TW201032805A

TW201032805A - Pharmaceutical compositions comprising a compound having suppressive effect on nutrient digestion or absorption and a cyclohexanecarboxamide derivative

Info

Publication number: TW201032805A
Application number: TW099105552A
Authority: TW
Inventors: Hideo Yukioka
Original assignee: Shionogi & Co
Priority date: 2009-02-27
Filing date: 2010-02-26
Publication date: 2010-09-16
Also published as: AR075631A1; WO2010098298A1

Abstract

It is found that a pharmaceutical composition can meaningly decrease body weight, which comprises a compound having suppressive effect on nutrient digestion or absorption, pharmaceutically acceptable salts or solvates thereof, and a compound represented by the formula (I) (in formula, R1 is alkyl; R2 is hydrogen atom, or alkyl, Z is substituted or non-substituted alkyl, substituted or non-substituted alkenyl, substituted or non-substituted amino, substituted or non-substituted alkoxy, substituted or non-substituted hydrocarbon cyclic group, or substituted or non-substituted heterocyclic group). The said pharmaceutical composition is useful for the treatment or prevention of obesity and the disorders related to obesity.

Description

201032805 六、發明說明：【發明所屬之技術領域】本發明與具有營養素消化吸收抑制作用之化合物與環己烷甲醯胺衍生物組合而成之醫藥組成物有關。詳言之，本發明與具有營養素消化吸收抑制作用之化合物、其製藥上容許之鹽或其等之溶劑合物，與下列式（I)表示之化合物、其製藥上容許之鹽或其等之溶劑合物組合而成之醫藥組成物有關。該醫藥組成物極有用於預防或治療肥胖或肥 m w 胖相關疾病。201032805 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a pharmaceutical composition in which a compound having a nutrient absorption and absorption inhibiting action and a cyclohexane formamide derivative are combined. In particular, the present invention and a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or the like It is related to the pharmaceutical composition in which the solvate is combined. The pharmaceutical composition is extremely useful for preventing or treating obesity or fat m w fat related diseases.

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基。） φ 【先前技術】肥胖之定義爲相對於除去脂肪之體重而言，體內蓄積過剩之脂肪或脂肪組織之狀態，被認爲是健康問題之主要危險因子。身體質量指數（BMI、Body Mass Index)是將成人 (15歲以上）之團體或個人分類爲體重過重或肥胖時共同使用之身高體重比之單純指數。其定義爲體重（公斤）除以身高（公尺）的平方所得比値（kg/m2)。世界衛生組織將BMI爲 2 5 kg/m2以上定爲「體重過重」，30 kg/m2以上定爲「肥胖」。 201032805 另一方面，曰本肥胖學會定BMI爲25 kg/m2以上爲「肥胖」。其原因爲包含如糖尿病或血脂異常之肥胖相關疾病患者數隨BMI之增加而增多，且於BMI爲25 kg/m2時該疾病患者數之平均値達到1.0以上之故。依世界衛生組織2005 年之調查，全世界約有16億人爲體重過重，而至少4億人爲肥胖。肥胖主要因相對於身體活動或日常生活之熱量消耗，熱量攝取比例之增加而引起。近年來由於攝取含高脂肪、高糖分食物之增加而導致肥胖人數增加，預測2015年全世界有7億人以上被診斷爲肥胖。關於預防或治療肥胖之藥劑，己知有具有食欲抑制作用之化合物芬氟拉明（Fenfluramine)及百憂解（Fluoxetin)等選擇性血清素再吸收抑制劑，馬吲哚（Mazindol)等，具有營養素消化吸收抑制作用之化合物等。關於具有營養素消化吸收抑制作用之化合物，如具有糖吸收抑制作用之化合物 (α -葡萄醣苷酶抑制劑、SGLT - 2抑制劑等，具有脂肪吸 φ 收抑制作用之化合物等。具有脂肪吸收抑制作用之化合物，如脂肪酶抑制劑（具有胃脂肪酶抑制作用之化合物、具有胰臟脂肪酶抑制作用之化合物等）、膽酸吸附樹脂等。奧利司他（Orlistat)是具有胰臟脂肪酶抑制作用之抗肥胖藥。非專利文獻1報告指出經丨年期之臨床試驗結果，奧利司他投藥組之1 /3以上肥胖患者表現較投藥前之體重減少1 0 %以上體重。再者，具有糖類吸收抑制作用之化合物達帕弗淨 201032805 (Dapagliflozin)(SGLT — 2抑制劑）及具有脂肪吸收抑制作用之化合物奧利司他（THL)己知除表現體重增加抑制作用外，亦表現攝食亢進作用（參照非專利文獻2、尤其是第3 圖及非專利文獻3)。非專利文獻4報告己知爲NPY Y5受體拮抗劑之MK -0557，對肥胖患者在臨床上未表現顯著之體重減少。該文獻強烈暗示抑制NPY Y5受體對體重減少並無顯著之作用。又，MK — 0557以下列結構式表示。(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group.) φ [Prior Art] Obesity is defined as the weight relative to fat removal. The state of excess fat or fat tissue in the body is considered to be a major risk factor for health problems. The Body Mass Index (BMI) is a simple index that classifies adults or groups of individuals (over 15 years of age) into height-to-weight ratios that are used together when they are overweight or obese. It is defined as the weight (kg/m2) obtained by dividing the body weight (kg) by the square of the height (meter). The World Health Organization has designated BMI of 25 kg/m2 or more as "overweight" and 30 kg/m2 or more as "obesity". 201032805 On the other hand, the Sakamoto Obesity Society has a BMI of 25 kg/m2 or more as “fat fat”. The reason for this is that the number of patients with obesity-related diseases such as diabetes or dyslipidemia increases with the increase in BMI, and the average number of patients with the disease at a BMI of 25 kg/m2 is 1.0 or more. According to a 2005 survey by the World Health Organization, approximately 1.6 billion people worldwide are overweight and at least 400 million are obese. Obesity is mainly caused by an increase in caloric intake relative to physical activity or daily calorie consumption. In recent years, the number of obese people has increased due to the increase in the intake of high-fat, high-sugar foods. It is predicted that more than 700 million people worldwide will be diagnosed with obesity in 2015. As for the agent for preventing or treating obesity, there are known selective serotonin reuptake inhibitors such as Fenfluramine and Fluoxetin, and Mazindol, etc., having an appetite suppressing effect. A compound that inhibits the absorption and absorption of nutrients. A compound having a nutrient absorption and absorption inhibitory action, such as a compound having an action of inhibiting glucose absorption (α-glucosidase inhibitor, SGLT-2 inhibitor, etc., a compound having a fat absorption inhibitory effect, etc.) has a fat absorption inhibiting action. Compounds such as lipase inhibitors (compounds with gastric lipase inhibition, compounds with pancreatic lipase inhibition, etc.), bile acid adsorption resins, etc. Orlistat is a pancreatic lipase inhibitor Anti-obesity drugs for action. Non-Patent Document 1 reports that the results of clinical trials over the leap period have resulted in more than one-third of obese patients in the orlistat administration group losing more than 10% of their body weight before administration. Compounds with a saccharide absorption inhibitor, Dapafloxacin 201032805 (Dapagliflozin) (SGLT-2 inhibitor) and a compound with a fat absorption inhibitory effect, orlistat (THL), are known to exhibit in addition to the inhibition of weight gain. The hyperactive action (see Non-Patent Document 2, in particular, Fig. 3 and Non-Patent Document 3). Non-Patent Document 4 reports that it is known MK -0557, an NPY Y5 receptor antagonist, did not show significant weight loss in obese patients. This paper strongly suggests that inhibition of NPY Y5 receptor has no significant effect on weight loss. In addition, MK - 0557 has the following structure Expression.

非專利文獻5報告奧利司他與MK— 0557之同時投藥與奧利司他之單劑投藥比較結果，體重並無顯著減少。該文獻強烈暗示抑制NPY Y5受體並不提高奧利司他之體重減少效率。奧利司他與NPY Y5受體拮抗劑之倂用或配合劑記載於專利文獻1、2及3。但該等專利文獻未記載實施例或具體數據，亦無揭示或暗示實際效果。式⑴表示之化合物己知具有NPY Y5受體特異性拮抗作用（參照專利文獻4及專利文獻5)。 201032805Non-Patent Document 5 reports that the simultaneous administration of orlistat and MK-057 is compared with the single dose of orlistat, and the body weight is not significantly reduced. This literature strongly suggests that inhibition of the NPY Y5 receptor does not increase the weight loss efficiency of orlistat. The use or combination of orlistat and NPY Y5 receptor antagonists is described in Patent Documents 1, 2 and 3. However, the patent documents do not disclose examples or specific data, nor do they disclose or imply actual effects. The compound represented by the formula (1) is known to have an NPY Y5 receptor-specific antagonistic action (see Patent Document 4 and Patent Document 5). 201032805

(式中，R1爲烷基，R2爲氫原子或烷基，Z 未被取代之烷基、被取代或未被取代之烯基、被取代之胺基、被取代或未被取代之烷氧基、被取代之環狀烴基、或被取代或未被取代之雜非專利文獻6報告，經1年期之臨床試驗式（I)表示之化合物之1種化合物（a)，其投藥組肥胖患者表現較投藥前之體重減少5%以上體重文獻5記載上述式（I)表示之化合物表現攝食; 又，化合物（a)以下列結構式表示。 ⑻ 但有關具有營養素消化吸收抑制作用之化名式（I)表示之化合物組合而成之醫藥組成物，則ΐ 無揭示或暗示。先前技術文獻專利文獻1:國際公開第W02003/07 25 77號專利文獻2:國際公開第W02004/014884號專利文獻3 :國際公開第WO2004/0090 1 5號專利文獻4:國際公開第WO2001/37826號專利文獻5 :國際公開第W02006/001 3 1 8號 I被取代或芝取代或未芝取代或未 ί基）。与果’上述匕1/3以上。又，專利 3制作用。物與上述何文獻均 201032805 非專利文獻 1 : The Journal of the American Medical Association(1999)281,235-242 非專利文獻 2: International Journal of Obesity (1987) 1 l,Suppl.3,35-42 非專利文獻 3 : Obesity 15(Suppl.9):A121，2007 非專利文獻 4 : Cell Metabolism 4,275-282,2006 非專利文獻 5: 0besity(2007)，15(8)，2027-2042 φ 非專利文獻 6 :鹽野義製藥株式會社、“ Shionogi announces positive top-line efficacy results from year-long studies of velneperit, a novel NPY Y5 receptor antagonist being investigated for the treatment of obesity”、[online]、平成 21 年 2 月 17 日、鹽野義製藥、Internet < URL: http://www.shi onogi.co.jp/ir_en /news/detail/e_09 0217-2.pdf >Wherein R1 is alkyl, R2 is hydrogen or alkyl, Z is unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted amine, substituted or unsubstituted alkoxy A non-patent document 6 in which a substituted cyclic hydrocarbon group or a substituted cyclic hydrocarbon group or a substituted or unsubstituted compound is reported, a compound (a) of a compound represented by the formula (I) in a one-year clinical trial, the administration group is obese The patient showed a 5% or more body weight reduction before administration. The literature 5 describes that the compound represented by the above formula (I) exhibits food intake; and the compound (a) is represented by the following structural formula. (8) However, the pseudonym having the nutrient absorption and absorption inhibition effect (I) The composition of the compound represented by the combination of the compounds is not disclosed or suggested. Prior Art Document Patent Document 1: International Publication No. WO2003/07 25 77 Patent Document 2: International Publication No. WO2004/014884 Patent Literature 3: International Publication No. WO2004/0090 1 Patent Document 4: International Publication No. WO2001/37826 Patent Document 5: International Publication No. WO2006/001 No. 3 No. 1 is substituted or replaced with or substituted with or not ). With the fruit 'the above 匕 1/3 or more. Also, the patent 3 is used for production. And the above documents are all 201032805 Non-Patent Document 1: The Journal of the American Medical Association (1999) 281, 235-242 Non-Patent Document 2: International Journal of Obesity (1987) 1 l, Suppl. 3, 35-42 Non-patent literature 3 : Obesity 15 (Suppl. 9): A121, 2007 Non-Patent Document 4: Cell Metabolism 4, 275-282, 2006 Non-Patent Document 5: 0besity (2007), 15 (8), 2027-2042 φ Non-Patent Document 6: Salt "Yonyigi announces positive top-line efficacy results from year-long studies of velneperit, a novel NPY Y5 receptor antagonist being investigated for the treatment of obesity", [online], February 17, 2011 Yan Yeyi Pharmaceutical, Internet < URL: http://www.shi onogi.co.jp/ir_en /news/detail/e_09 0217-2.pdf >

非專利文獻7:鹽野義製藥株式會社、”1st Half and 2nd Quarter of Fiscal 2009 Financial Results”、[online]、平成 21 年 11 月 5 日、鹽野義製藥、Internet < URL:http:"www.shionogi.co.jp/ir_en/explanatory/pdf/e_p09 1105.pdf> 【發明內容】 [發明欲解決之課題] 本發明之目的爲提供對預防或治療肥胖或肥胖相關疾病非常有用之一種醫藥組成物。 201032805 [解決課題之方法] 本發明者等經精心硏究，發現下述之結果。倂用（包含共同投藥）具有營養素消化吸收抑制作用之化合物及環己院甲醯胺衍生物之式（I)表示之化合物結果，在肥胖模式實驗小鼠以用量依賴性顯著抑制體重。 RVq.nh d%Non-Patent Document 7: Yan Yeyi Pharmaceutical Co., Ltd., "1st Half and 2nd Quarter of Fiscal 2009 Financial Results", [online], November 5, 2011, Yan Yeyi Pharmaceutical, Internet < URL: http:&quot [www.shionogi.co.jp/ir_en/explanatory/pdf/e_p09 1105.pdf> [Summary of the Invention] [Problem to be Solved by the Invention] An object of the present invention is to provide a very useful one for preventing or treating diseases related to obesity or obesity. Pharmaceutical composition. 201032805 [Method for Solving the Problem] The inventors of the present invention have carefully studied and found the following results. The results of the compound represented by the formula (I) of the compound having the nutrient digestion and absorption inhibitory effect and the cyclohexylamine derivative were used (including the co-administration), and the mice were tested in the obese model to significantly inhibit the body weight in a dose-dependent manner. RVq.nh d%

