JPH04124135A - Antidiabetic drug - Google Patents
Antidiabetic drugInfo
- Publication number
- JPH04124135A JPH04124135A JP24482190A JP24482190A JPH04124135A JP H04124135 A JPH04124135 A JP H04124135A JP 24482190 A JP24482190 A JP 24482190A JP 24482190 A JP24482190 A JP 24482190A JP H04124135 A JPH04124135 A JP H04124135A
- Authority
- JP
- Japan
- Prior art keywords
- antidiabetic drug
- formula
- present
- hormone
- active ingredient
- 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.)
- Pending
Links
- 239000003472 antidiabetic agent Substances 0.000 title claims abstract description 21
- 229940127003 anti-diabetic drug Drugs 0.000 title claims abstract description 19
- 241000238631 Hexapoda Species 0.000 claims abstract description 11
- 230000029052 metamorphosis Effects 0.000 claims abstract description 11
- 229940088597 hormone Drugs 0.000 claims abstract description 10
- 239000005556 hormone Substances 0.000 claims abstract description 10
- 239000000126 substance Substances 0.000 claims abstract description 6
- 239000002075 main ingredient Substances 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 14
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 abstract description 10
- 239000008280 blood Substances 0.000 abstract description 8
- 210000004369 blood Anatomy 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 102000004877 Insulin Human genes 0.000 abstract description 5
- 108090001061 Insulin Proteins 0.000 abstract description 5
- 229940125396 insulin Drugs 0.000 abstract description 5
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 abstract description 4
- 150000003431 steroids Chemical class 0.000 abstract description 4
- 230000002427 irreversible effect Effects 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 2
- 240000000031 Achyranthes bidentata Species 0.000 abstract 1
- 244000000626 Daucus carota Species 0.000 abstract 1
- 235000002767 Daucus carota Nutrition 0.000 abstract 1
- IOUVKUPGCMBWBT-DARKYYSBSA-N Phloridzin Natural products O[C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-DARKYYSBSA-N 0.000 abstract 1
- 208000017169 kidney disease Diseases 0.000 abstract 1
- IOUVKUPGCMBWBT-UHFFFAOYSA-N phloridzosid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-UHFFFAOYSA-N 0.000 abstract 1
- IOUVKUPGCMBWBT-QNDFHXLGSA-N phlorizin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-QNDFHXLGSA-N 0.000 abstract 1
- 235000019139 phlorizin Nutrition 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 14
- 206010012601 diabetes mellitus Diseases 0.000 description 12
- 241000196324 Embryophyta Species 0.000 description 7
- 239000013078 crystal Substances 0.000 description 6
- 230000002485 urinary effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000051325 Glucagon Human genes 0.000 description 2
- 108060003199 Glucagon Proteins 0.000 description 2
- 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 2
- 241001465754 Metazoa Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 2
- 229960004666 glucagon Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- NKDFYOWSKOHCCO-YPVLXUMRSA-N 20-hydroxyecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)(O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 NKDFYOWSKOHCCO-YPVLXUMRSA-N 0.000 description 1
- HXWZQRICWSADMH-SEHXZECUSA-N 20-hydroxyecdysone Natural products CC(C)(C)CC[C@@H](O)[C@@](C)(O)[C@H]1CC[C@@]2(O)C3=CC(=O)[C@@H]4C[C@@H](O)[C@@H](O)C[C@]4(C)[C@H]3CC[C@]12C HXWZQRICWSADMH-SEHXZECUSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- DCEFCUHVANGEOE-UHFFFAOYSA-N Ecdysterone Natural products CC(CC(C)(C)O)C(O)C(C)(O)C1CCC2(O)C3=CC(=O)C4CC(O)C(O)CC4(C)C3CCC12C DCEFCUHVANGEOE-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- NKDFYOWSKOHCCO-UHFFFAOYSA-N beta-ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C)(O)C(O)CCC(C)(O)C)CCC33O)C)C3=CC(=O)C21 NKDFYOWSKOHCCO-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 230000000081 effect on glucose Effects 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 238000007446 glucose tolerance test Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 239000000864 hyperglycemic agent Substances 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野Ｊ
本発明は昆虫変態ホルモンを用いた抗糖尿病薬に関する
ものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application J] The present invention relates to an antidiabetic drug using insect metamorphosis hormone.
従来、抗糖尿病薬とじては種々のものが提案されている
が、未だ充分満足すべきものは得られていない。Various antidiabetic drugs have been proposed in the past, but none have yet been found to be fully satisfactory.
