JPH0940579A - Suppressant for relapse and keloplasty in postoperative anastomosed part of inflammatory bowel disease - Google Patents
Suppressant for relapse and keloplasty in postoperative anastomosed part of inflammatory bowel diseaseInfo
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- JPH0940579A JPH0940579A JP7212846A JP21284695A JPH0940579A JP H0940579 A JPH0940579 A JP H0940579A JP 7212846 A JP7212846 A JP 7212846A JP 21284695 A JP21284695 A JP 21284695A JP H0940579 A JPH0940579 A JP H0940579A
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- Prior art keywords
- inflammatory bowel
- postoperative
- suppressing
- drug
- bowel disease
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Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は炎症性腸疾患治療剤に関
するものである。より詳細には、炎症性腸疾患の外科手
術に用いられ、炎症性腸疾患の再発およびケロイド形成
の抑制に有効なフィブリン糊製剤に関するものである。TECHNICAL FIELD The present invention relates to a therapeutic agent for inflammatory bowel disease. More specifically, the present invention relates to a fibrin glue preparation which is used for surgery of inflammatory bowel disease and is effective in suppressing recurrence of inflammatory bowel disease and keloid formation.
【０００２】[0002]
【従来技術および発明が解決しようとする問題点】潰瘍
性大腸炎やクローン病などの非特異的炎症性腸疾患(Ｉ
ＢＤ:inflammatorybowel disease)は、原因不明の難治
性疾患である。潰瘍性大腸炎は、主に大腸の潰瘍形成性
炎症性疾患であり、クローン病は、肉芽腫性病変で腸管
のどの部位にも発生し得る。BACKGROUND OF THE INVENTION Problems to be Solved by the Invention Non-specific inflammatory bowel diseases such as ulcerative colitis and Crohn's disease (I)
BD: inflammatory bowel disease) is a refractory disease of unknown cause. Ulcerative colitis is an ulcerative inflammatory disease of the large intestine, and Crohn's disease is a granulomatous lesion that can occur anywhere in the intestinal tract.
【０００３】ＩＢＤの主な治療法は、ステロイド剤やサ
ラゾピリンなどの薬物療法である。特に、ステロイド剤
の有効性は確立されている(Truelove et al.:Lancet,2:
p.1086-1088(1978))。しかし、投与量や投与法、副作
用、薬剤の到達性については問題が残り、その後検討さ
れてきた。The main treatments for IBD are drug therapies such as steroids and salazopyrine. In particular, the efficacy of steroids has been established (Truelove et al .: Lancet, 2 :
p.1086-1088 (1978)). However, problems remain regarding the dose, administration method, side effects, and drug accessibility, and they have been investigated since then.
【０００４】例えば、潰瘍性大腸炎における難治性症例
や重症例の場合は、貧血・低蛋白血症を伴い全身状態が
悪いうえに、長期間の薬物投与により下痢などの副作用
も被っている。従って、先ず、炎症の進展を止め、全身
状態の改善を図った後に、手術をすることが死亡率の改
善に寄与すると考えられ、この様な観点から馬場らによ
りステロイドの動注療法が試みられるようになった(馬
場正三:Jap. J. Gastroenterol,69:p.913-915,(197
1))。For example, in the case of refractory cases or severe cases of ulcerative colitis, the general condition is accompanied by anemia and hypoproteinemia, and side effects such as diarrhea due to long-term drug administration. Therefore, it is thought that first, by stopping the progress of inflammation and improving the general condition, then performing surgery will contribute to the improvement of the mortality rate. From such a viewpoint, Baba et al. Try steroid intraarterial therapy. Baba Shozo: Jap. J. Gastroenterol, 69 : p.913-915, (197
1)).
