JPH0543472A - Antidigestible ulcer agent and its production - Google Patents
Antidigestible ulcer agent and its productionInfo
- Publication number
- JPH0543472A JPH0543472A JP3226610A JP22661091A JPH0543472A JP H0543472 A JPH0543472 A JP H0543472A JP 3226610 A JP3226610 A JP 3226610A JP 22661091 A JP22661091 A JP 22661091A JP H0543472 A JPH0543472 A JP H0543472A
- Authority
- JP
- Japan
- Prior art keywords
- substance
- water
- extract
- ulcer agent
- organic solvent
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 208000025865 Ulcer Diseases 0.000 title abstract description 22
- 231100000397 ulcer Toxicity 0.000 title abstract description 21
- 239000000126 substance Substances 0.000 claims abstract description 30
- 125000000129 anionic group Chemical group 0.000 claims abstract description 12
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 241000251591 Halocynthia roretzi Species 0.000 claims abstract description 8
- 239000004615 ingredient Substances 0.000 claims abstract description 7
- 125000000524 functional group Chemical group 0.000 claims abstract description 6
- 230000002467 anti-pepsin effect Effects 0.000 claims description 19
- 239000003699 antiulcer agent Substances 0.000 claims description 18
- 241000251557 Ascidiacea Species 0.000 claims description 15
- 239000004480 active ingredient Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 7
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 5
- 210000003205 muscle Anatomy 0.000 claims description 5
- 210000001835 viscera Anatomy 0.000 claims description 5
- 239000003456 ion exchange resin Substances 0.000 claims description 3
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 7
- 230000002829 reductive effect Effects 0.000 abstract description 6
- 230000002496 gastric effect Effects 0.000 abstract description 5
- 239000007788 liquid Substances 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 230000001747 exhibiting effect Effects 0.000 abstract description 3
- 230000006378 damage Effects 0.000 abstract description 2
- 230000001939 inductive effect Effects 0.000 abstract description 2
- 210000004400 mucous membrane Anatomy 0.000 abstract 3
- 208000027418 Wounds and injury Diseases 0.000 abstract 1
- 208000014674 injury Diseases 0.000 abstract 1
- 230000017074 necrotic cell death Effects 0.000 abstract 1
- 230000002633 protecting effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000000767 anti-ulcer Effects 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 230000002209 hydrophobic effect Effects 0.000 description 6
- 239000003957 anion exchange resin Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 208000008469 Peptic Ulcer Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000000274 adsorptive effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000003729 cation exchange resin Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 208000011906 peptic ulcer disease Diseases 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010042220 Stress ulcer Diseases 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010067993 Mucosal necrosis Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 241000251555 Tunicata Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000010171 animal model Methods 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
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 210000003736 gastrointestinal content Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000008881 mucosal defense Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】この発明は、消化性潰瘍に対して
抑制作用や、胃粘膜保護作用等を有する抗消化性潰瘍剤
であって、特にマボヤ（学名はHalocynthia roretzi、
以下単にマボヤと称す）から抽出された成分を含有する
抗消化性潰瘍剤とその製造方法に関する。FIELD OF THE INVENTION The present invention relates to an anti-peptic ulcer agent having an inhibitory action against peptic ulcer, a gastric mucosal protective action, etc., and particularly, ascidian (scientific name: Halocynthia roretzi,
The present invention relates to an anti-peptic ulcer agent containing a component extracted from (hereinafter referred to as maboya) and a method for producing the same.
【０００２】[0002]
【従来の技術】従来、マボヤは、津軽海峡沿岸や三陸海
岸沿岸で主に多くとれ、養殖も行なわれて、食用に供さ
れているものである。このマボヤの薬理作用について
は、特開昭６３−３０７８７５号公報に開示されている
ように、細菌及びカビに対する抗菌作用を有するという
報告がなされている。また、沖縄の海で採取されたホヤ
の一種に、強い抗腫瘍活性が認められるという報告もあ
る。2. Description of the Related Art Heretofore, ascidians have been found mainly in the coasts of the Tsugaru Strait and the coast of Sanriku Coast, and have been cultured and used for food. Regarding the pharmacological action of this ascidian, it has been reported that it has an antibacterial action against bacteria and mold, as disclosed in JP-A-63-307875. There is also a report that a kind of sea squirt collected in the sea of Okinawa has strong antitumor activity.
