JPH02290821A - Collagen synthesis inhibitor and its production - Google Patents

Collagen synthesis inhibitor and its production

Info

Publication number
JPH02290821A
JPH02290821A JP1111261A JP11126189A JPH02290821A JP H02290821 A JPH02290821 A JP H02290821A JP 1111261 A JP1111261 A JP 1111261A JP 11126189 A JP11126189 A JP 11126189A JP H02290821 A JPH02290821 A JP H02290821A
Authority
JP
Japan
Prior art keywords
collagen synthesis
extract
inhibitor
extracted
essence
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
Application number
JP1111261A
Other languages
Japanese (ja)
Inventor
Yoshiyuki Shimai
島居 義侑
Takeshi Shigematsu
重松 剛
Shingo Tajima
多島 新吾
Takeji Nishikawa
武二 西川
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pias Corp
Original Assignee
Pias Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Pias Corp filed Critical Pias Corp
Priority to JP1111261A priority Critical patent/JPH02290821A/en
Publication of JPH02290821A publication Critical patent/JPH02290821A/en
Pending legal-status Critical Current

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Abstract

PURPOSE:To obtain the subject inhibitor having specifically suppressing effects on human collagen synthesis, comprising essence extracted from root of Salvia miltiorrhiza Bunge as an active ingredient. CONSTITUTION:A dried raw material of root of Salvia miltiorrhiza Bunge is refluxed with a solvent such as lower alcohol under heating or immersed warmly or coolly to give essence having inhibitory action on collagen synthesis or the extract is fractionated in a water phase, then adsorbed on a column and eluted with a solvent such as lower alcohol to give high purity essence. 0.01 to 20wt.%, preferably 1 to 15wt.% of the essence is contained as an active ingredient to give a collagen synthesis inhibitor. The inhibitor is effective for treating scar after operation, thermal scar, sclerodermia, and organ fibrosis such as hidebound disease pulmonary fibrosis, arteriosclerosis or liver cirrhosis.

Description

【発明の詳細な説明】 (産業上の利用分野) 本発明はコラーゲン合成阻害剤とその製造方法に関する
. (従来の技術) 一般に、術後の廠痕や熱傷性廠痕、或いは強皮症,肺線
維症,動脈硬化等の臓器線維症は、何らかの原因により
コラーゲン合成の異常冗進が起こり、線維化が進んで組
織の硬化変化を生ずることが主要な成因と考えられてい
る。
DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a collagen synthesis inhibitor and a method for producing the same. (Prior art) In general, postoperative scars, burn scars, or organ fibrosis such as scleroderma, pulmonary fibrosis, and arteriosclerosis are caused by abnormal acceleration of collagen synthesis due to some cause, resulting in fibrosis. The main cause is thought to be the progression of tissue hardening and changes.

そこで、このようなコラーゲン合成を阻害してこれらの
疾患を治療するために、副腎皮質ホルモン剤,D−ペニ
シラミン.抗ヒスタミン剤等が治療薬として用いられて
いる。
Therefore, in order to treat these diseases by inhibiting such collagen synthesis, adrenocortical hormone agents, D-penicillamine. Antihistamines and the like are used as therapeutic agents.

(発明が解決しようとする課題) しかしながら、副腎皮質ホルモンは、副腎皮質機能を低
下させ、それに基づいて種々の副作用を生シ、また、D
−ペニシラミンはラチズムや薬疹等の副作用を生ずると
いう問題がある。
(Problems to be Solved by the Invention) However, adrenal cortical hormones reduce adrenal cortical function, resulting in various side effects and D.
- Penicillamine has the problem of causing side effects such as latism and drug eruption.

さらに、抗ヒスタミン剤は、コラーゲン合成阻害作用が
弱く、従って上記のような疾患に対する薬理効果は小さ
い。
Furthermore, antihistamines have a weak inhibitory effect on collagen synthesis, and therefore have little pharmacological effect on the above-mentioned diseases.

よって、いずれにしても、従来では副作用や薬理効果等
の種々の面で満足すべきコラーゲン合成阻害剤は未だ開
発されていなかったのである。
Therefore, in any case, a collagen synthesis inhibitor that is satisfactory in various aspects such as side effects and pharmacological effects has not yet been developed.