(式中，R1爲烷基，R2爲氫原子或烷基，z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。再者，倂用具有ΝΡγ Y5受體拮抗作用之式⑴表示之化合物與具有營養素消化吸收抑制作用之化合物時，與各別化合物治療之合計比較，發現有相加以上之體重減少。亦即與非專利文獻5之記載相異，倂用時之體重抑制較各別化合物單獨治療之合計爲大。如考慮非專利文獻5記載抑制NPY Y5受體並不提高奧利司他之體重減少效率時，此相加以上之體重減少效果並非NPY Y5受體拮抗作用，而係因式（I)表示之化合物特有之作用所致。具有營養素消化吸收抑制作用之化合物如非專利文獻2、非專利文獻3 等所記載，一方面表現體重增加抑制作用，一方面表現攝食亢進作用。又，本發明者等發現倂用具有營養素消化吸收抑制作用之化合物與式（I)表示之化合物，能夠抑 201032805 制因具有營養素消化吸收抑制作用之化合物導致之攝食亢進作用。因此’本發明之醫藥組成物與具有營養素消化吸收抑制作用之化合物單劑比較時，能夠表現非常強大之體重減少效果。因而，本發明之醫藥組成物當做肥胖之治療劑或預防劑非常有用。亦即’本發明與以下各項有關。 (1)一種醫藥組成物，其係由具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物組合而成之醫藥組成物；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). Further, when a compound represented by the formula (1) having an ΝΡγ Y5 receptor antagonistic action and a compound having a nutrient absorption and absorption inhibiting action were used, it was found that the weight loss was increased in comparison with the total of the treatments of the respective compounds. That is, unlike the description in Non-Patent Document 5, the weight loss at the time of use is larger than the total treatment of the individual compounds alone. When it is considered that the inhibition of the NPY Y5 receptor does not increase the weight loss efficiency of orlistat in Non-Patent Document 5, the weight loss effect on the addition is not the NPY Y5 receptor antagonism, but is expressed by the formula (I). The specific effect of the compound. The compound having a nutrient absorption and absorption inhibiting action is described in Non-Patent Document 2, Non-Patent Document 3, etc., and exhibits a function of suppressing weight gain on the one hand and a hyperfeeding action on the other hand. Further, the present inventors have found that a compound having a nutrient absorption and absorption inhibiting action and a compound represented by the formula (I) can inhibit the feeding action caused by a compound having a nutrient absorption and absorption inhibiting action in 201032805. Therefore, when the pharmaceutical composition of the present invention is compared with a single agent having a nutrient absorption and absorption inhibiting action, it is possible to exhibit a very strong body weight reducing effect. Therefore, the pharmaceutical composition of the present invention is very useful as a therapeutic or prophylactic agent for obesity. That is, the present invention relates to the following items. (1) A pharmaceutical composition which is a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a pharmaceutical composition obtained by combining the solvates thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (2) 如第（1)項記載之醫藥組成物，該醫藥組成物爲配合劑。 (3) 如第（1)項記載之醫藥組成物，該醫藥組成物爲含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，與含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之套組； 10- 201032805(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (2) The pharmaceutical composition according to the item (1), wherein the pharmaceutical composition is a compounding agent. (3) The pharmaceutical composition according to the item (1), which is a pharmaceutical composition containing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a formula ( I) a kit of the indicated compound and its pharmaceutically acceptable salt or its solvate; 10-201032805

N-Z 〇) (式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被、取代或未被取代之烯基、被取代或$ 被取代之胺基、被取代或未被取代之烷氧基、被取代或$ 被取代之環狀烴基、或被取代或未被取代之雜環基）。 (4) 如第（1)〜（3)項中任一項記載之醫藥組成物，其中該 ¥ 具有營養素消化吸收抑制作用之化合物爲具有脂肪吸收抑制作用之化合物。 (5) 如第（4)項記載之醫藥組成物，其中該具有脂肪吸收抑制作用之化合物爲具有皞臟脂肪酶抑制作用之化合物。 (6) 如第（5)項記載之醫藥組成物，其中該具有胰臟脂肪酶抑制作用之化合物爲奧利司他。 (7)如第（1)〜（6)項中任一項記載之醫藥組成物，其中該式（I)表示之化合物爲下式（a)表示之化合物。NZ 〇) (wherein R 1 is an alkyl group, R 2 is a hydrogen atom or an alkyl group, and Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, substituted or substituted Amino group, substituted or unsubstituted alkoxy group, substituted or substituted cyclic hydrocarbon group, or substituted or unsubstituted heterocyclic group). (4) The pharmaceutical composition according to any one of (1) to (3), wherein the compound having a nutrient absorption and absorption inhibiting action is a compound having a fat absorption inhibiting action. (5) The pharmaceutical composition according to the item (4), wherein the compound having a fat absorption inhibiting action is a compound having a sputum lipase inhibiting action. (6) The pharmaceutical composition according to the item (5), wherein the compound having pancreatic lipase inhibitory action is orlistat. The pharmaceutical composition according to any one of the items (1) to (6), wherein the compound represented by the formula (I) is a compound represented by the following formula (a).

(8) 如第（1)〜（7)項中任一項記載之醫藥組成物，其係用於預防或治療肥胖或肥胖相關疾病或肥胖症之體重管理》 (9) 如第（8)項記載之醫藥組成物，其中之肥胖相關疾病爲貪食症（Addephagia)、高血壓、葡萄糖耐量異常、糖尿病、新陳代謝症候群、脂肪代謝異常、動脈硬化、高尿酸血症、 -11 - 201032805 痛風、脂肪肝、子宮內膜癌、乳癌、攝護腺癌、大腸癌、變形性關節症、腰痛、阻塞型睡眠呼吸中止症候群、冠狀動脈疾病、腦梗塞、月經異常、普瑞德威利氏症候群 (Prader-Willi Syndrome)、弗勒利希症候群（Froehlich Syndrome)、或匹克威特症候群（Pickwickian Syndrome)。 (10)—種藥劑之肥胖或肥胖相關疾病之預防或治療效果之增強劑，該藥劑中含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物；(8) The pharmaceutical composition according to any one of the items (1) to (7) for use in the prevention or treatment of obesity or obesity-related diseases or weight management of obesity (9) as in (8) The pharmaceutical composition described in which obesity-related diseases are Addephagia, hypertension, impaired glucose tolerance, diabetes, metabolic syndrome, abnormal fat metabolism, arteriosclerosis, hyperuricemia, -11 - 201032805 gout, fat Liver, endometrial cancer, breast cancer, prostate cancer, colorectal cancer, osteoarthritis, low back pain, obstructive sleep-absorptive syndrome, coronary artery disease, cerebral infarction, menstrual abnormalities, Predwell's syndrome (Prader) -Willi Syndrome), Froehlich Syndrome, or Pickwickian Syndrome. (10) An agent for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease, which comprises a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基），及含有具有營養素消化吸收抑制作用之化合物及其製藥上容許 w 之鹽或其等之溶劑合物之藥劑。 (11) 一種藥劑之肥胖或肥胖相關疾病之預防或治療效果之增強劑，該藥劑含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group, and a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable amount thereof An agent of a salt or a solvate thereof. (11) An agent for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease of a medicament, which comprises a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未 -12- 201032805 被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）；及含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物。 (12)—種含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，其係用於與含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶 • 劑合物之藥劑倂用；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, substituted or not substituted by -12-201032805 An amine group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group; and a compound having a nutrient absorption and absorption inhibiting action and A pharmaceutically acceptable salt or a solvate thereof. (12) A pharmaceutical agent comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, which is used in combination with a compound represented by the formula (I) and a pharmaceutically acceptable compound thereof The use of a salt or a solvent thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (13)—種含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，其係用於與含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑倂用；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (13) A pharmaceutical agent comprising a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, which is used in combination with a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable substance thereof The use of a salt or a solvate thereof;

N-Z (I) (式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未 -13- 201032805 被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (14)如第（12)項或第（13)項記載之藥劑，其係用於肥胖或肥胖相關疾病之預防或治療或肥胖症之體重管理。再者，以下之發明亦包含於本發明之範圍內。 ❹ (15)—種肥胖或肥胖相關疾病之預防或治療或肥胖症之體重管理方法，其係包含將具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與式（I) 表示之化合物及其製藥上容許之鹽或其等之溶劑合物組合投藥之步驟；NZ (I) (wherein R 1 is an alkyl group, R 2 is a hydrogen atom or an alkyl group, and Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, substituted or not - 13- 201032805 A substituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (14) The agent according to Item (12) or (13), which is used for the prevention or treatment of obesity or obesity-related diseases or the weight management of obesity. Furthermore, the following invention is also included in the scope of the invention. (15) A method for preventing or treating obesity or obesity-related diseases or a method for managing body weight of obesity, which comprises a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like a step of administering a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未 ® 被取代之環狀烴基、或被取代或未被取代之雜環基）。 (16)—種具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物，用於製造醫藥組成物之用途，該醫藥組成物係用於肥胖或肥胖相關疾病之預防或治療或肥胖症之體重管理； -14- 201032805(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (16) a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound represented by the formula (I), and a pharmaceutically acceptable salt thereof or a solvate thereof, For the manufacture of a pharmaceutical composition for the prevention or treatment of obesity or obesity-related diseases or weight management of obesity; -14- 201032805

Ο) (式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (17) —種誘導或促進體重減少、或維持或管理體重之 φ 方法，其係包含將具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物組合投藥之步驟；Ο) (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (17) A method for inducing or promoting weight loss, or maintaining or managing body weight, comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof and the like (I) a step of administering a combination of the indicated compound and a pharmaceutically acceptable salt thereof or a solvate thereof;

RkNHV^ ° 0 . ΌγΝ-ζ 0) (式中，R1爲烷基，R2爲氫原子或烷基，Ζ爲被取代或 ©未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (18)—種具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物，用於製造醫藥組成物之用途，該醫藥組成物係用於誘導或促進體重減少、& 維持或管理； -15- 201032805 Ν-Ζ (I) τχχχ (式中，R1爲院基’ R2爲氫原子或院基，Ζ爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、.被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (19) 一種醫藥組成物，其係爲誘導或促進體重減少、或維持或管理體重，將具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物組合而成；RkNHV^ ° 0 . ΌγΝ-ζ 0) (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, and hydrazine is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, A substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (18) a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound represented by the formula (I), and a pharmaceutically acceptable salt thereof or a solvate thereof, For the manufacture of a pharmaceutical composition for inducing or promoting weight loss, & maintenance or management; -15- 201032805 Ν-Ζ (I) τχχχ (wherein R1 is a hospital base 'R2 is a hydrogen atom or a substituent, Ζ is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (19) A pharmaceutical composition which is a compound which inhibits or promotes weight loss, or maintains or manages body weight, and which has a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like, and a formula (I) a combination of the indicated compound and its pharmaceutically acceptable salt or its solvate;

(式中，R1爲烷基，R2爲氫原子或烷基，Ζ爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (20)—種含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之肥胖或肥胖相關疾病之預防或治療效果之增強方法，其係包含式（1) 表示之化合物及其製藥上容許之鹽或其等之溶劑合物之投藥步驟； -16- 201032805(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, hydrazine is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (20) A method for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease containing a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which comprises a formula ( 1) a pharmaceutical step of expressing a compound and a pharmaceutically acceptable salt thereof or a solvate thereof; -16- 201032805

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代_ 未被取代之烷基、被取代或未被取代之烯基、被取代或$ 被取代之胺基、被取代或未被取代之烷氧基、被取代或$ 被取代之環狀烴基、或被取代或未被取代之雜環基）。 (21)—種式（I)表示之化合物及其製藥上容許之鹽等之溶劑合物之用途，其係用於製造含有具有營養素消吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶冑H 合物之藥劑之肥胖或肥胖相關疾病之預防或治療效果之g 強劑；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, and Z is a substituted/unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or substituted amino group, A substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (21) The use of a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof, and the like, for use in the manufacture of a compound having a nutrient absorption inhibition effect and a pharmaceutically acceptable salt thereof or a strong agent for preventing or treating the obesity or obesity-related diseases of the agent of the lysate H compound;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (22)—種式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物，其係用於增強含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之肥胖或肥胖相關疾病之預防或治療效果； -17- 0) 201032805(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (22) a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for enhancing a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or The preventive or therapeutic effect of obesity or obesity-related diseases of solvate-like agents; -17- 0) 201032805

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (2 3)—種含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之肥胖或肥胖相關疾病之預防或治療效果之增強方法，其係包含具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之投藥步驟； RVNH、r^ R2 cfb 〇) ο (式中，R1爲烷基，R2爲氫原子或烷基，Ζ爲被取代或 ® 未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未 $取代之環狀烴基、或被取代或未被取代之雜環基）。 (24)—種具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之用途，其係用於製造含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑 &物之藥劑之肥胖或肥胖相關疾病之預防或治療效果之增強劑； -18- 201032805 N-Z (I) ^Hv〇/ ο (式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (25)—種具有營養素消化吸收抑制作用之化合物及其 φ 製藥上容許之鹽或其等之溶劑合物，其係用於增強含有式 (I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之肥胖或肥胖相關疾病之預防或治療效果；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (2 3) A method for enhancing the prophylactic or therapeutic effect of an obesity or obesity-related disease containing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof, which comprises a nutrient a step of administering a compound which inhibits digestion and absorption and a pharmaceutically acceptable salt thereof or a solvate thereof; RVNH, r^ R2 cfb 〇) ο (wherein R1 is an alkyl group, and R2 is a hydrogen atom or an alkyl group, Ζ is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted amino, substituted or unsubstituted alkoxy, substituted or unsubstituted a cyclic hydrocarbon group or a substituted or unsubstituted heterocyclic group). (24) A use of a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for producing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof Or an agent for the prevention or treatment of obesity or obesity-related diseases of a solvent & medicinal agent; -18- 201032805 NZ (I) ^Hv〇/ ο (wherein R1 is an alkyl group and R2 is a hydrogen group Atom or alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, substituted Or an unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (25) a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for enhancing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or The preventive or therapeutic effect of an obesity or obesity-related disease of a solvate thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未 φ 被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 (26) —種如第（1)項記載之醫藥組成物之製造方法，其特徵爲將具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物進行混合；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). (26) A method for producing a pharmaceutical composition according to the item (1), which is characterized in that a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and the like are Mixing the compound represented by I) and its pharmaceutically acceptable salt or its solvate;