【０００３】従来の抗消化性潰瘍剤としては、Ｈ2−ブ
ロッカー（例えばシメチジン）などの胃粘膜に対する攻
撃因子を抑制する薬剤や、スクラルファートなどの防御
因子を補強する薬剤があり、現在前者のタイプの薬剤が
多く用いられ効果を上げている。As conventional anti-peptic ulcer agents, there are agents that suppress gastric mucosal attack factors such as H 2 -blockers (for example, cimetidine) and agents that reinforce defense factors such as sucralfate, and are currently of the former type. Many of these drugs are used to increase the effect.
【０００４】[0004]
【発明が解決しようとする課題】しかしながら、上記マ
ボヤの抽出物あるいはその成分物質が、抗消化性潰瘍作
用を有するという報告はなく、抗消化性潰瘍剤としてマ
ボヤの抽出物を用いるという報告もない。However, there is no report that the above ascidian extract or its component substances have an anti-peptic ulcer action, and there is no report that the ascidian extract is used as an anti-peptic ulcer agent. ..
【０００５】一方、上記攻撃因子を抑制する薬剤は、急
性の潰瘍に対しては有効であるが、治療後薬剤投与を中
止すると、多くの症例に再発が見られるという問題があ
り、再発防止のためには、粘膜防御機能を増強するよう
に作用する薬剤が必要であった。On the other hand, drugs that suppress the above-mentioned attack factors are effective against acute ulcers, but if the drug administration is stopped after the treatment, there is a problem that recurrence is observed in many cases, and thus prevention of recurrence occurs. In order to do so, a drug that acts to enhance the mucosal defense function was required.
【０００６】この発明は、上記従来の技術の問題点に鑑
みて成されたもので、粘膜保護作用を有し、消化性潰瘍
の抑制効果が高い抗消化性潰瘍剤とその製造方法を提供
することを目的とする。The present invention has been made in view of the above problems of the prior art, and provides an anti-peptic ulcer agent having a mucosal protective action and a high effect of suppressing peptic ulcer, and a method for producing the same. The purpose is to
【０００７】[0007]
【課題を解決するための手段】この発明の抗消化性潰瘍
剤は、マボヤから水混和性有機溶媒で抽出した成分を減
圧下濃縮したものであり、この抽出成分が、粘膜壊死誘
発物質であるアルコールの経口投与や、ストレスによる
胃粘膜損傷を抑制するというものである。The anti-peptic ulcer agent of the present invention is obtained by concentrating components extracted from ascidian with a water-miscible organic solvent under reduced pressure, and the extracted components are mucosal necrosis-inducing substances. Oral administration of alcohol and suppression of gastric mucosal damage due to stress.
【０００８】この抽出成分のうちの特に有効な成分は、
陰イオン性物質又は陰イオン性を示すことが可能な官能
基を有する物質であり、親水性が高い物質である。Among the extracted components, the particularly effective component is
It is an anionic substance or a substance having a functional group capable of exhibiting anionic property, and is a substance having high hydrophilicity.
【０００９】この有効成分の抽出方法は、マボヤの被の
うを除去し、筋肉及び内臓を細かく砕き、水混和性有機
溶媒中に浸漬する。そして、抽出成分が溶けた上記水混
和性有機溶媒を減圧下濃縮して溶媒及び水分を除去し、
有効成分の濃縮エキスを得るものである。In this method of extracting the active ingredient, the ascidian capsules are removed, the muscles and internal organs are finely crushed, and immersed in a water-miscible organic solvent. Then, the water-miscible organic solvent in which the extracted components are dissolved is concentrated under reduced pressure to remove the solvent and water,
A concentrated extract of the active ingredient is obtained.
【００１０】さらに有効成分を特定し抽出するには、上
記濃縮エキス分を再び溶媒中に溶かし、イオン交換樹脂
でイオン交換により、陰イオン性物質又は陰イオン性官
能基を有する物質を分離した後、溶媒及び水分を除去し
て有効成分を濃縮する。また、疎水性物質吸着樹脂等を
用いて、親水性物質を分離し、有効成分である親水性の
高い物質を抽出するものである。In order to further identify and extract the active ingredient, the concentrated extract is again dissolved in a solvent, and an anionic substance or a substance having an anionic functional group is separated by ion exchange with an ion exchange resin. The solvent and water are removed to concentrate the active ingredient. In addition, a hydrophilic substance is separated by using a hydrophobic substance adsorption resin or the like, and a highly hydrophilic substance that is an active ingredient is extracted.
【００１１】[0011]
【作用】この発明の抗消化性潰瘍剤の薬理作用について
以下に説明する。先ず、上記濃縮エキスを、界面活性剤
（例えば、アトラス社のTween80等の非イオン性界面活
性剤）を０．５％含む水溶液に懸濁したものを、検体液
として用い、対照には媒体のみを用いた。また、使用実
験動物には、ＳＤ系雄性ラット（体重１６０〜２３０
ｇ）を、１群５〜８匹にして検証に用いた。The pharmacological action of the anti-peptic ulcer agent of the present invention will be described below. First, a suspension of the above concentrated extract in an aqueous solution containing 0.5% of a surfactant (for example, a nonionic surfactant such as Tween 80 manufactured by Atlas) was used as a sample solution, and only a medium was used as a control. Was used. In addition, male SD rats (body weight: 160-230) were used as experimental animals.
g) was used for verification by making 5 to 8 animals per group.
【００１２】また、潰瘍観察及び潰瘍強度判定には、胃
の食道側及び十二指腸側の両側を糸で結紮して胃を摘出
し、胃に１０％ホルマリン生食液６ｍｌを注入し、同じ
液に浸漬して固定した。そして、固定後、胃を大彎に沿
って切開し、実体顕微鏡下で潰瘍係数（潰瘍の長さの合
計）を測定した。For ulcer observation and ulcer strength determination, both the esophageal side and the duodenal side of the stomach were ligated with a thread, the stomach was excised, and 6 ml of 10% formalin saline was injected into the stomach and immersed in the same liquid. And fixed it. Then, after fixation, the stomach was incised along the greater curvature, and the ulcer index (total ulcer length) was measured under a stereoscopic microscope.
【００１３】ここでの統計処理には、潰瘍係数は各個体
の潰瘍の全長の平均値で示し、潰瘍の抑制率は下記の式
により算出した。 抑制率（％）＝（１−被検体群の潰瘍係数／対照群の潰
瘍係数）×１００ 潰瘍係数の有意差検定には、Studentのt検定法を用い、
対照群との間で行なった。In the statistical processing here, the ulcer coefficient was represented by the average value of the total length of the ulcer of each individual, and the ulcer inhibition rate was calculated by the following formula. Suppression rate (%) = (1-ulcer coefficient of subject group / ulcer coefficient of control group) × 100 The t-test method of Student was used for the significant difference test of the ulcer coefficient.
It carried out between the control group.
【００１４】先ず、アルコール潰瘍に対する作用を示
す。２４時間絶食させたラットに、各群毎に検体液もし
くは媒体を、経口投与し、１時間後に１５０mMの塩酸を
含む６０％エタノール（体重１ｋｇあたり５ｍｌ）を経
口投与した。そして、エタノール投与後２時間絶食、絶
水下で放置し、屠殺して観察した。その結果、上記抽出
エキスの投与量と潰瘍係数の関係を表１に示す。First, the action on alcohol ulcer will be shown. Rats that had been fasted for 24 hours were orally administered with a sample solution or a medium for each group, and 1 hour later, 60% ethanol containing 150 mM hydrochloric acid (5 ml per 1 kg of body weight) was orally administered. Then, after administration of ethanol, the animals were fasted for 2 hours, allowed to stand under waterless conditions, slaughtered, and observed. As a result, Table 1 shows the relationship between the dose of the above extract and the ulcer index.
