JPS63115817A - Hepatic disease remedy composition - Google Patents
Hepatic disease remedy compositionInfo
- Publication number
- JPS63115817A JPS63115817A JP61262427A JP26242786A JPS63115817A JP S63115817 A JPS63115817 A JP S63115817A JP 61262427 A JP61262427 A JP 61262427A JP 26242786 A JP26242786 A JP 26242786A JP S63115817 A JPS63115817 A JP S63115817A
- Authority
- JP
- Japan
- Prior art keywords
- water
- tritoqualine
- high polymer
- soluble high
- composition
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 18
- 208000019423 liver disease Diseases 0.000 title claims abstract description 8
- IRGJVQIJENCTQF-UHFFFAOYSA-N tritoqualine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=C(OCC)C(OCC)=C(OCC)C(N)=C2C(=O)O1 IRGJVQIJENCTQF-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims abstract description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims abstract description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims abstract description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229920003169 water-soluble polymer Polymers 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 4
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 229920000642 polymer Polymers 0.000 abstract 5
- 229960002634 tritoqualine Drugs 0.000 abstract 5
- 238000010828 elution Methods 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 238000000975 co-precipitation Methods 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 206010011878 Deafness Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000000043 antiallergic agent 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
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- -1 dipropyl methyl Chemical group 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（Ｎ業上の利用分野）
本発明はトリトクプリン含有肝疾患治療薬組成物に関す
る。さらに詳しくは、トリトクアリンの水に対する溶解
速度を高める上で有用なトＩＪ ）クアリン含有肝疾患
治療薬組成物に関する。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a therapeutic composition for liver diseases containing tritocuprine. More specifically, the present invention relates to a tritoqualin-containing liver disease therapeutic composition useful for increasing the dissolution rate of tritoqualin in water.
（従来の技術）
トリトクアリン（Ｔｒｉ℃ｏｑｕａｌｉｎθ）は、下記
構造式（１）で示される７−アミノ−μ、ｚ、６−）リ
エト牛シーＪ−（ｊ、ｔ、７．！−テトラヒドローｌ−
メトキシ−６−メチル−／、Ｊ−ジオキン口（＜ｚ、ｒ
−Ｆｌイソキノリン−！−イル）フタライド（０−ｍ−
０，）であフ、トリトカリン（Ｔｒｉｔｏａａｌｉｎｅ
）又はハイボスタミン（Ｍｙｐ０８ｔａｍｉ−ｎｓ）と
も呼ばれる。(Prior art) Tritoqualin (Tri°Cqualinθ) is a 7-amino-μ, z, 6-) lyetoxyl-(j, t, 7.!-tetrahydro l-) represented by the following structural formula (1).
Methoxy-6-methyl-/, J-dioquine (<z, r
-Fl isoquinoline-! -yl) phthalide (0-m-
0,) deaf, tritocalin (Tritoaline)
) or hybostamine (Myp08tami-ns).
トリトクアリンは、ト ロツパでは抗アレルギー剤とし
て使用されているが、ｆ＆近、肝疾患の治療に有効であ
ることが見い出された。Tritoqualin, which is used as an anti-allergy agent in Trotpa, has been found to be effective in treating liver disease.
（発明が解決しようとする問題点）
溶出性が悪く、バイオアベイラビリティ−（Ｂｉｏａｖ
ａｉｌａｂｉｌｉ℃ｙ、生物学的利用性）が低いという
欠点があった。(Problems to be solved by the invention) Poor dissolution and bioavailability (Bioav
It had the disadvantage of low ailabiliy (℃y, bioavailability).
（問題点を解決する大めの手段）
本発明者らＦｉ、）す）クアリンの組成物における上記
の欠点を解消するために鋭慧研究を１ねた結釆、トリト
クプリンと水溶性高分子とをＭ機溶媒に溶解し共沈させ
る（以下、共沈法と称す）ことにより著しい滲出件の改
善が図れることと共ｔ４：、持続的な過飽和現象を呈す
ることを見か出し１木兄ＢＡに到達した。すなわち本発
明の要旨は、トリトクアリンと水溶性高分子とを有機溶
Ｇに溶解し１次りで溶媒を除去して共沈させることによ
り得られることを特徴とする肝疾患治療薬組成物に存す
る。(Large Means to Solve the Problems) The present inventors (Fi) have conducted extensive research in order to eliminate the above-mentioned drawbacks in the composition of quarine. It was discovered that by dissolving M in a solvent and co-precipitating it (hereinafter referred to as the coprecipitation method), it was possible to significantly improve the leaching problem, and also that a persistent supersaturation phenomenon was exhibited. reached. That is, the gist of the present invention resides in a liver disease therapeutic composition obtained by dissolving tritoqualin and a water-soluble polymer in an organic solution G, removing the solvent in the first step, and co-precipitating the composition. .
以下１本発明の詳細な説明する。Hereinafter, one aspect of the present invention will be explained in detail.
