JPS63198628A - Improver for functional disorder caused by stress comprising cistanocides as active ingredient - Google Patents
Improver for functional disorder caused by stress comprising cistanocides as active ingredientInfo
- Publication number
- JPS63198628A JPS63198628A JP62029534A JP2953487A JPS63198628A JP S63198628 A JPS63198628 A JP S63198628A JP 62029534 A JP62029534 A JP 62029534A JP 2953487 A JP2953487 A JP 2953487A JP S63198628 A JPS63198628 A JP S63198628A
- Authority
- JP
- Japan
- Prior art keywords
- stress
- active ingredient
- improver
- formula
- cistanocides
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000004480 active ingredient Substances 0.000 title claims abstract description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 6
- 125000005640 glucopyranosyl group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 241000196324 Embryophyta Species 0.000 abstract description 6
- 230000003071 parasitic effect Effects 0.000 abstract description 3
- 239000000284 extract Substances 0.000 abstract description 2
- 230000006870 function Effects 0.000 abstract description 2
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 244000025254 Cannabis sativa Species 0.000 abstract 1
- 241000336315 Cistanche salsa Species 0.000 abstract 1
- 241000308150 Orobanchaceae Species 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 230000009329 sexual behaviour Effects 0.000 description 21
- 239000003814 drug Substances 0.000 description 15
- -1 phenylpropanoid glycosides Chemical class 0.000 description 15
- 229940079593 drug Drugs 0.000 description 14
- 230000000694 effects Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 230000006399 behavior Effects 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 6
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 229930182470 glycoside Natural products 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 229930015704 phenylpropanoid Natural products 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 241000411851 herbal medicine Species 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000001766 physiological effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000195888 Physcomitrella Species 0.000 description 3
- 230000002180 anti-stress Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
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- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000000287 crude extract Substances 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 description 2
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000237537 Ensis Species 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 208000020358 Learning disease Diseases 0.000 description 1
- 241000234435 Lilium Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 208000019914 Mental Fatigue Diseases 0.000 description 1
- 241000204801 Muraenidae Species 0.000 description 1
- 208000007379 Muscle Hypotonia Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 208000012545 Psychophysiologic disease Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000009529 body temperature measurement Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000002021 butanolic extract Substances 0.000 description 1
- 229940074360 caffeic acid Drugs 0.000 description 1
- 235000004883 caffeic acid Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- FSBUXLDOLNLABB-ISAKITKMSA-N echinacoside Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC(=O)\C=C\C=2C=C(O)C(O)=CC=2)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)O[C@@H](OCCC=2C=C(O)C(O)=CC=2)[C@@H]1O FSBUXLDOLNLABB-ISAKITKMSA-N 0.000 description 1
- NJYVDFDTLLZVMG-UHFFFAOYSA-N echinacoside Natural products CC1OC(OC2C(O)C(OCCc3ccc(O)c(O)c3)OC(COC4OC(CO)C(O)C(O)C4O)C2OC(=O)C=Cc5cc(O)cc(O)c5)C(O)C(O)C1O NJYVDFDTLLZVMG-UHFFFAOYSA-N 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 230000012173 estrus Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000037805 labour Diseases 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
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- 230000002250 progressing effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
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- 230000036280 sedation Effects 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
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- 230000004580 weight loss Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は医薬、殊に肉促蓉から抽出されたシスツノサイ
ド類を有効成分とするストレスによる機能障害改善剤に
係る。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to pharmaceuticals, particularly to an agent for improving functional disorders caused by stress, which contains cystunosides extracted from Physcomitrella sinensis as an active ingredient.
（従来の技術）
肉促蓉は中華人民共和国における最古の本草書である「
神農本草経」にも収載されているように、古来から利用
されてきた生薬の一つであり、補養、強壮生薬として肉
促蓉丸、還少丹、葎蓉潤腸丸等の漢方処方に用いられ、
又単独で或は他の生薬類と共に薬用酒に用いられてきて
おり、今日においても貴重な藁材とされている。(Prior art) ``Niku Zhu Rong'' is the oldest herbal book in the People's Republic of China.
It is one of the herbal medicines that has been used since ancient times, as listed in the ``Shin-nong Bencao-jing'', and is used in Chinese herbal medicine prescriptions as supplementary and tonic herbal medicines, such as ``Jiyuu Ronggan'', ``Kanshaodan'', and ``Bayong Junchogan''. used,
It has also been used alone or together with other herbal medicines to make medicinal sake, and even today it is considered a valuable straw material.
肉促蓉とはハマウツボ科の寄生植物であって中華人民共
和国、モンゴル人民共和国及びシベリア地方に産するホ
ンオニク ［“Ｃｔｓｔａｎｃｂｃｓａｌｓａ″（Ｃ，
Ａ、 Ｍｅｙ、） Ｇ、 Ｂｅｅｋｌの全草を乾燥した
ものを本来指体するものであるが、その同属植物である
“Ｃ１５ｔａｎｃｈｅ ｄｅｓｅｒｔｉｅｏｌａ″Ｙ、
Ｃ。Ctstancbcsalsa is a parasitic plant of the Moray family that grows in the People's Republic of China, the People's Republic of Mongolia, and Siberia.
A, Mey,) G, C15tanche desertieola"Y, which is a plant of the same genus, is the dried whole plant of Beekl.
C.
ｉ、Ｃ１５ｔａｎｃｈｅ ａｍｂｉＢａ” （Ｂｇｅ、
） ｃ、 Ｂｃｃｋ及び“Ｃ１５ｔａｎｃｈｅ ５ｉｎ
ｅｎｓｉｓ″Ｇ、 Ｂｅｃｋも肉促蓉の基源植物とされ
ている［「中巧大辞典」及び馬咳泉「内蒙古大学学報（
自然科学）第６９頁、１９７７年１．一方、ハマウッポ
科の他の寄生植物であるオニク（”Ｂｏｓｃｈｎｉａｋ
ｉｉ ｒｏｓｓｉｃａ”Ｆｅｄｔｓｃｈ、 ｅｔ Ｆｌ
ｅｒｏｖ）は和産肉提蓉又は草提蓉と称されており、こ
れが肉促蓉と同様の目的に供されることもある。i, C15tanche ambiBa” (Bge,
) c, Bcck and “C15tanche 5in
Ensis''G, Beck are also considered to be the source plants of Meat-promoting lily.