本発明は、このような問題点を解決するためになされた
もので、上記のような術後の廠痕や熱傷性廠痕、或いは
強皮症.肺線維症,動脈硬化等の臓器線維症等のコラー
ゲン線維の増加と関連の深い疾患に対し、コラーゲン合
成を特異的に抑制して症状の改善をはかりうるようなコ
ラーゲン合成阻害剤を提供することを課題とする。
The present invention has been made to solve these problems, and is intended to prevent the above-mentioned postoperative scars, burn scars, or scleroderma. To provide a collagen synthesis inhibitor capable of specifically suppressing collagen synthesis and improving symptoms of diseases closely related to an increase in collagen fibers, such as pulmonary fibrosis and organ fibrosis such as arteriosclerosis. The task is to

(課題を解決するための手段) 本発明は、このような課題を解決するために、コラーゲ
ン合成阻害剤及びその製造方法としてなされたもので、
コラーゲン合成阻害剤としての特徴は、丹参(Salv
ia miltiomhiza Bange)の根から
抽出されたコラーゲン合成阻害作用を有するエキスを有
効成分として含有してなることにある。
(Means for Solving the Problems) In order to solve the above problems, the present invention has been made as a collagen synthesis inhibitor and a method for producing the same.
Danshen (Salv) is characterized as a collagen synthesis inhibitor.
The product contains as an active ingredient an extract extracted from the roots of I.ia miltiomhiza Bange, which has a collagen synthesis inhibiting effect.

また、コラーゲン合成阻害剤の製造方法としての特徴は
、丹参(Salvia miltiomhiza Ba
nge)の根の乾燥原料を低級アルコール等の溶剤とと
もに加熱還流し、又は温浸若しくは冷浸して抽出し、そ
の後、その抽出されたコラーゲン合成阻害作用を有する
エキスを配合して製造することにある。
In addition, the feature of the method for producing collagen synthesis inhibitors is that Salvia miltiomhiza Ba
The method is to extract the dried raw material of the roots of (E. nge) with a solvent such as a lower alcohol by heating and refluxing, or by soaking or cold soaking, and then blending the extracted extract with an inhibitory effect on collagen synthesis. .

さらに、他の製造方法としての特徴は、上記のように抽
出されたエキスを、さらに水相に分画した後、カラムに
吸着し、その後、低級アルコール等の溶剤にて抽出し、
その抽出されたコラーゲン合成阻害作用を有するエキス
を配合して製造することにある。
Furthermore, the feature of another production method is that the extract extracted as described above is further fractionated into an aqueous phase, adsorbed on a column, and then extracted with a solvent such as a lower alcohol.
The purpose is to manufacture the product by blending the extracted extract with an inhibitory effect on collagen synthesis.

(実施例) 以下、本発明の実施例について説明する。(Example) Examples of the present invention will be described below.

災施倣上 本実施例は、コラーゲン合成阻害剤の製造方法としての
実施例である。
This example is an example of a method for producing a collagen synthesis inhibitor.

先ず、丹参(Salvia miltiomhiza 
Bange)の根を乾燥し、細断若しくは粉状化した乾
燥原料を準備する。
First, Salvia miltiomhiza
A dry raw material is prepared by drying the root of A. Bange and shredding or pulverizing it.

次に、この原料をメタノールとともに加熱還流する。Next, this raw material is heated to reflux together with methanol.

その後、加熱還流された液を濾過し、その濾過後に得ら
れる抽出物を濃縮して所望のエキスを得る。
Thereafter, the heated and refluxed liquid is filtered, and the extract obtained after the filtration is concentrated to obtain a desired extract.

このようにして得られたエキスを各種の水性成分,粉末
成分等に配合することにより、コラーゲン合成阻害剤が
製造されることとなるのである。
By blending the extract thus obtained with various aqueous components, powder components, etc., collagen synthesis inhibitors are manufactured.

丈施桝又 本実施例は、コラーゲン合成阻害剤の製造方法としての
他の実施例である。
This example is another example of a method for producing a collagen synthesis inhibitor.

本実施例においては、上記実施例1のように加熱還流に
よって抽出物を得た後、その抽出物を、水と酢酸エチル
との混合液に溶解して水相に分画し、その分画成分をカ
ラムの一種であるMCI GELCHP 20Pに吸着
させる。
In this example, after obtaining an extract by heating and refluxing as in Example 1 above, the extract was dissolved in a mixture of water and ethyl acetate and fractionated into an aqueous phase. The components are adsorbed onto MCI GELCHP 20P, which is a type of column.

その後、上記力ラム吸着後の成分をメタノールで抽出し
て所望のエキスが得られることとなる。
Thereafter, the components after the force-ram adsorption are extracted with methanol to obtain a desired extract.

