TWI225789B - Compositions inhibiting muscle atrophy - Google Patents

Abstract

Compositions containing as the active ingredient polyphenols separated and purified from a fruit (for example, a fruit of Rosaceae) have an effect of inhibiting muscle atrophy (in particular, disuse muscle atrophy) of mammals. These compositions are also useful in inhibiting a decrease in bone weight and a decrease in bone salt content in disuse muscle atrophy.

Description

1225789 五、發明說明（1) 技術領逾 本t明為關於肌萎縮抑制組成物及抑制骨重量和骨鹽量 降低之組成物，更詳言之，為關於含有果實聚苯酚作為有 效成分之肌萎縮抑制組成物，及抑制廢用性肌萎縮時之骨 重量及骨鹽量降低之組成物。 背景技術 « 肌萎縮（muscular atrophy)可大致分成非活動性（廢用 性）肌萎縮（disuse atrophy)和進行性肌萎縮 (progressive muscular atrophy)，且進行肌萎縮中包含 例如肌萎縮性側索硬化症、進行性脊髓性肌萎縮、 Kugelbag .Welander 病、Werdnig-Hoffmann 病等之神經原 性肌萎縮（neurogenic atrophy)及例如進行性肌營養不良 (Ducchenne型、Becker型、肢帶型、顏面型甲上腕型、肌 緊張性營養不良）等之肌原性肌萎縮（myogenic atrophy ) 〇 於其中，亦已提出在石膏固定的廢用性肌萎縮時，於萎 縮之肌肉内察見TBA(硫巴比妥酸）反應陽性物質（TBARS)的 增加、氧化型殼胱甘肽（GSSG)的增加、GSSG相對於總穀胱 甘肽之比的增加，並且令脂過氧化反應亢進及氧化應力的 增加（Kondo，H，等人，Acta· Physiol· Scand·， 142， 527-528(1990)。亦提出萎縮肌的氧化應力增加，乃令萎 縮肌中抗氧化酶的活性增加（Kondo，H.等人，Am. J. Physiol·，265，E8 39-E844( 1 993 ))。又，於石膏固定之 廢用性肌萎縮時，於萎-縮肌肉之微粒體部分中察見鐵的增1225789 V. Explanation of the invention (1) The technical details are related to the muscular atrophy inhibiting composition and the composition that inhibits the reduction of bone weight and bone salt. More specifically, it refers to the muscle containing fruit polyphenol as an active ingredient. Atrophy inhibiting composition and composition for inhibiting reduction of bone weight and bone salt amount in waste muscle atrophy. BACKGROUND ART «Muscular atrophy can be roughly divided into inactive (disuse) atrophy and progressive muscular atrophy, and performing muscular atrophy includes, for example, amyotrophic lateral sclerosis Disease, progressive spinal muscular atrophy, Kugelbag. Welander disease, Werdnig-Hoffmann disease, and other neurogenic atrophy (Ducchenne type, Becker type, limb band type, facial type nails) Myogenic atrophy, such as upper wrist type, muscular dystrophy, etc. 〇 Among them, it has also been proposed that in the atrophic muscle atrophy, TBA (thiobarbi) Increase in TBT), TBARS, oxidized chitosan (GSSG), GSSG to total glutathione, and increase in lipid peroxidation and oxidative stress ( Kondo, H, et al., Acta · Physiol · Scand ·, 142, 527-528 (1990). It is also proposed that the increased oxidative stress of atrophic muscles increases the activity of antioxidant enzymes in atrophic muscles. (Kondo, H. et al., Am. J. Physiol., 265, E8 39-E844 (1 993)). Also, in the disuse muscle atrophy of gypsum fixation, in the microsomal part of the atrophic-atrophic muscle See the increase in iron

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加及TBARS的增加，且此鐵之增加乃令羥基自由基的產生 增大並且令過氧化脂質增加（Kondo，H•等人，Acta·Adding to the increase in TBARS, and this increase in iron increases the production of hydroxyl radicals and increases the peroxide lipids (Kondo, H • et al., Acta ·

Physiol· Scand·， 142， 527-528(1991))。 因此，認為氧化應力為對於廢用性肌萎縮的進行造成影 響’且氧化應力為影響廢用性肌萎縮的進行，並以投與抗 氧化物質維生素E之試驗進行檢討（Kondo，H·等人，Acta·Physiol. Scand., 142, 527-528 (1991)). Therefore, it is considered that oxidative stress affects the progress of disused muscular atrophy 'and oxidative stress affects the progress of disused muscular atrophy, and it is reviewed based on the test of the administration of antioxidant vitamin E (Kondo, H. et al. , Acta ·

Physiol· Scand·，142，52 7-5 28 ( 1 99 1 ))，提出在以維生 素E減輕萎縮肌肉的氧化應力下，則可抑制肌萎縮的進 行。又，Appel 1等人亦報告經由維生素E的腹腔内投與，Physiol · Scand ·, 142, 52 7-5 28 (1 99 1)) proposes that by using vitamin E to reduce the oxidative stress of atrophic muscles, muscle atrophy can be suppressed. In addition, Appel 1 and others also reported intraperitoneal administration via vitamin E,

則可抑制石膏固定時的廢用性肌萎縮（Appell，H, j.等 人，Int· J· Sports Med·， 18， 157-160(1997))。 更且，廢用性肌萎縮時之萎縮肌肉中之鐵之增加，是否 參與肌萎縮之進行，已有報告經由鐵篏合劑之去鐵敏 (Deferoxamine, DFX)之投與進行檢討（Kondo, H.等人， Pflugers Arch.，421，295-297( 1 992 ))，若根據該報 導，則指示鐵在廢用性肌萎縮之氧化應力中擔任重要角 色。It can inhibit waste muscle atrophy during plaster fixation (Appell, H, j. Et al., Int. J. Sports Med., 18, 157-160 (1997)). Furthermore, whether the increase in iron in atrophic muscles during disuse muscle atrophy is involved in the progress of muscle atrophy has been reported through the administration of a deferoxamine (DFX) iron mixture (Kondo, H Et al., Pflugers Arch., 421, 295-297 (1 992)), according to this report, indicate that iron plays an important role in the oxidative stress of disused muscular atrophy.

另一方面，廣泛已知聚苯酚為經由自由基清除作用而具 有抗氧化能力。聚苯酚之一的黃酮類已被報導不僅具有自 由基清除作用’且亦具有過渡金屬的欲合作用（Afanasev， Ι·Β·等人，Bio Chem· Pharmacol·，38， 1 763- 1 769 ( 1 989 ))。 又，迄今已報導肌肉量與骨鹽密度之間具有正的相關關 係（Nichols，D.L.等人，Med· Sci. Sports Exerc·，27,On the other hand, polyphenols are widely known to have anti-oxidation ability through a radical scavenging action. Flavonoids, one of the polyphenols, have been reported not only to have free radical scavenging effects, but also to synergize with transition metals (Afanasev, IB, et al., Bio Chem. Pharmacol., 38, 1 763-1 769 ( 1 989)). Also, a positive correlation between muscle mass and bone mineral density has been reported so far (Nichols, D.L. et al., Med Sci. Sports Exerc., 27,