Natural Science), p. 69, 1977, 1. On the other hand, another parasitic plant of the Boschniaceae family, Boschniak
ii rossica"Fedtsch, et Fl
erov) is called Japanese Nikkudaiyo or Sodaiyo, and this is sometimes used for the same purpose as Nikuyakuyo.
肉促蓉の薬理乃至生理作用については血圧降下作用（中
国医学科学院ｒ １９５６年輪文報告会論文摘要ＩＩＪ
第７０頁、１９５６年１及び唾液分泌促進作用（「中朽
研究文献摘要」第２５９頁、１９７５年）が知られてお
り、又肉促蓉の構成成分についてはアルカロイドや結晶
性物質の存在が報告されてきているが、その詳細は未だ
不明の侭であり、充分に解明されるには至っていない。Regarding the pharmacological and physiological effects of ``Niku Yakuryo'', the blood pressure lowering effect (Chinese Academy of Medical Sciences r 1956 Rinbun Report Conference Paper Abstracts IIJ)
70, 1956, 1 and saliva secretion stimulating effect ("Summary of Research Literature", p. 259, 1975), and the presence of alkaloids and crystalline substances in the constituent components of Nikutsuyou. Although it has been reported, the details are still unknown and have not been fully elucidated.
一方、本発明によるシスソノサイド類と化学構造的に近
縁の化合物としては、一般式にて示されるフェニルプロ
パノイド配糖体類がある。このフェニルプロパノイド配
糖体類に属する公知化合物としてはモクセイ科植物のラ
イラック、ネズミモチ及びキンモクセイから並びにハマ
ウッポ科植物のナンバンギセル、ゴマノハグサ科のキリ
等から単離されているアクチオサイド（Ｒ３、Ｒ４・ハ
イドロキシル基、Ｒ５、Ｒ６＝水素原子）を初めとして
例えば下記の化合物がある。On the other hand, compounds chemically structurally closely related to the cissonosides according to the present invention include phenylpropanoid glycosides represented by the general formula. Known compounds belonging to the phenylpropanoid glycosides include actiosides (R3, R4, hydroxyl, group, R5, R6=hydrogen atom) as well as the following compounds.
盃ｊＪ二し九工」−
（Ｒ３、Ｒ４・ ハイドロキシル基、
Ｒ５・ 水素原子基、
Ｒ６＝ β−Ｄ−グルコピラノシル基）２−アセ ル
アクー イド
（Ｒ，、Ｒ，＝ ハイドロキシル基、Ｒ，＝ アセ
チル基、
Ｒ６・ 水素原子）、
スマンス イドＢ
（Ｒ３＋ Ｒ４、Ｒ２、Ｒ６・ 水素原子）、フォルシ
ソ イドＢ
（Ｒ３、Ｒ，＝ ハイドロキシル基、Ｒ，＝ 水素
原子、
Ｒ６・ β−ドアビオフラノシル基）
これらのフェニルプロパノイド配糖体の薬理乃至生理作
用についてはエチナコサイド及びフォルシソサイドＢが
共に抗菌作用を有している旨報告されており（＾、 ５
ｔｏｌ１等“Ｈｅ１ｖ。- (R3, R4, hydroxyl group, R5, hydrogen atom group, R6 = β-D-glucopyranosyl group) 2-acelaquid (R,, R, = hydroxyl group, R, = Acetyl group, R6/Hydrogen atom), Sumansoid B (R3+ R4, R2, R6/Hydrogen atom), Forcisoid B (R3, R, = Hydroxyl group, R, = Hydrogen atom, R6/β-dobio Regarding the pharmacological and physiological effects of these phenylpropanoid glycosides, it has been reported that both echinacoside and forcisoside B have antibacterial effects (^, 5).
tol1 etc. “He1v.
Ｃｈｉｓ、 Ａｃｔａ、”第２３８頁、１９５０年及び
遠藤等「日本生薬学会第２８年会講演要旨集」第２０頁
、１９８１年）、又アクチオサイドが抗バーキンソニズ
ム作用及びβ−遮断作用を有している旨報告され（西ド
イツ国特許出願公開第２６０９５３３号公報）、更に抗
腫瘍作用を有している旨報告されている（沼田等「第３
３回日本生薬学会近畿支部総会講演要旨集」第７６頁、
１９８３年）。Chis, Acta,” p. 238, 1950 and Endo et al., “Proceedings of the 28th Annual Meeting of the Japanese Society of Herbal Pharmaceutical Sciences,” p. 20, 1981), and actioside has anti-Birkinsonian action and β-blocking action. (West German Patent Application Publication No. 2609533), and it has also been reported to have antitumor effects (Numata et al. ``No. 3'').
Collection of abstracts from the 3rd Annual General Meeting of the Kinki Branch of the Japanese Society of Pharmacological Pharmacology,” p. 76,
(1983).
上記の公知フェニルプロパノイド配糖体が有しているこ
れらの薬理乃至生理作用並びに肉促蓉に関して従来報告
されてきた既述の薬理乃至生理作用である血圧降下作用
及び唾液分泌促進作用は、肉促蓉の伝承的効能即ち「五
労七傷」とはニュアンスを異にしているものと考えられ
る。蓋し、「五労七傷」とは各種のストレスに基因して
生じる生体臓器の機能低下や精神的疲労により生じる諸
症状を緩和し、延いては治癒させることを指体するもの
と解されるからである。These pharmacological and physiological effects possessed by the above-mentioned known phenylpropanoid glycosides, as well as the previously described pharmacological and physiological effects that have been reported regarding meat stimulation, such as blood pressure lowering effect and saliva secretion promoting effect, are It is thought that the nuance is different from the traditional efficacy of promotion, which means ``five labors and seven wounds''. On the other hand, the term ``go-ro-shichi-ki'' is understood to refer to the alleviation and eventual healing of various symptoms caused by the decline in the function of vital organs and mental fatigue caused by various types of stress. This is because that.