このようなエキスを、上記実施例1と同様に各種の水性
成分、粉末成分等に配合することにより、コラーゲン合
成阻害剤が製造されることとなるのである。
A collagen synthesis inhibitor is produced by blending such an extract with various aqueous components, powder components, etc. in the same manner as in Example 1 above.

ス11辻1 本実施例は、コラーゲン合成阻害剤の一例としての外用
剤についての実施例である。
This example is an example of an external preparation as an example of a collagen synthesis inhibitor.

その処方例は次のとおりである。An example of its prescription is as follows.

成分         重量% 丹参抽出エキス       15 白色ワセリン        60 精製ラノリン       25 夾搭性土 本実施例は、コラーゲン合成阻害剤の一例としてのゲル
基剤についての実施例である。
Ingredients Weight % Danshen extract 15 White petrolatum 60 Purified lanolin 25 Containing properties Tsuchimoto Examples are examples of gel bases as an example of collagen synthesis inhibitors.

成分         重量% 丹参抽出エキス       10 グリセリンモノステアレー}   10グリセリン  
     l0 ベントナイト         3 精製水          67 炎権医1 本実施例は、コラーゲン合成阻害剤の一例としての注射
液についての実施例である。
Ingredients Weight% Danshen extract 10 Glycerin monostearate 10 Glycerin
10 bentonite 3 purified water 67 flame doctor 1 This example is an example of an injection solution as an example of a collagen synthesis inhibitor.

成分         重量% 丹参抽出エキス        5 注射用蒸留水       95 拭胱開土 上記のようなコラーゲン合成阻害剤のコラーゲン合成に
対する抑制効果を、ヒト正常皮膚線維芽細胞のコラーゲ
ン合成量より判定した。
Ingredients Weight % Danshen extract 5 Distilled water for injection 95 Bladder swabbing The inhibitory effect of the above-mentioned collagen synthesis inhibitor on collagen synthesis was determined from the amount of collagen synthesis in normal human skin fibroblasts.

試験した試料は、上記実施例2のようにカラム通過後に
メタノール抽出したエキスである。
The sample tested was an extract extracted with methanol after passing through a column as in Example 2 above.

被験試料は上記被験物質をメタノールに溶解して調製し
た。
A test sample was prepared by dissolving the above test substance in methanol.

コントロールはメタノールのみとした。被験物質の濃度
は、1,Opl/rtrl、5 μl/rnll, i
oμ1/m、20μladである.正常のヒト皮膚組織
(前腕)より線維芽細胞を培養し、各試料添加後に2日
間培養し、その間におけるトリチウム標識プロリンのコ
ラーゲンへの合成量(取込量)より測定した。
The control was methanol only. The concentration of the test substance was 1, Opl/rtrl, 5 μl/rnll, i
oμ1/m, 20μlad. Fibroblasts were cultured from normal human skin tissue (forearm) and cultured for 2 days after addition of each sample, and the amount of tritium-labeled proline synthesized (incorporated) into collagen during that time was measured.

結果は、図面に示すように濃度依存的にコラーゲン合成
量が減少し、非コラーゲン蛋白の合成には影響が少なく
、特異的なコラーゲン阻害効果を有することが判明した
As a result, as shown in the figure, the amount of collagen synthesis decreased in a concentration-dependent manner, and the synthesis of non-collagen proteins was little affected, indicating that it had a specific collagen inhibiting effect.

試駁貫l 表1 次に、被験物質の細胞毒性及びDNA合成阻害への影響
を調べる目的で、試験例lと同様の試料を用いてDNA
合成量を調べた。
Test Example 1 Table 1 Next, in order to investigate the effect of the test substance on cytotoxicity and inhibition of DNA synthesis, DNA was tested using the same sample as in Test Example 1.
The amount of synthesis was investigated.

結果は、上記表1のとおりであった。The results were as shown in Table 1 above.

この結果、被験物質の各濃度におけるDNA合成阻害率
に大きな変化のないことが判明した。
As a result, it was found that there was no significant change in the DNA synthesis inhibition rate at each concentration of the test substance.

尚、コラーゲン合成阻害剤中の丹参エキスの配合量は上
記各実施例に限定されるものではないが、0.01〜2
0重景%、特に1〜15重景%であることが好ましい。
Incidentally, the amount of Danshen extract in the collagen synthesis inhibitor is not limited to the above examples, but is 0.01 to 2.
It is preferable that the ratio is 0%, particularly 1 to 15%.