（発明が解決しようとする課が１
従って、本発明が解決しようとする課題は、的確な薬理
効果を示す抗糖尿病薬を提供することである。(Problem to be Solved by the Invention: 1) Therefore, the problem to be solved by the present invention is to provide an antidiabetic drug that exhibits accurate pharmacological effects.
１課題を解決するための手段］
本発明の発明者は上記の課題を解決することを目的とし
た研究過程において、グレジステロン。1. Means for Solving the Problems] In the course of research aimed at solving the above problems, the inventors of the present invention developed gleisterone.
イノコステロンなど昆虫類・甲殻類の変態ホルモンが植
物界にも広く分布しており、その特異な生物活性が注目
されていることに着目し、更に研究を重ねた結果、本発
明を完成した。We focused on the fact that metamorphosis hormones of insects and crustaceans, such as inocosterone, are widely distributed in the plant world, and their unique biological activities are attracting attention, and as a result of further research, we completed the present invention.
即ち、本発明の発明者の一人は、古くから我が国で利尿
・強壮の効果があるとされている本邦産の牛膝（ゴシツ
）の基原植物であるヒナタイノコズチの根から、昆虫変
態ホルモンであるエグシステロンならびにこれと同効物
質であるイノコステロンを単離し、これらの活性物質に
ついて調べたところ、これらはすべてステロイド骨格を
有していることが判明した。That is, one of the inventors of the present invention has developed an insect metamorphosis hormone from the roots of the Japanese ox-knee plant, the root plant of the Japanese goshitsu, which has long been known in Japan to have diuretic and tonic effects. When we isolated a certain egcysterone and its equivalent substance, inocosterone, and investigated their active substances, we found that they all have a steroid skeleton.
そこで、それらか高等動物に対して如何なる生理作用を
示すかについて検ｉ４ した結束、エグシステロンおよ
び類、緑化合物か１１ηｊ処置によってグルカゴン投与
による血糖の上昇を抑制することか判明した。さらに、
そのメカニスム解明の研究を通して腎障害を伴わず高血
糖を低下させ、ランケルハシス島β細胞の負担を軽減し
、インスリン合成能を恢復をはかることを知得して、本
発明を完成させたのである。Therefore, we investigated the physiological effects of these compounds on higher animals, and found that the increase in blood sugar caused by glucagon administration can be suppressed by treatment with existerone, green compounds, and 11ηj. moreover,
Through research to elucidate the mechanism, they learned that hyperglycemia can be lowered without renal damage, the burden on Rankerhasis islet β cells is reduced, and insulin synthesis ability is restored, and the present invention was completed.
而して、本発明の抗糖尿病薬は、
一般式
式中
で表わされる昆虫変態ホルモンを主剤とすることを特徴
とするものである。Therefore, the antidiabetic drug of the present invention is characterized by containing an insect metamorphosis hormone represented by the general formula as a main ingredient.
次（二本発明抗塘尿病薬について詳細に説明する−
本発明抗糖尿病薬は、北述したよつに、−船人（１）で
表わされる昆虫変態ホルモンを主剤とするので、ます、
この化合物について説明すると、これは牛膝類の他にブ
ラシル人参なと広く植物界に分布するステロイド体であ
る。Next (2) The antidiabetic drug of the present invention will be explained in detail.As mentioned above, the antidiabetic drug of the present invention is based on the insect metamorphosis hormone represented by Funen (1).
To explain this compound, it is a steroid that is widely distributed in the plant kingdom, including bovine genus and brassyl ginseng.
化学構造式からみると、５β（）（）ステロイド骨格（
こ２β 、 ３β 、 １４ ａ −２０（Ｒ）
−ｐｅｎｔａｈ５：ｄｒｏｘｙ−７−ｅｎ−６−。From the chemical structural formula, 5β () () steroid skeleton (
This 2β, 3β, 14a-20(R)
-pentah5: droxy-7-en-6-.
ｎｅの共通構造をもつ一連の化合物である。A series of compounds with a common structure of ne.
従って、本発明抗糖尿病薬の主剤たる昆虫変態ホルモン
は、例えば次のようなものが含まれる。Therefore, the insect metamorphosis hormone that is the main ingredient of the antidiabetic drug of the present invention includes, for example, the following.