\\312\2d-code\89-ll\89118696.ptd 第5頁 1225789 五、發明說明（3) 178-182(1995))、不動時之肌肉量降低且亦伴隨骨重量及 骨鹽量降低（Grobus，R.K·等人，Enfocrinology，I" 2264 - 2270 ( 1 984 ) ;Weinreb，M·，等人，B〇ne， ，1〇， 187 一 194(1989))。 ’ ’ « 聚苯紛的製法已知有由屬於薔薇科之果實的未熟果每， 予以搾汁、萃取並且精製之方法（特開平7_285876號公Λ報’ 或將葡萄之果實的搾汁渣或種子於水中以701以上萃取 時，其前處理為於未滿70 t下與水接觸並且除去水溶性物 花等色青(ΡΓ〇 —，ηΐ“η)的製法(專利第269〇^ 目的為在於提供肌萎縮抑制劑，特別為對於石 員口疋所造成之廢用性肌萎縮具有抑制、 劑。 4从禾的肌委縮抑制 發明 本發明者等人，為了達成上述目的而 程中，在指出氧化應力所參與的廢用 研究之過 具有抗氧化作用之物質則可將其有 …由攝取 種具有抗氧化作用之物質重覆進行檢饒點’對於各 ”聚笨酚對於上述的廢用性肌萎縮1右:、，，發現特 二番，同時發現對於廢用性肌萎縮C果之事 完成本發明。 制之事實，於是達到 :=據本發明，則可提供含有果實 ”，、八特徵之肌萎縮抑制組成物。 酚作為有效成分\\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 5 1225789 V. Description of the invention (3) 178-182 (1995)), the muscle mass decreases when not moving, and it is also accompanied by a decrease in bone weight and bone salt (Grobus, RK, et al., Enfocrinology, I " 2264-2270 (1,984); Weinreb, M., et al., Bone, 10, 187-194 (1989)). '«Polyphenylene is known to be produced by extracting, extracting, and refining unripe fruits of the family Rosaceae (Japanese Patent Publication No. 7_285876), or extracting the juice of grape fruits or When seeds are extracted in water with 701 or more, the pre-treatment is a method for preparing cyan (PΓ〇—, ηΐ “η) in contact with water and removing the water-soluble substance under 70 t (Patent No. 269〇 ^) The purpose of the present invention is to provide a muscular atrophy inhibitor, in particular, it has an inhibitor and an agent for the disuse of muscular atrophy caused by oral cavity. 4 Inhibition of muscle contraction by the inventors The present inventors and others, in order to achieve the above object, It is pointed out that the substances with anti-oxidant effect involved in the waste research involved in oxidative stress can be re-examined by ingesting species with anti-oxidant substances. Sexual muscle atrophy 1 Right: ,,, found two special, at the same time found the completion of the present invention for the wasteful muscle atrophy C fruit. The fact of the system, then reached: = According to the present invention, you can provide fruit containing ",, Eight Feature Muscles Atrophy suppression composition. Phenol as an active ingredient

1225789 五、發明說明⑷ ^ 成發:月，則可提供係為廢用性肌萎縮抑制％ 之上述肌萎縮抑制組成物。 刺組 成：為廢;丨：提供含有果實聚苯盼作為有效 低之、•且成： 用肌萎縮時之骨重量及骨鹽量降 發明立最佳刑態 羊述本發明組成物中作為有效成分$罢#取# 该果實聚苯酚為包含由屬於成刀之果只聚本酚，則 果、梨子、棑+、回微科之果實，特別為由蘋 聚苯酚餾分、$ + @榨，十果汁、卒取液所精製之 色月等。此聚苯酚餾分之精製：：::，所卒取之原化 附劑進行處理，且聚苯 2汁果'汁卒取液以吸 出，則可將聚苯附⑽以含水酒精予以溶 此聚幕紛餾分其次經由濃 更且，將聚苯龄館分之漠縮液；以液體製劑。 理，則亦可取得粉末製劑。 噴霧乾燥或冷凍乾燥處 於上述中，原料為屬於薔薇科之 例如蘋果、梨子、桃子等，且 果貫，具體而言可列舉 可使用成熟果實、或未熟果實均；以蘋果為佳。又，果實 酚化合物、及含有大量具有廣泛=由含有更多之聚苯 而言，則以未熟果實為特佳。 乍用之各種活性成分 摊汁方法為將原料洗淨，並就 一邊弄碎、壓榨取得榨汁果汁，&冢樣或一邊添加亞硫酸 乂佳為添加果膠分解酶。 第7頁 \\312\2d-code\89-ll\89118696.ptd 1225789 五、發明說明（5) 其次，由離心分離、過濾等手段，取得澄清果汁之方法。 又，萃取方法為將洗淨之原料與醇類（乙醇、甲醇等）混合 弄碎，並就其原樣浸潰及壓榨、或一邊加熱迴流一邊=口 取，其次經由減壓濃縮除去醇類後，離心分離及過濾，或 i以有機溶劑（己烷、氯仿等）進行分配及過濾，取得^清 取液之方法。 精製方法可為令上述之澄清果汁或澄清萃取液，通過充 真以令聚苯酚類選擇性吸附且溶離之吸附劑，例如苯乙烯 -一乙烯基苯系之合成吸附樹脂、陰離子交換樹脂、十八 ，基化學鍵結型石夕膠⑽s)等之柱中’ 。其:欠，通過蒸館水將其洗淨後，於柱中通過:刀〜被 ==彳如乙醇)溶液、較佳為約5〇%醇 ' 盼館分：以溶出、回收。將所得之聚苯盼溶二 為添加韻果酸等之有機於Γ Λ實&本紛液體製劑（較佳 茨不Π文f I頁機酸）。更且，將液 或添加糊精等之粉末助劑，進 厂/、原樣 可取得果實聚苯酴粉=劑進订嘴霧乾無或冷壤乾燥，則 本發明所用之果實聚苯酚的組 型式之咖啡酸衍生物、針巷:缺成為早純t本盼化合物 4欠㈣1、：：： 香五酸衍生物、黃烷-3-醇類 (兒木馱類）、兴酮-3_醇類(槲皮酮配糖體 爾酮類（根皮素配糖體類）等、或一/化查 式之縮合型單寧類等佔大部分次以间刀子&本酚化合物型 本發明之肌萎縮抑味丨丨έ日士、t从 有效成分，調製成—般的醫筚：：土？, f實聚苯酚作為 奴W資柰。口及食品型態，並且對包含 麵 \\312\2d-code\89-ll\89118696.ptd 12257891225789 V. Description of the invention 成 ^ Hair formation: Month, the above-mentioned muscular atrophy inhibiting composition which is a% inhibition of disuse muscle atrophy can be provided. Thorn composition: as waste; 丨: Provide polyphenylene containing fruit as effective, low and effective: Use the bone weight and bone salt content of muscle atrophy to reduce the optimal penal state of sheep. The composition of the present invention is effective Ingredient $ 494 # 取 # The fruit polyphenol is a polyphenol containing the fruit that belongs to the knife, and the fruit, pear, 、 +, and the fruit of Weike, especially the polyphenol fraction from Ping, $ + @press, Juices and color moons refined by fluid extraction. Refining of this polyphenol fraction ::::, the original aquatizing agent taken for processing, and the polyphenyl 2 juice fruit juice extract to suck out, you can dissolve the polyphenylene oxide with water alcohol Mufen fraction is followed by thickening, and the polyphenylene age fraction is shrunken; the liquid preparation is used. It is also possible to obtain powder preparations. In the above, spray-drying or freeze-drying is used. The raw materials are from the family Rosaceae, such as apples, pears, peaches, and the like, and the fruit is consistent. Specific examples include mature and unripe fruits. Apples are preferred. In addition, the fruit contains a large amount of phenolic compounds, and from the viewpoint of containing more polybenzene, it is particularly preferable that the fruit is unripe. The various active ingredients used at first are the method of washing the raw materials, and crushing and squeezing to obtain the juice, and adding sulphite, or adding sulfite. It is better to add pectinolytic enzyme. Page 7 \\ 312 \ 2d-code \ 89-ll \ 89118696.ptd 1225789 V. Description of the invention (5) Secondly, the method of clarifying the juice is obtained by centrifugation and filtration. In addition, the extraction method is to mix the washed raw materials with alcohols (ethanol, methanol, etc.) and crush them, and immerse and squeeze them as they are, or take them under heating while refluxing, and then remove the alcohols by concentration under reduced pressure. , Centrifugation and filtration, or i using organic solvents (hexane, chloroform, etc.) for distribution and filtration to obtain ^ clear liquid extraction method. The refining method may be an adsorbent for making the above-mentioned clarified fruit juice or clarified extract liquid to make polyphenols selectively adsorb and dissolve by filling, such as a styrene-monovinylbenzene-based synthetic adsorption resin, anion exchange resin, ten Eight, in the column of the base chemical bond type Shi Xijiao ⑽). It: owe, wash it with steamed water, and then pass it through the column: knife ~ be = = 彳 such as ethanol) solution, preferably about 50% alcohol 'Hope to collect: to dissolve, recover. The obtained polyphenylene oxide was organically added to rhodamine and the present liquid preparation (preferably Cibu f.p.p. organic acid). In addition, if a liquid or a powdered additive such as dextrin is added into the factory, the fruit polyphenylene oxide powder can be obtained as it is. Types of caffeic acid derivatives, needle lanes: lack of early-purity t this desired compound 4 ㈣1 ::: pentanoic acid derivatives, flavan-3-ols (gerberyls), xanthone-3_ Alcohols (quercetin glycosides, ketones (phlorizin glycosides), etc.), or condensed tannins, etc. account for most of the time. Invented muscle atrophy and taste 丨 丨 Japanese, t from the active ingredients, prepared into a general medical formula :: earth ?, f real polyphenols as slaves W food. Mouth and food types, and contains noodles \ \ 312 \ 2d-code \ 89-ll \ 89118696.ptd 1225789

五、發明說明（6) 人類之哺乳動物投與或供食用。 ▲將本發明組成物調製成醫藥品型態時，所得之醫藥品蜇 態可使用有效成分與通常的製劑載體，經由二般的製劑化 手段進行調製。此處之製劑載體根據製劑的使用又塑態，町 p示通常所使用的充填劑、增量劑、黏合劑、附濕劑、崩 散劑、界面活性劑、潤滑劑等之稀釋劑或賦形劑了且其玎 根據所得製劑之投與單位型態而適當選擇使^ : 上，醫藥製劑之投與單位型態可根據治療目的而選擇各 ，型態，其代表例可列舉錠劑、丸劑、散劑、⑧劑、懸浮 j、乳劑、顆粒劑、膠囊劑、注射劑（液劑、懸浮劑等） 成形，錠劑型態時，上述之製劑載體可使用例如乳糠、 ^ ^氯化鈉、葡萄糖、尿素、澱粉、碳酸鈣、高嶺土、5. Description of the invention (6) Human mammals are administered or provided for food. ▲ When the composition of the present invention is prepared into a pharmaceutical form, the obtained pharmaceutical form can be prepared by using an active ingredient and a general preparation carrier through two general preparation methods. The formulation carrier here is also plastic according to the use of the formulation. It shows the diluents or excipients of fillers, extenders, adhesives, moisturizers, disintegrating agents, surfactants, lubricants, etc. that are commonly used. The dosage unit is appropriately selected according to the dosage unit type of the obtained preparation. In the above, the dosage unit type of the pharmaceutical preparation can be selected according to the purpose of the treatment. The typical examples include tablets and pills. , Powder, tincture, suspension j, emulsion, granules, capsules, injections (liquid, suspension, etc.) in the form of tablets, the above-mentioned preparation carriers can use, for example, milk bran, ^ sodium chloride, Glucose, urea, starch, calcium carbonate, kaolin,

、、、口曰=纖維素、矽酸、磷酸鉀等之賦形劑丨水、乙醇 =醇、單糖漿、葡萄糖液、澱粉液、明膠溶液、羧甲基纖 $素、羥丙基甲基纖維素、羥丙基纖維素、甲基纖雉素、 2 Γ婦基吼α各烷酮等之黏合劑；羧甲基纖維素鈉、羧甲基 纖維^、低取代度羥丙基纖維素、交聯羧甲基纖維素 $ 乾燥I粉、藻酸鈉、洋菜粉末、昆布多糖粉末、破酸 ^ ^ a ^酸詞、叛曱基殿粉納、部分α化澱粉等之崩散 :酸梨糖酸酐脂肪_類、月桂基硫酸鈉、硬 ^ /由酯專之界面活性劑；白糖、硬脂精、可可脂、 氮化’由等之崩散抑制劑；四級銨鹼、月桂基硫酸鈉等之吸 進劑、甘油、澱粉等之保濕劑；澱粉、乳糠、高嶺Excipients: cellulose, silicic acid, potassium phosphate, etc. Water, ethanol = alcohol, monosyrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, hydroxypropylmethyl Adhesives of cellulose, hydroxypropyl cellulose, methylcellulose, 2 Γ alkynyl alkanone, etc .; sodium carboxymethyl cellulose, carboxymethyl cellulose ^, low-substituted hydroxypropyl cellulose , Cross-linked carboxymethyl cellulose $ Dry I powder, sodium alginate, agar powder, konbu polysaccharide powder, acid breaking ^ ^ a ^ acid word, besom powder, sodium starch, etc. disintegration: Sodium sorbitan fats_, sodium lauryl sulfate, hard ^ / ester specific surfactants; white sugar, stearin, cocoa butter, nitriding, etc .; disintegration inhibitors; quaternary ammonium base, laurel Sodium sulfate and other humectants, glycerin, starch and other humectants; starch, milk bran, kaolin

1225789 五、發明說明（7) 土、膨潤土、膠體狀矽酸等之吸附劑；精製滑石、硬脂酸 鹽、硼酸粉末、聚乙二醇等之潤滑劑等。 更且，錠劑視需要可作成施以通常劑皮之錠劑，例如糖 衣錠、明膠包被錠、腸溶被錠、薄膜塗層錠或雙重錠、多 · 層旋。 - 成形為丸劑型態時，其製劑載體可使用例如葡萄糖、乳 糖、澱粉、可可脂、硬化植物油、高嶺土、滑石等之賦形 劑；***膠粉末、黃耆膠粉末、明膠、乙醇等之黏合 劑；昆布多糖、洋菜等之崩散劑等。 膠囊劑可將有效成分與上述例示之各種製劑載體混合 後，充填至硬質明膠膠囊、軟質膠囊等即可調製。 又，液劑（懸浮劑）、顆粒劑等亦可使用上述之各種製劑 載體，依常法則可輕易調製。 更且，於醫藥製劑中，視需要可含有著色劑、保存劑、 — 香料、風味劑、甜味劑等及其他之醫藥品。 ， 上述醫藥製劑中所必須含有之有效成分果實聚苯酚之份 量，並無特別限定，可由廣泛範圍中適當選取，但通常若 為醫藥製劑中含有約1〜70重量％左右即可。 上述醫藥製劑之投與量可根據其用法，患者年齡、性別 等條件、疾病程度等而適當選取，其通常令有效成分為可 發揮其本來作用之有效量即可。該份量可根據所用之有效 成分而適當決定，並無特別限制，一般為成人1日體重每1 公斤每1日以約0. 5〜5 0 0毫克左右即可，且該製劑可為1日 1回或分成2〜4回投與。1225789 V. Description of the invention (7) Adsorbents for soil, bentonite, colloidal silicic acid, etc .; lubricants such as refined talc, stearates, boric acid powder, polyethylene glycol, etc. Furthermore, if necessary, the lozenges can be made into lozenges, such as sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets or double tablets, and multi-layered spines. -When it is formed into a pill form, its formulation carrier can use excipients such as glucose, lactose, starch, cocoa butter, hardened vegetable oil, kaolin, talc, etc .; gum arabic powder, tragacanth powder, gelatin, ethanol, etc. Agents; disintegrating agents such as kumbu polysaccharides, agar, etc. Capsules can be prepared by mixing the active ingredient with various formulation carriers as exemplified above and filling them into hard gelatin capsules, soft capsules, and the like. In addition, liquid preparations (suspensions), granules, and the like can also be prepared using the above-mentioned various preparation carriers, and can be easily prepared according to the usual rules. Furthermore, the pharmaceutical preparation may contain a coloring agent, a preservative, a flavor, a flavoring agent, a sweetener, and other pharmaceuticals as needed. The amount of the fruit polyphenol, which is an effective ingredient that must be contained in the above-mentioned pharmaceutical preparations, is not particularly limited and may be appropriately selected from a wide range, but it is generally sufficient if the pharmaceutical preparation contains about 1 to 70% by weight. The dosage of the above pharmaceutical preparations can be appropriately selected according to its usage, conditions such as the age, sex of the patient, and the degree of the disease, etc. It is usually sufficient that the effective ingredient is an effective amount that can exert its original effect. The amount can be appropriately determined according to the active ingredients used, and is not particularly limited. Generally, an adult's weight per day is about 0.5 to 500 mg per 1 kg, and the preparation can be 1 day. 1 round or divided into 2 to 4 rounds of administration.

89118696.ptd 第10頁 1225789 五、發明說明（8) " ' &又，本發明組成物亦可實用為食品型態。此處，食品型 態為例如包含飲料、錠劑、可嚼錠劑、點心類、塊狀型 態、餅乾、糕點等通常之全部的食品型態。 將通常所知 糖醇類、甜 增黏劑、界 流動性改善 上述添加劑 食品型態之本發明組成物可於有效成分中 之各種添加劑成分，例如糖類（募糖類除外） 味料等、職形劑、黏合劑、崩散劑、潤滑劑 面活性劑、電解質、香料、色素、pH調整劑 知維生素類等予以適當配合添加則可調製。上述添加劑 可例示例如小麥澱粉、馬鈴薯澱粉、玉米澱粉、糊精二 澱粉類；蔗糖、葡萄糖、果糖、麥芽糖、木糖、乳糖等 糖類，山梨醇、甘露醇、多元醇、木糖醇等之糖醇類·石来 酸鈣、硫酸鈣等之赋形劑；澱粉、糖類、明膠、***夕牛 ，糊精、甲基纖維素、聚乙烯基咄咯烷酮、聚乙烯、 經丙基纖維素、咕吨膠、果膠、黃耆膠、絡蛋白、 f黏合劑或增黏劑；白胺酸、異白胺酸、L—纈胺酸、糖 酉二硬化油、硬脂酸、硬脂酸鎮、滑石、$ P ?月曰專之界面活性劑；阿斯巴甜、阿 其他之st—=甜 品型態調ί發明組成物之此些食 此所得之本發明食品可經口 。苴 般若以錠劑為例，則將〗鍵_ e R * 〃攝取（服用）Ι — 量為其大致之標準 叙約0·5〜6克之鍵劑攝取數錠之 第11頁 89H8696.ptd 1225789 五、發明說明（11) 碳酸氫鈉 22% 檸檬酸鈉 適量 碳酸鉀 0.4% 香料·著色料 微量 合計 100%(全量5克） <實施例9配方> AP 40% L-抗壞血酸 11% L-酒石酸 23% 甜味料 適量 碳酸氫鈉 22% 擰檬酸銨 0. 8 °/〇 氰鈷胺素（維生素B12) 微量 檸檬酸鈉 微量 碳酸鉀 0. 4°/〇 香料·著色料 微量 合計 100%(全量4. 6 ) <實施例1 0配方〉 AP 40% L-酒石酸 29% 甜味料 適量 碳酸氫鈉 24% 檸檬酸鐵銨 3.6% 氰鈷胺素 微量 « Φ89118696.ptd Page 10 1225789 V. Description of the invention (8) " '& Furthermore, the composition of the present invention can also be practically used in the form of food. Here, the food type is, for example, a general food type including a drink, a lozenge, a chewable lozenge, a snack, a block type, a biscuit, and a cake. Commonly known sugar alcohols, sweet tackifiers, and fluidity-improving additives of the present invention can be used as various additives in the active ingredients, such as sugars (except sugars), flavors, etc. Additives, adhesives, disintegrating agents, lubricants, surfactants, electrolytes, perfumes, pigments, pH adjusters, vitamins, and the like can be prepared by appropriate addition. Examples of the above-mentioned additives include wheat starch, potato starch, corn starch, dextrin distarch; sugars such as sucrose, glucose, fructose, maltose, xylose, and lactose; sugars such as sorbitol, mannitol, polyol, and xylitol; Alcohols, excipients such as calcium selenate, calcium sulfate; starch, sugars, gelatin, Arabian cattle, dextrin, methyl cellulose, polyvinylpyrrolidone, polyethylene, propyl cellulose , Gutton gum, pectin, tragacanth, complex protein, f-adhesive or thickener; leucine, isoleucine, L-valine, glycerol second hardened oil, stearic acid, stearin Acidic town, talc, $ P? Month-specific surfactants; aspartame, other st- = dessert-type modulation of the composition of the invention, the food of the present invention can be obtained by mouth. In general, if a tablet is taken as an example, the key _ e R * 〃 is ingested (taken) Ⅰ — the amount is approximately the standard 0.5 ~ 6 grams of the key agent to take several tablets of 89H8696.ptd 1225789 V. Description of the invention (11) Sodium bicarbonate 22% Sodium citrate Appropriate amount of potassium carbonate 0.4% Flavor and coloring material trace total 100% (5 g in total) < Example 9 formulation > AP 40% L-Ascorbic acid 11% L -Tartaric acid 23% sweetener moderate amount of sodium bicarbonate 22% ammonium citrate 0.8 ° / 〇 cyanocobalamin (vitamin B12) trace sodium citrate trace potassium carbonate 0.4 ° / 〇 perfume · coloring material trace total 100% (total amount of 4.6) < Example 1 0 Formula> AP 40% L-tartaric acid 29% sweetener moderate amount of sodium bicarbonate 24% ferric ammonium citrate 3.6% trace amount of cyanocobalamin Φ

\\312\2d-code\89-ll\89118696.ptd 第14頁 1225789 五、發明說明（12) 0.5% 微量 100%(全量4克） 碳酸鉀 香料·著色料 合計 實施例1 1〜1 8 同實施例7〜1 0處理，調製下述表2所示組成之發泡製劑 型態之本發明組成物。 [表2 ] 構成成分(％) 實施例No. 11 12 13 14 15 16 17 18 AP 40 30 40 60 50 35 45 35 L-抗壞血酸 11 16 10 8 10 10 10 13 L-酒石酸 23 23 23 13 19 20 20 25 甜味料 適量 適量 適量 適量 適量 適量 適量 適量 福酸氫鈉 22 22 23 15 15 20 20 23 檸檬酸鐵銨 0.8 0.8 1.0 0.8 0.8 - - 0.7 檸檬酸第1鐵鈉 - - - - '- 1.2 - - mmm - - - - - - 0.8 - 氰鈷胺素 微量 微量 微量 微量 微量 微量 微量 微量 —檸檬酸鈉 適量 適量 適量 適量 適量 適量 適量 適量 香料·色素 適量 適量 適量 適量 適量 適量 適量 適量 全重量(g) 4.6 4.6 4.7 4.6 4.6 4.7 4.7 5.4 « 實施例1 9〜2 5 將下述表3所示之各成分（毫克）混合’並經由直接壓縮 法，調製可嚼錠型態之本發明組成物。\\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 14 1225789 V. Description of the invention (12) 0.5% Trace amount 100% (4g in total) Potassium carbonate flavor · Coloring material total Example 1 1 ~ 1 8 In the same manner as in Examples 7 to 10, the composition of the present invention in the form of a foaming preparation having the composition shown in Table 2 below was prepared. [Table 2] Component (%) Example No. 11 12 13 14 15 16 17 18 AP 40 30 40 60 50 35 45 35 L-ascorbic acid 11 16 10 8 10 10 10 13 L-tartaric acid 23 23 23 13 19 20 20 25 Sweet Seasoning Moderate Moderation Moderation Moderation Moderation Moderation Moderation Moderation Moderation Moderate Moderation Moderate Sodium Hydrogen Formate 22 22 23 15 15 20 20 23 Ammonium Citrate 0.8 0.8 1.0 0.8 0.8--0.7 1st Sodium Iron Citrate----'-1.2 --mmm------0.8-Cyanocobalamin Trace Trace Trace Trace Trace Trace Trace Trace-Sodium citrate, appropriate amount, appropriate amount, appropriate amount, appropriate amount, appropriate amount, appropriate amount, appropriate amount, appropriate amount, appropriate amount, appropriate amount, full weight (g ) 4.6 4.6 4.7 4.6 4.6 4.7 4.7 5.4 «Example 1 9 ~ 2 5 The ingredients (mg) shown in Table 3 below were mixed 'and the composition of the present invention in the form of a chewable tablet was prepared by a direct compression method.

\\312\2d-code\89-ll\89118696.ptd 第15頁 1225789 五、發明說明（13) [表3] 構成成分(mg) 實施例Να 丨 19 20 21 22 23 24 25 AP 1800 3600 4620 700 3330 600 350 蔗糖酯 40 80 841 20 80 15 7 聚葡葡糖 150 400 300 100 300 60 60 蔗糖 100 200 200 20 200 80 20 維生素C 150 320 200 20 200 - - 柑橘果汁粉末 80 150 - - 100 20 5 檸檬果汁粉末 - - 84 40 - 10 5 酒石酸 - - - - 460 95 50 NaHCO, - - - 500 100 50 K2CO, 30 40 40 40 30 8 8 香料·甘味料 適量 適量 適量 適量 適量 適量： 適量 全重量(毫克） 2400 4950 5580 1000 5200 1000 5000 實施例26〜34 將下述表4所示之各成分混合，加水至全量為100毫升 調製成健康飲料型態之本發明組成物。 [表4] ) 構成成分 (100毫升中） 實 施 例No. 26 27 28 29 30 31 32 33 34 /3-胡蘿蔔素(毫克） 3 5 10 15 1 2 30 5 3 聚葡萄糖(克） 5 3 5 7 4 2 10 20 20 乳化劑(毫克） 6 10 20 30 5 6 20 15 8 油劑(毫克） 100 90 80 120 50 50 200 70 60 ( 果糖(克） - 15 10 15 15 15 5 10 檸檬酸(毫克） 200 400 100 300 50 20 - - - 酒石酸(毫克） - - 50 - 50 10 100 200 - 乳酸(毫克） - - - - 50 10 100 - 200 抗壞血酸(毫克） 300 200 100 50 30 150 200 1000 50 生育酚(毫克） 10 5 10 20 20 0.5 20 10 5 AP(克） 2 5 10 3 8 7 5 12 10 香料·甘味料 適量 適量 適量 適量 適量 適量 適量 適量 適量 II 1 \\312\2d-code\89-ll\89118696.ptd 第 16 頁 1225789 五、發明說明（14) 實施例3 5〜4 5 將下述表5所示之各成分混合，加水至全量為1 〇 〇毫升’ 調製成飲料型態之本發明組成物。 尚，表中之氣體體積值為令溶液與同體積之二氧化碳氣 體溶解時視為1，所算出之表示二氧化碳含量之指標’此 數值愈大則表示二氧化碳含量愈大。 [表5] 構成成分 (100毫升中） 實施例No. 35 36 37 38 39 40 41 42 43 44 45 AP(克） 3 12 9 1 8 2 4 10 15 7 13 異構糖(克） 8 - - 7 7 8 5 - - 9 - 精製白糖(克） - 1 8 3 7 5 3 - - - - 果糖(克） 2 6 - 1 - - 3 - - - 60 葡萄糖(克） 2 2 - - 2 - 3 - - 2 4 檸檬酸(毫克） 3 2 - - 8 - - 2 5 - - 酒石酸(毫克） - 2 - 2 - - - - - 10 - 蘋果酸(毫克） 4 - 8 - 5 - 4.5 - - - - 乳酸(毫克） 8 - - 2 - 20 - - - 10 - 檸檬酸鈉(毫克） 20 30 10 - 80 - 讎 100 55 70 - 酒石酸鈉(毫克） 60 - - 60 25 70 - - - 30 20 蘋果酸鈉(毫克） - 80 150 - - 100 45 - 10 - 50 乳酸鈣(毫克） - - - - 15 10 - - - - 5 氯化鈣(毫克） - - 4 - 1 1.5 - - 2 - - 氯化鉀(毫克） - 3 - 2 - - 5 - 1 1 - 氯化鎂(毫克） 2 - 1 - - - - - 1 - - 果汁(％) 3 - 1 0.5 0.1 - - 讎 - 2 0.3 香料·甘味料 適量 適量 適量 適量 適量 適量 適量 適量 適量 適量 適量 氣體體積 - - - - - 3.0 2.0 2.5 2.3 3.3 1.5 pH 5.0 6.3 5.8 4.9 5.8 5.3 5.5 5.6 6.4 5.6 5.9 «\\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 15 1225789 V. Description of the invention (13) [Table 3] Component (mg) Example Nα 丨 19 20 21 22 23 24 25 AP 1800 3600 4620 700 3330 600 350 Sucrose Ester 40 80 841 20 80 15 7 Polyglucose 150 400 300 100 300 60 60 Sucrose 100 200 200 20 200 80 20 Vitamin C 150 320 200 20 200--Citrus Juice Powder 80 150--100 20 5 Lemon Juice Powder--84 40-10 5 Tartaric Acid----460 95 50 NaHCO,---500 100 50 K2CO, 30 40 40 40 30 8 8 Spices, sweeteners, moderate, moderate, moderate, moderate (Mg) 2400 4950 5580 1000 5200 1000 5000 Examples 26 to 34 The ingredients shown in Table 4 below were mixed, and water was added to a total amount of 100 ml to prepare a composition of the present invention in the form of a healthy beverage. [Table 4]) Components (in 100 ml) Example No. 26 27 28 29 30 31 32 33 34 / 3-carotene (mg) 3 5 10 15 1 2 30 5 3 Polydextrose (g) 5 3 5 7 4 2 10 20 20 Emulsifier (mg) 6 10 20 30 5 6 20 15 8 Oil (mg) 100 90 80 120 50 50 200 70 60 (Fructose (g)-15 10 15 15 15 5 10 Citric acid ( Mg) 200 400 100 300 50 20---tartaric acid (mg)--50-50 10 100 200-lactic acid (mg)----50 10 100-200 ascorbic acid (mg) 300 200 100 50 30 150 200 1000 50 Tocopherols (mg) 10 5 10 20 20 0.5 20 10 5 AP (g) 2 5 10 3 8 7 5 12 10 Spices and sweeteners appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount II 1 \\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 16 1225789 V. Description of the invention (14) Example 3 5 ~ 4 5 The ingredients shown in Table 5 below are mixed, and water is added to a total amount of 100 ml 'to prepare a beverage type. The composition of the present invention is still in the state. However, the gas volume value in the table is regarded as 1 when the solution is dissolved with the same volume of carbon dioxide gas. Index indicating carbon dioxide content 'The larger the value, the larger the carbon dioxide content. [Table 5] Composition (100 ml) Example No. 35 36 37 38 39 40 41 42 43 44 45 AP (g) 3 12 9 1 8 2 4 10 15 7 13 Isomerized sugar (g) 8--7 7 8 5--9-Refined white sugar (g)-1 8 3 7 5 3----Fructose (g) 2 6-1- -3---60 Glucose (g) 2 2--2-3--2 4 Citric acid (mg) 3 2--8--2 5--Tartaric acid (mg)-2-2----- 10-Malic acid (mg) 4-8-5-4.5----Lactic acid (mg) 8--2-20----10-Sodium citrate (mg) 20 30 10-80-雠 100 55 70- Sodium tartrate (mg) 60--60 25 70---30 20 Sodium malate (mg)-80 150--100 45-10-50 calcium lactate (mg)----15 10----5 Chlorine Calcium (mg)--4-1 1.5--2--Potassium chloride (mg)-3-2--5-1 1-Magnesium chloride (mg) 2-1-----1--Fruit juice ( ％) 3-1 0.5 0.1--雠-2 0.3 Spices, sweeteners, right amount, right amount, right amount, right amount, right amount Moderate Moderate Moderate Gas volume-----3.0 2.0 2.5 2.3 3.3 1.5 pH 5.0 6.3 5.8 4.9 5.8 5.3 5.5 5.6 6.4 5.6 5.9 «

\\312\2d-code\89-ll\89118696.ptd 第17頁 1225789 五、發明說明（15) j式驗例1 萎縮抑制試驗例 以下列方法進行試驗。 (1)供試動物 微生物學的品質：SPF/VAF)全部\\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 17 1225789 V. Description of the invention (15) J-type test example 1 Atrophy suppression test example The test was performed by the following method. (1) Microbiological quality of test animals: SPF / VAF) All

Wistar系公鼠（12週齡 使用2 1隻。 7 (2 )實驗群： 11 貫驗群：AP投與群（a群 對照群：（C群、η =1〇) (3) 實驗方法： 鼠為以每1籠1隻之條件下飼養，並以工2小 期 (明期8:00-20:00) 。 τ ] a θ η 』 將鼠j戊巴必妥鈉(5〇毫克/公斤）全身麻醉下，於右側 根關Ip部令足根關節伸展之狀態下施以石膏固定、。石春 固定，進行12日，誘發其廢用性萎縮。於解除石立‘ 迅速採集兩側的平行肌及脛骨。 、m (4) 試驗飼料投與方法 於石貧固定期間中，A群為給與市隹 侧其組成示於表π中添加1%AP之料AIN 「AD」），C群為給與未添加AP的粉末飼料AiN^=為Wistar male rats (21 at 12 weeks of age. 7 (2) Experimental group: 11 Consecutive group: AP administration group (a control group: (C group, η = 10)) (3) Experimental method: The mice were raised under the condition of 1 per cage, and the labor period was 2 hours (8: 00-20: 00 tomorrow). Τ] a θ η ① Rat pentobarbital sodium (50 mg / Kg) Under general anesthesia, cast gypsum in the state where the right root root Ip part stretches the foot root joint. Shichun fixation is carried out for 12 days, which induces its atrophic atrophy. When Shi Li's was lifted, rapid collection of the two Parallel muscles and tibia., M (4) Test feed administration method During the period of stone-poor fixation, group A is given to the market side and its composition is shown in Table π with 1% AP added material (AIN "AD"), C The group was given a powder feed AiN without added AP ^ =

1225789 五、發明說明（16) [表6 ] 組成(g/kg食餌） AIN-93G AD 玉米澱粉*1 529.49 524.49 酪蛋白 200.00 200.00 蔗糖*2 100.00 100.00 大豆油*1 70.00 70.00 纖維素粉末Μ 50.00 45.00 礦物質混合物(AIN-93型)*1 35.00 35.00 維生素混合物(AIN-93型)*丨 10.00 10.00 L-胱胺酸*3 3.00 3.00 酒石酸膽鹼*3 2.50 2.50 AP 0.00 10.00 第三丁基羥基醌*3 0.014 0.014 總能量(MJ) 15.60 15.60 尚，表6中，※1為Oriental酵母公司製，※2為KS公司 製，※3為和光純藥工業公司製。 飲食為一邊將攝食量調整至群間的攝食量不會產生差異 且一邊以給僻配對飼養（pair feeding)l日投與2回。飲食 時間為8 : 0 0-9 : 0 0及20 : 0 0-2 1 : 0 0。實驗期間中的飲水為自 由攝取自來水。 (5 )測定項目： •體重及攝食量： 體重為每天早上攝取食物後（9 : 0 0 )測定。攝食量為於每 日、9 : 0 0和2 1 : 0 0之飲食終了後，測定攝食前後之飼料箱 重量，並以其差視為攝食量。所有測定均使用電動天平。 •平行肌萎縮率： 平行肌為於採集後迅速地秤量，並以液態氮冷凍且以冷1225789 V. Description of the invention (16) [Table 6] Composition (g / kg bait) AIN-93G AD corn starch * 1 529.49 524.49 casein 200.00 200.00 sucrose * 2 100.00 100.00 soybean oil * 1 70.00 70.00 cellulose powder M 50.00 45.00 Mineral mixture (type AIN-93) * 1 35.00 35.00 Vitamin mixture (type AIN-93) * 丨 10.00 10.00 L-cystine * 3 3.00 3.00 Choline tartrate * 3 2.50 2.50 AP 0.00 10.00 Third butyl hydroxyquinone * 3 0.014 0.014 Total energy (MJ) 15.60 15.60 In Table 6, ※ 1 is made by Oriental Yeast Company, ※ 2 is made by KS Company, ※ 3 is made by Wako Pure Chemical Industries, Ltd. As for the diet, the feeding amount was adjusted to the feeding amount between the groups without causing a difference, and the pair was fed twice a day with pair feeding. The eating time is 8: 0 0-9: 0 0 and 20: 0 0-2 1: 0 0. Drinking water during the experiment was free to tap water. (5) Measurement items: • Body weight and food intake: Body weight is measured after taking food every morning (9: 0). The food intake was determined after each day, 9: 0 0 and 21: 0 0, the weight of the feed box before and after the meal was measured, and the difference was regarded as the food intake. All measurements were performed using an electric balance. • Parallel muscle atrophy rate: Parallel muscles are weighed quickly after collection, frozen in liquid nitrogen and frozen

\\312\2d-code\89-ll\89118696.ptd 第 19 頁 1225789 五、發明說明（17) 凍保存（-80 °C )直到分析為止。肌肉萎縮率為以下式算 出。 肌萎縮率（％ )=[(對側肌濕重量—萎縮肌濕重量）/對側肌 濕重量]X 1 0 0 ； •平行肌中游離鐵濃度： 肌肉中的游離鐵為根據將Zhang等人方法（Zhang, D.等 · 人，Biochem· Mol· Biol· Int.， 35， 635-641(1995))加 以改變之Ma等人之方法（Ma，Υ·等人，Path. Int.，47， 203-208(1997))進行萃取。將肌肉組織約2〇毫克以Hanks 溶液1· 8毫升予以均質化，且於此均質液5〇〇微升中加入 80mM硝基三醋酸（NTA)溶液（PH 7.0，50微升）並攪拌後， 於室溫下放置3 0分鐘。將此溶液使用超過濾器（分級分子 量3 萬，Wetrafree CL UFC4LTK25 、Millipore 公司製）進 行離心過濾（4 °C、3 0 0 0 r pm、6 0分鐘）。將回收的過濾液進 行超離心（4 °C、214〇rpm、60分鐘）。回收上清液。將此上 、 清液作為游離鐵測定用樣品溶液。樣品溶液之鐵濃度為根 據石墨原子化法之原子吸光度分析法進行測定。 •脛骨之乾燥重量及灰重量： 於預先恆量化及秤量之試管中放入骨樣品，並於真空供 爐中乾燥直到恆量化為止（1 〇 〇 °c、抽真空、6日）。秤量此 ¥ 時之重量，由其與試管重量之差，算出骨的乾燥重量。 又’令乾燥的骨樣品以烘爐予以灰化（6 0 0 °C、3日），冷卻 至室溫後，秤量重量。由此時之重量與試管重量之差，算 出灰重量。 ^\\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 19 1225789 V. Description of the invention (17) Frozen storage (-80 ° C) until analysis. The muscle atrophy rate is calculated by the following formula. Muscle atrophy rate (%) = [(wet weight of contralateral muscle-wet weight of atrophic muscle) / wet weight of contralateral muscle] X 1 0 0; • Free iron concentration in parallel muscles: Free iron in muscle is based on Zhang et al. Human method (Zhang, D. et al., Biochem. Mol. Biol. Int., 35, 635-641 (1995)), modified by the Ma et al. Method (Ma, Y. et al., Path. Int., 47, 203-208 (1997)). About 20 mg of muscle tissue was homogenized with 1.8 ml of Hanks' solution, and 500,000 microliters of the homogenate was added with 80 mM nitrotriacetic acid (NTA) solution (pH 7.0, 50 microliters) and stirred. , Let stand at room temperature for 30 minutes. This solution was subjected to centrifugal filtration (4 ° C, 300 rpm, 60 minutes) using an ultrafilter (classified molecular weight 30,000, Wetrafree CL UFC4LTK25, manufactured by Millipore). The recovered filtrate was subjected to ultracentrifugation (4 ° C, 2140 rpm, 60 minutes). The supernatant was recovered. The supernatant and the supernatant were used as a sample solution for measuring free iron. The iron concentration of the sample solution was measured according to the atomic absorbance analysis method of the graphite atomization method. • Dry weight and ash weight of the tibia: Bone samples were placed in test tubes that were previously quantified and weighed, and dried in a vacuum oven until constant quantification (1000 ° c, vacuum, 6 days). Weigh the weight at this ¥ and calculate the dry weight of the bone from the difference between it and the weight of the test tube. Furthermore, the dried bone samples were ashed in an oven (600 ° C, 3 days), cooled to room temperature, and weighed. From the difference between the weight at this time and the weight of the test tube, calculate the ash weight. ^