【００１５】[0015]
【表１】 [Table 1]
【００１６】この結果から、この発明の上記抽出エキス
を投与したものについて明らかに潰瘍の抑制効果が認め
られ、強い胃粘膜保護作用があることがわかる。From these results, it can be seen that the one to which the above-mentioned extract of the present invention is administered has a clear ulcer inhibitory effect and has a strong protective effect on the gastric mucosa.
【００１７】次にストレス潰瘍に対しては、上記ラット
に前述の検体液又は媒体を経口投与し、３０分後にスト
レスケージに入れ、５時間２３℃の水槽に浸漬した後、
屠殺して前述のように潰瘍を観察した。その結果は表２
に示すように、ストレス性潰瘍に対しても抑制効果があ
ることがわかる。Next, for stress ulcers, the above-mentioned test liquid or medium was orally administered to the above rats, placed 30 minutes later in a stress cage and immersed for 5 hours in a water bath at 23 ° C.
It was sacrificed and the ulcer was observed as described above. The results are shown in Table 2.
As shown in, it can be seen that it also has an inhibitory effect on stress ulcers.
【００１８】[0018]
【表２】 [Table 2]
【００１９】この発明の上記抽出成分の毒性について
は、ｄｄＹ系マウスを用いて、この発明の上記抽出成分
を単回投与により調べたが、1000mg/kgの経口投与にお
いて、全く死亡例はなかった。Regarding the toxicity of the above extract of the present invention, the above extract of the present invention was examined by a single administration using ddY mice, but no death occurred at the oral administration of 1000 mg / kg. ..
【００２０】さらに、上記抽出成分を陽イオン交換樹脂
と陰イオン交換樹脂とを用いてイオン性により分割し
て、陽イオン性物質除去部分と、陰イオン性物質除去部
分のアルコール潰瘍に対する抗潰瘍作用を調べた。その
結果、抗潰瘍活性を示す有効成分は、強塩基性陰イオン
交換樹脂に吸着されるものであった。すなわち、活性本
体は、陰イオン性物質又は陰イオン性を示すことが可能
な官能基を有するものである。Further, the above-mentioned extracted components are ionicly divided by using a cation exchange resin and an anion exchange resin, and the cation substance-removed portion and the anion substance-removed portion have an antiulcer action against alcohol ulcer. I checked. As a result, the active ingredient showing antiulcer activity was adsorbed on the strongly basic anion exchange resin. That is, the active substance has an anionic substance or a functional group capable of exhibiting anionic property.
【００２１】また、上記抽出物質を、疎水性物質を吸着
し易い樹脂を用いて親水性物質と疎水性物質に分けてア
ルコール潰瘍に対する抗潰瘍作用を調べた結果、上記抽
出成分のうち親水性の高い物質に抗潰瘍活性が見られ
た。The extracted substance was divided into a hydrophilic substance and a hydrophobic substance by using a resin which easily adsorbs a hydrophobic substance, and the antiulcer action against alcohol ulcer was examined. Antiulcer activity was found in the higher substances.
【００２２】この発明の抗消化性潰瘍剤を人体に投与す
る場合、そのエキスのまま軟エキス剤として用いること
ができ、さらに、製剤用の賦形剤、結合剤等を配合して
錠剤や顆粒剤に成形して経口投与することもできる。こ
の発明の抗消化性潰瘍剤の投与量は、患者の年齢、体
重、疾患の程度によって適宜増減するが、経口投与の場
合、通常成人で、１日あたり１〜１０００ｍｇ／ｋｇ程
度が好ましく、１回又は数回に分けて投与する。When the anti-peptic ulcer agent of the present invention is administered to a human body, it can be used as a soft extract as it is, and it is further mixed with an excipient for formulation, a binder and the like to give tablets and granules. It can also be orally administered after molding into a drug. The dose of the anti-peptic ulcer agent of the present invention may be appropriately increased or decreased depending on the age, body weight and degree of disease of the patient, but in the case of oral administration, it is usually 1 to 1000 mg / kg per day in an adult, and preferably 1 to 1000 mg / kg. Administer in single or divided doses.