現代は、社会機構が複雑化し技術革新も極めて急速に進
行しつつあり、従ってこのような環境条件下に生活する
人々には知らず知らずの内に多大なストレスが掛かり且
つ蓄積されるのが実情である。このような現代において
、社会生活を健全に営んで行くためには抗ストレス作用
物質が極めて有用である。In modern times, social institutions are becoming more complex and technological innovation is progressing extremely rapidly, and the reality is that people living under such environmental conditions are subject to and accumulate a great deal of stress without realizing it. be. In these modern times, anti-stress substances are extremely useful for leading a healthy social life.
本発明者等は肉促蓉の上記の伝承的効能に着目して従来
から肉促蓉について研究を重ねて来たが、その結果肉促
蓉には２′−アセチルアクチオサイド、オスマンスサイ
ドＢ、アクチオサイド、エチナコサイド等の各種フェニ
ルプロパノイド配糖体の他に下記のフェニルプロパノイ
ド配糖体（シスタフサイド類）が含有されていることを
見出し、これを報告すると共にそれらの単離法について
特許出願をなしく小林等ｒ Ｃｈｅｗ、 Ｐｈａｒｍ、
Ｂｕｌｌ、 Ｊ第３２巻、第３００９及び３８８０頁
、１９８４年及び特願昭６Ｏ−２９３３５）、更にこれ
らのシスタフサイド類がストレスによる機能障害の改善
剤として有効であることを見出して関連特許出願をなし
た（特願昭６０−１８３９５３３）。The present inventors have focused on the above-mentioned traditional effects of Nikkutsuyou and have conducted research on Nikkutsuyou. In addition to various phenylpropanoid glycosides such as B, actioside, and ethinacoside, we have discovered that the following phenylpropanoid glycosides (cystafsides) are contained, and have reported this and have patented their isolation method. Kobayashi et al. Chew, Pharm,
Bull, J Vol. 32, pp. 3009 and 3880, 1984 and Japanese Patent Application No. 6O-29335), and further discovered that these cystufsides were effective as agents for improving functional disorders caused by stress, and filed a related patent application. (Patent application 1839533/1983).
ζス ′＾
（前記の一般式ＩＩにおいてＲ３：ハイドロキシル基、
Ｒ４：メトキシル基、
Ｒ５：水素原子、Ｒ６：β−Ｄ−グルコピラノシル基）
２ノ！二コこ仁五」−
（前記の一般式ＩＩにおいてＲ，、Ｒ４：メトキシル基
、Ｒ２：水素原子、
Ｒ６：β−Ｄ−グルコピラノシル基）
乞ム又１１血り工
（前記の一般式ＩＩにおいてＲ５：ハイドロキシル基、
Ｒ４：メトキシル基、
Ｒ５＋ Ｒ６：水素原子〉
２）！！竺し仁ド」−
（前記の一般式ＩＩにおいてＲ３，Ｒ４：メトキシル基
、Ｒ５＋ Ｒ６：水素原子）本発明者等は肉促蓉の構成
成分について更に研究を続けた結果、肉促蓉には一般式
（式中Ｒ□は水素原子又はハイドロキシル基を意味し、
Ｒ２はα−Ｌ−ラムノピラノシル−（１−＋３）−〇−
グルコピラノシル基を意味する）
にて示されるシスタフサイド類も含有されていることが
判明した。ζsu'^ (In the above general formula II, R3: hydroxyl group,
R4: methoxyl group, R5: hydrogen atom, R6: β-D-glucopyranosyl group) 2no! - (In the above general formula II, R,, R4: methoxyl group, R2: hydrogen atom, R6: β-D-glucopyranosyl group) R5: hydroxyl group,
R4: methoxyl group, R5+ R6: hydrogen atom> 2)! ! - (In the above general formula II, R3, R4: methoxyl group, R5+ R6: hydrogen atom) As a result of further research by the present inventors on the constituent components of Nikutsuyou, we found that General formula (in the formula, R□ means a hydrogen atom or a hydroxyl group,
R2 is α-L-rhamnopyranosyl-(1-+3)-〇-
It was also found that cystaphsides represented by (meaning glucopyranosyl group) were also contained.
鋭意研究の結果、これらのシスタンサイド類即ち
シス ′Ｆ
（Ｒ１：ハイドロキシル基）
及び
シスタン イドＩ
（Ｒ１：水素原子）
は抗ストレス作用を有していることが見出されて本発明
が完成されるに至った。As a result of extensive research, it was discovered that these cisternides, ie, cis 'F (R1: hydroxyl group) and cystane I (R1: hydrogen atom), have anti-stress effects, and the present invention was completed. It came to be.
（発明の目的）
従って、本発明の目的は生薬殊に肉促蓉から得られた物
質を有効成分とする抗ストレス剤を提供し、これによっ
てストレスによる機能障害の改善を図ることにある。(Objective of the Invention) Therefore, the object of the present invention is to provide an anti-stress agent containing as an active ingredient a substance obtained from herbal medicines, particularly Physcomitrella sinensis, and thereby improve functional disorders caused by stress.
（目的を達成するための手段及び作用）本発明によれば
、上記の目的は一般式
（式中Ｒ８及びＲ２は前記の意味を有する）にて示され
るシスソノサイド。類の少なくとも一種を有効成分とし
て含有していることを特徴とする、ストレスによる機能
障害改善剤により達成される。(Means and effects for achieving the object) According to the present invention, the above object is a cissonocide represented by the general formula (wherein R8 and R2 have the above-mentioned meanings). This is achieved by a stress-induced dysfunction improving agent, which is characterized by containing at least one of the following as an active ingredient.