-19- 201032805 (式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代被取代之胺基、被取代或未被取代之烷氧基、被取代或$ 被取代之環狀烴基、或被取代或未被取代之雜環基）。 [發明效果] 本發明之醫藥組成物作爲肥胖或肥胖相關疾病之治胃劑或預防劑非常有用。又，該醫藥組成物在肥胖症之體S 康管理上非常有用。馨【實施方式】用以實施發明之形態「具有營養素消化吸收抑制作用之化合物」己知爲預防或治療肥胖之藥劑，如具有糖吸收抑制作用之化合物、具有脂肪吸收抑制作用之化合物等。關於具有糖吸收抑制作用之化合物，可舉例如抑制分解雙糖爲單糖之酵素作用、並控制血液由消化器官吸收葡萄糖之化合物α -葡萄 φ 醣苷酶抑制劑（Acarbose、Voglibose等；日本藥理學雜誌 1 18:340-346(2001) 、 Pharmacology Biochemistry-19- 201032805 (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted substituted amine group , a substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). [Effect of the Invention] The pharmaceutical composition of the present invention is very useful as a gastric or prophylactic agent for obesity or obesity-related diseases. Moreover, the pharmaceutical composition is very useful in the management of obesity. [Embodiment] The present invention is a compound for preventing or treating obesity, such as a compound having a sugar absorption inhibiting action and a compound having a fat absorption inhibiting action. Examples of the compound having a sugar absorption-inhibiting action include a compound α-glucoside glucosidase inhibitor (Acarbose, Voglibose, etc.; Journal 1 18:340-346 (2001), Pharmacology Biochemistry

Behavior 1 9:7 1 -78( 1 9 83))，抑制由腎臟再吸收糖類之化合物 SGLT - 2 抑制劑（Dapagliflozin、Remogliflozin、KGT - 1075 等；Journal of Medicinal Chemistry 52(7):1 7 85 - 1 794(2009)) 等。本申請案之「具有營養素消化吸收抑制作用之化合物」，以達帕弗淨（Dapagliflozin )、利莫弗淨 (Remogliflozin)、具有脂肪吸收抑制作用之.化合物等較 -20- 201032805 佳。「具有脂肪吸收抑制作用之化合物」包含脂肪酶抑制劑（具有胃脂肪酶抑制作用之化合物、具有胰臟脂肪酶抑制作用之化合物等）、膽酸結合樹脂等。「膽酸結合樹脂」包含貴舒醇（Colestyramine)、可利舒散（Colestyramide)等。貴舒醇（Colestyramine)與可利舒散 (C'olestyramide)爲陰離子交換樹脂，在消化器官中與膽酸結 ^ 合以抑制吸收脂肪（Expert Opinion on Investigational Drugs 15:1337-51(2006))。「具有胰臟脂肪酶抑制作用之化合物」包含奧利司他 (Orlistat)、尼泊司他汀（Lipstatin)、潘林西（Panclicin)、新利司他（Cetilistat)等。尼泊司他汀（美國專利第4598089號說明書）爲源自微生物之天然產物，而奧利司他（Or list at)則是將尼泊司他汀氫化者。潘林西是奧利司他（Orlistat)之類似物（Journal of Antibiotics 47(12):1 369- 1 375(1 994)。新利 Ο 司他爲具有與奧利司他（Orlistat)不同化學結構之胰臟脂肪酶抑制劑（Current Opinion in Investigational Drugs 9:414-21 (2008))。「奧利司他（Orlistat)」爲控制或預防肥胖及血脂異常之習知化合物。其化學名爲具（3S，4S) - 3 -己基-4 -[(2S) - 2 -羥基十三基]-2 -氧雜環丁酮之N -甲醯基-L -白胺酸酯。關於奧利司他（Orlistat)之體重增加抑制作用記載於非專利文獻1。Orlistat(奧利司他）之製造方法，藥劑 -21- 201032805 等開示如下。美國專利第4598089號說明書、美國專利第 5246960號說明書、美國專利第4931463號說明書、美國專利第5175186號說明書、美國專利第4983746號說明書、美國專利第5245056號說明書、美國專利第5399720號說明書、國際公開第WO97/032409號、國際公開第WO00/0 9122 號、國際公開第WO00/09 123號、歐洲專利第524495號說明書。「具有營養素消化吸收抑制作用之化合物」除表現營養素之消化吸收抑制作用外，亦表現攝食亢進作用。非專利文獻3記載具有糖吸收抑制作用之達帕弗淨除表現體重增加抑制作用外，亦表現攝食亢進作用。另外，非專利文獻2記載具有脂肪吸收抑制作用之奧利司他（Orlistat)除表現體重增加抑制作用外，亦表現攝食亢進作用》使用於本發明之醫藥組成物之環己烷甲醯胺衍生物爲如下所示之化合物。即以式（I)表示之化合物、其製藥上容 φ 許之鹽或其等之溶劑合物。Behavior 1 9:7 1 -78( 1 9 83)), a SGLT-2 inhibitor that inhibits the reabsorption of carbohydrates by the kidney (Dapagliflozin, Remogliflozin, KGT-1075, etc; Journal of Medicinal Chemistry 52(7): 1 7 85 - 1 794 (2009)) and so on. The "compound having a nutrient absorption and absorption inhibiting action" in the present application is preferably a compound such as Dapagliflozin, Remogliflozin, or a compound having a fat absorption inhibitory effect, -20-201032805. The "compound having a fat absorption inhibiting action" includes a lipase inhibitor (a compound having a gastric lipase inhibiting action, a compound having a pancreatic lipase inhibiting action, etc.), a cholic acid binding resin, and the like. The "cholate-binding resin" includes Colestyramine, Colestyramide, and the like. Colestyramine and C'olestyramide are anion exchange resins that bind to bile acids in the digestive organs to inhibit absorption of fat (Expert Opinion on Investigational Drugs 15:1337-51 (2006)) . "Compound having pancreatic lipase inhibition" includes Orlistat, Lipstatin, Panclicin, Cetilistat, and the like. Nibastatin (U.S. Patent No. 4,598,089) is a natural product derived from microorganisms, and Orlistat is a hydrogenated linorestatin. Panlinsi is an analogue of Orlistat (Journal of Antibiotics 47(12): 1 369-1 375 (1 994). The new lysine has a different chemical structure than Orlistat. "Current Opinion in Investigational Drugs 9: 414-21 (2008)." Orlistat is a traditional compound that controls or prevents obesity and dyslipidemia. 3S,4S) - 3 -Hexyl-4 -[(2S)-2-hydroxytridecyl]-2-oxobutanone N-methylindenyl-L-leucine. About Orlistat The weight-inhibiting action of (Orlistat) is described in Non-Patent Document 1. Orlistat (Orlistat) manufacturing method, Pharmacy-21-201032805, etc., as described below, U.S. Patent No. 4,598,089, U.S. Patent No. 5,246,960, Patent No. 4,931,463, U.S. Patent No. 5,175, 186, U.S. Patent No. 4,983,746, U.S. Patent No. 5,245, 056, U.S. Patent No. 5,399, 720, International Publication No. WO97/032409, International Publication No. WO 00/0 9122 , International Publication No. WO00/09 No. 123, European Patent No. 524495. "Compound having a nutrient absorption and absorption inhibiting effect" exhibits a hyperpigmentation action in addition to the digestion and absorption inhibiting action of nutrients. Non-Patent Document 3 describes Dapaver having a sugar absorption inhibiting action. In addition to the effect of suppressing the increase in body weight, it also exhibits hypersensitivity. In addition, Non-Patent Document 2 describes that Orlistat, which has a fat absorption-inhibiting effect, exhibits hypersensitivity in addition to the effect of suppressing body weight gain. The cyclohexanecarbamamine derivative of the pharmaceutical composition of the present invention is a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof.

