation method and traditional chinese medicine preparation thereof | |
| TW201106959A (en) | Composition for preventing or treating irritable bowel syndrome | |
| CN101933963B (en) | Nasal in-situ gel for treating headache | |
| US8158171B2 (en) | Methods of lowering blood cholesterol via oral fenugreek seed extract compositions | |
| CN108420890B (en) | Composition with blood fat reducing effect and preparation method thereof | |
| CN105519731A (en) | Dried tangerine peel tea effervescent tablet and preparation method thereof | |
| KR20200087606A (en) | Compositions for Improving Memory Power and Learning Ability, and Relaxing stress | |
| TW200920391A (en) | Multi-target post-receptor action used in pharmaceutical composition for depression treatment | |
| CN104548020B (en) | A kind of purposes of pharmaceutical composition in treatment senile dementia is prepared | |
| TWI698184B (en) | Pumpkin seed extract, method for producing the same and the use thereof | |
| CN1686514A (en) | Chinese medicinal preparation for treating anxietas, depression and its production method | |
| WO2004000341A1 (en) | The pharmaceutical formulation of traditional chinese medicine for abstinence of drug and preparation method and use thereof | |
| CN109394977A (en) | A kind of Chinese medicine composition and preparation method and application with hypolipemic function | |
| CN108785649B (en) | Composition for controlling weight of pressure type obesity | |
| CN107362223A (en) | A kind of Chinese medicine composition containing Cornu Cervi cowl glue and preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |