JPS59225122A - Remedy and improver for cancerous cachexia - Google Patents

Abstract

PURPOSE:To remedy and to imporve cachexia such as cancerous cachexia, cachexia of collagen diseases, containing a protease as an active ingredient. CONSTITUTION:A remedy and improver for cachexia containing a protenase(e.g., trypsin, alpha-chymotrypsin, bromelain, pronase, etc.) as an active ingredient. Especially pronase improves immunoglobulin value and is effective for remedying and improving cachexia. This agent can be aministered orally and parentarally by conventional pharmaceutical manufacturing. Its effect is promoted by using it together with a carcinostatic agent, drug for the liver, drug for the kidney, antibiotic, etc. A dose is 2-400,000 serratiopeptidase unit in case of serratiopeptidase, and 10,000-500,000 tyrosine unit in case of pronase by oral medication to attain the purpose.

Description

【発明の詳細な説明】 本発明は悪液質治療改善剤に関する。[Detailed description of the invention] The present invention relates to an agent for improving cachexia treatment.

悪液質の治療は現在のところ、輸血や輸液療法に頼って
全身状態の回復を待つのみで、優れた治療法も特効薬も
無い状況から悪液質の治療及び改善薬が切望されていた
。At present, the only way to treat cachexia is to rely on blood transfusions and infusion therapy and wait for the general condition to recover, and there is no excellent treatment or specific medicine, so there has been a strong need for drugs to treat and improve cachexia.

本発明者は悪液質を鋭意研究の結果、蛋白分解酵素が悪
液質の治療に有効であることを見出し本発明に至った。As a result of intensive research into cachexia, the present inventor discovered that proteolytic enzymes are effective in treating cachexia, leading to the present invention.

本発明における悪液質とは例えば癌悪液質、こう原病悪
液質等の本来の疾病が更に進行し新陳代謝障害、殊に血
漿蛋白の減少、脂肪減少による重篤な症状を惹起した状
態をさす。Cachexia in the present invention is a state in which an original disease such as cancer cachexia or cholangiopathic cachexia has further progressed and caused serious symptoms due to metabolic disorders, especially plasma protein reduction and fat loss. point to

本発明の有効成分である蛋白分解酵素としては、例えば
トリプシン、α−キモ１ヘリプシン、プロメライン、パ
パイン、セラチオペプチダーゼ、ペプチダーゼ、セフア
ブローゼ、プロテアーゼ、プロナーゼ、プロザイム、ウ
ロキナーゼ、パンクレアチン、ブイプリノリジン、エラ
スターゼ、コラ−ゲナーゼなどがあげられ、これらを一
種又は二種以上を適宜組合わせて用いる。Examples of proteases that are active ingredients of the present invention include trypsin, α-chymo-1 helipsin, promelain, papain, seratiopeptidase, peptidase, cephabrose, protease, pronase, prozyme, urokinase, pancreatin, buiprinoridine, elastase, Examples include collagenase, and these may be used alone or in an appropriate combination of two or more.

本発明の悪液質治療改善剤は通常の製剤技術により、例
えば錠剤、カプセル剤、散剤、顆粒剤などとして経口的
に、注射剤、生薬、軟膏剤として非経口的に投与できる
。The cachexia treatment improving agent of the present invention can be administered orally in the form of tablets, capsules, powders, granules, etc., or parenterally in the form of injections, herbal medicines, and ointments, using conventional formulation techniques.

更に本則は他の薬剤、例えば制癌剤、肝臓薬、腎臓薬、
抗生物質、免疫賦活剤、降圧剤、抗アレルギー剤などと
併用しその効果を助長せしめる。Furthermore, the main rule is that other drugs such as anticancer drugs, liver drugs, kidney drugs,
It is used in combination with antibiotics, immunostimulants, antihypertensive agents, antiallergic agents, etc. to enhance their effects.

投与量は酵素の種類、疾病の程度、投与方法、剤型など
によっても異なるが、経口投与の場合は成人１人当り１
〜５０００ｍｇにより目的を達成できる。The dosage varies depending on the type of enzyme, degree of disease, administration method, dosage form, etc., but in the case of oral administration, 1 dose per adult.
~5000 mg can achieve the objective.

酵素の種類によっては腸溶経口製剤とするのが好ましい
。Depending on the type of enzyme, it is preferable to use enteric-coated oral preparations.