【０００５】しかしながら上述のステロイド動注療法に
も無効例が約３０％と少なからず存在すること、また再
投与時の有効率の低下も認められること、また、潰瘍性
大腸炎以外の炎症性腸疾患に対しては検討されていなか
ったことから、八木田らによりＩＢＤを対象に、ステロ
イドとウリナスタチンの併用動注療法が考案され優秀な
成績が報告された(八木田旭邦、他:日本臨床外科医学会
雑誌、49:p.590-596、(1988))。 すなわち、ステロイド
の全身性大量投与は、全身的副作用のために予後を不良
にすることの他に術後の感染あるいは創傷治癒の遅延を
きたすことが知られている。プロテアーゼインヒビター
であるウリナスタチンは、この様なステロイドの副作用
を軽減し、抗炎症作用については相加もしくは相乗的に
作用することから、ステロイドとウリナスタンの併用療
法は極めて合理的であると考えられた。However, the above-mentioned intra-arterial steroid therapy has a considerable number of ineffective cases of about 30%, a decrease in the effective rate upon re-administration is also observed, and inflammatory bowel other than ulcerative colitis. Since the disease had not been investigated, Yagida et al. Devised a combined intra-arterial therapy of steroids and ulinastatin for IBD and reported excellent results (Ayaguni Yagita, et al .: Japanese Clinical Surgical Medicine). Society Magazine , 49 : p.590-596, (1988)). That is, it is known that systemic large-scale administration of steroids not only worsens the prognosis due to systemic side effects but also causes postoperative infection or delay in wound healing. Since the protease inhibitor ulinastatin reduces such side effects of steroids and exerts an additive or synergistic effect on the anti-inflammatory action, it was considered that the combination therapy of steroids and ulinastane is extremely rational.
【０００６】近年、炎症性腸疾患の病態の形成にサイト
カインの関与、なかでも、ＴＮＦα、ＩＬ−６、ＩＬ−
８が活動期において高値を示すこと、そして炎症性腸疾
患の治療に、これらサイトカイン産生抑制作用のある薬
剤が有効であることが報告されている(八木田旭邦:消化
器外科、16:p.1931-1943、(1993))。 サイトカイン産生抑制作用のある薬剤としては、ウリナ
スタチン、メシル酸ガベキサート、メシル酸ナファモス
タット、メシル酸カモスタット、サラゾスルファピリジ
ン、メトロニダゾール、５ＡＳＡ、プラノトールが挙げ
られる。しかしながら、上述の如き内科的治療法に抵抗
性の場合は、外科的治療が適応となり、病変部の切除と
再建が行われる。In recent years, cytokines have been involved in the formation of pathological conditions of inflammatory bowel disease, among which TNFα, IL-6, IL-
It has been reported that 8 shows a high value in the active phase, and that these drugs having an inhibitory effect on cytokine production are effective for the treatment of inflammatory bowel disease (Ayaguni Yagita: Gastroenterological Surgery , 16 : p. 1931-1943, (1993)). Examples of the drug having an action of suppressing cytokine production include ulinastatin, gabexate mesylate, nafamostat mesylate, camostat mesylate, salazosulfapyridine, metronidazole, 5ASA and planotol. However, in the case of being resistant to the medical treatment method as described above, surgical treatment is indicated and excision and reconstruction of the lesion site are performed.
【０００７】外科的治療上問題となるのは、手術後の合
併症である。術後早期合併症としては、クローン病、潰
瘍性大腸炎ともに、創傷治癒の遅延並びに縫合不全が認
められることがある。 術後後期合併症としては、クロ
ーン病においては、腸管吻合部からの再発による吻合部
狭窄、内瘻・外瘻の発生、皮膚縫合部ケロイド形成が認
められ、潰瘍性大腸炎においても皮膚縫合部ケロイド形
成が認められる。 ハーパー(Harper)らによれば、クロ
ーン病の１０年目の累積再手術率をみると、小腸・大腸
型８２％、小腸型７９％、大腸型５９％であると報告し
ている(Harper,P.H. et al.:Dis. Colon Rectum.30:p.1
74-(1987))。A problem in surgical treatment is postoperative complications. Postoperative early complications may include delayed wound healing and suture failure in both Crohn's disease and ulcerative colitis. As postoperative late complications, in Crohn's disease, stenosis of the anastomosis due to recurrence from the anastomosis of the intestine, occurrence of internal and external fistula, keloid formation of the skin suture site, and skin suture site in ulcerative colitis were observed. Keloid formation is observed. According to Harper et al., The cumulative reoperation rate of Crohn's disease at 10 years was 82% in the small intestine / colon type, 79% in the small intestine type, and 59% in the large intestine type (Harper, PH et al.:Dis. Colon Rectum. 30 : p.1
74- (1987)).