尚、これらの有効成分としては単離精製されたものが好
ましいが、これらの少なくとも一方を含有する両分の状
態であっても使用することが可能である。Although it is preferable that these active ingredients be isolated and purified, they can also be used in the form of both components containing at least one of them.
（剤型及び投与量）
本発明によるストレスによる機能障害改善剤の剤型に格
別の制限はなく、従って肉促蓉から抽出された上記の一
般式Ｉにて示される化合物又は該化合物を含有する両分
をその侭投与することも、或は製剤化して投与すること
もできる。製剤化に際しては、粉末剤、細粒剤、顆粒剤
、錠剤、カプセル剤、液剤、シロップ剤等の経口投与剤
とすることも、或は注射剤、腸性剤等の非経口投与剤と
することもできる。(Dosage Form and Dosage) There is no particular restriction on the dosage form of the agent for improving stress-induced dysfunction according to the present invention, and therefore, it contains the compound represented by the above general formula I extracted from Physcomitrella sinensis or the compound represented by the above-mentioned general formula I. Both components can be administered separately or can be formulated and administered. When formulating the drug, it can be made into oral preparations such as powders, fine granules, granules, tablets, capsules, liquids, syrups, etc., or parenteral preparations such as injections and enteric preparations. You can also do that.
投与量は有効成分の種類、剤型、患者の年齢、体重、症
状等に依存するが、一般に、成人に対して経口投与する
場合には、有効成分化合物として０．０５−５ ｇ／日
を １−３回に分けて服用するのが好ましい。The dosage depends on the type of active ingredient, dosage form, patient's age, weight, symptoms, etc., but in general, when administered orally to adults, the active ingredient compound is 0.05-5 g/day. It is preferable to take the drug in 1-3 divided doses.
（発明の効果）
本発明による剤を投与すればストレスに基因して生じる
諸機能の障害殊に性機能障害、健忘症を軽減乃至治癒さ
せることができ、更には心身症の予防や治療を行うこと
ができる。(Effects of the Invention) By administering the agent according to the present invention, various functional disorders caused by stress, especially sexual dysfunction and amnesia, can be alleviated or cured, and psychosomatic disorders can be prevented and treated. be able to.
尚、本発明による剤の有効成分として用いられるシスツ
ノサイド類は毒性が極めて低く、従って本発明による剤
は使用安全性に優れている。Incidentally, the cistunosides used as the active ingredients of the agent according to the present invention have extremely low toxicity, and therefore the agent according to the present invention has excellent safety in use.
（製剤例等）
次に、本発明による剤に用いられる有効成分の製造例、
薬効薬理試験例及び製剤例に関連して本発明を更に詳細
に説明する。(Formulation examples, etc.) Next, production examples of active ingredients used in the agent according to the present invention,
The present invention will be explained in more detail with reference to pharmacological test examples and formulation examples.
ＬＨ！Ｌ（製造例）
肉促蓉（中国産市場品） １０ｋｇを細切し、メタノー
ル３６リツトルを添加し、攪拌下に還流加熱した。これ
を２時間宛２回繰り返し、得られた抽出液を合併して減
圧濃縮し、粗エキス４．５ｋｇを得た。この粗エキスを
水１．５リットルに懸濁させ、酢酸エチルエステル３リ
ツトル宛で２回洗浄し、水性層をｎ−ブタノール３リツ
トル宛で２回抽出し、ｎ−ブタノール抽出液を合併して
減圧濃縮し、ｎ−ブタノール可溶部３００ｇを得た。こ
れを水５リットルに溶解させ、ダイヤイオンＨＰ−２０
を２リツトル充填したカラムに通導し、水２０リットル
で洗浄し、メタノール１０リツトルで溶出させてダイヤ
イオン吸着部７５ｇを得た。このダイヤイオン吸着部を
水５００ｍ１に溶解させ、ポリアミドＣ−２００を １
ｋｇ充填したカラムに通導し、水３リットルで洗浄し、
メタノール５リツトルで溶出させて粗シスタンサイド４
０ｇ（以下「画分ｌ」と称する）を得た。この画分ｌを
、ワコーゲルＣ−３００を５００ｇ充填したカラムによ
るクロマトグラフィーに付し、添付図面に示される通り
のＴＬＣグラム［薄層板ニジリカゲル６０ Ｆ２５４
（メルク社製）、展開溶タンール／水（６： ４ ：
１）、発色＝２０％硫酸溶液の噴霧後に１０５℃で加
熱］を指標としてクロロホルム／メタノール／水（６：
４ ： １）で繰り返し精製した後に、セファデック
スＬｌ（−２０を１００ｇ充填したカラムによるクロマ
トグラフィーに付し、上記のＴＬＣグラムを指標として
水／メタノール（１： １）で分画溶出させることによ
りシスタンサイドＦ （１５０ｍｇ）とシスタンサイド
Ｉ （１２０ｍｇ）を得た。LH! L (Manufacturing Example) 10 kg of meat soup root (market product from China) was cut into pieces, 36 liters of methanol was added thereto, and the mixture was heated under reflux while stirring. This was repeated twice for 2 hours, and the resulting extracts were combined and concentrated under reduced pressure to obtain 4.5 kg of crude extract. This crude extract was suspended in 1.5 liters of water, washed twice with 3 liters of ethyl acetate, the aqueous layer was extracted twice with 3 liters of n-butanol, and the n-butanol extracts were combined. It was concentrated under reduced pressure to obtain 300 g of n-butanol soluble portion. Dissolve this in 5 liters of water and use Diaion HP-20.
The mixture was passed through a column filled with 2 liters of chlorine, washed with 20 liters of water, and eluted with 10 liters of methanol to obtain 75 g of diamond ion adsorption area. This diamond ion adsorption part was dissolved in 500 ml of water, and 1 ml of polyamide C-200 was added.
kg packed column, washed with 3 liters of water,
Elute with 5 liters of methanol to obtain crude cystane side 4.