また投与量を各酵素の酵素単位で表わした場合にはセラ
チオペプチダーゼは２〜４０万セラチオペプチダ一ゼ単
位、プロメラインは４万〜８０万単位、ストレゾ１−キ
ナーゼは２万〜８０万単位、エラスターゼは１千〜１０
万工ラスターゼ単位、プロナーゼは１万〜５０万チロシ
ン単位の経口投与により目的を達成することが出来る。In addition, when the dosage is expressed in enzyme units of each enzyme, 20,000 to 400,000 to 400,000 units of serratiopeptidase, 40,000 to 800,000 units to promeline, and 20,000 to 800,000 units to Streso-1-kinase. Elastase is 1,000 to 10
The purpose can be achieved by oral administration of 10,000 to 500,000 tyrosine units of Manju Lastase units and Pronase.

製剤例１ セラチオペプチダーゼ１．　ＯＯｇ　、乳糖６０ｇ、コ
ンスターチア０ｇを混合したのち、３％ヒドロキシメチ
ルセルロース水溶液を性別練合する。混合物を整粒し、
この粒状物に対し０．３％のステアリン酸マグネシウム
を混合して打錠し、錠剤とする。Formulation Example 1 Seratiopeptidase 1. After mixing OOg, 60 g of lactose, and 0 g of cornstarch, a 3% aqueous hydroxymethylcellulose solution was mixed. Sort the mixture,
The granules are mixed with 0.3% magnesium stearate and compressed into tablets.

製剤例２ エラスターゼ１．０　ｇ及び乳糖２０ｇを混合し顆粒に
成形したのち、ステアリン酸マグネシウムを用い混合し
、錠剤とする。Formulation Example 2 1.0 g of elastase and 20 g of lactose are mixed and formed into granules, and then mixed with magnesium stearate to form tablets.

製剤例３ プロナーゼ２０ｇ、乳糖４０ｇを混合し、ヒドロキシプ
ロピルメチルセルロース１０ｇを加え顆粒に成形したの
ち酢酸セルロースを用い均等に被膜し、腸溶性顆粒とす
る。Formulation Example 3 20 g of pronase and 40 g of lactose are mixed, 10 g of hydroxypropyl methyl cellulose is added, the mixture is formed into granules, and the mixture is evenly coated with cellulose acetate to form enteric-coated granules.

製剤例４ セラチオペプチダーゼ２０ｇ、乳糖４０ｇを混合し、ヒ
ドロキシプロピルメチルセルロース１０ｇを加え顆粒に
成形したのち酢酸セルロースを用い均等に被膜し、腸溶
性顆粒とする。Formulation Example 4 20 g of serratiopeptidase and 40 g of lactose are mixed, 10 g of hydroxypropyl methyl cellulose is added and formed into granules, which are then evenly coated with cellulose acetate to form enteric granules.

製剤例５ 製剤例３にて得られたプロナーゼ腸溶性顆粒をカプセル
に充填し、カプセル剤とする。Formulation Example 5 The pronase enteric granules obtained in Formulation Example 3 are filled into capsules to prepare capsules.

臨床例１ ５６歳の男性、７年前に上ガク痛手術、４年前再発入院
。Clinical case 1: A 56-year-old man underwent upper pain surgery 7 years ago and was hospitalized for recurrence 4 years ago.

入院時、全身衰弱甚だしく、赤血球数３２０万、白血球
数３０００、蛋白分画は障害されアルブミンは減少、Ａ
／Ｇは低下、脂肪代謝も障害された。At the time of admission, the patient's entire body was severely weakened, with red blood cell count of 3.2 million and white blood cell count of 3,000, protein fraction impaired and albumin decreased.
/G decreased, and fat metabolism was also impaired.

コレステロール値も低下、所謂、癌悪液質の状態であっ
た。Cholesterol levels also decreased, indicating a state of so-called cancer cachexia.

白血球数少く悪液質のため抗癌剤の投与、放射線治療は
慎重をきして行い、輸血や輸液療法により体力の保持に
つとめるにすぎなかった。Due to his low white blood cell count and cachexia, he was carefully administered anti-cancer drugs and radiation therapy, and was only able to maintain his physical strength through blood transfusions and fluid therapy.

プロナーゼによる治療： エンピナースＰ（科研製薬株式会社製。腸溶剤、１銑中
プロナーゼ９　、０００チロシン単位含有）を１日６錠
、毎食後２錠ずつ経口投与、投薬８週後赤血球数、白血
球数、蛋白分画、コレステロール値が著しく改善共に浮
遊細胞も消失し、悪液質の状態を脱した。Treatment with pronase: Empinase P (manufactured by Kaken Pharmaceutical Co., Ltd., enteric-coated formulation, containing 1 pronase 9,000 tyrosine units) was orally administered 6 tablets per day, 2 tablets after each meal, and the number of red blood cells and white blood cells was measured 8 weeks after administration. , protein fraction, and cholesterol levels improved significantly, floating cells also disappeared, and the patient was released from cachexia.

その結果を第１表に示す。The results are shown in Table 1.