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或$ 被取代之環狀烴基、或被取代或未被取代之雜環基）。厂烷基」爲碳數1〜10之直鏈狀或支鏈狀烷基。包t -22- 201032805 碳數1〜6之烷基、碳數1〜4之院基、碳數1〜3之烷基等。如甲基、乙基、正丙基、異丙基、正丁基、異丁基、二級丁基、三級丁基、正戊基、異戊基、新戊基、己基、異己基、正庚基、異庚基、正辛基、異辛基、正壬基、正癸基等。R1以異丙基或三級丁基特佳。「烷基」之取代基，如 (1)鹵素； ^ (2)氰基； © (3)可被1個以上選自如下述所定義之取代基群/5中之可取代基所取代（i)羥基、（ii)烷氧基、（iii)硫醇基、（iv)烷硫基、（v)醯基、（vi)醯氧基、（vii)羧基、（viii)烷氧羰基、 (ix)亞胺基、（X)胺甲醯基、UO硫胺甲醯基、烷胺甲醯基、（xiii)烷硫胺甲醯基、（xiv)胺基、（xv)烷胺基、或（xvi) 雜環羰基等。取代基群Θ爲由鹵素，可被保護之羥基、硫醇基、院〇氧基、烯基、胺基、烷胺基、烷氧羰胺基、烷硫基、醯基、羧基、烷氧羰基、胺甲醯基、氰基、環烷基、苯基、苯氧基、烷苯基、烷氧苯基、鹵化苯基、萘基、及雜環基所構成。「烯基」爲在任意位置具有1個以上雙鍵結之碳數2 〜10之直鏈狀或支鏈狀烯基。包含碳數2〜8之烯基、碳數 3〜6之烯基。如乙烯基、丙烯基、異丙烯基、丁烯基、異丁烯基、異戊烯基（prenyl)、丁二烯基、戊烯基、異戊烯基、 -23- 201032805 戊二烯基、己烯基、異己烯基、己二烯基、庚烯基、辛烯基、壬烯基、癸烯基等。「烯基」之取代基，如由鹵素、烷氧基、烯基、胺基、烷胺基、烷氧羰胺基、烷硫基、醯基、羧基、烷氧羰基、胺甲醯基、氰基、環烷基、苯基、烷苯基、烷氧苯基、萘基、及雜環基選取1個以上之取代基等。「烷氧基」爲上述「烷基」與氧原子鍵結之基。具體例如甲氧基、乙氧基、正丙氧基、異丙氧基、正丁氧基、異丁氧基、二級丁氧基、三級丁氧基、正戊氧基、異戊氧基、新戊氧基、己氧基、異己氧基、正庚氧基、異庚氧基、正辛氧基、異辛氧基等。「烷氧基」之取代基如由上述取代基群；S選取之1個以上之取代基，並以苯基、烷苯基、烷氧苯基、萘基、及雜環基較佳。「院硫基」' 「院胺甲酿基」、「院胺硫甲醯基」、參「院胺基J 、「院亞磺酿基」、「焼磺醯基」、「院胺擴醯基」、「羥院基」、「烷苯基」、「烷氧烷基」、「齒化烷基」、或「苯烷硫基」之烷基部分與上述「焼基」相同。「烷氧羰基」、「烷氧烷基」、「烷氧羰胺基」、「院氧苯基」、或「苯烷氧基」之烷基部分與上述「燒基」相同。「胺基」之取代基如由上述取代基群Θ、取代或未取 -24- 201032805 代之苯醯基、或取代或未取代之雜環羰基（在此取代基爲選自羥基、烷基、烷氧基、烷硫基之1個以上之取代基）選取之1個以上之取代基。「環烴基」包含「環烷基」、「環烯基」、「雙環烷基」、及「芳基」。「環烷基」爲碳數3〜8之環狀烷基。包含5或6環狀之烷基。如環丙基、環丁基、環戊基、環己基、環庚基、 _ 及環辛基等。「環烯基」爲上述環烷基之環中任意位置具有1個以上雙鍵結者。如環丙烯基、環丁烯基、環戊烯基、環己烯基、環己二烯基等。「雙環烷基」爲2個環共有2個或以上原子之碳數5 〜8之脂肪族環去除1個氫所形成之基。具體如雙環[2.1〇] 戊基、雙環[2.2.1]庚基、雙環[2.2.2]辛基、及雙環[3.2.1] 辛基等。 Ο 「芳基」爲單環或多環之芳香族碳環基。包含苯基、萘基、蒽基、菲基等。又，亦包含與其他非芳香族碳環基縮合之芳基。如二氫節基、節基、聯苯基、危基、四氫葶基及莽基等。其中以苯基特佳。「環烴基」之取代基如由取代基群^及上述取代基群点選取之1個以上之取代基等，環中任意位置均可被取代。取代基群α爲由： U)鹵素； -25- 201032805 (2) 側氧基； (3) 氰基； (4) 硝基； (5) 可被烷基或羥基取代之亞胺基； (6) 可被分別由取代基群0中選取之1個以上可取代基取代之（i)羥基、（ii)烷基、（iii)烯基、（iv)烷氧基、（v)羧基、 (vi)烷氧羰基、（vii)醯基、（viii)醯氫基、（ix)亞胺基、（X) 硫醇基、（xi)烷硫基、（xii)胺甲醯基、（xiii)烷胺甲醯基、（xiv) 環烷胺甲醯基、（XV)胺硫甲醯基、（xvi)烷胺甲醯基、（xvii) 烷亞磺醯基、（xviii)烷磺醯基、（xix)胺磺醯基、（XX)烷胺磺醯基、及（xxi)環烷胺磺醯基等； (7) 可被分別選自取代基群A、烷基、烷氧烷基、可被保護之羥烷基、鹵化烷基、烷磺醯基、及芳烷磺醯基之1 個以上取代基取代之⑴環烷基、（ii)環烯基、（iii)環烷氧基、（iv)胺基、及（v)伸烷二氧基；及 # (8)可被分別選自取代基群/3、烷基、鹵化烷基、及側氧基之1個以上取代基取代之⑴苯基、（ii)萘基、（iii)苯氧基、（iv)苯烷氧基、（v)苯硫基、（vi)苯烷硫基、（vii)苯偶氮基、（viii)雜環基、（ix)雜環氧基、（x)雜環硫基、（Xi)雜環羰基、及（xii)雜環磺醯基所構成之群。「環烷羰基」、「環烷胺磺醯基」、「環烷氧基」之環烷基部分與上述「環烷基」相同。「芳磺醯基」之芳基部分與上述「芳基」相同。 -26- 201032805 「雜環基」爲由環中具有1個以上任由〇、S及N選擇之雜原子之雜環所衍生之基。如4〜8員環（以5〜7員環較佳）或2〜3個此等環縮合之環，且至少其中1個環爲由環中具有1〜3個任由〇、s及N選擇之雜原子之環所衍生之基。如多個環縮合時在任一環可具有鍵。具體例如包含吡咯基、咪唑基、吡唑基、吡啶基、嗒阱基 (pyridazinyl)、嘧啶基、吡阱基（Pyrazinyl)、***基、三畊基、 φ 四唑基、異噚唑基、噚唑基、噚二唑基、異噻唑基、噻唑基、噻二唑基、呋喃基、噻吩基、吲哚基、異吲哚基、吲唑基、吲哚畊基（indolizinyl)、吲哚啉基、異吲哚啉基、喹啉基、異喹琳基、碎啉基（cinnolinyl)、吹哄基（phthalazinyl)、喹哩琳基、萘啶基、喹曙啉基、嘌呤基、喋啶基、苯并哌喃基、苯并咪唑基、苯并異噚唑基、苯并噚唑基、苯并噚二唑基、苯并異噻唑基、苯并噻唑基、苯并噻二唑基、苯并呋喃基、異苯并呋喃基、〇苯并噻吩基、苯并***基、咪唑吡啶基、***吡啶基、咪唑噻唑基、吡阱嗒哄基、唾唑啉基、萘啶基、四氫喹啉基、四氫苯并噻吩基、味哩基、AT陡基、卩ll|_基（xanthenyl)、菲噻哄基 (phenothiazinyl)、菲曙噻基（phenoxathiinyl)、菲哄基 (phenoxazinyl)'二苯并呋喃基、二噚烷基（dioxanyl)、硫化二嫌基（thiiranyl)、環氧乙院基（oxiranyl)、噻崠基（oxathiolanyl)、 ΰί 丁陡基（azetidinyl)、硫她基（thianyl)、妣略陡基、卩比略啉基、咪唑啶基、咪唑啉基、吡唑啶基、吡唑啉基、哌啶基、哌畊基 -27- 201032805 (piprazinyl)、味啉基（morpholinyl)、N -味啉基（morpholino)、味啉硫基、N -味啉硫基、二氫吡啶基、四氫呋喃基、四氫哌喃基、四氫噻唑基、四氫異噻唑基等。其中，以咪唑基、苯并噻唑基、異噻唑基、苯并哌喃基、N -味啉基、吡啶基、喹啉基、及嘧啶基等特佳。「雜環基」之取代基可例示如與上述「環烴基」被取代時相同之取代基。「雜環氧基」、「雜環硫基」、「雜環羰基」、及「雜 w 環磺醯基」之雜環基部分與上述「雜環基」相同。「醯基」包含以下各基。 (1) 碳數1〜10、並以碳數1〜6較佳、碳數1〜4更佳之直鏈狀或支鏈狀烷羰基或烯羰基。 (2) 碳數4〜9、並以碳數4〜7較佳之環烷羰基。 (3) 碳數7〜11之芳羰基。如甲醯基、乙醯基、丙醯基、丁醯基、異丁醯基、戊 φ 醯基、三甲基乙醯基、己醯基、丙烯醯基、丙炔醯基、甲基丙烯醯基、巴豆醯基（crotonoyl)、環丙羰基、環己羰基、環辛羰基、及苯（甲）醯基等。「醯氧基」之醯基部分亦與上述相同。「可被保護之羥基」、「可被保護之羥烷基」之保護基包含通常使用之所有羥基保護基。如醯基（乙醯基、三氯乙醯基、苯（甲）醯基等），烷氧羰基（三級丁氧羰基等），烷磺醯基（甲磺醯基等），烷氧烷基（甲氧甲基等），三烷矽基（三 -28- 201032805 級丁二甲基矽基等）等。「鹵素」包含氟、氯、溴、及碘。以氟及氯特佳。「鹵化苯基」及「鹵化烷基」之鹵素部分與上述「鹵素」相同。「伸烷基」爲連接1〜6個亞甲基之2價之基。包含連接2〜6個亞甲基之2價之基、連接3〜6個亞甲基之2價之基。如亞甲基、伸乙基、三亞甲基、四亞甲基、五亞甲基、及六亞甲基等。其中以四亞甲基特佳。參「伸烷二氧基」之伸烷基部分與上述「伸烷基」相同，並以亞甲二氧基、伸乙二氧基較佳。式（I)表示之化合物具有不對稱碳原子時，包含外消旋體及所有立體異構物（非鏡像異構物、鏡像異構物等）。又，式（I)表示之化合物具有1個以上雙鍵，且雙鍵之取代基組態（configuration)存在幾何異構物時，包含所有幾何異構物 (即順式（Z)及反式（E))。 φ 「製藥上容許之鹽」可舉例如鹽酸、硫酸、硝酸或磷酸等無機酸之鹽；對甲苯磺酸、甲磺酸、草酸或檸檬酸等有機酸之鹽；銨、三甲基銨、三乙基銨等有機鹼之鹽；鈉或鉀等鹼金屬鹽；及鈣或鎂等鹼土金屬鹽等。「溶劑合物」如化合物或其鹽之水合物、醇合物等。如1水合物、2水合物、1醇合物、2醇合物等。本發明之醫藥組成物含有之化合物之前藥（prodrug)包含於本發明之醫藥組成物含有之化合物之範圍。本發明之 -29- 201032805 醫藥組成物含有之化合物之前藥爲本發明之醫藥組成物含有之化合物之功能性衍生物，在生體中容易轉換成本發明之醫藥組成物含有之化合物。因此，本發明之醫藥組成物含有之「化合物」，係以本發明之醫藥組成物之要素具體開示之化合物、或視情況而未具體開示之化合物，但包含投給肥胖及肥胖相關疾病患者後在活體中轉換成上述具體化合物之化合物。前藥衍生物之適當選擇及通常之製劑程序，如記載於 Design of Prodrugs(ed.H.Bundgaard, Elsevier, 1985) 〇使用於本發明之醫藥組成物之式（I)表示之化合物，尤以下列化合物、其製藥上容許之鹽、或其溶劑合物等爲較佳。 *(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). The alkyl group is a linear or branched alkyl group having 1 to 10 carbon atoms. Package t -22- 201032805 Alkyl group having 1 to 6 carbon atoms, a group having a carbon number of 1 to 4, an alkyl group having 1 to 3 carbon atoms, and the like. Such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, secondary butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, isohexyl, N-heptyl, isoheptyl, n-octyl, isooctyl, n-decyl, n-decyl and the like. R1 is preferably isopropyl or tertiary butyl. a substituent of "alkyl" such as (1) halogen; ^(2) cyano; © (3) may be substituted by one or more substituents selected from the group of substituents/5 as defined below ( i) a hydroxyl group, (ii) an alkoxy group, (iii) a thiol group, (iv) an alkylthio group, (v) a mercapto group, (vi) a decyloxy group, a (vii) carboxyl group, a (viii) alkoxycarbonyl group, (ix) imine group, (X) amine carbenyl group, UO thiamine carbenyl group, alkylamine carbenyl group, (xiii) alkylthiocarbamyl group, (xiv) amine group, (xv) alkylamino group Or (xvi) a heterocyclic carbonyl group or the like. The substituent group Θ is a halogen, a protected hydroxyl group, a thiol group, a decyloxy group, an alkenyl group, an amine group, an alkylamino group, an alkoxycarbonylamino group, an alkylthio group, a decyl group, a carboxyl group, an alkoxy group. A carbonyl group, an amine carbenyl group, a cyano group, a cycloalkyl group, a phenyl group, a phenoxy group, an alkylphenyl group, an alkoxyphenyl group, a halogenated phenyl group, a naphthyl group, and a heterocyclic group. The "alkenyl group" is a linear or branched alkenyl group having 2 or more carbon atoms having one or more double bonds at any position. It contains an alkenyl group having 2 to 8 carbon atoms and an alkenyl group having 3 to 6 carbon atoms. Such as vinyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, -23- 201032805 pentadienyl, Alkenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl and the like. a substituent of "alkenyl" such as halogen, alkoxy, alkenyl, amino, alkylamino, alkoxycarbonyl, alkylthio, decyl, carboxy, alkoxycarbonyl, amidyl, One or more substituents such as a cyano group, a cycloalkyl group, a phenyl group, an alkylphenyl group, an alkoxyphenyl group, a naphthyl group, and a heterocyclic group are used. The "alkoxy group" is a group in which the above "alkyl group" is bonded to an oxygen atom. Specifically, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, di-butoxy, tert-butoxy, n-pentyloxy, isopentyloxy Base, neopentyloxy, hexyloxy, isohexyloxy, n-heptyloxy, isoheptyloxy, n-octyloxy, isooctyloxy and the like. The substituent of the "alkoxy group" is preferably one or more substituents selected from the group consisting of the above substituent groups; and a phenyl group, an alkylphenyl group, an alkoxyphenyl group, a naphthyl group, and a heterocyclic group. "Honey Sulphur", "Honey Alkyl", "Professional Acetone", "Amiline J", "Ya Sulfogen", "Sulphuric Acid", "Amine Dilatation" The alkyl group of the "base", "hydroxyl group", "alkylphenyl", "alkoxyalkyl", "dentated alkyl" or "phenylthio" is the same as the above "thiol". The alkyl moiety of "alkoxycarbonyl", "alkoxyalkyl", "alkoxycarbonylamino", "homoyloxyphenyl" or "phenylalkoxy" is the same as the above "alkyl group". The substituent of the "amino group" is, for example, substituted or unsubstituted from the above substituent group, a benzoinyl group of the substituent -24-32,830,805 or a substituted or unsubstituted heterocyclic carbonyl group (wherein the substituent is selected from a hydroxyl group, an alkyl group) One or more substituents selected from one or more substituents of an alkoxy group or an alkylthio group. The "cycloalkyl group" includes "cycloalkyl group", "cycloalkenyl group", "bicycloalkyl group", and "aryl group". The "cycloalkyl group" is a cyclic alkyl group having 3 to 8 carbon atoms. Contains a 5 or 6 cyclic alkyl group. Such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, _ and cyclooctyl and the like. The "cycloalkenyl group" has one or more double bonds at any position in the ring of the above cycloalkyl group. For example, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cyclohexadienyl group or the like. The "bicycloalkyl group" is a group formed by removing one hydrogen from an aliphatic ring having 5 or more carbon atoms of two or more atoms in two rings. Specifically, it is a bicyclo[2.1〇]pentyl group, a bicyclo[2.2.1]heptyl group, a bicyclo[2.2.2]octyl group, and a bicyclo[3.2.1]octyl group. 「 "Aryl" is a monocyclic or polycyclic aromatic carbocyclic group. Containing phenyl, naphthyl, anthracenyl, phenanthryl and the like. Further, it also contains an aryl group which is condensed with other non-aromatic carbocyclic groups. Such as dihydrogenation, nodal, biphenyl, dangerous, tetrahydroindenyl and fluorenyl. Among them, phenyl is preferred. The substituent of the "cycloalkyl group" may be substituted at any position in the ring, such as one or more substituents selected from the group of substituents and the above group of substituents. The substituent group α is composed of: U) halogen; -25- 201032805 (2) pendant oxy group; (3) cyano group; (4) nitro group; (5) imine group which may be substituted by alkyl group or hydroxy group; 6) (i) a hydroxyl group, (ii) an alkyl group, (iii) an alkenyl group, (iv) an alkoxy group, a (v) carboxyl group, which may be substituted by one or more substituents selected from the substituent group 0, respectively. (vi) alkoxycarbonyl, (vii) mercapto, (viii) anthracenyl, (ix) imine, (X) thiol, (xi)alkylthio, (xii)aminecarboxamide, ( Xiii) alkylamine methyl sulfhydryl, (xiv) cycloalkylamine methyl sulfhydryl, (XV) amine thiomethionyl, (xvi) alkylamine methyl sulfhydryl, (xvii) alkylsulfinyl, (xviii) alkane Sulfhydryl, (xix) sulfonyl, (XX) alkylamine sulfonyl, and (xxi) cycloalkylamine sulfonyl, etc.; (7) may be selected from the group consisting of substituent A, alkyl, alkoxy (1) cycloalkyl, (ii) cycloalkenyl, (iii) ring substituted with one or more substituents of an alkyl group, a protected hydroxyalkyl group, a halogenated alkyl group, an alkanesulfonyl group, and an aralkyl sulfonyl group An alkoxy group, (iv) an amine group, and (v) an alkylenedioxy group; and #(8) may be selected from a substituent group /3, an alkyl group, an alkyl halide group, respectively. And (1) phenyl, (ii) naphthyl, (iii) phenoxy, (iv) phenylalkoxy, (v) phenylthio, (vi) phenyl sulfide, substituted with one or more substituents of a pendant oxy group a group, (vii) phenyl azo group, (viii) heterocyclic group, (ix) heterocyclic oxy group, (x) heterocyclic thio group, (Xi) heterocyclic carbonyl group, and (xii) heterocyclic sulfonyl group The group of constituents. The cycloalkyl moiety of "cycloalkylcarbonyl", "cycloalkanolsulfonyl" and "cycloalkoxy" is the same as the above "cycloalkyl". The aryl moiety of "arylsulfonyl" is the same as the above "aryl". -26- 201032805 "Heterocyclyl" is a group derived from a heterocyclic ring having one or more hetero atoms selected from hydrazine, S and N in the ring. For example, a 4 to 8 member ring (preferably a 5 to 7 member ring) or 2 to 3 rings with such ring condensation, and at least one of the rings has 1 to 3 rings, s, and N in the ring. The base derived from the ring of the hetero atom is selected. For example, when a plurality of rings are condensed, they may have a bond in either ring. Specifically, for example, it includes a pyrrolyl group, an imidazolyl group, a pyrazolyl group, a pyridyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a triazolyl group, a tritonyl group, a φ tetrazolyl group, an isoxazolyl group. , carbazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, furyl, thienyl, fluorenyl, isodecyl, oxazolyl, indolizinyl, anthraquinone Porphyrin group, isoindolyl group, quinolyl group, isoquinolinyl group, cinnolinyl group, phthalazinyl group, quinalinyl group, naphthyridinyl group, quinoxalinyl group, fluorenyl group, Acridinyl, benzopipetanyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiazide Azolyl, benzofuranyl, isobenzofuranyl, fluorenyl benzothiophenyl, benzotriazolyl, imidazolidinyl, triazole pyridyl, imidazothiazolyl, pyridinyl, oxazolinyl, Naphthyridinyl, tetrahydroquinolyl, tetrahydrobenzothiophenyl, miso, AT steep, xanthenyl, phenothiazinyl, phenanthrene Phenoxathiinyl, phenoxazinyl 'dibenzofuranyl, dioxanyl, thiiranyl, oxiranyl, oxathiolanyl, Ϋ́ί azetidinyl, thianyl, 陡陡 steep, 卩pyrrolidino, imidazolidinyl, imidazolinyl, pyrazolyl, pyrazolinyl, piperidinyl, piperene基-27- 201032805 (piprazinyl), morpholinyl, morpholino, tyrosine thio, N-tyrosylthio, dihydropyridyl, tetrahydrofuranyl, tetrahydropyranyl , tetrahydrothiazolyl, tetrahydroisothiazolyl and the like. Among them, an imidazole group, a benzothiazolyl group, an isothiazolyl group, a benzopiperidyl group, an N-morpholinyl group, a pyridyl group, a quinolyl group, and a pyrimidinyl group are particularly preferable. The substituent of the "heterocyclic group" is exemplified by the same substituent as when the above "cycloalkyl group" is substituted. The heterocyclic group moiety of "heterocyclic oxy group", "heterocyclic thio group", "heterocyclic carbonyl group", and "hetero-cyclosulfonyl group" is the same as the above "heterocyclic group". "Base" includes the following bases. (1) A linear or branched alkylcarbonyl group or an olefinic carbonyl group having 1 to 10 carbon atoms and preferably 1 to 6 carbon atoms and more preferably 1 to 4 carbon atoms. (2) A cycloalkylcarbonyl group having 4 to 9 carbon atoms and preferably 4 to 7 carbon atoms. (3) An aromatic carbonyl group having 7 to 11 carbon atoms. Such as formazan, ethyl, propyl, butyl, isobutyl, pentanyl, trimethylethyl, hexyl, propylene, propynyl, methacryl, croton Crotonoyl, cyclopropylcarbonyl, cyclohexylcarbonyl, cyclooctylcarbonyl, and phenyl(methyl)fluorenyl. The thiol moiety of "oxyl group" is also the same as above. The protecting group of "protectable hydroxyl group" and "protectable hydroxyalkyl group" includes all the hydroxy protecting groups which are usually used. Such as fluorenyl (ethenyl, trichloroethyl, phenyl (methyl) fluorenyl, etc.), alkoxycarbonyl (tertiary butoxycarbonyl, etc.), alkanesulfonyl (methanesulfonyl, etc.), alkoxylated A group (methoxymethyl group, etc.), a trialkyl fluorenyl group (three-28-201032805 grade butylated dimethyl fluorenyl group, etc.). "Halogen" contains fluorine, chlorine, bromine, and iodine. Fluorine and chlorine are preferred. The halogen moiety of "halogenated phenyl" and "halogenated alkyl" is the same as the above "halogen". "Alkyl" is a divalent group connecting 1 to 6 methylene groups. It comprises a divalent group connecting 2 to 6 methylene groups and a divalent group connecting 3 to 6 methylene groups. Such as methylene, ethyl, trimethylene, tetramethylene, pentamethylene, and hexamethylene. Among them, tetramethylene is especially good. The alkylene moiety of the "alkylene dioxyl group" is the same as the above "alkylene group", and is preferably a methylenedioxy group or an ethylenedioxy group. When the compound represented by the formula (I) has an asymmetric carbon atom, it contains a racemate and all stereoisomers (non-image isomers, mirror image isomers, etc.). Further, the compound represented by the formula (I) has one or more double bonds, and when the substituent configuration of the double bond is present in the geometric isomer, all geometric isomers (ie, cis (Z) and trans are included. (E)). φ "Pharmaceutically acceptable salt" may, for example, be a salt of an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid; a salt of an organic acid such as p-toluenesulfonic acid, methanesulfonic acid, oxalic acid or citric acid; ammonium or trimethylammonium; a salt of an organic base such as triethylammonium; an alkali metal salt such as sodium or potassium; and an alkaline earth metal salt such as calcium or magnesium. The "solvate" is a hydrate, an alcoholate or the like of a compound or a salt thereof. For example, 1 hydrate, 2 hydrate, 1 alcoholate, 2 alcoholate, and the like. The prodrug of the compound contained in the pharmaceutical composition of the present invention is included in the range of the compound contained in the pharmaceutical composition of the present invention. -29-201032805 The present invention contains a compound which is a functional derivative of a compound contained in the pharmaceutical composition of the present invention, and is easily converted into a compound contained in the pharmaceutical composition of the invention in a living body. Therefore, the "compound" contained in the pharmaceutical composition of the present invention is a compound specifically expressed by the elements of the pharmaceutical composition of the present invention, or a compound not specifically disclosed, but includes a patient who is administered to an obesity or obesity-related disease. A compound that is converted into a specific compound as described above in a living body. Suitable selection of prodrug derivatives and usual formulation procedures are as described in Design of Prodrugs (ed. H. Bundgaard, Elsevier, 1985), compounds of formula (I) used in the pharmaceutical compositions of the invention, especially The column compound, a pharmaceutically acceptable salt thereof, or a solvate thereof and the like are preferred. *