0 g (hereinafter referred to as "fraction 1") was obtained. This fraction 1 was subjected to chromatography using a column packed with 500 g of Wako Gel C-300, and the TLC gram as shown in the attached drawing [thin plate Nijirica Gel 60 F254
(manufactured by Merck & Co., Ltd.), developing solution tanhol/water (6:4:
1), color development = heating at 105°C after spraying with 20% sulfuric acid solution] was used as an indicator for chloroform/methanol/water (6:
After repeated purification with 4:1), it was subjected to chromatography using a column packed with 100 g of Sephadex Ll (-20), and fractionated and eluted with water/methanol (1:1) using the above TLC gram as an indicator. Cistanside F (150 mg) and Cistanside I (120 mg) were obtained.
これらのシスツノサイド類の物理化学的性質は下記の通
りであった。The physicochemical properties of these cistunosides were as follows.
シスタン イドＦ
旋光度（ＭｅＯＨ） ：
［ａ１％’ −８３，５°（ｃ ＝ ０．９）３４３０
、１６９♂、 １６３４．１６０６．１５２０ＦＤ−Ｍ
Ｓスペクトル（ａ／Ｚ） ：
５１１ （Ｍ ＋ Ｎａ）＋
ＩＨ−ＮＭＲスペクトル（メタノール−４４）δＰＰＭ
：
１．１１ （３Ｈ，ｄ、 Ｊ ：６Ｈｚ、ラム
ノースのｃｎ、）
４．５７ （ＩＩ、 ＴＩ、 Ｊ ＝ ８Ｈｚ
、グルコースのＨ−１）
５．１５ （ＩＨ，ｂｒ ｓ、ラムノースの６
．２８ （ＩＨ，ｄ、 Ｊ ＝ １６Ｈｚ。Cystane F Optical rotation (MeOH): [a1%' -83,5° (c = 0.9) 3430
, 169♂, 1634.1606.1520FD-M
S spectrum (a/Z): 511 (M + Na) + IH-NMR spectrum (methanol-44) δPPM
: 1.11 (3H, d, J: 6 Hz, cn of rhamnose,) 4.57 (II, TI, J = 8 Hz
, H-1 of glucose) 5.15 (IH, br s, 6 of rhamnose
．． 28 (IH, d, J = 16Hz.
Ａｒ−ＣＨ＝卯−）
６．７ − ７．２ （３Ｈ，Ａｒ−Ｈ）７．６０
（ＩＨ，ｄ、Ｊ ＝ １６Ｈｚ。Ar-CH=rabbit-) 6.7 - 7.2 (3H, Ar-H) 7.60
(IH, d, J = 16Hz.
Ａｒ−Ｃｊｉ、＝ＣＨ−）
＋３Ｃ−ＮＭＲケミカルシフト（メタノール−ｄ４）：
カフェー酸 １ ； １２７．８
２ ； １１４．９
３ ； １４９．６
４ ； １４６．７
５ 、 １１６．６
６ ； １２３．１
α； １６８ｊ
β、 １１５．４
γ； １４７．８
グルコース ｌα； ９４．０
β、 ９８．１
２ α、 ７１．２
β： ７４．７
３ α、 ７９．２
β、 ８１．６
４ α； ７０ｊ
β； ７０．３
５ α、 ７６．１
β； ７７．４
６ α、 ６２．５
β、 ６２．５
ラムノース １ ； １０２．９２； ７
２．２
３； ７２．３
４： ７３．９
５； ７０．９
６： １ｇ、４
シスタン イドエ
旋光度（ＭｅＯＨ） ：
３４３０、１６９８．１６３４．１６０６．１５１８’
トＮ＆［Ｒスペクトル（メタノール−ｄ４）δ ｐｐｍ
：
１．１０ （３Ｈ，ｄ、 Ｊ ＝ ６Ｈｚ、ラ
ムノースのＣＨ，）
４．６０ （１Ｂ、 ｄ、 Ｊ ＝ ８Ｈｚ、
グルコースのＨ−１）
５．１８ （ＩＨ，ｂｒ ｓ、 ラムノース
のＨ−１）
６．３６ （ＩＨ，ｄ、Ｊ ＝ １６
Ｈｚ。Ar-Cji, =CH-) +3C-NMR chemical shift (methanol-d4):
Caffeic acid 1; 127.8 2; 114.9 3; 149.6 4; 146.7 5, 116.6 6; 123.1 α; 168j β, 115.4 γ; 147.8 Glucose lα; 94. 0 β, 98.1 2 α, 71.2 β: 74.7 3 α, 79.2 β, 81.6 4 α; 70j β; 70.3 5 α, 76.1 β; 77.4 6 α , 62.5 β, 62.5 Rhamnose 1; 102.92; 7
2.2 3; 72.3 4: 73.9 5; 70.9 6: 1g, 4 Cistern Ide optical rotation (MeOH): 3430, 1698.1634.1606.1518'
N & [R spectrum (methanol-d4) δ ppm
: 1.10 (3H, d, J = 6Hz, CH of rhamnose,) 4.60 (1B, d, J = 8Hz,
H-1 of glucose) 5.18 (IH, br s, H-1 of rhamnose) 6.36 (IH, d, J = 16
Hz.
Ａｒ−ＣＨ＝Ｃｊｉ、−）
６．８４ （２Ｈ，ｄ、 Ｊ ＝９Ｈｚ、 ｐ
−フマル酸のＨ−３，５）
７．５１ （２Ｂ、 ｄ、 Ｊ ＝９Ｈｚ、
ｐ−フマル酸の）Ｉ−２，６）
７．７０ （ＩＨ，ｄ、Ｊ ＝ １６
Ｈｚ。Ar-CH=Cji, -) 6.84 (2H, d, J = 9Hz, p
-H of fumaric acid-3,5) 7.51 (2B, d, J = 9Hz,
of p-fumaric acid) I-2,6) 7.70 (IH, d, J = 16
Hz.