【０００８】近年、器械吻合を用いて吻合する術式が広
まりつつあるが、直腸粘膜が、１〜２cm残ることも吻合
部からの再発再燃を助長している。現在のところ、術後
の再発再燃やケロイド形成、縫合不全を防止する有効な
方法は確立されていない。[0008] In recent years, a surgical technique of anastomosis using an instrumental anastomosis is becoming widespread, but the fact that the rectal mucosa remains for 1 to 2 cm promotes relapse and recurrence from the anastomosis site. At present, no effective method has been established to prevent postoperative relapse, keloid formation, or suture failure.
【０００９】本発明は、炎症性腸疾患の外科手術に用い
られ、術後の吻合部再発およびケロイド形成の抑制に有
効な薬剤を提供しようとするものである。The present invention is intended to provide a drug which is used in a surgical operation for inflammatory bowel disease and is effective in suppressing postoperative recurrence of the anastomosis and keloid formation.
【００１０】[0010]
【課題を解決するための手段】本願発明者らは上述の諸
課題に鑑み鋭意検討し、炎症性腸疾患においては過剰な
サイトカインやロイコトリエンが産生され、これらが創
面に浸出することにより、術後の吻合部合併症をきたす
と考えた。本願発明に関与する炎症性サイトカインとし
ては、ＩＬ−１β、ＴＮＦ、ＩＬ−６、ＩＬ−８、また
ロイコトリエンとしては、ＬＴＢ4(ロイコトリエンビー
フォー)などが例示される。 一方、薬剤の到達性の観
点から、外科手術時に腸管の接着、閉鎖に用いられてい
るフィブリン糊の利用について検討を進め、サイトカイ
ンやロイコトリエン産生を抑制する炎症性腸疾患治療剤
をフィブリン糊に混合したところ、薬剤の徐放に有用と
の知見を得た。さらに、サイトカインやロイコトリエン
産生を抑制する炎症性腸疾患治療剤をフィブリン糊に混
合して吻合部に塗布したところ、吻合部再発およびケロ
イド形成の抑制に効果的であることを見い出した。 こ
こに、炎症性腸疾患の術後の再発およびケロイド形成の
抑制に、サイトカイン並びにロイコトリエンの産生を抑
制する薬剤を含有するフィブリン糊からなる薬剤を提供
する本発明を完成した。 以下に本発明をさらに詳細に
説明する。Means for Solving the Problems The inventors of the present invention have made extensive studies in view of the above-mentioned problems, and in inflammatory bowel disease, excessive cytokines and leukotrienes are produced, and these are leached on the wound surface, resulting in postoperative It was thought to cause complications in the anastomotic region. Examples of inflammatory cytokines involved in the present invention include IL-1β, TNF, IL-6 and IL-8, and examples of leukotrienes include LTB4 (leukotriene befor). On the other hand, from the viewpoint of drug reachability, we are proceeding with studies on the use of fibrin glue, which is used for adhesion and closure of the intestinal tract during surgery, and mix a fibrin glue with a therapeutic agent for inflammatory bowel disease that suppresses cytokine and leukotriene production. As a result, they found that the drug was useful for sustained release. Furthermore, when a therapeutic agent for inflammatory bowel disease that suppresses cytokine and leukotriene production was mixed with fibrin glue and applied to the anastomosis, it was found to be effective in suppressing recurrence of the anastomosis and keloid formation. The present invention has been completed to provide a drug comprising fibrin glue, which contains a drug that suppresses the production of cytokines and leukotrienes, for suppressing the postoperative recurrence of inflammatory bowel disease and keloid formation. Hereinafter, the present invention will be described in more detail.