【００２３】[0023]
【実施例】以下この発明の抗消化性潰瘍剤とその製造方
法についての実施例を示す。ここでは、被のうを除去し
たマボヤ８８匹を、消化管内容物および解剖時に出た浸
出液を除き、筋肉と内臓部分を細かく砕き、メタノール
中に浸漬し、有効成分の抽出を行なった。抽出に際し、
数リットルのメタノールに１〜３日漬け、この上澄み液
を採取し、残った固形分にさらにメタノールを数リット
ル加えて抽出を行ない、これを数回繰り返した。そし
て、合計２２リットルのメタノールを使用して抽出を行
なった。この後、有効成分を含む上澄み液を減圧下濃縮
し、メタノール及び水分を除去し、４０８ｇの濃縮エキ
スを得た。EXAMPLES Examples of the anti-peptic ulcer agent of the present invention and the method for producing the same will be shown below. Here, 88 ascidians from which the ancalyx was removed were subjected to extraction of the active ingredient by removing the digestive tract contents and the exudate generated at the time of dissection, crushing the muscle and viscera into fine pieces, and immersing them in methanol. When extracting
The mixture was immersed in several liters of methanol for 1 to 3 days, the supernatant was collected, and several liters of methanol was further added to the remaining solid content for extraction, which was repeated several times. Then, extraction was performed using a total of 22 liters of methanol. Then, the supernatant containing the active ingredient was concentrated under reduced pressure to remove methanol and water, and 408 g of a concentrated extract was obtained.
【００２４】この濃縮エキスについて、その有効成分の
性質を特定するため、この濃縮エキスを、エタノールと
水が５０％ずつの液に溶かして懸濁液を作成し、この液
を、スチレン−ジビニルベンゼン共重合体のスルホン化
物である強酸性陽イオン交換樹脂（ダウエックス５０
Ｗ、ダウケミカル社製、米国）のＮａ型樹脂と、スチレ
ン−ジビニルベンゼン共重合体に第４級アンモニウム基
を導入した樹脂である強塩基性陰イオン交換樹脂（ダウ
エックス１、ダウケミカル社製、米国）のＣｌ型樹脂の
２種類のイオン交換樹脂を各々担体としてカラムクロマ
トグラフィーに付し、５０％エタノール水で溶出した。
そして、非吸着成分を含んだ上記２種類の溶出液を、減
圧下で濃縮乾燥して、陽イオン性物質除去部分と、陰イ
オン性物質除去部分とを得た。In order to specify the properties of the active ingredient of this concentrated extract, the concentrated extract was dissolved in a liquid containing 50% ethanol and 50% water to prepare a suspension, and this liquid was added to styrene-divinylbenzene. Strongly acidic cation exchange resin (Dowex 50) which is a sulfonated product of a copolymer.
W type, Dow Chemical Co., USA Na type resin, and a strongly basic anion exchange resin (Dowex 1, Dow Chemical Co., Ltd.) which is a resin in which a quaternary ammonium group is introduced into a styrene-divinylbenzene copolymer. Column chromatography using two types of ion exchange resins, Cl type resins of US, USA) as carriers, and eluting with 50% ethanol water.
Then, the above-mentioned two kinds of eluates containing non-adsorbed components were concentrated and dried under reduced pressure to obtain a cationic substance-removed portion and an anionic substance-removed portion.
【００２５】また、上記濃縮エキスの水懸濁液を、スチ
レンとジビニルベンゼンを重合させたハイポーラスポリ
マーであり疎水性物質を吸着し易い樹脂（アンバーライ
トＸＡＤ−２、ロームアンドハース社製、米国）を担体
としたカラムクロマトグラフィーに付し、水洗後、メタ
ノールと水の混合液で溶出分画した。各画分を減圧下で
濃縮乾燥し、親水性物質と、疎水性物質に分けた。A resin (Amberlite XAD-2, manufactured by Rohm and Haas Company, USA, which is a high-porous polymer obtained by polymerizing styrene and divinylbenzene and which easily adsorbs a hydrophobic substance, is used as an aqueous suspension of the concentrated extract. Was subjected to column chromatography using as a carrier, washed with water, and then eluted and fractionated with a mixed solution of methanol and water. Each fraction was concentrated and dried under reduced pressure to be divided into a hydrophilic substance and a hydrophobic substance.