1225789 五、發明說明（18) •脛骨之鈣含量·· 於測定灰重量之樣品中，加入約2毫升之濃硝酸，並於 加熱繪圖器中以1 3 0 °C加熱乾燥。將此操作重覆2回，並令 所得之樣品溶解於1 %硝酸且依序稀釋，於最終稀釋樣品溶 液中添加氣化鑭作為安定劑。其次，將樣品溶液依據火焰 法之原子吸光分析法（壓縮空氣-乙炔氣體、測定波 長：422.7111111、縫隙：1.3111111、？11〇1:〇11131電壓：56(^、燈電流· 7 · 5 m A )測定。玻璃容器為使用全部經1 %硝酸予以酸處理 者。 (6 )統計方法 數據為全部以平均值及標準偏差表示。以配對七試驗進 行同一個體之石膏固定之萎縮侧後肢與對照側後肢的比 較，檢討石膏固定之影響。以不配對t試驗進行人群與c群 的比較。將P <0· 05時視為有意義差。 (7 )結果 結果不於下述表7及表8。1225789 V. Description of the invention (18) • Calcium content of the tibia · To the sample for measuring the ash weight, add about 2 ml of concentrated nitric acid, and heat and dry at 130 ° C in a heating plotter. This operation was repeated 2 times, and the obtained sample was dissolved in 1% nitric acid and sequentially diluted, and lanthanum gasification was added to the final diluted sample solution as a stabilizer. Next, the sample solution was subjected to the flame atomic absorption spectrometry method (compressed air-acetylene gas, measurement wavelength: 422.7111111, gap: 1.3111111,? 11〇1: 〇11131 voltage: 56 (^, lamp current · 7 · 5 m A ) Measurement. Glass containers are all treated with 1% nitric acid. (6) Statistical method data are all expressed as mean and standard deviation. Seven pairs of experiments were performed on the atrophy side hindlimb and control side of the same individual Comparison of hind limbs, reviewing the effect of plaster fixation. Comparison of the population and group C was performed by unpaired t test. P < 0.05 was regarded as a significant difference. (7) Results The results are not in the following Tables 7 and 8 .