-30- 201032805-30- 201032805

或 ΟOr Ο

|-Me s /XXr 知。f，UOMe 〜 V，’Oc:切。〜|-Me s /XXr Know. f, UOMe ~ V, 'Oc: cut. ~

又，下列化合物爲更佳。 AOftXCF3 (b)Also, the following compounds are more preferred. AOftXCF3 (b)

式（I)表示之化合物之體重增加抑制作用記載於非專利文獻6。又’專利文獻5記載式（I)表示之化合物不僅表現體重增加抑制作用，亦表現攝食抑制作用。上述使用於本發明之醫藥組成物之式⑴表示之化合 201032805 物，可依國際公開 WO0 1 /37826號、WO2003/076374號、 W02006/001318號、特開2005 — 255630號所記載之方法進行調製。具體而言，可舉例如下述之方法。The weight-inhibiting action of the compound represented by the formula (I) is described in Non-Patent Document 6. Further, Patent Document 5 discloses that the compound represented by the formula (I) exhibits not only an effect of suppressing body weight gain but also an action of suppressing food intake. The compound of the formula (1) used in the above-mentioned pharmaceutical composition of the present invention, which is represented by the formula (1), can be prepared according to the method described in WO01/37826, WO2003/076374, WO2006/001318, and JP-A-2005-255630. . Specifically, for example, the following method can be mentioned.

❹ (式中，Hal爲鹵素，其他記號如同前述定義）❹ (where Hal is halogen, other marks are as defined above)

步驟A 在適當溶劑中並視須要於鹼存在下，將化合物（IV)與具有與目標化合物對應之取代基R1之化合物（V)進行反應得化合物（II)。溶劑如四氫呋喃、二甲基甲醯胺、二乙基醚、二氯甲烷、甲苯、苯、二甲苯、環己烷、己烷、氯仿、醋酸乙酯、醋酸丁酯、戊烷、庚烷、二噚烷、丙酮、乙腈、水及其等 ® 之混合溶劑等。其中以二噚烷、二氯甲烷較佳。至於鹼，如氫氧化鈉、氫氧化鉀、氫氧化鋰等。反應溫度爲約〇°C〜50°C，並以約20°C〜30°C較佳。反應時間爲約5分鐘〜30小時，並以約5〜20小時較佳。化合物（IV)及（V)可使用習知化合物，亦可使用依常法由習知之化合物合成之化合物。Step A The compound (IV) is reacted with a compound (V) having a substituent R1 corresponding to the target compound in a suitable solvent and in the presence of a base to obtain a compound (II). Solvents such as tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, A mixed solvent of dioxane, acetone, acetonitrile, water, and the like. Among them, dioxane and dichloromethane are preferred. As for the base, such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like. The reaction temperature is about 〇 ° C to 50 ° C and is preferably from about 20 ° C to 30 ° C. The reaction time is from about 5 minutes to 30 hours, and preferably from about 5 to 20 hours. As the compound (IV) and (V), a conventional compound can be used, and a compound synthesized from a conventional compound by a usual method can also be used.