【００２６】上記濃縮エキスから分離した成分について
の、アルコール潰瘍に対する抑制効果は、陽イオン交換
樹脂の非吸着成分に抗潰瘍作用がみられたが、陰イオン
交換樹脂の非吸着成分には抗潰瘍作用はみられなかっ
た。また、上記疎水性物質を吸着し易い樹脂の非吸着成
分に、強い抗潰瘍作用がみられた。Regarding the inhibitory effect on the alcohol ulcer of the components separated from the above concentrated extract, the non-adsorptive component of the cation exchange resin showed an anti-ulcer action, but the non-adsorptive component of the anion exchange resin showed anti-ulcer. No effect was seen. Further, a strong antiulcer action was observed in the non-adsorptive component of the resin that easily adsorbs the hydrophobic substance.
【００２７】[0027]
【発明の効果】この発明の抗消化性潰瘍剤は、優れた胃
粘膜保護作用があり、安全性が高く、医薬として極めて
有効なものである。この発明の抗消化性潰瘍剤の製造方
法は、自然界に存在するマボヤから、有効成分を抽出す
るものであり、有効成分の抽出が容易であり、抽出され
た成分の安全性が高く、医薬としての効果も極めて高い
ものである。INDUSTRIAL APPLICABILITY The anti-peptic ulcer agent of the present invention has an excellent gastric mucosal protective action, is highly safe, and is extremely effective as a medicine. The method for producing an anti-peptic ulcer agent of the present invention is to extract an active ingredient from ascidian that naturally exists, the active ingredient can be easily extracted, and the extracted ingredient is highly safe and can be used as a medicine. The effect of is also extremely high.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 川筋 透 富山県射水郡小杉町中太閤山17−１ 富山 県薬事研究所内 (72)発明者 上野 美穂 富山県射水郡小杉町中太閤山17−１ 富山 県薬事研究所内 (72)発明者 岩上 敏 富山県射水郡小杉町中太閤山17−１ 富山 県薬事研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Toru Kawasuji 17-1 Nakataikoyama, Kosugi-cho, Imizu-gun, Toyama Prefecture Inside Toyama Pharmaceutical Research Institute (72) Miho Ueno 17-1 Nakataikoyama, Kosugi-cho, Imizu-gun, Toyama Prefecture Toyama Prefectural Pharmaceutical Research Institute (72) Inventor Satoshi Iwakami 17-1 Nakataikoyama, Kosugi-cho, Imizu-gun, Toyama Prefecture Toyama Prefectural Pharmaceutical Research Institute
Claims (6)
混和性有機溶媒により抽出された成分を主成分とする抗
消化性潰瘍剤。1. An anti-peptic ulcer agent comprising a component extracted from ascidian (Halocynthia roretzi) with a water-miscible organic solvent as a main component.
混和性有機溶媒により抽出された成分であって、陰イオ
ン性物質又は陰イオン性官能基を有する物質を主成分と
する抗消化性潰瘍剤。2. An anti-peptic ulcer agent, which is a component extracted from ascidian (Halocynthia roretzi) with a water-miscible organic solvent, and which contains an anionic substance or a substance having an anionic functional group as a main component.
混和性有機溶媒により抽出された成分であって、親水性
が高い物質を主成分とする抗消化性潰瘍剤。3. An anti-peptic ulcer agent, which is a component extracted from ascidian (Halocynthia roretzi) with a water-miscible organic solvent and which has a highly hydrophilic substance as a main component.