1225789 (平均±標準偏差） A群(本發明群） C群(對照群） 石膏前體重(g) 石膏後體重(g) 374.5± 21.4 360.2± 21.6 372.6± 22.5 359.3± 26.3 平均攝食量(g/d) 13.6± 1.3 13.6± 1.2 AP 攝取量(mg/kg/d) 379± 36 - 平行肌重量(mg) 萎縮側 對照側 肌萎縮率 112± 10* 193± 12 41.8± 5.5* 104± 9* 200± 14 48.1± 4.1 游離鐵濃度(//g/g) 萎縮側 對照側 萎縮側/對照佩％) 1.7± 0.6 2·0± 0.8 91.2± 24.5? 2.1± 1.1* 1.6± 0.7 131.9± 35.4 # p < 0.05 VS.對，照(|j(paired t test) p< 0.05 vs. C 群(unpaired t test) 五、發明說明（19) [表7] [表8 ] (平均±標準偏差） A群(本發明群） C群(對照群） 脛骨乾燥重量(mg) 萎縮側 S_J 萎,i#』/對照側(％) 491.1± 30.8 497.5± 22.6 98.8± 6.4 489.8± 19.2* 506.2± 30.2 96.9± 3.7 灰重量(mg) 萎縮側 對照側 萎縮側/對照側(％) 297.2± 18.5 308.2± 14.6 96.5± 5.8 294.8± 7.5* 312.5± 15.7 94.5± 2.9 鈣含量(mg) 萎縮側 對照側 萎縮側/對照側(％) 95.0± 7.2 98.2± 4.8 96·8± 6.4 91.5± 3.3* 96.5± 4.9 94.9± 2.7 *·· p< 0.05 vs·對照側(paired t test) ❿ iBi \\312\2d-code\89-ll\89118696.ptd 第22頁 1225789 五、發明說明（20) 由該表7及8可匈知τ 體重及攝食量： 列情事。 於石膏固定期間中， 並未察見差異。石膏固二群（A群及C群）體重減少，於群間 差異。A群之AP平均胃攝"^期間中的攝食量於群間並未察見 士標準偏差）。 篁為379 ± 36毫克/公斤/天（平均 肌萎縮率： A群之肌萎縮率為比[ (41.8±5.5V.S. 48.1+7不出更低13%之有意義的低值 平行肌中游離鐵濃度：· 1 /°，P < 〇 · 01) 平行肌中之游離鐵濃度，於 示出有意義的更高值，作 萎縮侧為比對照側顯 未察見差異。 —； 中則在萎縮側與對照側中 A群與C群之間未察見差異。 肉中游離鐵濃度之比率，以A 、 ； 1照側之萎縮側之肌 低值。 群為比C群顯示出有意義的更 脛骨之乾燥重量、灰重量及鈣含量· 脛骨之乾燥重量，於C群之萎縮相 意義的更低值，但於A群中之墓扩〇二比對照側顯示出有 異。萎縮側/對照側（％)為在Α群群、對照側並未察見差 脛骨之灰重量，於C群之萎縮側為比未昭^見有意義差。 義的更低值，但於A群中之萎縮側與昭…、側顯不出有意 異。萎縮側/對照侧（％)為在A群與^群^側並未察見差 差。 〃 中並未察見有意義 \\312\2d-code\89-l1\89118696.ptd 第23頁 五、發明說明（21) 脛骨之鈣含量，、、 f的更低值，：於A於群縮側為比對照側顯示出有意 異。萎縮侧/對照側 委縮側與對照側並未察見差 差。 （)為在A群與c群中並未察見有意義 由以上情事，可知春 行肌的萎縮，且可 二固定中投與AP，則可有效抑制平 含量之減少。此經由之乾燥重量，*重量及鈣 參與抑制萎縮肌中之游^ ；；抑制平行肌之萎縮，認為其 生 鐵之增加。 右根據本發明，目丨丨 ^ 量和骨鹽量降低、:^供肌萎縮抑制組成物及抑制骨重 待抑制石膏固定黧2 ?，且此組成物於攝取下固然可期 所相關之高齡者廢用性肌萎縮，對於氧化應力 可期待抑制肌命i T萎 c〇penia)和進行性肌萎縮亦 例於肌肉量而抑：:、：低。& ’抑制肌肉量之降低乃為比 肉力量之維量的降低。特別於高齡者中，肌 危險降低】於個體平衡能力之維持’，令倒轉之 4 &並且亦可預防倒轉所造成之骨折及其對於睡眠 所k成的強烈危險。又，因為肌肉為生體内最大的能 里耗組織’故維持肌肉量可防止糖代謝及脂質代謝的亞 W 亦可期待預防糖尿病和動脈硬化等的生活習慣疾 ^ ° ^且’亦可期待抑制已報導隨著肌肉量降低而減少之 骨重量和骨鹽密度的降低。1225789 (mean ± standard deviation) Group A (group of the present invention) Group C (control group) Weight before gypsum (g) Weight after gypsum (g) 374.5 ± 21.4 360.2 ± 21.6 372.6 ± 22.5 359.3 ± 26.3 Mean food intake (g / d) 13.6 ± 1.3 13.6 ± 1.2 AP intake (mg / kg / d) 379 ± 36-Parallel muscle weight (mg) Atrophy rate Control muscle atrophy 112 ± 10 * 193 ± 12 41.8 ± 5.5 * 104 ± 9 * 200 ± 14 48.1 ± 4.1 Free iron concentration (// g / g) Atrophy side (control side atrophy side / control wear%) 1.7 ± 0.6 2 · 0 ± 0.8 91.2 ± 24.5? 2.1 ± 1.1 * 1.6 ± 0.7 131.9 ± 35.4 # p < 0.05 VS. Yes, according to (| j (paired t test) p < 0.05 vs. C group (unpaired t test) V. Description of the invention (19) [Table 7] [Table 8] (mean ± standard deviation) Group A (group of the present invention) Group C (control group) Dry weight of tibia (mg) Atrophy side S_J atrophy, i # "/ control side (%) 491.1 ± 30.8 497.5 ± 22.6 98.8 ± 6.4 489.8 ± 19.2 * 506.2 ± 30.2 96.9 ± 3.7 Ash weight (mg) Atrophy side Control side Atrophy side / Control side (%) 297.2 ± 18.5 308.2 ± 14.6 96.5 ± 5.8 294.8 ± 7.5 * 312.5 ± 15.7 94.5 ± 2.9 Calcium content (mg) Atrophy side Control side Atrophy side / Correct Side (%) 95.0 ± 7.2 98.2 ± 4.8 96 · 8 ± 6.4 91.5 ± 3.3 * 96.5 ± 4.9 94.9 ± 2.7 * · p < 0.05 vs. control side (paired t test) ❿ iBi \\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 22 1225789 V. Description of the invention (20) From Tables 7 and 8, it can be known that τ weight and food intake: listed. During the period of plaster fixation, no difference was observed. The weight loss of the two groups (groups A and C) was different between the groups. The average gastric intake of APs in group A during the period (without seeing the standard deviation of the group). 379 is 379 ± 36 mg / kg / day (average muscle atrophy rate: the muscle atrophy rate of group A is not less than a significant low value of free iron concentration in parallel muscles of 13% lower than [(41.8 ± 5.5VS 48.1 + 7) : 1 / °, P < 〇 01) The free iron concentration in the parallel muscles shows a significantly higher value, and the atrophy side shows no difference than the control side. —; The middle side is on the atrophy side. No difference was seen between groups A and C in the control side. The ratio of the free iron concentration in the meat was A, 1; the muscle on the atrophy side of the photo side was low. The group showed a more significant tibia than the group C The dry weight, ash weight, and calcium content · The dry weight of the tibia has a lower value in the atrophic phase of group C, but the tomb expansion in group A is different from the control side. Atrophy side / control side (%) Is the ash weight of the poor tibia not seen in the group A and the control side, and the sign of the atrophy of the group C is significantly worse than that of the unidentified. The lower value of the meaning, but the atrophy of the group A No significant difference with Zhao ..., the atrophy side / control side (%) is that no difference is seen in the A group and the ^ group ^ side. Significance \\ 312 \ 2d-code \ 89-l1 \ 89118696.ptd Page 23 V. Description of the invention (21) The calcium content of the tibia, the lower value of f, f is: A on the group contraction side is better than the control side Shows intentional differences. No difference was seen between the atrophy side / control side atrophy side and control side. () In the above case, it is clear that the atrophy of the spring muscles can be seen from the above events. The second fixed medium dose of AP can effectively suppress the reduction of flat content. The dry weight, * weight, and calcium involved in the inhibition of swimming in atrophic muscles ^; inhibit the atrophy of parallel muscles, it is believed that the increase of pig iron. Right basis According to the present invention, the amount and the amount of bone salt are reduced, and the composition for inhibiting donor muscle atrophy and inhibiting bone weight are to be inhibited by gypsum fixation, and the composition can be expected to be used by elderly people who consume it. With muscular atrophy, oxidative stress can be expected to inhibit muscle atrophy (Copenia) and progressive muscle atrophy are also exemplified by the amount of muscle::,: Low. & ‘Suppressing the reduction in muscle mass is a reduction in the dimension of specific strength. Especially in the elderly, the muscle risk is reduced] in maintaining the individual's ability to balance, and it can prevent the fracture caused by the inversion and its strong danger to sleep. In addition, because muscle is the largest energy-consuming tissue in the body, maintenance of muscle mass can prevent glucose metabolism and lipid metabolism. It can also be expected to prevent lifestyle disorders such as diabetes and arteriosclerosis. Inhibition has been reported as a decrease in bone weight and a decrease in bone density as muscle mass decreases.

1225789 圖式簡單說明 Φ \\312\2d-code\89-ll\89118696.ptd 第25頁1225789 Schematic description Φ \\ 312 \ 2d-code \ 89-ll \ 89118696.ptd Page 25

Claims (1)

^M^J9U86g6 六、申請專利範圍‘ ι一種肌萎縮抑制組成 93. 7. 3 0 替換禾 Φ 上·一往肌委縮抑 為有=，於醫藥謙含有、=為含有蘋果聚苯酸作 2.如申請專利範圍第丨項纪/H0重量％左右。 為廢用性肌萎縮抑制組成物°。 委縮抑制組成物，其 3 ·如申清專利範 ^ 為醫藥品用組成物或食品、用組成物肌萎縮抑制組成物，其 4· 一種抑制廢用性肌萎縮時之 成物’其特徵為含有韻果聚苯料為量降，之組 果聚苯酚之醫藥製劑的投與量日人—刀二该含有頻 flR〜上丄 馬母曰成人母人每公斤投ik 與 該製劑1日投與1次或者分為2〜4次投” 5 ·=申印專利範圍第4項記載之抑制廢用性肌萎縮時之 骨重1及骨鹽量降低之組成物，其為醫藥品用組成物或食 品用組成物。 C:\ 總檔\89\89118696\89118696(替換）-2.ptc 第26頁^ M ^ J9U86g6 VI. Application scope of patent 'ι A composition for inhibiting muscle atrophy 93. 7. 3 0 Replace He Φ 上 · 一向 一 肌肌 结 变为 有 =, Yu Yaoqian contains, = contains apple polybenzoic acid for 2 . Such as the scope of the patent application of the first period / H0% by weight. It is a wasteful muscular atrophy suppression composition °. A contraction-inhibiting composition, which is 3. As claimed in the patent application of the patent ^ is a composition for medicine or food, a composition for inhibiting muscle atrophy, and 4. It is a product for inhibiting wasteful muscle atrophy. Its characteristics are: The amount of polyphenol containing rhizoma polyphenols is reduced. The dosage of the medicinal preparation of polyphenols of the group of fruits is daily—knife 2. The frequency of flR ~ the upper horse mother should be ik per kg and the preparation should be administered on the 1st. And 1 or divided into 2 to 4 shots "5 · = Composition for reducing bone weight 1 and bone salt reduction in waste muscle atrophy as described in item 4 of the scope of patent application, which is a composition for pharmaceuticals Or food composition. C: \ master file \ 89 \ 89118696 \ 89118696 (replace) -2.ptc page 26