また、丹参エキス以外の他の成分の種類も上記実施例に
限定されるものではなく、水性成分,粉末成分,界面活
性剤,保湿剤,防腐剤.酸化防止剤.色素.香料等種々
のものを配合することが可能である. さらに、投与形態としては、外用.内服.静脈注射,筋
肉注射等問うものではない。
Further, the types of components other than Danshen extract are not limited to the above examples, and include aqueous components, powder components, surfactants, humectants, and preservatives. Antioxidant. Pigment. It is possible to mix various things such as fragrances. Furthermore, the administration form includes external use. Oral medication. There is no question of intravenous injection, intramuscular injection, etc.

さらに、用途も医薬品に限定されるものではなく、種々
の用途に使用可能である。
Furthermore, the application is not limited to pharmaceuticals, and can be used for various purposes.

さらに、上記実施例1.2のコラーゲン合成阻害剤の製
造方法においては、原料をメタノールによって抽出した
が、メタノールに代えてエタノールを使用することも可
能であり、また、低級アルコール以外の溶剤を使用する
ことも可能である。
Furthermore, in the method for producing a collagen synthesis inhibitor in Example 1.2 above, the raw materials were extracted with methanol, but it is also possible to use ethanol instead of methanol, and it is also possible to use a solvent other than lower alcohols. It is also possible to do so.

また、該実施例では丹参の乾燥した原料を使用したが、
使用する原料は必ずしも乾燥したものでなくともよい. さらに、該実施例では、加熱還流によって抽出を行った
が、加熱還流に限らず、たとえば温浸や冷漫によって抽
出してもよい. さらに、上記実施例2では、抽出物を分画させる水相と
して水と酢酸エチルの混合液を用いたが、分両用の水相
の種類もこれに限定されない。
In addition, in this example, dried raw material of Danshen was used, but
The raw materials used do not necessarily have to be dry. Further, in this example, extraction was carried out by heating under reflux, but the extraction is not limited to heating under reflux, and extraction may also be performed by, for example, digestion or cooling. Furthermore, in the above Example 2, a mixture of water and ethyl acetate was used as the aqueous phase for fractionating the extract, but the type of the aqueous phase for both fractionation is not limited thereto.

さらに、分画成分を吸着させるカラムも該実施例のMC
I GEL CHP 20Pに限定されるものではなく
たとえば}IP20等のカラムを使用することも可能で
あり、その種類は問わない. その他、コラーゲン合成阻害剤の製造のための作業条件
等も問わない。
Furthermore, the column for adsorbing the fractionated components was also the MC of this example.
The column is not limited to I GEL CHP 20P, and for example, it is also possible to use a column such as IP20, and the type thereof is not limited. In addition, the working conditions for producing the collagen synthesis inhibitor are not limited.

(発明の効果) 叙上のように、本発明のコラーゲン合成阻害剤は、ヒト
のコラーゲン合成を特異的に抑制する効果を有するもの
である。
(Effects of the Invention) As described above, the collagen synthesis inhibitor of the present invention has the effect of specifically suppressing collagen synthesis in humans.

従って、コラーゲン合成の異常元進を抑制できるために
、臓器.M織の線維化,硬化が阻止され、その結果、外
科手術後に生じる術後廠痕、熱傷、交通事故等の後に生
じるケロイドや肥厚性廠痕、及び強皮症,肺線維症,動
脈硬化症.肝硬変等の臓器線維症の治療に有効な効果を
有するに至った。
Therefore, since the abnormal progression of collagen synthesis can be suppressed, organs. Fibrosis and hardening of the M tissue is inhibited, resulting in postoperative scars that occur after surgery, keloids and hypertrophic scars that occur after burns, traffic accidents, etc., as well as scleroderma, pulmonary fibrosis, and arteriosclerosis. .. It has been shown to be effective in treating organ fibrosis such as liver cirrhosis.

また、本発明の製造方法においては、上記のような丹参
のエキスを確実に抽出することができ、特に水相での分
画やカラムの吸着を行えば、より純度の高いエキスが得
られるという効果がある。
In addition, in the production method of the present invention, it is possible to reliably extract the extract of Danshen as described above, and in particular, if fractionation in the aqueous phase and adsorption in a column are performed, an extract with higher purity can be obtained. effective.

【図面の簡単な説明】[Brief explanation of drawings]

図面は、丹参抽出エキスのコラーゲン合成抑制量の試験
結果を示す棒グラフである。
The figure is a bar graph showing the test results of the amount of inhibition of collagen synthesis by Danshen extract.