工ｎｏｋｏｓｔｅｒｏｎｅ
Ｃｙａｓｔｅｒｏｎｅ
ρ−Ｅｃｄｙｓｏｎｅ
０Ｈ
ｐｏｎａｓｔａｒｏｎｅ Ａ
Ｒｕｂｒｏｓｔｒｏｎｅ
Ｐｏｎａｇｔｅｒｏｎｅ Ａ
［実施例］
上記構造の昆虫変態ホ几モジは、いすねも種々の方法に
より植物界かｔつ抽出・分離することかできるか、その
−例を挙げれば、原料植物の根もしくは全草の風乾物を
ド記に示す方法で抽出し、ブタノールで抽出される両分
をアルミナのカラムクロマトグラフィーで精製して粗結
晶を単離する粗結晶エタノール、酢酸エチルの混液から
再結晶を繰返し無色針状結晶とする。Ecdysone 0H Ponastarone A Rubrostrone Ponagterone A [Example] Is it possible to extract and separate the insect metamorphosis of the above structure from the plant kingdom by various methods? For example, crude crystal ethanol is obtained by extracting the air-dried material of the root or whole plant of the raw material plant using the method shown in the following, and then purifying both components extracted with butanol using alumina column chromatography to isolate crude crystals. , and is repeatedly recrystallized from a mixture of ethyl acetate to give colorless needle-shaped crystals.
↓ アルミナカラムで処理
粗結晶
↓酢酸エチルニチノールで再結晶
無色針状晶
（エクジステロン、融点２・１０゛［分解点］）上記方
法により得られた化合物（＋）〜（１２〕を含め、−船
人（１）で表わされる昆虫変態ホルモンは、精製すれば
全般的に無色透明の結晶であって、本発明抗糖尿病用薬
は該昆虫変態ホルモンをｔ剤として、従来公知の方法に
より錠剤、散剤、顆粒剤、カプセル剤等々の適宜剤形に
製剤することができる。↓ Crude crystals treated with alumina column ↓ Recrystallized with ethylnitinol acetate Colorless needle crystals (ecdysterone, melting point 2.10゛ [decomposition point]) Compounds (+) to (12) obtained by the above method, including - ship The insect metamorphosis hormone represented by human (1) is generally colorless and transparent crystals when purified, and the antidiabetic drug of the present invention can be prepared in the form of tablets, powders, etc. by using the insect metamorphosis hormone as a T-agent by a conventionally known method. , granules, capsules, and other appropriate dosage forms.
［発明の作用及び効果１
本発明は上記構成の抗糖尿病薬剤に係るものであって、
従来の血糖降下剤は、膵からのインスリン分泌を刺激す
る作用と肝での糖放出抑制を増強、筋や脂肪組織での糖
移送促進作用、末梢組織におけるインスリン受容体の数
の増加によるインスリン作用の増強などの膵外性作用な
どが挙げられる。[Actions and Effects of the Invention 1 The present invention relates to an antidiabetic drug having the above structure,
Conventional hypoglycemic agents have the effect of stimulating insulin secretion from the pancreas, increasing the suppression of sugar release in the liver, promoting sugar transport in muscle and adipose tissue, and increasing the number of insulin receptors in peripheral tissues, thereby increasing the insulin effect. Examples include extrapancreatic effects such as enhancement of
しかし、それらは適量投与１食事の不規則、肝障害、腎
障害などによる低血糖の発現する欠点がある。また、副
作用の少ない作用の緩和なものも見出されているが、い
まだ的確な効果を示すものは得られない。However, these drugs have the disadvantage of causing hypoglycemia due to irregular meals, liver damage, kidney damage, etc. after administration of appropriate doses. In addition, although some drugs with less side effects and milder effects have been found, no drug has yet been found that exhibits precise effects.
本発明者らは、副作用の少ないすぐれた高血糖降下剤を
得る目的で、種々検討を爪ねた結果、微量のエクシステ
ロン投与で、グルカゴンによるラットの高血糖を低下さ
せるメカニスムか、インスリン様作用によるものではな
く、腎における糖再吸収機能の抑制によると思われる尿
糖増加を伴うことを見出した。これらの事実に基づき、
当該新規抗糖尿病薬は、フロリシンのような不可逆的な
腎障害を惹き起さずに高血糖を一時的にＦげ、ランケル
ハンス島β細胞の負担を軽減して、インスリン合成能の
恢復をはかる目的のために利用する二とが可能であるの
で、本発明抗糖尿病薬はこれを糖尿病臨床に適用できる
ものである。With the aim of obtaining an excellent hyperglycemic agent with few side effects, the present inventors have conducted various studies and found that the mechanism by which administration of a trace amount of existerone lowers glucagon-induced hyperglycemia in rats has an insulin-like effect. It was found that this was accompanied by an increase in urinary sugar, which was thought to be due to suppression of the sugar reabsorption function in the kidneys, rather than due to this. Based on these facts,
The purpose of this new antidiabetic drug is to temporarily relieve hyperglycemia without causing irreversible renal damage like phloricin, reduce the burden on Lankerhans islet β cells, and restore insulin synthesis ability. Therefore, the antidiabetic agent of the present invention can be applied to clinical diabetes treatment.
而して、本発明は上記構成の抗糖尿病薬に係るものであ
って、各種糖尿病に悩む患者に投与して膵ランゲルハン
ス島β細胞におけるインスリン合成能の恢復をはかるも
のではあるが、この薬理効果を実際の患者に本発明抗糖
尿病薬を投与して確認することには、現時点では種々の
問題があるので、動物実験によりその効果を確認するこ
ととした。Therefore, the present invention relates to an antidiabetic drug having the above structure, which is administered to patients suffering from various types of diabetes in order to restore insulin synthesis ability in pancreatic Langerhans islet β cells. At present, there are various problems in confirming this by administering the antidiabetic drug of the present invention to actual patients, so we decided to confirm its effectiveness through animal experiments.
即ち、；ｒ」記工′７レス梁＝シ１■を滅菌生理食塩液
に溶解し、これをストし７［・ゾ［・シシ投与による糖
尿病ラット ＩＩ １１＋１糖直！Ｏ（＋ 〜６００ｍ
ｇ ／ ｄ）腹腔内に１回投与したところ、本発明抗糖
尿病薬は、第１図の図表に示すように、・４〜６時間後
に血糖値か減少をきたし、−時的に元へ戻ったのち、再
び４８時間後におよそ投与時の５０％はとに低下したの
である。That is, ;r'' was dissolved in sterile physiological saline, and this was added to diabetic rats II 11+1 sugar conversion by administration of 7[・zo[・shishi! O(+ ~600m
g/d) When administered once intraperitoneally, the anti-diabetic drug of the present invention, as shown in the diagram in Figure 1, - after 4 to 6 hours, the blood sugar level decreased, and - returned to its original level over time. Then again, after 48 hours, the dose had dropped to about 50% of the dose.
尚、：３ないし５匹の重症度および中等度の糖尿ラット
それぞれに対し、エクシステロシＩ ｍｇ ／ ｋｚを
２４時間ごとに腹腔内投与したときの尿中への糖の排泄
量を測定した。その結果、第２図の図表に示すとおり、
重症糖尿ラット群においては、２゜３日目に尿糖の増加
が見られ、中等度糖尿ラットにおいては、２，３．４日
目にほぼ１．５倍の尿糖の増加が見られた。ついで、投
与経路を経口で同じ実験を行った４
その結果は第；３図の図表に示すとおり、尿糖の増加が
１日遅れて殆と全く同様の傾向か認められた。また、重
症度糖尿ラットに対し５■／ｋｇ経口投与、シたところ
、やはり１日遅れて同じく尿糖の増加傾向を示した。−
万、血糖値はおよそ２０％および５０％はと改善してい
た。In addition, when Existerosi I mg/kz was intraperitoneally administered every 24 hours to 3 to 5 severely and moderately diabetic rats, the amount of sugar excreted into the urine was measured. As a result, as shown in the diagram in Figure 2,
In the severely diabetic rat group, an increase in urinary sugar was observed on days 2 and 3, and in the moderately diabetic rats, an increase of approximately 1.5 times in urinary sugar was observed on days 2 and 3.4. . Next, the same experiment was conducted using the oral administration route.4 As shown in the chart in Figure 3, the increase in urinary sugar was delayed by one day, but almost exactly the same trend was observed. In addition, when the drug was orally administered to severely diabetic rats at 5 μ/kg, urinary sugar showed the same tendency to increase after a delay of one day. −
However, blood sugar levels had improved by approximately 20% and 50%.