步驟B -32- 201032805 在適當溶劑中，將化合物（II)與具有與目標化合物對應之取代基Z及R2之化合物（ΙΠ)進行反應。溶劑如四氫呋喃、二甲基甲醯胺、二乙基醚、二氯甲烷、甲苯、苯、二甲苯、環己烷、己烷、氯仿、醋酸乙酯、醋酸丁酯、戊烷、庚烷、二噚烷、丙酮、乙腈、水及其等之混合溶劑等。其中以二甲基甲醯胺、四氫呋喃、醋酸乙酯較佳。如有需要，可在3-二（環己亞胺）甲烷（又二環己碳二亞胺）、1 -乙基-3 - (3 -二甲胺基）碳二亞胺（WSCD ;水溶性碳二亞胺）等縮合劑及/或1 -羥基苯并***、3,4 -二氫-3 -羥基-4 -側氧基-1，2,3 -苯并三阱等酸性添加劑存在下進行反應即可。反應溫度爲約0°C〜50°C，並以約20°C〜30°C較佳》反應時間爲約5分鐘〜30小時，並以約5〜20小時較佳。 φ 如有需要，在反應之適當階段將化合物之胺基依常法進行保護亦可。保護基可使用酞醯亞胺、烷氧羰基、烯氧羰基、鹵化烷氧羰基、芳烷氧羰基、三烷矽基、烷磺醯基、鹵化烷磺醯基、芳磺醯基、烷羰基、芳羰基等。保護後在上述各步驟進行反應，並在適當階段及適當溶劑中，以酸或鹼處理去保護即可。溶劑可使用四氫呋喃、二甲基甲醯胺、二乙基醚、二氯甲烷、甲苯、苯、二甲苯、環己烷、己烷、氯仿、醋酸乙酯、醋酸丁酯、戊烷、庚烷、 -33- 201032805 二噚烷、丙酮、乙腈、水及其等之混合溶劑等，鹼如肼、吡啶、氫氧化鈉、氫氧化鉀等，酸如鹽酸、三氟乙酸、氟化氫酸等。本發明之醫藥組成物有用於預防或治療肥胖及肥胖相關疾病患者等，及伴隨攝取食物過多與運動不足而體內蓄積過多脂肪之疾病患者。「肥胖」定義爲蓄積過多脂肪組織之狀態，但目前尙無正確、簡便且實用之體脂肪量測定方法，而使用由身高與體重求得之指標，即身體質量指數（BMI)。BMI之定義爲體重（公斤）除以身高（公尺）之平方之値（kg/m2)表示。依世界衛生組織及美國國立衛生硏究所之定義，BMI爲25kg/m2 以上之患者判定爲體重過重，30kg/m2以上之患者判定爲肥胖。但於東方人，如與白人比較時，在較低之身體質量指數（BMI)即增加肥胖相關疾病之又發病。例如於日本，即便 ' φ BMI爲約25kg/m2，肥胖相關疾病之糖尿病或血脂異常等發病1種以上之患者甚多。因此，日本肥胖學會定義BMI爲 25kg/n^以上爲肥胖。須要醫學介入之肥胖患者，有BMI爲30kg/m2以上且發生肥胖相關疾病者，有BMI爲30kg/m2以上但未發生肥胖相關疾病者，或有BMI爲25kg/m2以上及/或內臟脂肪面積（VFA)爲100cm2以上並至少發生2種肥胖相關疾病者等。肥胖相關疾病如高血壓、葡萄糖耐性異常、糖尿病、 -34- 201032805 脂肪代謝異常、血脂異常、高尿酸血症、痛風、脂肪肝、冠狀動脈疾病、腦梗塞等。本案說明書中之「肥胖」（肥胖症）包括各種原因引起之肥胖，包含遺傳性或環境性之原因。「肥胖相關疾病」爲伴隨肥胖、或因肥胖引起、或肥胖之結果引起之疾病。肥胖相關疾病例如貪食症 (Addephagia)、高血壓、葡萄糖耐性異常、糖尿病、新陳代謝症候群、脂肪代謝異常、動脈硬化、高尿酸血症、痛風、脂肪肝、子宮內膜癌、乳癌、攝護腺癌、大腸癌、變形性關節症、腰痛、阻塞型睡眠呼吸中止症候群、冠狀動脈疾病（冠狀動脈性心臟病）、腦梗塞、月經異常、普瑞德威利氏症候群、弗勒利希氏症候群、匹克威特氏症候群等。本發明之醫藥組成物有用於減輕左心室肥大之危險及肥胖之次級結果之危險。又，本發明之醫藥組成物亦有用於阿茲海默症之治療。 0 「新陳代謝症候群」在「有關成人血液中高膽固醇之檢測、評估、治療之全國膽固醇教育計劃專家討論會」之第3次報告書（ATP— III)中定義（參照E.S.Ford等、JAMA， vol.287(3), P5 3 6-3 59、2002 年 1 月 16 曰）。簡言之，在腹部肥胖、血中三酸甘油酯過高、低HDL膽固醇、高血壓、空腹血糖高等中具有3種以上症狀者即定義爲新陳代謝症候群。「糖尿病」包含胰島素依賴性糖尿病（IDDM、第一型 -35- 201032805 糖尿病）與非胰島素依賴性糖尿病（NIDDM、之雙方。第一型糖尿病因絕對性缺乏胰島霁素是調節葡萄糖利用之激素。第二型糖尿病對胰島素不能適切反應而引起，即使胰島葬上升時亦發生。第二型糖尿病患者多屬肥辟藥組成物有用於第一型糖尿病及第二型糖療。本發明之醫藥組成物對於第二型糖尿病效。本發明之醫藥組成物亦有用於妊娠性糖或預防。肥胖及肥胖相關疾病之「治療」，表肥胖患者之體重而投給本發明之醫藥組成個結果爲與即將開始投給本發明之醫藥組者之體重比較時，該患者之體重可能減少。個結果爲能夠預防經先前之食物療法、運動果減少之體重不再增加。治療之其他結果爲 φ 相關疾病之發病及/或嚴重度。治療之其他鞋減少之體重或管理體重。依據治療，能夠通物或熱量之攝取（包含減少食物總攝取量或物、脂肪等特定食物之攝取），阻止吸收營i 下降’須要減少體重患者之體重抑制或體重治療’非因抑制代謝率下降或其追加性抑帯I 升導致代謝率之改變及/或因體重減少而常亦能夠限制於最小範圍。第二型糖尿病）而引起，胰島則因身體組織 :之分泌正常或 :。本發明之醫尿病雙方之治 :之治療特別有尿病之治療及/ :爲減少或維持丨。該治療之一 :物前之肥胖患該治療之另一〖或藥物療法結丨能夠減低肥胖 ί果爲能夠維持【當減少患者食減少碳水化合 i，抑制代謝率【管理等。依據 1 ’如代謝率上導致之抗代謝 -36- 201032805 肥胖及肥胖相關疾病之「預防」，表示爲減少或維持具有肥胖危險患者之體重而投給本發明之醫藥組成物。該預防之一個結果爲與即將開始投給本發明之醫藥組成物前之具有肥胖危險患者之體重比較時，該被測驗者之體重可能減少。該預防之另一個結果爲能夠預防經先前之食物療法、運動或藥物療法結果減少之體重不再增加（即能夠體重管理）。預防之其他結果爲具有肥胖危險患者在未肥胖前進行治療時能夠預防肥胖症發生。預防之其他結果爲具有肥胖危險患者在未肥胖前進行治療時能夠減低肥胖相關疾病之發病及/或嚴重度。預防之其他結果爲能夠延長對抗體重增加。預防之其他結果爲能夠預防體重之再增加。再者，對於己肥胖患者開始治療時，上述「治療」能夠防止肥胖相關疾病之發病、進展或嚴重度。本發明之醫藥組成物，係將具有營養素消化吸收抑制作用之化合物及其製藥上容Step B - 32 - 201032805 The compound (II) is reacted with a compound (ΙΠ) having a substituent Z and R2 corresponding to the target compound in a suitable solvent. Solvents such as tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, A mixed solvent of dioxane, acetone, acetonitrile, water, and the like. Among them, dimethylformamide, tetrahydrofuran, and ethyl acetate are preferred. If necessary, in 3-di(cycloheximide)methane (also dicyclohexylcarbodiimide), 1-ethyl-3-(3-dimethylamino)carbodiimide (WSCD; water soluble) Equivalent condensing agent and/or acidic additives such as 1-hydroxybenzotriazole, 3,4-dihydro-3-hydroxy-4-sideoxy-1,2,3-benzotrimole The reaction can be carried out in the presence of it. The reaction temperature is about 0 ° C to 50 ° C, and preferably about 20 ° C to 30 ° C. The reaction time is about 5 minutes to 30 hours, and preferably about 5 to 20 hours. φ If necessary, the amine group of the compound may be protected by a conventional method at an appropriate stage of the reaction. As the protecting group, a quinone imine, an alkoxycarbonyl group, an alkoxycarbonyl group, a halogenated alkoxycarbonyl group, an aralkoxycarbonyl group, a trialkylsulfonyl group, an alkanesulfonyl group, a halogenated alkanesulfonyl group, an arylsulfonyl group, an alkylcarbonyl group can be used. , arylcarbonyl and the like. After the protection, the reaction is carried out in each of the above steps, and the treatment is carried out by treatment with an acid or an alkali at an appropriate stage and in a suitable solvent. As the solvent, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane can be used. -33- 201032805 Dioxane, acetone, acetonitrile, water, and the like, a base such as hydrazine, pyridine, sodium hydroxide, potassium hydroxide, etc., such as hydrochloric acid, trifluoroacetic acid, hydrogen fluoride, and the like. The pharmaceutical composition of the present invention is useful for preventing or treating diseases such as obesity and obesity-related diseases, and patients suffering from excessive body fat and insufficient exercise to accumulate excess fat in the body. "Obesity" is defined as the state in which too much fat tissue is accumulated. However, there is no correct, simple, and practical method for measuring body fat, and the body mass index (BMI) is used for the height and weight. BMI is defined as the weight (kg) divided by the square of height (meters) (kg/m2). According to the definition of the World Health Organization and the National Institutes of Health in the United States, patients with a BMI of 25 kg/m2 or more were judged to be overweight, and patients above 30 kg/m2 were judged to be obese. However, in the Orientals, when compared with whites, the lower body mass index (BMI) increases the incidence of obesity-related diseases. For example, in Japan, even if the 'φ BMI is about 25 kg/m 2 , there are many patients with diabetes or dyslipidemia such as obesity-related diseases. Therefore, the Japanese Obesity Society defines a BMI of 25 kg/n or more as obesity. Obese patients requiring medical intervention, those with BMI of 30kg/m2 or higher and obesity-related diseases, those with BMI of 30kg/m2 or higher but no obesity-related diseases, or BMI of 25kg/m2 or more and/or visceral fat area (VFA) is 100 cm 2 or more and at least two types of obesity-related diseases occur. Obesity-related diseases such as hypertension, impaired glucose tolerance, diabetes, abnormal fat metabolism, dyslipidemia, hyperuricemia, gout, fatty liver, coronary artery disease, cerebral infarction, etc. The term "obesity" (obesity) in the present specification includes obesity caused by various causes, including genetic or environmental causes. "obesity-related diseases" are diseases caused by obesity, or caused by obesity, or obesity. Obesity-related diseases such as Addephagia, hypertension, impaired glucose tolerance, diabetes, metabolic syndrome, abnormal fat metabolism, arteriosclerosis, hyperuricemia, gout, fatty liver, endometrial cancer, breast cancer, prostate cancer , colorectal cancer, osteoarthritis, low back pain, obstructive sleep-disordered breathing syndrome, coronary artery disease (coronary heart disease), cerebral infarction, menstrual abnormalities, Predwell's syndrome, Fleulich's syndrome, Pickett's syndrome, etc. The pharmaceutical composition of the present invention has a risk of reducing the risk of left ventricular hypertrophy and the secondary result of obesity. Further, the pharmaceutical composition of the present invention is also useful for the treatment of Alzheimer's disease. 0 "Metabolic Syndrome" is defined in the third report (ATP-III) of the "National Cholesterol Education Program Expert Seminar on the Detection, Evaluation and Treatment of High Cholesterol in Adult Blood" (see ESFord et al., JAMA, vol. 287(3), P5 3 6-3 59, January 16, 2002 曰). In short, those with more than three symptoms in abdominal obesity, high blood triglyceride, low HDL cholesterol, high blood pressure, and high fasting blood glucose are defined as metabolic syndrome. "Diabetes" includes insulin-dependent diabetes mellitus (IDDM, type I-35-201032805 diabetes) and non-insulin-dependent diabetes mellitus (NIDDM, both. Type I diabetes is an absolute lack of insulin that regulates glucose utilization. Type 2 diabetes is caused by an inability to respond to insulin, even if the islet burial increases. The second type of diabetes patients are mostly fat medicinal compositions for type 1 diabetes and type 2 saccharide therapy. The pharmaceutical composition of the present invention is also used for gestational sugar or prevention. "Treatment" of obesity and obesity-related diseases, and the weight of obese patients is administered to the medicine of the present invention. When the body weight of the medical group to be administered to the present invention is compared, the patient's body weight may be reduced. The result is that the weight loss can be prevented from being reduced by the previous food therapy and the exercise fruit. The other result of the treatment is φ related disease. The onset and/or severity of treatment. Other shoes that reduce weight or manage weight. Ingestion of whole substances or calories (including reducing the total intake of food or the intake of specific foods such as fats and fats), preventing the decline of the absorption camp, 'the need to reduce the body weight of patients with weight loss or body weight treatment' Incidental sputum I liters lead to changes in metabolic rate and/or can often be limited to a minimum range due to weight loss. Type 2 diabetes), islet is caused by body tissue: secretion is normal or:. The treatment of both sides of the urinary tract of the present invention: the treatment of urinary diseases and/or : for reducing or maintaining sputum. One of the treatments: obesity in front of the body Another treatment of the drug 〖 or drug therapy can reduce obesity ί fruit to be able to maintain [when reducing the patient's food to reduce carbohydrates i, inhibit metabolic rate [management and so on. Anti-metabolism based on 1 ' metabolic rate - 36- 201032805 "Prevention of obesity and obesity-related diseases" means administering the pharmaceutical composition of the present invention to reduce or maintain the body weight of a patient at risk of obesity. One result of this prevention is that the weight of the subject may be reduced when compared to the weight of a patient at risk of obesity before the administration of the pharmaceutical composition of the present invention. Another consequence of this prevention is the ability to prevent a decrease in body weight (i.e., weight management) that is reduced by previous food therapy, exercise, or medication therapy results. Other outcomes of prevention are those with a risk of obesity who can prevent obesity when they are not being treated with obesity. Other outcomes of prevention are those with a risk of obesity who can reduce the onset and/or severity of obesity-related diseases when treated without pre-obesity. The other result of prevention is the ability to prolong the fight against weight gain. The other result of prevention is the ability to prevent further weight gain. Furthermore, the above "treatment" can prevent the onset, progression or severity of obesity-related diseases when starting treatment for obese patients. The pharmaceutical composition of the present invention is a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutical composition thereof

許之鹽或其等之溶劑合物，與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物組合而成之醫藥組成物；a pharmaceutical composition obtained by combining a salt of a salt thereof or a solvate thereof, a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或$ 被取代之胺基、被取代或未被取代之烷氧基、被取代或$ -37- 201032805 被取代之環狀烴基、或被取代或未被取代之雜環基）。在此，「組合而成之醫藥組成物」包含使用各化合物作爲合劑之形式或同時投給之形式。又，本發明包含將具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物進行混合爲特徵之上述醫藥組成物之製造方法；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or substituted amino group, A substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group of $-37- 201032805, or a substituted or unsubstituted heterocyclic group). Here, the "combined pharmaceutical composition" includes a form in which each compound is used as a mixture or a form to be administered at the same time. Further, the present invention encompasses a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or the like a method for producing the above pharmaceutical composition characterized by mixing;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。詳言之，本發明之醫藥組成物，爲含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之配合劑之醫藥組成物，(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). In particular, the pharmaceutical composition of the present invention is a compound containing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like, and a compound represented by the formula (I) and a pharmaceutically acceptable compound thereof. a pharmaceutical composition of a compounding agent of a salt or a solvate thereof,