Ａｒ−Ｃ！Ｌ＝Ｃト）
”Ｃ−ＮＭＲケミカルシフト（メタノール−６４）：ｐ
−フマル酸 １ ： １２７．２２ ； １
１６．９
３ 、 １３１ｊ
４ ； １６１ｊ
５ 、 １３１４
６ ； １１６．９
α ； １６ｇ、３
β ； １１５．０
γ ； １４７．６
グルコース ｌα； 、 ９４．１β； ９
ｇ、２
２ α； ７１．２
β； ７４．７
３ α： ７９．２
β； ８１．７
４ α： ７Ｇ、４
β、 ７０．４
５ α： ７６．１
β： ７７．４
６ α； ６２．４
β： ６２．５
ラムノース １ 、 １０３．０
２、 ７２．１
３； ７２．３
４； ７３．８
５、 ７０．９
６； １ｇ、４
元素分析（Ｃ２１Ｈ２８０１２・１／２ Ｈ２Ｏ） ：
理論 ： Ｃ，５２，５４； Ｈ，６，０２夷測 ：
Ｃ，５２，３９： Ｈ，６，０７龜夏 ｑ■１１ユ
（１）目的
斎藤等の方法（「第１６回和漢薬シンポジウム講演要旨
集」第６６頁、１９８３年）に従い、ストレス負荷後に
生じる実験動物の性行動障害及び学習記憶障害に対して
、本発明による剤の有効成分が及ぼす影響を調べる。Ar-C! L=C) "C-NMR chemical shift (methanol-64): p
-Fumaric acid 1: 127.22; 1
16.9 3, 131j 4; 161j 5, 1314 6; 116.9 α; 16g, 3 β; 115.0 γ; 147.6 Glucose lα; 94.1β; 9
g, 2 2 α; 71.2 β; 74.7 3 α: 79.2 β; 81.7 4 α: 7G, 4 β, 70.4 5 α: 76.1 β: 77.4 6 α; 62.4 β: 62.5 Rhamnose 1, 103.0 2, 72.1 3; 72.3 4; 73.8 5, 70.9 6; 1g, 4 Elemental analysis (C21H28012・1/2 H2O):
Theory: C, 52, 54; H, 6, 02 Measurement:
C, 52, 39: H, 6, 07 Guxia q ■ 11 Yu (1) Purpose According to the method of Saito et al. (“The 16th Japanese and Chinese Medicine Symposium Lecture Abstracts” p. 66, 1983), the The effect of the active ingredient of the agent according to the present invention on sexual behavior disorders and learning and memory disorders in experimental animals is investigated.
（２）実験動物
９週令以上であって性行動の正常なＩＶ−Ｃ５系の雄性
マウス（体重２ｇ −３２ｇ）を選び、１週間にわたり
温度２３±１℃、湿度５５±５ｘの条件下で予備飼育し
た。(2) Experimental Animals Select male mice of the IV-C5 strain (weight 2g-32g) that are 9 weeks old or older and have normal sexual behavior. Preliminary breeding was carried out.
この場合の「性行動が正常」とは、個室ケージで飼育し
た雄性マウスを、エストラジオールｌＯμｓ／ｋｇの連
日皮下投与により発情状態になされている雌性マウス１
０匹と毎日１０分間同居させる場合に、１週間に５回以
上イントロミッションに成功することを指体する。In this case, "normal sexual behavior" refers to male mice raised in private cages that are brought into estrus by daily subcutaneous administration of lOμs/kg of estradiol.
If you live with 0 animals for 10 minutes every day, aim to successfully complete intromissions at least 5 times a week.
（３）ストレス負荷
実験動物である雄性マウスを宙吊り状態で且つ鼻先が水
面に接触する程度の高さレベル位置に固定させ、この状
態を試験初日は３０分間維持させ、２日目以降は宙吊り
時間を徐々に延長して試験最終日の１５日日日は２時間
にわたり宙吊り状態に維持させてストレスを負荷した。(3) Stress loading A male mouse, which is an experimental animal, was suspended in the air and fixed at a height such that the tip of its nose touched the water surface, and this condition was maintained for 30 minutes on the first day of the test, and from the second day onwards, the hanging time was This was gradually extended, and on the final day of the test, the 15th, the subjects were kept suspended in the air for two hours to stress them.
このようにして１５日間の試験期間にわたり連日ストレ
スを負荷させても、対照のストレス非負荷群と比較して
体重減少は認められず、又運動協調性障害、筋緊張度低
下、自発運動の低下及び探索運動の低下は認められなか
ったが、性行動と学習記憶行動に低下が認められた。Even when stress was applied every day over a 15-day test period, no weight loss was observed compared to the control non-stressed group, and there was also impaired motor coordination, decreased muscle tone, and decreased locomotor activity. Although no decrease in exploratory movement was observed, a decrease was observed in sexual behavior and learning and memory behavior.
（４）実験方法と被験薬物の効果判定方法上記のストレ
ス負荷は毎日規定の時刻（午後１時）から行い、試験群
についてはストレス負荷後に被験薬物を経口投与し、翌
朝の９時から学習（記憶）行動を調べ、これを１５日間
にわたり繰り返し、被験薬物の及ぼす影響乃至効果を検
討する。(4) Experimental method and method for evaluating the effect of the test drug The stress load described above was carried out every day from the specified time (1:00 p.m.), and for the test group, the test drug was orally administered after the stress load, and the learning (from 9:00 a.m. the next morning) Memory) behavior is examined, and this is repeated for 15 days to examine the effects or effects of the test drug.
（ａ）性行動の判定
エストラジオールが１θμｓ／ｋｇの用量で連日皮下投
与された各雌性マウス１０匹が入れられたケージ（３０
ｘ ４０ ｘ ２０ｃ重）内に実験動物である雄性マウ
ス１匹を１日１回１０分間同居させ、その間にリッキン
グ、マウンティング及びイントロミッションの各性行動
を行った回数及び行動を起こす迄の時間を測定した。こ
の場合に一群ｌＯ匹とし、群間の有意差検定には分散分
析法を採用した。(a) Determination of sexual behavior A cage (30
A male experimental animal (male mouse) was housed in a 40 x 20 cm cage for 10 minutes once a day, and the number of times each sexual behavior (licking, mounting, and introduction) was performed during that time and the time until the behavior occurred were recorded. It was measured. In this case, one group consisted of 10 animals, and analysis of variance was used to test for significant differences between groups.