まず、上記共沈法で用いられる水溶性高分子としては、
ポリビニルピロリドン、ポリエチレングリコール、ヒド
ロキシプロピルセルロース。First, the water-soluble polymers used in the coprecipitation method are as follows:
Polyvinylpyrrolidone, polyethylene glycol, hydroxypropylcellulose.
ヒドロキシプロピルメチルセルロース、メチルセルロー
ス、ポリビニルアルコール、ポリアクリル酸ナトリウム
、ゼラチン、力にボキシメチルセルロースナトリウム等
が挙げられ、これらは本部で用いてもλ種以上を組み合
わせて用いても良い。これらのうち特にポリビ二ルビロ
リドシ、ポリエチレングリコール、ヒドロキシプロピル
セルロース及びとドロ中ジプロピルメチルセルロースか
らなる群よシ選ばれる／ｌｌｉ又は２ａ１以上が好まし
く用いられる。これら水溶性高分子の使用量はトリトラ
フ１フフ重量部に対して／−１ａｇ量部、好ましくは２
〜６重量部が適当である。Examples include hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, sodium polyacrylate, gelatin, and sodium boxymethylcellulose, and these may be used alone or in combination of λ or more types. Among these, /lli or 2a1 or more selected from the group consisting of polyvinyl pyrolyte, polyethylene glycol, hydroxypropyl cellulose, and dipropyl methyl cellulose are preferably used. The amount of these water-soluble polymers used is /-1ag part, preferably 2 parts by weight per 1 part by weight of tritrough.
~6 parts by weight is suitable.
共沈法で用いら九る有機溶媒としては、トリトクプリン
及び水溶性高分子の両方を溶解するものであれば何ら制
限はないが、特にメタノール又はクロロホルムが好まし
い。The organic solvent used in the coprecipitation method is not particularly limited as long as it dissolves both tritocuprine and the water-soluble polymer, but methanol or chloroform is particularly preferred.
実際の方法としては、トリトクアリン及び水溶性高分子
を両者を溶解させる有機溶媒中で溶解し、常温若しくは
必要に応じて加熱した状態で、必要に応じて真空下で該
溶媒を除去して共沈させれば良い。The actual method involves dissolving tritoqualin and a water-soluble polymer in an organic solvent that dissolves both, and removing the solvent under vacuum at room temperature or heating as necessary to coprecipitate. Just let it happen.
本発明の共沈法で得られるトリトクアリンの組成物はそ
れ自体で用いることもできるし、また他に薬理学的に許
容される／、ｔｉｔ又は２種以上の適当な担体、賦形剤
、結合剤、滑沢剤、崩壊剤その他と混合し、粉末（散剤
等）顆粒剤１錠剤、カプセル剤、坐剤等の製剤として経
口的又は餞粘膜的に投与することができる。The composition of tritoqualin obtained by the coprecipitation method of the present invention can be used by itself, or can be used with other pharmacologically acceptable carriers, excipients, and binders. It can be mixed with agents, lubricants, disintegrants, etc., and administered orally or via the mucosal membrane in the form of powders (powders, etc.), granules, single tablets, capsules, suppositories, etc.
トリトクアリンの投与量は１通常７０〜２０００ｍｙ／
成人・／日当シ程度が採用される。The dosage of tritoqualin is 1 usually 70 to 2000 my/
An adult/daily rate will be applied.
（実施例）
以下、実施例によシ本発明倉更に具体的に説明するが１
本発明はその要旨を越えない限シ以下の実施例によって
限定され石ものではない。(Example) Hereinafter, the present invention will be explained in more detail with reference to an example.
The present invention is not limited to the following examples unless it exceeds the gist thereof.
実施例１
トリトクアリン３１とポリビニルピロリドン（ＧＡＦ社
Ｈ”ｐｖＰＫ−３０”）ｉｊｓをエタノール１ｏｏｏ−
に溶解する。次いで、 ｕ、ｏ’でエタノールを徐々に
飛ばし共沈物を得た。共沈物をさらに≠θ°で！時間真
空乾燥し１本発明の組成物を得た。Example 1 Tritoqualin 31 and polyvinylpyrrolidone (GAF H"pvPK-30") ijs were mixed with ethanol 1ooo-
dissolve in Next, ethanol was gradually removed using u and o' to obtain a coprecipitate. More coprecipitation at ≠θ°! After drying under vacuum for an hour, a composition of the present invention was obtained.
実施例コ
実施例／のポリビニルピロリドンのかわ）にポリエチレ
ングリー−ルｔｏｏｏ（日本油脂社製）を用い、以下同
様に操作し１本発明の組成物を得た。EXAMPLE 1 A composition of the present invention was obtained by using polyethylene glycol too (manufactured by NOF Corporation) as the glue for polyvinylpyrrolidone in Example 2 and following the same procedure.