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未 -38- 201032805 被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）；含含有具有營養素消化吸收抑制作用之化合物及其上容許之鹽或其等之溶劑合物而成之藥劑，與含有式（I)表示之化合物及其製藥上容許之鹽或其¥ 之溶劑合物而成之藥劑之套組；Wherein R1 is alkyl, R2 is hydrogen or alkyl, Z is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or not substituted at -38- 201032805 An amine group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group; and a compound containing a nutrient absorption and absorption inhibiting action thereof a pharmaceutical agent comprising a salt or a solvate thereof, and a pharmaceutical composition comprising a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。本發明之醫藥組成物，不受所使用具有營養素消化1¾ φ 收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物及式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之用量比之限定。本發明之醫藥組成物爲配合劑時，式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物對所配合具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之重量比，如爲100:1〜1:1〇〇，並以10:1 〜1: 10較佳，5: 1〜1: 5更佳。本發明之醫藥組成物爲套組時，套組所準備式（I)表示 -39- 201032805 之化合物及其製藥上容許之鹽或其等之溶劑合物對所配合具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之重量比，如爲100: 1〜1: 100,並以10: 1〜1: 10較佳，5: 1〜1: 5更佳。本發明之醫藥組成物之套組舉列如下，但本發明不受此等之限定。 (a) 在同一包裝中包含第1經口投藥劑與第2經口投藥劑之套組：第1經口投藥劑：含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物，第2經口投藥劑：含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物。 (b) 在同一包裝中包含經口投藥劑及靜脈點滴用小瓶 φ 之套組：含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物之經口投藥劑，及含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物之靜脈點滴用小瓶。 (c) 在同一包裝中包含第1封裝室與第2封裝室之套組 -40- 201032805 (輸液包）：第1封裝室：含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物，第2封裝室：含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物。 (d) 在同一包裝中包含：含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物之藥劑，及搭配倂用含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之使用方法之說明書之套組。 (e) 在同一包裝中包含：含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物與製藥上容許之載體及/或賦形劑之混合物之藥劑，及搭配倂用具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之使用方法說明書之套組。上述套組之1包裝中所含各小瓶數、各藥劑數並無限定。如各小瓶或各藥劑分别爲1〜5個。並以各小瓶或各藥劑分别爲1〜3個較佳。 -41 - 201032805 本案說明書中之「藥劑」爲含有有效成分化合物之組成物。「經口投藥藥劑」爲使用經口投藥途徑投藥之藥劑。本發明之醫藥組成物以套組使用時，先投給含有式（I) 表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，隨後再投給含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑亦可。又，另一形式爲先投給含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥 ’ 劑，隨後再投給含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑亦可。又，另一形式爲同時投給含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑及含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑亦可。使用於本發明之醫藥組成物之藥劑，可以經口、非經 Φ 口之任意方法進行投藥。經口投藥依常法調製錠劑、顆粒劑、九劑、液劑、糖漿劑、口腔錠（Backal)劑、或舌下劑等通常所使用劑型投藥即可，非經口投藥如肌肉投藥、靜脈投藥等注射劑，栓塞劑、經皮吸收劑、吸入劑等通常所使用任何劑型均可適合投藥。使用於本發明之醫藥組成物之化合物（具有營養素消化吸收抑制作用之化合物及式⑴表示之化合物）之有效量’可因應須要與適合其劑型之賦形劑、黏合劑、濕潤劑、 -42- 201032805 崩解劑、潤滑劑、稀釋劑等各種醫藥用添加劑混合而成醫藥製劑。調製注射劑時將有效成分與適當載體共同進行滅菌處理製成製劑即可。賦形劑如乳糖、白糖、葡萄糖、澱粉、碳酸鈣或結晶纖維素等。黏合劑如甲基纖維素、羧甲基纖維素、羥丙基纖維素、明膠或聚乙烯吡咯酮等。崩解劑如羧甲基纖維素、羧甲基纖維素鈉、澱粉、精胺酸鈉、洋菜粉或月桂基硫酸鈉等。潤滑劑如滑石、硬脂酸鎂或聚乙二醇（macrogol)等。栓塞劑之基劑可使用可可脂、聚乙二醇或甲基纖維素等。調製成液劑或乳化性（又乳濁性）、懸浮性注射劑時，可適當添加通常使用之助溶劑、懸浮化劑、乳化劑、安定化劑、保存劑、等滲壓劑等。經口投藥時可添加矯味劑、 φ 芳香劑等。使用於本發明之醫藥組成物之藥劑投藥量，以考慮患者之年齡、體重，疾病種類及程度，投藥途徑等後設定爲宜，如對成人經口投藥時，當做有效成分使用於本發明之醫藥組成物之具有營養素消化吸收抑制作用之化合物或式 (I)表示之化合物通常爲 0·05〜100mg/kg/日，並以 0.1〜 50mg/kg/日範圍內較佳。非經口投藥時因投藥途徑而大異，當做有效成分使用於本發明之醫藥組成物之具有營養 -43- 201032805 素消化吸收抑制作用之化合物或式⑴表示之化合物通常爲 0.005〜5 0mg/kg/日，並以〇.(H〜10mg/kg/日範圍內較佳。此等分成1日1次〜數次投藥即可。本發明之套組中所含具有營養素消化吸收抑制作用之化合物爲奧利司他時，該藥劑以1日1次〜3次或連續性釋放形式’每1日可投藥約20mg〜約1200mg，並以約60mg 〜約600mg較佳，約I20mg〜約4 00mg更佳。如將該藥劑 ®120mg以1日3次或以連續性釋放形式投藥則更佳。本發明之套組中含有奧利司他之藥劑之處方，記載於如美國專利第6004996號說明書。本發明之醫藥組成物之使用方法可舉例如下述，但此等並不限定本發明。 (1)具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，及式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物當做同一藥劑之一部分 φ 同時投藥之肥胖或肥胖相關疾病之預防或治療方法（投藥上述配合劑之預防或治療方法）。 (2)以獲得組合治療利益爲目的之適當投藥計劃之一部分，將含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，及含有式⑴表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑分別投藥之肥胖或肥胖相關疾病之預防或治療方法（使用上述套組之預防或治療方法）。 -44- 201032805 適當之投藥計劃、各投藥時之投藥量、及各藥劑之具體投藥間隔，均依所使用藥劑之具體組合、患者之病情及病情之嚴重性等而決定。投藥計劃可舉例如下述，但此等並不限定本發明之.醫藥組成物之投藥計劃。 (1) 具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物及式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之配合劑，以1日1次〜3 次投藥。 (2) 含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，及含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，以1日1次〜3次共同投藥。 (3) 含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑以1日1次投藥，含有具有營養素消 φ 化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑以1日1次〜3次投藥。 (4) 先投藥含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，經數日〜數週後倂用含有式 (I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑及含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑。 (5) 先投藥含有具有營養素消化吸收抑制作用之化合 -45- 201032805 物及其製藥上容許之鹽或其等之溶劑合物之藥劑，經數日〜數週後倂用含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑及含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑。本發明之醫藥組成物可再組合其他抗肥胖藥使用。又，依據投藥本發明之醫藥組成物之藥物療法，亦可組合食物療法、運動療法及其他藥物療法使用。「飮食療法」如減飲食療法、低熱量飲食（LCD)療法、極低熱量飮食（VLCD)療法、減熱量飮食（RCD)療法等。「減飲食療法」爲每日攝取熱量抑制在1200大卡（kcal) 程度之輕度飲食療法。「低熱量飲食療法」爲每日攝取熱量限制在約600〜 1200大卡程度之飮食療法。例如以平衡良好之飮食攝取該低熱量，或以高脂肪低熱量飮食、高蛋白質低熱量飲食等富含特殊營養素之飮食攝取該低熱量等。「極低熱量飮食療法」爲每日攝取熱量限制在約2〇〇〜600大卡程度之飮食療法。係以重度肥胖患者爲對象之半飢餓療法。「減熱量飲食療法」爲攝取由基本代謝所計算得每日必須熱量減去約800大卡之飮食之飮食療法。本發明之醫藥組成物與抗肥胖療法組合使用時，能夠利用各種投藥計劃，可舉例如下述。 -46 - 201032805 (1) 同時開始飲食療法及/或運動療法與使用本發明之醫藥組成物之藥物療法。 (2) 先實施飮食療法及/或運動療法數日〜數週，減少體重某一程度後，開始實施使用本發明之醫藥組成物之藥物療法。又，本發明亦包含下述之形式。包含將具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物組合投藥之步驟之誘導或促進體重減少、或維持或管理體重之方法；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). The pharmaceutical composition of the present invention is not affected by the use of a compound having a nutrient-digesting inhibitor and a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof The amount of the solvate or the like is limited. When the pharmaceutical composition of the present invention is a compounding agent, the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof or the like, and a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof The weight ratio of the solvate or the like thereof is, for example, 100:1 to 1:1 Torr, and preferably 10:1 to 1:10, more preferably 5:1 to 1:5. When the pharmaceutical composition of the present invention is a kit, the formula (I) of the kit represents a compound of -39-201032805 and a pharmaceutically acceptable salt thereof or a solvate thereof, which has a nutrient absorption and absorption inhibitory effect. The weight ratio of the compound and its pharmaceutically acceptable salt or its solvate is, for example, 100:1 to 1:100, and preferably 10:1 to 1:10, more preferably 5:1 to 1:5. . The kit of the pharmaceutical composition of the present invention is as follows, but the present invention is not limited thereto. (a) A kit containing the first oral administration and the second oral administration in the same package: The first oral administration: a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable salt thereof or a mixture of a solvate and a pharmaceutically acceptable carrier and/or excipient, and a second oral administration: a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof and the like A pharmaceutically acceptable carrier and/or mixture of excipients. (b) A kit containing a vial for intravenous administration and a vial for intravenous drip in the same package: a compound containing a nutrient absorption and absorption inhibiting compound, a pharmaceutically acceptable salt thereof, or the like, and a pharmaceutically acceptable substance Oral administration of a mixture of a carrier and/or an excipient, and a solvate comprising the compound of the formula (I) and a pharmaceutically acceptable salt thereof or the like, and a pharmaceutically acceptable carrier and/or excipient The mixture was intravenously dripped with a vial. (c) Kits containing the first and second encapsulation chambers in the same package -40-201032805 (infusion package): Package 1: Containing compounds with nutrient absorption and absorption inhibition and their pharmaceutically acceptable salts Or a mixture of a solvate thereof or a pharmaceutically acceptable carrier and/or excipient, a second packaging chamber: a compound comprising the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or the like A pharmaceutically acceptable carrier and/or mixture of excipients. (d) in the same package: an agent comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier and/or excipient, and A kit for use in conjunction with a method of using a pharmaceutical preparation containing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof. (e) in the same package: a pharmaceutical composition containing a compound of the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier and/or excipient, and A kit using instructions for the use of a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof. The number of vials and the number of each drug contained in the package of the above kit are indefinite. For example, each vial or each of the medicaments is 1 to 5 pieces. It is preferably 1 to 3 in each vial or each of the medicines. -41 - 201032805 The "agent" in the present specification is a composition containing a compound of an active ingredient. The "oral drug" is an agent that is administered by the oral administration route. When the pharmaceutical composition of the present invention is used in a kit, it is first administered to a medicament containing a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof, and then administered with a nutrient absorption and absorption inhibition. The acting compound and its pharmaceutically acceptable salt or its solvate may also be used. Further, another form is a drug which is administered to a compound containing a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, and then administered to a compound containing the formula (I) and A pharmaceutically acceptable salt or a solvate thereof may also be used. Further, another form is a pharmaceutical agent comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof Or a solvate agent thereof or the like. The agent for use in the pharmaceutical composition of the present invention can be administered by any method, either by mouth or by Φ. Oral administration can be carried out according to the usual method of preparing tablets, granules, nine doses, liquid preparations, syrups, oral tablets (Backal) agents, or sublingual agents, and the like, and the dosage forms such as muscle administration can be administered by oral administration. Injectables such as intravenous administration, embolization agents, transdermal absorption agents, inhalants, and the like can be suitably administered in any dosage form. The effective amount of the compound (the compound having the nutrient digestion and absorption inhibiting action and the compound represented by the formula (1)) used in the pharmaceutical composition of the present invention may be required to be compatible with an excipient, a binder, a wetting agent, and the like suitable for the dosage form thereof. - 201032805 A pharmaceutical preparation is prepared by mixing various pharmaceutical additives such as a disintegrant, a lubricant, and a diluent. When the injection is prepared, the active ingredient may be sterilized together with an appropriate carrier to prepare a preparation. Excipients such as lactose, white sugar, glucose, starch, calcium carbonate or crystalline cellulose. Binders such as methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, gelatin or polyvinylpyrrolidone. A disintegrating agent such as carboxymethylcellulose, sodium carboxymethylcellulose, starch, sodium sulphate, acacia powder or sodium lauryl sulfate. Lubricants such as talc, magnesium stearate or macrogol. The base of the embolic agent may be cocoa butter, polyethylene glycol or methyl cellulose. When a liquid preparation, an emulsifying (and opaque) or a suspension injection is prepared, a commonly used cosolvent, a suspending agent, an emulsifier, a stabilizer, a preservative, an isotonic agent, or the like can be appropriately added. A flavoring agent, a φ fragrance, or the like may be added during oral administration. The dosage of the pharmaceutical composition used in the pharmaceutical composition of the present invention is preferably set in consideration of the age, weight, type and degree of the disease, the administration route, and the like, and is used as an active ingredient in the present invention when administered orally to an adult. The compound having a nutrient absorption and absorption inhibitory effect of the pharmaceutical composition or the compound represented by the formula (I) is usually from 0.05 to 100 mg/kg/day, and preferably from 0.1 to 50 mg/kg/day. When it is administered orally, it is greatly different depending on the route of administration. The compound which is used as an active ingredient in the pharmaceutical composition of the present invention having the nutrient-43-201032805 digestive absorption-inhibiting effect or the compound represented by the formula (1) is usually 0.005 to 50 mg/ Kg / day, and preferably in the range of H ~ 10mg / kg / day. This can be divided into 1 to several times a day. The kit of the present invention contains nutrient digestion and absorption inhibition When the compound is orlistat, the agent can be administered from about 20 mg to about 1200 mg per day, and from about 60 mg to about 600 mg, preferably from about 20 mg to about 4, in one or three or one continuous release forms per day. More preferably, it is more preferably 00 mg. It is more preferred to administer 120 mg of the agent to the drug once a day or in a continuous release form. The kit of the present invention contains the agent of orlistat, as described in U.S. Patent No. 6,004,996. The method of using the pharmaceutical composition of the present invention is, for example, the following, but the present invention is not limited thereto. (1) A compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like , and the combination of formula (I) And a pharmaceutically acceptable salt thereof or a solvate thereof, etc., as a part of the same medicament, a method for the prophylaxis or treatment of obesity or obesity-related diseases (administered by the above-mentioned compounding agent) (2) An agent containing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a compound containing the compound represented by the formula (1) and a pharmaceutical thereof, which are part of an appropriate administration plan for the purpose of obtaining a combination therapeutic benefit A method for the prevention or treatment of obesity or obesity-related diseases to which the above-mentioned salt or its solvate is administered separately (using the prevention or treatment method of the above kit). -44- 201032805 Appropriate administration plan, each administration The dosage of the drug and the specific administration interval of each agent are determined according to the specific combination of the agent to be used, the severity of the patient's condition and the severity of the disease, etc. The administration plan may be, for example, the following, but the invention is not limited thereto. Drug administration plan for pharmaceutical composition. (1) Compounds with nutrient digestion and absorption inhibition and their pharmaceutically acceptable A compound of a salt or a solvate thereof and a compound represented by the formula (I), and a pharmaceutically acceptable salt thereof or a solvate thereof, are administered once or three times a day. (2) Formula ( I) a compound represented by the compound and a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutical agent comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, etc. (1) A pharmaceutical agent containing a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof, is administered once a day, and contains nutrients. The drug for the absorption inhibiting compound and the pharmaceutically acceptable salt thereof or the solvate thereof is administered once to three times a day. (4) A pharmaceutical composition containing a compound represented by the formula (I), a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutical composition containing the compound of the formula (I) and a pharmaceutical thereof after several days to several weeks An agent for a salt or a solvate thereof, and a drug comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof. (5) First, a drug containing a compound having a nutrient absorption and absorption inhibiting action -45 - 201032805 and a pharmaceutically acceptable salt thereof or a solvate thereof, and containing the formula (I) after several days to several weeks An agent for a compound and a pharmaceutically acceptable salt thereof or a solvate thereof, and a drug comprising a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof. The pharmaceutical composition of the present invention can be used in combination with other anti-obesity agents. Further, the drug therapy according to the pharmaceutical composition of the present invention can also be combined with food therapy, exercise therapy and other drug therapy. "Picking therapy" such as diet therapy, low-calorie diet (LCD) therapy, very low calorie diet (VLCD) therapy, and calorie-reducing diet (RCD) therapy. "Diet Diet Therapy" is a mild diet that inhibits daily calorie intake at a level of 1200 kcal. "Low-calorie diet therapy" is a foraging therapy that limits calorie intake to about 600 to 1200 kcal per day. For example, the low-calorie is taken in a well-balanced foraging diet, or the low-calorie is ingested by a diet rich in special nutrients such as high-fat, low-calorie foraging, high-protein low-calorie diet, and the like. "Very Low Calorie Foraging Therapy" is a foraging therapy that limits calorie intake to about 2 to 600 calories per day. A half-stardication therapy for severely obese patients. "Reducing calorie diet therapy" is a dieting therapy that takes about 800 calories per day from the basic metabolism. When the pharmaceutical composition of the present invention is used in combination with an anti-obesity therapy, various administration plans can be used, and the following are exemplified below. -46 - 201032805 (1) At the same time, diet therapy and/or exercise therapy and drug therapy using the pharmaceutical composition of the present invention are started. (2) The foraging therapy and/or exercise therapy is carried out for several days to several weeks, and after a certain degree of weight reduction, the drug therapy using the pharmaceutical composition of the present invention is started. Further, the present invention also encompasses the following forms. a step of administering a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or a solvate thereof, in combination with a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof a method of inducing or promoting weight loss, or maintaining or managing body weight;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未 φ 被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。本發明之醫藥組成物所含具有營養素消化吸收抑制作用之化合物及式（I)表示之化合物，分別以不同作用機制表現誘導抑制體重之作用、促進抑制體重之作用、及/或維持或管理體重之作用。再者，本發明亦包含下述之形式。含具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑（其中含式（I)表示之化 -47- 201032805 合物及其製藥上容許之鹽或其等之溶劑合物）之肥胖或月巴胖相關疾病之預防或治療效果之增強劑；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). The pharmaceutical composition of the present invention contains a compound having a nutrient absorption and absorption inhibiting action and a compound represented by the formula (I), which respectively exhibit a function of inhibiting body weight, promoting the effect of inhibiting body weight, and/or maintaining or managing body weight by different action mechanisms. The role. Furthermore, the present invention also encompasses the following forms. An agent comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, wherein the compound of the formula (I) is represented by the compound -47-201032805 and a pharmaceutically acceptable salt thereof or An enhancer for the prophylactic or therapeutic effect of obesity or sulphate-related diseases;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未 ® 被取代之環狀烴基、或被取代或未被取代之雜環基）。含式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑（其中含具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物）之肥胖或肥胖相關疾病之預防或治療效果之增強劑；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). An agent comprising a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, etc., which comprises a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, etc. An enhancer for the prevention or treatment of obesity or obesity-related diseases;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，能夠增强式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之肥胖或肥胖相關疾病之預防或治療效果。式（I)表示之化合物及其製藥上容許 -48- 201032805 之鹽或其等之溶劑合物，能夠增强具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之肥胖或肥胖相關疾病之預防或治療效果。因此，本發明之醫藥組成物與單獨使用各化合物時比較，能夠以極大效率預防或治療肥胖或肥胖相關疾病。以下敘述，使用奧利司他爲具有營養素消化吸收抑制作用之化合物，使用化合物（a)爲式（I)表示之化合物進行之實施例，再詳細說明本發明，但此等並不限定本發明。 0 實施例1 取7週齡雄性C57BL/6J小鼠（體重20.4〜24.2kg;購自日本CLEA公司），餵食高脂肪食料（Test Diet公司製）5週以誘導肥胖。其次，將羥丙基甲基纖維素（信越化學公司製）之0.5 %水溶液，經口投給1日2次（上午8:30 - 11:〇〇、下午14:30 - 17:00)共4週，藉以馴化適應本操作。根據小鼠體重與4週馴化期間之平均體重改變量分爲以下6組。亦即：（1)對照組（0.5%羥丙基甲基纖維素l〇ml/kg) ; (2)化合物 ® (a)50mg/kg組；（3)奥利司他12.5mg/kg組；（4)奧利司他 25mg/kg 組：（5)化合物（a)50mg/kg+ 奧利司他 12.5mg/kg 組；（6)化合物（a)50mg/kg +奧利司他25mg/kg組。各組均以1日2次（上午8:30 — 11:00、下午15:00 — 18:00)連績投藥4週。投藥開始時小鼠之體重爲30.1〜34.9g。連績投藥 4週結果’與對照組比較平均體重時（2)化合物（a)50mg/kg 組抑制〇.9g ; (3)奧利司他12.5mg/kg組抑制0.6g ; (4)奧利司他25mg/kg組抑制2.1g。至於共同投藥之各組，貝[J (5) -49- 201032805 化合物（a)50mg/kg+奧利司他12.5mg/kg組抑制2.5g; (6) 化合物（a)50mg/kg +奧利司他25mg/kg組抑制4.2g。由此等結果可知化合物（a)與奧利司他共同投藥時，有相加以上之體重抑制效果。亦即與各藥物單獨作用之和比較時獲得相加以上之效果（參照第1圖及第2圖。第2圖中之化合物（a) +奧利司他即指化合物（a) 5 0 m g / k g +奧利司他2 5 m g / k g)。另一方面，與對照組比較4週之攝食量時（2)化合物 (a)50mg/kg組抑制2.5g; (3)奧利司他12.5mg/kg組增加 © 7.6g; (4)奧利司他25mg/kg組增力口 14.5g。至於共同投藥之各組，則（5)化合物（a) 5 0 m g / k g +奧利司他1 2 · 5 m g / k g組增加 7.4g; (6)化合物（a)50mg/kg +奧利司他 25mg/kg組增加 8.4g。此等結果表示奧利司他引起之攝食亢進作用因共同投藥化合物U)而被抑制。 [產業上利用之可能性] 本發明之醫藥組成物作爲肥胖或肥胖相關疾病之治療劑或預防劑非常有用。又，該醫藥組成物在肥胖症之體重 ® 管理上非常有用。【圖式簡單說明】第1圖：對肥胖模式實驗小鼠投藥4週時累計體重之變化第2圖：試驗最終日時對照組與治療組之體重差【主要元件符號說明】無。 -50-(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). A compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which can enhance the obesity or obesity of the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof or the like The prevention or treatment effect of related diseases. A compound represented by the formula (I) and a pharmaceutically acceptable salt thereof, which is a pharmaceutically acceptable salt of -48-201032805, or a solvate thereof, which is capable of enhancing a compound having a nutrient absorption and absorption inhibiting action, a pharmaceutically acceptable salt thereof, or the like The preventive or therapeutic effect of obesity or obesity-related diseases. Therefore, the pharmaceutical composition of the present invention can prevent or treat obesity or obesity-related diseases with great efficiency as compared with when each compound is used alone. Hereinafter, the present invention will be described in detail using an example in which orlistat is a compound having a nutrient absorption and absorption inhibiting effect and a compound (a) is a compound represented by the formula (I), but the present invention is not limited thereto. . 0 Example 1 7-week-old male C57BL/6J mice (body weight: 20.4 to 24.2 kg; purchased from CLEA, Japan) were fed with a high-fat diet (manufactured by Test Diet Co., Ltd.) for 5 weeks to induce obesity. Next, a 0.5% aqueous solution of hydroxypropylmethylcellulose (manufactured by Shin-Etsu Chemical Co., Ltd.) was orally administered twice a day (8:30 - 11:00 am, 14:30 - 17:00 pm). 4 weeks, by domestication to adapt to this operation. The following six groups were classified according to the body weight of the mice and the average body weight change during the 4-week acclimation period. That is: (1) control group (0.5% hydroxypropyl methylcellulose l〇ml/kg); (2) Compound® (a) 50 mg/kg group; (3) Orlistat 12.5 mg/kg group (4) Orlistat 25 mg/kg Group: (5) Compound (a) 50 mg/kg + Orlistat 12.5 mg/kg group; (6) Compound (a) 50 mg/kg + Orlistat 25 mg/ Kg group. Each group was administered for 4 weeks on a one-time basis (8:30 to 11:00 am, 15:00 to 18:00 pm). The body weight of the mice at the start of administration was 30.1 to 34.9 g. The results of 4 weeks of continuous administration were compared with the control group. (2) Compound (a) 50 mg/kg group inhibited 〇.9 g; (3) Orlistat 12.5 mg/kg group inhibited 0.6 g; (4) The lesitastat 25 mg/kg group inhibited 2.1 g. For each group administered together, Bay [J (5) -49- 201032805 Compound (a) 50 mg / kg + orlistat 12.5 mg / kg group inhibited 2.5 g; (6) Compound (a) 50 mg / kg + Orly The statin 25 mg/kg group inhibited 4.2 g. From the results, it was found that the compound (a) had a weight-inhibiting effect when it was co-administered with orlistat. That is, the effect of the addition is obtained when compared with the sum of the individual effects of the respective drugs (refer to Fig. 1 and Fig. 2. The compound (a) in the second figure + orlistat means the compound (a) 5 0 mg / kg + orlistat 2 5 mg / kg). On the other hand, when compared with the control group for 4 weeks of food intake (2) Compound (a) 50 mg/kg group inhibited 2.5 g; (3) Orlistat 12.5 mg/kg group increased by 7.6 g; (4) The amount of the booster 25mg/kg group was 14.5g. For each group administered together, (5) compound (a) 50 mg / kg + orlistat 1 2 · 5 mg / kg group increased by 7.4 g; (6) compound (a) 50 mg / kg + Ollie The statin 25mg/kg group increased by 8.4g. These results indicate that the food intake caused by orlistat is inhibited by co-administration of compound U). [Possibility of Industrial Applicability] The pharmaceutical composition of the present invention is very useful as a therapeutic or prophylactic agent for obesity or obesity-related diseases. Moreover, the pharmaceutical composition is very useful in the management of body weight of obesity. [Simplified illustration] Fig. 1: Changes in cumulative body weight at 4 weeks of administration in obese model mice. Figure 2: Difference in body weight between control group and treatment group at the end of the test [Explanation of main component symbols] None. -50-