Claims (1)

【特許請求の範囲】 1、丹参(Salvia miltiomhiza B
ange)の根から抽出されたコラーゲン合成阻害作用
を有するエキスを有効成分として含有してなることを特
徴とするコラーゲン合成阻害剤。 2、丹参(Salvia miltiomhiza B
ange)の根の乾燥原料を低級アルコール等の溶剤と
ともに加熱還流し、又は温浸若しくは冷浸して抽出し、
その後、その抽出されたコラーゲン合成阻害作用を有す
るエキスを配合して製造することを特徴とするコラーゲ
ン合成阻害剤の製造方法。 3、丹参(Salvia miltiomhiza B
ange)の根の乾燥原料を低級アルコール等の溶剤と
ともに加熱還流し、又は温浸若しくは冷浸して抽出し、
次にその抽出物を水相に分画した後にカラムに吸着し、
その後、低級アルコール等の溶剤にて抽出し、その抽出
されたコラーゲン合成阻害作用を有するエキスを配合し
て製造することを特徴とするコラーゲン合成阻害剤の製
造方法。
[Claims] 1. Salvia miltiomhiza B
1. A collagen synthesis inhibitor comprising, as an active ingredient, an extract extracted from the roots of A. ange and having a collagen synthesis inhibiting effect. 2. Salvia miltiomhiza B
The dried raw material of the root of A. ange is extracted by heating under reflux, or by soaking or cold soaking with a solvent such as a lower alcohol,
A method for producing a collagen synthesis inhibitor, which comprises subsequently blending the extracted extract having a collagen synthesis inhibitory effect. 3. Salvia miltiomhiza B
The dried raw material of the root of A. ange is extracted by heating under reflux, or by soaking or cold soaking with a solvent such as a lower alcohol,
Next, the extract is fractionated into an aqueous phase and adsorbed onto a column.
A method for producing a collagen synthesis inhibitor, which comprises the steps of: extracting with a solvent such as a lower alcohol; and blending the extracted extract with an inhibitory effect on collagen synthesis.
JP1111261A 1989-04-28 1989-04-28 Collagen synthesis inhibitor and its production Pending JPH02290821A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP1111261A JPH02290821A (en) 1989-04-28 1989-04-28 Collagen synthesis inhibitor and its production

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP1111261A JPH02290821A (en) 1989-04-28 1989-04-28 Collagen synthesis inhibitor and its production

Publications (1)

Publication Number Publication Date
JPH02290821A true JPH02290821A (en) 1990-11-30

Family

ID=14556718

Family Applications (1)

Application Number Title Priority Date Filing Date
JP1111261A Pending JPH02290821A (en) 1989-04-28 1989-04-28 Collagen synthesis inhibitor and its production

Country Status (1)

Country Link
JP (1) JPH02290821A (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000057913A1 (en) * 1999-03-25 2000-10-05 Welfide Corporation Preventives/remedies for interstitial pneumonia and pulmonary fibrosis
JP2006298896A (en) * 2005-03-22 2006-11-02 Iskra Ind Co Ltd Hyperlipemia remedy, arteriosclerosis remedy and liver function remedy
CN103623109A (en) * 2013-11-03 2014-03-12 崔合芳 Traditional Chinese medicine composition for treating ischemic cerebrovascular disease and preparation method thereof
CN104189409A (en) * 2014-07-30 2014-12-10 严中明 Traditional Chinese medicine for treating idiopathic pulmonary fibrosis (IPF)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000057913A1 (en) * 1999-03-25 2000-10-05 Welfide Corporation Preventives/remedies for interstitial pneumonia and pulmonary fibrosis
US6844354B1 (en) 1999-03-25 2005-01-18 Mitsubishi Pharma Corporation Agent for prophylaxis and treatment of interstitial pneumonia and pulmonary fibrosis
JP4531990B2 (en) * 1999-03-25 2010-08-25 田辺三菱製薬株式会社 Preventive and therapeutic drugs for interstitial pneumonia and pulmonary fibrosis
JP2006298896A (en) * 2005-03-22 2006-11-02 Iskra Ind Co Ltd Hyperlipemia remedy, arteriosclerosis remedy and liver function remedy
CN103623109A (en) * 2013-11-03 2014-03-12 崔合芳 Traditional Chinese medicine composition for treating ischemic cerebrovascular disease and preparation method thereof
CN104189409A (en) * 2014-07-30 2014-12-10 严中明 Traditional Chinese medicine for treating idiopathic pulmonary fibrosis (IPF)

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