第１表 ＊印は異常値を示す。Table 1 *marks indicate abnormal values.

臨床例２　こう原病悪液質の治療 ５１歳の男性。４年前に、高熱を伴なった悪臭を放つ鼻
炎にて外来を訪れた。Ｘ線、血液検査、バイオプシー検
査により上記疾患と診断した。一般血液検査の他、蛋白
分画、コレステロール、免疫グロブリン値を検査したと
ころ甚だしく障害されていた。Clinical case 2 A 51-year-old man treated for cachexia. Four years ago, the patient visited the outpatient clinic with a foul-smelling rhinitis accompanied by a high fever. The patient was diagnosed with the above disease through X-rays, blood tests, and biopsy tests. In addition to general blood tests, tests on protein fraction, cholesterol, and immunoglobulin levels revealed that the patient was severely impaired.

本症例はプロナーゼによる治療の前は、他の大病院にて
副腎皮質ホルモン療法を受は一時快方に向ったが、その
後度々再発を繰返していた。Prior to treatment with pronase, this case received adrenocortical hormone therapy at another large hospital, and the patient temporarily recovered, but the patient had repeated recurrences thereafter.

本疾患の治療法は現在副腎皮質ホルモン投与による以外
にはないか木症例は副腎皮質ホルモンの既投与量か多量
になっているうえ、血漿蛋白分画が著るしく障害されて
いた。Currently, there is no treatment for this disease other than administration of adrenocortical hormones.The patient had already been administered a large amount of adrenocortical hormones, and the plasma protein fraction was significantly impaired.

プロナーゼによる治療： エンピナースＰ（科研製薬株式会社製）を−日６錠、毎
食後２錠ずつ内服せしめ経過を観察した。Treatment with pronase: Enpinase P (manufactured by Kaken Pharmaceutical Co., Ltd.) was administered orally, 6 tablets per day, 2 tablets after each meal, and the progress was observed.

３週間後、蛋白分画、免疫グロブリン、赤血球数、白血
球数も次第に改善され、５週間後悪液質の状態を脱した
。また、興味深いことに免疫グロブリン値の改善が認め
らオした。Three weeks later, the protein fraction, immunoglobulin, red blood cell count, and white blood cell count gradually improved, and the patient was out of cachexia after five weeks. Interestingly, an improvement in immunoglobulin levels was also observed.

しかも局所の病像にも改善が認められた。Furthermore, an improvement was observed in the local pathology.

その結果を第２表に示す。The results are shown in Table 2.

第２表 手続補正書（自発） 昭和５８年６月、２８日 特許庁長官　若杉和夫　殿 １、事件の表示 昭和５８年特許願第８９２９０号 ３、補正をする者 事件との関係　　　特許出願人 ４、補正の対象 明細書の発明の詳細な説明の欄 ５、補正の内容 （１）明細書第４真下６行目の「臨床例１」を「臨床例
１　癌悪液質の治療」に訂正する。Table 2 Procedural Amendment (Voluntary) June 28, 1980 Commissioner of the Patent Office Kazuo Wakasugi 1, Indication of the case 1989 Patent Application No. 89290 3, Person making the amendment Relationship with the case Patent applicant 4 , Column 5 of Detailed Description of the Invention in the Specification Subject to Amendment, Contents of the Amendment (1) "Clinical Example 1" in the 6th line directly below the 4th line of the specification is corrected to "Clinical Example 1 Treatment of Cancer Cachexia" do.

（２）明細書第６真下６行目の「イオプシー検査により
上記疾患と診断した。」を「イオブシー検査により進行
性壊痕性鼻炎と診断し、悪液質の状態であった。」に訂
正する。(2) In the 6th line directly below the 6th line of the specification, "The above disease was diagnosed by an iopsy test" was corrected to "The patient was diagnosed with progressive necrotic rhinitis by an iopsy test, and was in a state of cachexia." do.

（３）明細書箱７頁１行目の「その後度々再発を繰返し
ていた。」を［その後度々再発し、その都度副腎皮質ホ
ルモン療法を繰返していた。」に訂正する。(3) In the first line of page 7 of the statement box, ``I had repeated recurrences after that.'' [After that, I had frequent recurrences, and adrenocortical hormone therapy was repeated each time. ” is corrected.

Claims (1)

【特許請求の範囲】 １）蛋白分解酵素を有効成分とする悪液質治療改善剤 ２）蛋白分解酵素がプロナーゼであることを特徴とする
特許請求の範囲第１項記載の悪液質治療改善剤[Claims] 1) A cachexia treatment improving agent containing a protease as an active ingredient; 2) A cachexia treatment improvement agent according to claim 1, characterized in that the protease is pronase. agent