（ｂ）学習（記憶）行動の判定
電流（ＤＣ３６Ｖ、 ０．１ｍＡ＞が流れている床にゴ
ム栓（直径５ｃ＋ａ、高さ５ｃ＋＊）を載置し、実験動
物である雄性マウスに５分間はこのゴム栓上から降りな
いように学習させておく、この学習処置を施した雄性マ
ウスを上記のゴム栓の上に乗せ、５分間以内に誤ってゴ
ム栓上がら降りた回数を測定した。この場合の群間の有
意差検定には分散分析法を採用した。(b) Judgment of learning (memory) behavior A rubber plug (diameter 5c+a, height 5c+*) was placed on the floor where a current (DC36V, 0.1mA>) was flowing, and a male mouse, which is an experimental animal, was A male mouse that had been trained not to get off the rubber stopper was placed on the rubber stopper, and the number of times it accidentally climbed up and off the stopper within 5 minutes was measured. Analysis of variance was used to test for significant differences between groups.
り５）結果及び解析
（ａ）性行動について
ｉ）結果
ストレス負荷による性行動の低下及び各被験薬物の投与
によるその回復程度を調べた結果は下記の表に示される
通りであった。5) Results and analysis (a) Regarding sexual behavior i) Results The decrease in sexual behavior due to stress load and the degree of recovery thereof by administration of each test drug were investigated. The results are shown in the table below.
ｉｆ）雄性マウスの性行動はリッキング、マウンティン
グ、イントロミッション、***の経過を辿る。従って、
成る処置を施した雄性マウスが発情状態の雌性マウスと
同居した時にその性行動に如何なる変化が生じるかを調
べることにより当該処置の影響乃至効果を判定すること
ができる。即ち、一定時部内に一群１０匹中それぞれの
性行動をとる回数が多い程、及び性行動を起こす迄の時
間が短い程性行動が活発であると判断することができる
。if) Sexual behavior in male mice follows the steps of licking, mounting, introduction, and ejaculation. Therefore,
The influence or effectiveness of the treatment can be determined by examining what changes occur in the sexual behavior of male mice treated with a female mouse in heat. That is, it can be determined that the more frequently each of the 10 animals in a group engages in sexual behavior within a certain period of time, and the shorter the time until sexual behavior occurs, the more active the sexual behavior is.
前記の表から明らかなように、ストレスの負荷された雄
性マウスの性行動は全般的に低下する。ストレスを負荷
させた被験群とストレスを負荷させなかった対照群とを
比較する場合に初期の性行動であるリッキングよりも後
期の性行動になる程顕著な差異が認められる。尚、各性
行動を起こす回数及び開始迄の所要時間について述べれ
ば、ストレス負荷は個々のマウスが性行動をとる回数を
減少させ且つ性行動を開始する迄に要する時間に遅れが
が認められた。As is clear from the table above, the sexual behavior of stressed male mice is generally reduced. When comparing the stressed test group and the non-stressed control group, a more pronounced difference is observed in the later stages of sexual behavior compared to licking, which is the early stage of sexual behavior. Regarding the number of times each sexual behavior occurs and the time required to initiate it, stress load reduced the number of times each individual mouse engaged in sexual behavior, and it was observed that there was a delay in the time required to initiate sexual behavior. .
このように、ストレス負荷により性行動の低下した雄性
マウスに被験薬物を投与することにより性行動に明らか
な改善が認められた。このことは、被験薬物が、ストレ
スに基因する性機能の低下を有効に改善する効果を有し
ていることを示すものである。Thus, by administering the test drug to male mice whose sexual behavior had decreased due to stress, a clear improvement in sexual behavior was observed. This indicates that the test drug has the effect of effectively improving the decline in sexual function caused by stress.
（ｂ）学習（記憶）行動について ｉ）結果 試験結果は第２及び３図に示される 通りであった。(b) Regarding learning (memory) behavior i) Results The test results are shown in Figures 2 and 3. It was on the street.
ｆｉ）解析
５分間の試験時間内に誤ってゴム栓上から降りてしまっ
た１５日間の試験期間内における平均回数が、ストレス
非負荷の対照群に対して、ストレスの負荷された被験群
においては有意に増加し、これからストレス負荷により
学習行動において有意の低下が生じることが判る。fi) Analysis: The average number of times during the 15-day test period of accidentally falling off the rubber stopper during the 5-minute test period was higher in the stressed test group than in the non-stressed control group. It can be seen that there is a significant decrease in learning behavior due to stress load.
ストレス負荷により学習行動がこのように低下した雄性
マウスに被験薬物を投与することにより、誤ってゴム栓
上から降りてしまう回数は明らかに減少する傾向が見ら
れた。By administering the test drug to male mice whose learning behavior had decreased in this way due to stress, there was a clear tendency to reduce the number of times they accidentally fell off the rubber stopper.
これらの事実は、ストレスに基因する記憶能力減退改善
効果を被験薬物が有していることを示すものである。These facts indicate that the test drug has the effect of improving memory ability decline caused by stress.
（急性毒性試験）
ｄｌＹ系マウス（体重２５−３０ｇ）を温度２３±１’
Ｃ１湿度５５±５％の室内で自由給餌、自由給水の条件
下で１週問予備飼育して健康状態の良好な個体を選び、
１群５匹とした０次いで１８時間絶食させた後に被験薬
物（シスタンサイドＦ及びＩ）を各５０θ識ｇ／ｋｇの
用量で経口投与した。(Acute toxicity test) dlY mice (body weight 25-30 g) were incubated at a temperature of 23 ± 1'
C1: In a room with a humidity of 55 ± 5%, animals with free feeding and water were preliminarily reared for one week to select individuals in good health.
After fasting for 18 hours, test drugs (cystansides F and I) were orally administered at a dose of 50θg/kg each.