及び内臓を細かく砕き、水混和性有機溶媒中に浸漬し、
抽出成分が溶けた上記水混和性有機溶媒から溶媒及び水
分を除去して抽出成分を濃縮する抗消化性潰瘍剤の製造
方法。4. The muscle and internal organs of ascidian (Halocynthia roretzi) are finely crushed and immersed in a water-miscible organic solvent,
A method for producing an anti-peptic ulcer agent, which comprises removing the solvent and water from the water-miscible organic solvent in which the extract component is dissolved to concentrate the extract component.
及び内臓を細かく砕き、水混和性有機溶媒中に浸漬し有
効成分を抽出し、抽出成分が溶けた溶媒を、イオン交換
樹脂でイオン交換し陰イオン性物質又は陰イオン性官能
基を有する物質を分離し、溶媒及び水分を除去して抽出
成分を濃縮する抗消化性潰瘍剤の製造方法。5. Muscles and internal organs of ascidian (Halocynthia roretzi) are finely crushed, immersed in a water-miscible organic solvent to extract the active ingredient, and the solvent in which the extracted ingredient is dissolved is ion-exchanged with an ion-exchange resin to obtain anions. A method for producing an anti-peptic ulcer agent, which comprises separating a volatile substance or a substance having an anionic functional group, removing the solvent and water, and concentrating the extracted component.
及び内臓を細かく砕き、水混和性有機溶媒中に浸漬し有
効成分を抽出し、抽出成分が溶けた溶媒から親水性の高
い物質を分離し、溶媒及び水分を除去して抽出成分を濃
縮する抗消化性潰瘍剤の製造方法。6. The muscle and internal organs of ascidian (Halocynthia roretzi) are finely crushed and immersed in a water-miscible organic solvent to extract the active ingredient, and a highly hydrophilic substance is separated from the solvent in which the extracted ingredient is dissolved, And a method for producing an anti-peptic ulcer agent for removing water and concentrating an extract component.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3226610A JPH0543472A (en) | 1991-08-12 | 1991-08-12 | Antidigestible ulcer agent and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3226610A JPH0543472A (en) | 1991-08-12 | 1991-08-12 | Antidigestible ulcer agent and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0543472A true JPH0543472A (en) | 1993-02-23 |
Family
ID=16847900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3226610A Pending JPH0543472A (en) | 1991-08-12 | 1991-08-12 | Antidigestible ulcer agent and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0543472A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5873177A (en) * | 1996-05-20 | 1999-02-23 | Tokyo Electron Limited | Spin dryer and substrate drying method |
| WO2005120526A1 (en) * | 2004-06-11 | 2005-12-22 | Combi Corporation | Composition for inhibiting the progress of muscular dystrophy |
| WO2006008890A1 (en) * | 2004-06-11 | 2006-01-26 | Combi Corporation | Muscle strengthening composition |
| EP2692740A1 (en) * | 2012-07-30 | 2014-02-05 | Le Centre National De La Recherche Scientifique | Glycan compositions, processes for preparing the same and their uses as a drug |
-
1991
- 1991-08-12 JP JP3226610A patent/JPH0543472A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5873177A (en) * | 1996-05-20 | 1999-02-23 | Tokyo Electron Limited | Spin dryer and substrate drying method |
| WO2005120526A1 (en) * | 2004-06-11 | 2005-12-22 | Combi Corporation | Composition for inhibiting the progress of muscular dystrophy |
| WO2006008890A1 (en) * | 2004-06-11 | 2006-01-26 | Combi Corporation | Muscle strengthening composition |
| EP2692740A1 (en) * | 2012-07-30 | 2014-02-05 | Le Centre National De La Recherche Scientifique | Glycan compositions, processes for preparing the same and their uses as a drug |
| WO2014020047A1 (en) * | 2012-07-30 | 2014-02-06 | Centre National De La Recherche Scientifique | Glycan compositions, processes for preparing the same and their uses as a drug |
| JP2015527339A (en) * | 2012-07-30 | 2015-09-17 | サントル ナショナル ドゥ ラ ルシェルシュ シアンティフィク | Glycan compositions, processes for their preparation and their use as medicaments |
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