Claims

201032805 * 七、申請專利範圍： 1. 一種醫藥組成物，其係由具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，與式（1) 表示之化合物及其製藥上容許之鹽或其等之溶劑合物組合而成之醫藥組成物；201032805 * VII. Patent application scope: 1. A pharmaceutical composition which is a compound having a nutrient absorption and absorption inhibiting effect, a pharmaceutically acceptable salt thereof or a solvate thereof, and a compound represented by the formula (1) a pharmaceutical composition comprising a pharmaceutically acceptable salt or a solvate thereof;

⑩ （式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 2 ·如申請專利範圍第1項之醫藥組成物，該醫藥組成物爲配合劑。 3.如申請專利範圍第1項之醫藥組成物，該醫藥組成物係包含含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，與含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑之套組；10 (wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). 2. A pharmaceutical composition as claimed in claim 1 which is a compounding agent. 3. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises a pharmaceutical composition comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof; I) a kit of the indicated compound and its pharmaceutically acceptable salt or a solvate thereof;

(式中，R1爲烷基，R2爲氫原子或烷基’ Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或 -51 - 201032805 未被取代之環狀烴基、或被取代或未被取代之雜環基）。 4. 如申請專利範圍第丨至3項中任一項之醫藥組成物，其中具營養素消化吸收抑制作用之化合物爲具有脂肪吸收抑制作用之化合物。 5. 如申請專利範圍第4項之醫藥組成物，其中，具有脂肪吸收抑制作用之化合物爲具有胰臟脂肪酶抑制作用之化合物。(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, wherein Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group of -51 - 201032805, or a substituted or unsubstituted heterocyclic group). 4. The pharmaceutical composition according to any one of claims 3 to 3, wherein the compound having a nutrient absorption and absorption inhibiting action is a compound having a fat absorption inhibiting action. 5. The pharmaceutical composition according to claim 4, wherein the compound having a fat absorption inhibiting action is a compound having a pancreatic lipase inhibiting action.

6 ·如申請專利範圍第5項之醫藥組成物，其中，具有胰臟脂肪酶抑制作用之化合物爲奧利司他（Orlistat)。 7.如申請專利範圍第1至6項中任一項之醫藥組成物，其中式（I)表示之化合物爲下式（a)表示之化合物 (a)6. The pharmaceutical composition according to claim 5, wherein the compound having pancreatic lipase inhibitory action is Orlistat. 7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the compound represented by the formula (I) is a compound represented by the following formula (a) (a)

8 ·如申請專利範圍第1至7項中任一項之醫藥組成物，該醫藥組成物用於預防或治療肥胖或肥胖相關疾病或肥胖症之體重管理之目的。 9 ·如申請專利範圍第8項之醫藥組成物，其中肥胖相關疾病爲貪食症（Addephagia)、高血壓、葡萄糖耐性異常、糖尿病、新陳代謝症候群、脂肪代謝異常、動脈硬化、高尿酸血症、痛風、脂肪肝、子宫內膜癌、乳癌、攝護腺癌、大腸癌、變形性關節症、腰痛、阻塞型睡眠呼吸中止症候群、冠狀動脈疾病、腦梗塞、月經異常、普瑞德威利氏症候群（Prader-Willi Syndrome)、弗勒利希氏症候 -52- 201032805 群（Froehlich Syndrome)、或匹克威克氏症候群 (Pickwickian Syndrome) 〇 10.—種藥劑之肥胖或肥胖相關疾病之預防或治療效果之增強劑’該藥劑中含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物；The pharmaceutical composition according to any one of claims 1 to 7, which is for the purpose of preventing or treating weight management for obesity or obesity-related diseases or obesity. 9 · The pharmaceutical composition of claim 8 of the patent scope, wherein obesity-related diseases are Addephagia, hypertension, impaired glucose tolerance, diabetes, metabolic syndrome, abnormal fat metabolism, arteriosclerosis, hyperuricemia, gout , fatty liver, endometrial cancer, breast cancer, prostate cancer, colorectal cancer, osteoarthritis, low back pain, obstructive sleep apnea syndrome, coronary artery disease, cerebral infarction, menstrual abnormalities, Predwell's syndrome (Prader-Willi Syndrome), Fleulich syndrome - 52- 201032805 Group (Froehlich Syndrome), or Pickwickian Syndrome 〇 10. - The preventive or therapeutic effect of obesity or obesity-related diseases The enhancer' contains the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof or a solvate thereof;

Ζ爲被取代或$ (式中’ R1爲院基，R2爲氫原子或院基，被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基），及含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑。 1 1 · 種藥劑之肥胖或肥胖相關疾病之預防或治療效杲之 it強劑，該藥劑含有式⑴表示之化合物及其製藥上容言午或其等之溶劑合物之藥劑，Ζ is substituted or $ (wherein R1 is a hospital group, R2 is a hydrogen atom or a deutero group, a substituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amine group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group, and a compound having a nutrient absorption and absorption inhibiting effect and a pharmaceutically acceptable amount thereof An agent for a salt or a solvate thereof. 1 1 · An agent for the prevention or treatment of obesity or obesity-related diseases of a medicament, which comprises a compound represented by the formula (1) and a pharmaceutical agent thereof, or a solvate thereof, which is pharmaceutically acceptable,

(式中’ R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未 &取代之烷基、被取代或未被取代之烯基、被取代或未 Μ取代之胺基、被取代或未被取代之烷氧基、被取代或 $被取代之環狀烴基、或被取代或未被取代之雜環基）； &1有具有營養素消化吸收抑制作用之化合物及其製藥 -53- 201032805 上容許之鹽或其等之溶劑合物。 12.—種含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，其係用於與含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑倂用；(wherein R 1 is an alkyl group, R 2 is a hydrogen atom or an alkyl group, and Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted alkoxy group, a substituted or substituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group; &1 having a nutrient digestion and absorption inhibiting compound and a pharmaceutical thereof -53- 201032805 The permissible salt or its solvate. 12. An agent comprising a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, which is used for the compound containing the compound represented by the formula (I) and a pharmaceutically acceptable salt thereof Or a solvate for its use;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 13· —種含有式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑，其係用於與含有具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物之藥劑倂用；(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). 13. A pharmaceutical agent comprising a compound represented by the formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof, which is used in combination with a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof Or a solvate for its use;

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。 14.如申請專利範圍第12或13項之藥劑，該藥劑係用於肥胖或肥胖相關疾病之預防或治療或肥胖症之體重管理爲 -54- 201032805 目的。 15.—種如申請專利範圍第1項之醫藥組成物之製造方法，其特徵爲將具有營養素消化吸收抑制作用之化合物及其製藥上容許之鹽或其等之溶劑合物，與式（I)表示之化合物及其製藥上容許之鹽或其等之溶劑合物進行混合，(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group). 14. The medicament according to claim 12 or 13 for use in the prevention or treatment of obesity or obesity-related diseases or the weight management of obesity is -54-201032805. A method for producing a pharmaceutical composition according to claim 1, which is characterized in that a compound having a nutrient absorption and absorption inhibiting action and a pharmaceutically acceptable salt thereof or a solvate thereof, and the formula (I) a compound represented by the compound and a pharmaceutically acceptable salt thereof or a solvate thereof, etc.,

(式中，R1爲烷基，R2爲氫原子或烷基，Z爲被取代或未被取代之烷基、被取代或未被取代之烯基、被取代或未被取代之胺基、被取代或未被取代之烷氧基、被取代或未被取代之環狀烴基、或被取代或未被取代之雜環基）。(wherein R1 is an alkyl group, R2 is a hydrogen atom or an alkyl group, Z is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted amino group, A substituted or unsubstituted alkoxy group, a substituted or unsubstituted cyclic hydrocarbon group, or a substituted or unsubstituted heterocyclic group).