何れの被験薬物に関しても投与３０分後から体温降下が
認められたが、約３時間に回復し、この間に弱いながら
鎮静化の発現が認められた。死亡例は全くなかった。そ
の後、１週間にわたって体温の測定及び一般症状の観察
を行ったが、対照群との間に有意差は認められず、又剖
検によっても異常は何等認められなかつた。For all test drugs, a decrease in body temperature was observed 30 minutes after administration, but the temperature recovered in about 3 hours, and during this time, a slight onset of sedation was observed. There were no cases of death. Thereafter, body temperature measurements and general symptoms were observed over a period of one week, but no significant difference was found between the animals and the control group, and no abnormalities were found at autopsy.
このことは、本発明による剤の有効成分である被験薬物
の毒性が極めて低いことを示しており、従って本発明に
よる剤は使用安全性において優れていることを示唆して
いる。This shows that the toxicity of the test drug, which is the active ingredient of the agent according to the present invention, is extremely low, and therefore suggests that the agent according to the present invention has excellent safety in use.
ｍ（顆粒剤）
参考例１の途次で得た画分ｌ（シスタンサイドＦと １
とに未だ分画されていないもの）２０ｇに澱粉９５ｇ及
び乳糖８０ｇを添加して均一に混合し、次いでヒドロキ
シプロピル（５ｇ）エタノール溶液を用いて常法により
湿式製粒し、乾燥させ、整粒して顆粒剤を得た。m (granules) Fraction 1 obtained in the course of Reference Example 1 (cystane side F and 1
95 g of starch and 80 g of lactose are added to 20 g of unfractionated products) and mixed uniformly, then wet granulated using a conventional method using a hydroxypropyl (5 g) ethanol solution, dried, and sized. Granules were obtained.
１肚肚ユ（カプセル剤）
シスタンサイドＦ １ｇに乳糖１０ｇ及び澱粉８．５ｇ
を添加して均一に混合し、次いでヒドロキシプロピル（
０，５ｇ）エタノール溶液を用いて常法により湿式製粒
し、乾燥させ、整粒し、ｌカプセル当たり ２００ｍｇ
充填してカプセル剤を得た。1 肚肚yu (capsules) Cistanside F 1g, lactose 10g and starch 8.5g
Add and mix uniformly, then add hydroxypropyl (
0.5g) Wet granulation using an ethanol solution in a conventional manner, drying, sizing, and 200mg per 1 capsule.
Capsules were obtained by filling.
製ＪＬ［ｌ（内服用液剤）
シスタンサイド Ｆ Ｉｇと、ブドウ糖１０ｇと、適宜
量の香料とを１４％エタノール水溶液に溶解させ全量を
２００１となして内服用液剤を得た。JL [1 (liquid for internal use)] Cistanside F Ig, 10 g of glucose, and an appropriate amount of fragrance were dissolved in a 14% ethanol aqueous solution to make a total volume of 2001 to obtain a liquid for internal use.
第１図は肉促蓉から抽出されたシスタンサイドＦ及びＩ
の、 ＴＬＣグラムであり、第２及び３図はストレスが
マウスの学習記憶行動に及ぼす低下作用及び本発明によ
る剤の内でシスタンサイドＦおよび画分１がそれぞれ及
ぼすその改善作用を示すグラフである。
特許出願人 養命酒製造株式会社
第１図
第２図
ＢＣ
第３図
Ａ１Ｂ１Ｃ１
Ａ１：ストしス非負置ｆ学
日１：ストシズ負鞘１羊
Ｃ１，ストレス負荷−已分１枚季群
＊ Ｐ＞０．０１Figure 1 shows Cisternsides F and I extracted from Nikkusao.
Figures 2 and 3 are graphs showing the reducing effect of stress on the learning and memory behavior of mice, and the improving effects of cystaneside F and fraction 1, respectively, among the agents according to the present invention. . Patent applicant: Yomeishu Manufacturing Co., Ltd. Figure 1 Figure 2 BC Figure 3 A1B1C1 A1: Stoshisu non-negative f school day 1: Stoshisu negative sheath 1 sheep C1, stress load - 1 piece seasonal group * P >0.01
Claims (1)
、Ｒ＿２はα−Ｌ−ラムノピラノシル−（１→３）−Ｄ
−グルコピラノシル基を意味する） にて示されるシスタノサイド類の少なくとも一種を有効
成分として含有していることを特徴とする、ストレスに
よる機能障害改善剤。(1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, R_1 means a hydrogen atom or a hydroxyl group, and R_2 is α-L-rhamnopyranosyl-(1→3)-D
- means a glucopyranosyl group) An agent for improving functional disorders caused by stress, characterized in that it contains at least one type of cystanoside represented by the following as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62029534A JPH0623110B2 (en) | 1987-02-13 | 1987-02-13 | Agent for improving dysfunction caused by stress containing cystanoside as an active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62029534A JPH0623110B2 (en) | 1987-02-13 | 1987-02-13 | Agent for improving dysfunction caused by stress containing cystanoside as an active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63198628A true JPS63198628A (en) | 1988-08-17 |
| JPH0623110B2 JPH0623110B2 (en) | 1994-03-30 |
Family
ID=12278777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62029534A Expired - Lifetime JPH0623110B2 (en) | 1987-02-13 | 1987-02-13 | Agent for improving dysfunction caused by stress containing cystanoside as an active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0623110B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004014410A1 (en) * | 2002-08-12 | 2004-02-19 | Kyung Hee University | Composition comprising the extract of cistanche deserticola y.c. ma showing enhancing activity of the neurite outgrowth and neurotrophic effects |
-
1987
- 1987-02-13 JP JP62029534A patent/JPH0623110B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004014410A1 (en) * | 2002-08-12 | 2004-02-19 | Kyung Hee University | Composition comprising the extract of cistanche deserticola y.c. ma showing enhancing activity of the neurite outgrowth and neurotrophic effects |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0623110B2 (en) | 1994-03-30 |
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