試験例／
第１／改正日本薬局方の溶出試験法第２法（パドル法）
に従い、実施例／によフ得られた本発明の組成物の溶出
性を試験した。試験液にｆ’１ｐＨ１１，０のブリトン
ーロビンノン緩衝ｉ Ｐ ｏ 。Test example / 1st / Revised Japanese Pharmacopoeia dissolution test method 2 (paddle method)
Accordingly, the dissolution properties of the compositions of the present invention obtained in Examples/Mirror were tested. The test solution was Britton-Robinnon buffer i P o with f'1 pH 11.0.
−を用いた。試験温度は３０°十／℃、パドル回転数は
／ ００ ｒｐｍとし、各組成物は♂０メツシュパスの
粉末でトリトクアリンとして１００ｒｒｇ相当量添加し
た。- was used. The test temperature was 30°/°C, the paddle rotation speed was /00 rpm, and 100 rrg equivalent of tritoqualin was added to each composition as powder of ♂0 mesh pass.
グラフィー（ＩＩＩＰＬＯ） 法でトリトクアリン濃
度を測定した。対照として１００メツシユパスしたトリ
トクアリン微細化品を用いた。その結果を第１表及び第
１図に示す。The tritoqualin concentration was measured by the method of graphography (IIIPLO). As a control, a tritoqualin micronized product that had been subjected to 100 mesh passes was used. The results are shown in Table 1 and Figure 1.
第１表
（発明の効果）
第１表及び第１図よシ明らかなように本発明の組成物は
溶出性及び持続性に優れておシ１本発明によれば、バイ
オアベイラビリティ−（生物学的利用件）の高い肝疾患
治療薬を提供することができる。Table 1 (Effects of the Invention) As is clear from Table 1 and Figure 1, the composition of the present invention has excellent dissolution properties and persistence. It is possible to provide a drug for treating liver diseases that has a high number of applications.
第１図は実施例１（口で示す）で得られた本発明の組成
物と対照であるトリトクアリン原末（・で示す）の溶解
挙動を示す図である。縦軸は濃度を（／ ０−” ｒｑ
ｌｍｌ ）で示し、横軸は時間を（分）で示す。
点線（・・・・・）は飽和濃度を示す。FIG. 1 is a diagram showing the dissolution behavior of the composition of the present invention obtained in Example 1 (indicated by mouth) and the tritoqualin bulk powder (indicated by *), which is a control. The vertical axis represents the concentration (/0-” rq
lml), and the horizontal axis shows time in minutes. The dotted line (...) indicates the saturation concentration.
Claims (3)
解し、次いで溶媒を除去して、共沈させることにより得
られることを特徴とする肝疾患治療薬組成物。(1) A liver disease therapeutic composition obtained by dissolving tritoqualin and a water-soluble polymer in an organic solvent, then removing the solvent, and co-precipitating the same.
レングリコール、ヒドロキシプロピルセルロース及びヒ
ドロキシプロピルメチルセルロースからなる群より選ば
れる１種又は２種以上であることを特徴とする特許請求
の範囲第１項記載の組成物。(2) The composition according to claim 1, wherein the water-soluble polymer is one or more selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, hydroxypropylcellulose, and hydroxypropylmethylcellulose. thing.
に対して１〜１０重量部であることを特徴とする特許請
求の範囲第１項記載の組成物。(3) The composition according to claim 1, wherein the amount of water-soluble polymer used is 1 to 10 parts by weight per 1 part by weight of tritoqualin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61262427A JPS63115817A (en) | 1986-11-04 | 1986-11-04 | Hepatic disease remedy composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61262427A JPS63115817A (en) | 1986-11-04 | 1986-11-04 | Hepatic disease remedy composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63115817A true JPS63115817A (en) | 1988-05-20 |
Family
ID=17375632
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61262427A Pending JPS63115817A (en) | 1986-11-04 | 1986-11-04 | Hepatic disease remedy composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63115817A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01313419A (en) * | 1988-06-14 | 1989-12-18 | Kao Corp | Preparation composition for administration to rectum |
| WO1992001453A1 (en) * | 1990-07-19 | 1992-02-06 | Otsuka Pharmaceutical Co., Ltd. | Solid preparation |
| WO2002080904A1 (en) * | 2001-04-05 | 2002-10-17 | Kyowa Hakko Kogyo Co., Ltd. | Liver funcion protecting or ameliorating agent |
-
1986
- 1986-11-04 JP JP61262427A patent/JPS63115817A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01313419A (en) * | 1988-06-14 | 1989-12-18 | Kao Corp | Preparation composition for administration to rectum |
| WO1992001453A1 (en) * | 1990-07-19 | 1992-02-06 | Otsuka Pharmaceutical Co., Ltd. | Solid preparation |
| US5316773A (en) * | 1990-07-19 | 1994-05-31 | Otsuka Pharmaceutical Co., Ltd. | Particulate preparation containing a flourracil derivative and hydroxypropylmethyl-cellulose |
| WO2002080904A1 (en) * | 2001-04-05 | 2002-10-17 | Kyowa Hakko Kogyo Co., Ltd. | Liver funcion protecting or ameliorating agent |
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