次に、糖尿ラットにエダシステロシ１■／眩を腹腔内５
日連続投与して、ラットの経［コブドウ糖負荷試験に及
ぼす影響を検討した。重症度、中等度および軽度糖尿ラ
ットについて、それぞれの結果を第４図に示す。第４図
Ｃに示すとおり、軽度糖尿ラットにおいては、ニクジス
テロン投与により殆んと対照とした正常ラッ）・の血糖
レベルまで良好にコントロールされている。なお、投与
２Ｊ間後においても、１時間値、２時間値いずれもかな
りの改善効果の持績が認められた。第４図すに示すとお
り、中等度糖尿ラットにおいては、空腹時血糖値をはじ
め、１時間値および２時間後の血糖値はいずれもコント
ロールおよび投与的値に比し有意の差をもって明らかに
改善している。しかし、投与２週間後では空腹時血糖値
の改善効果は持続しているが、糖負荷に対しての効果は
みられなかった。さらに、重症糖尿ラットについては同
じ条件下では明らかな改善効果はみられなかったか、エ
クシステロン５■／臓腹腔内投与群においては、有意の
差をもって明らかに改善効果か認、めεつれた。Next, diabetic rats were given edasysterosis 1/5 times intraperitoneally.
The effect of continuous administration on daily glucose tolerance tests in rats was investigated. The results for severe, moderate and mildly diabetic rats are shown in FIG. 4. As shown in FIG. 4C, in mildly diabetic rats, blood sugar levels were well controlled by administration of nikdysterone to almost the same level as in normal control rats. In addition, even after 2 J of administration, a significant improvement effect was observed in both the 1-hour value and the 2-hour value. As shown in Figure 4, in moderately diabetic rats, fasting blood glucose levels, as well as 1-hour and 2-hour blood glucose levels, all clearly improved with significant differences compared to control and administered values. are doing. However, two weeks after administration, although the effect of improving fasting blood sugar level continued, no effect on glucose load was observed. Furthermore, in severe diabetic rats, no clear improvement effect was observed under the same conditions, but in the existerone 5/intraperitoneal administration group, a clear improvement effect was observed with a significant difference.
第１図乃至第４図はラットに本発明抗糖尿病薬を投す−
した結果を示す図表である。Figures 1 to 4 show the administration of the antidiabetic drug of the present invention to rats.
This is a chart showing the results.
Claims (1)
式、表等があります▼ で表わされる昆虫変態ホルモンを主成分とすることを特
徴とする抗糖尿病薬。[Claims] 1. An insect metamorphosis hormone represented by the general formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ In the formula, R is ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ▲There are mathematical formulas, chemical formulas, tables, etc.▼ An antidiabetic drug characterized by having the main ingredient as an antidiabetic drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24482190A JPH04124135A (en) | 1990-09-14 | 1990-09-14 | Antidiabetic drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24482190A JPH04124135A (en) | 1990-09-14 | 1990-09-14 | Antidiabetic drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH04124135A true JPH04124135A (en) | 1992-04-24 |
Family
ID=17124456
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24482190A Pending JPH04124135A (en) | 1990-09-14 | 1990-09-14 | Antidiabetic drug |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH04124135A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2924346A1 (en) * | 2007-11-30 | 2009-06-05 | Inst Biophytis Sas Soc Par Act | USE OF PHYTOECDYSONS IN THE PREPARATION OF A COMPOSITION FOR ACTING ON METABOLIC SYNDROME. |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4842872A (en) * | 1971-09-30 | 1973-06-21 |
-
1990
- 1990-09-14 JP JP24482190A patent/JPH04124135A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4842872A (en) * | 1971-09-30 | 1973-06-21 |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2924346A1 (en) * | 2007-11-30 | 2009-06-05 | Inst Biophytis Sas Soc Par Act | USE OF PHYTOECDYSONS IN THE PREPARATION OF A COMPOSITION FOR ACTING ON METABOLIC SYNDROME. |
| WO2009071804A3 (en) * | 2007-11-30 | 2010-04-22 | Institut Biophytis Sas | Use of phytoecdysones in the preparation of a composition for acting on metabolic syndrome |
| JP2011504921A (en) * | 2007-11-30 | 2011-02-17 | アンスティテュ．バイオフィティ．エスアエス | Use of plant ecdysone in the preparation of compositions acting on metabolic syndrome |
| US8236359B2 (en) | 2007-11-30 | 2012-08-07 | Institut Biophytis Sas | Use of phytoecdysones in the preparation of a composition for acting on the metabolic syndrome |
| AU2008332981B2 (en) * | 2007-11-30 | 2014-06-12 | Biophytis | Use of phytoecdysones in the preparation of a composition for acting on metabolic syndrome |
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