【００１１】本発明に係わる薬剤は、サイトカイン並び
にロイコトリエンの産生を抑制する薬剤を含有するフィ
ブリン糊からなる炎症性腸疾患の術後の再発およびケロ
イド形成の抑制に有効な薬剤であることを特徴とする。The drug according to the present invention is characterized in that it is a drug effective for suppressing postoperative recurrence of inflammatory bowel disease and keloid formation, which consists of fibrin glue containing a drug for suppressing the production of cytokines and leukotrienes. To do.
【００１２】本発明に用いられるサイトカイン並びにロ
イコトリエンの産生を抑制する薬剤は、ウリナスタチ
ン、メシル酸ガベキサート、メシル酸ナファモスタッ
ト、メシル酸カモスタット、サラゾスルファピリジン、
メトロニダゾール、５ＡＳＡ、プラウノトールなどから
選択され、これらは容易に入手可能である。The agents used in the present invention for suppressing the production of cytokines and leukotrienes include ulinastatin, gabexate mesylate, nafamostat mesylate, camostat mesilate, salazosulfapyridine,
It is selected from metronidazole, 5ASA, plaunotol and the like, and these are easily available.
【００１３】例えば、ウリナスタチンは、ミラクリッド
の商標で持田製薬株式会社より市販されている。メシル
酸ガベキサートは、エフオーワイの商標で小野薬品工業
株式会社より市販されている。メシル酸ナファモスタッ
トは、フサンの商標で鳥居薬品株式会社より市販されて
いる。メシル酸カモスタットは、フオイパンの商標で小
野薬品工業株式会社より市販されている。サラゾスルフ
ァピリジンは、サラゾピリンの商標で株式会社ミドリ十
字より市販されている。メトロニダゾールは、メトロニ
ダゾールの商標で株式会社科薬より市販されている。５
ＡＳＡは、メサラジンの商標で日清製粉株式会社より市
販されている。プラウノトールは、ケルナックの商標で
三共株式会社より市販されている。For example, ulinastatin is commercially available from Mochida Pharmaceutical Co., Ltd. under the trademark of Miraclid. Gabexate mesylate is marketed by Ono Pharmaceutical Co., Ltd. under the trademark FFO. Nafamostat mesylate is marketed by Torii Pharmaceutical Co., Ltd. under the trademark of Fusan. Camostat mesylate is marketed by Ono Pharmaceutical Co., Ltd. under the trademark of Foipan. Salazosulfapyridine is marketed by Midori Cross Co., Ltd. under the trademark of Salazopyrin. Metronidazole is a trademark of Metronidazole and is commercially available from Kayaku Co., Ltd. 5
ASA is marketed by Nisshin Seifun Co., Ltd. under the trademark of Mesalazine. Pronotol is marketed by Sankyo Co., Ltd. under the trademark Kernak.
【００１４】本発明に用いられるフィブリン糊は、フィ
ブリノーゲン、フィブリノーゲン溶解液(例えば、アプ
ロチニン液)、トロンビン、トロンビン溶解液(例えば、
カルシウム液)から構成される。The fibrin glue used in the present invention includes fibrinogen, fibrinogen solution (eg aprotinin solution), thrombin, thrombin solution (eg
Calcium solution).
【００１５】フィブリン糊は、上述のフィブリノーゲン
とトロンビンによるフィブリン生成反応を利用した二成
分系の組織接着剤である。すなわち、フィブリノゲン
は、トロンビンの作用を受けてフィブリンモノマーとな
り、次第に重合してフィブリンポリマーを形成し、さら
に血液凝固第XIII因子の作用により架橋形成され安定化
フィブリン塊となる。Fibrin glue is a two-component tissue adhesive that utilizes the fibrin formation reaction between fibrinogen and thrombin described above. That is, fibrinogen becomes a fibrin monomer by the action of thrombin, gradually polymerizes to form a fibrin polymer, and is further crosslinked by the action of blood coagulation factor XIII to form a stabilized fibrin clot.
【００１６】フィブリン糊は、外科手術の際の組織の接
着・閉鎖を目的に幅広く使用されている。例えば、脳硬
膜縫合部、胃切除後の縫合部、肝切離断端部、腸吻合
部、血管や神経の吻合部、鼓膜形成部などに塗布され、
塗布面にてフィブリンを生成し、固化することにより、
体液や血液の漏出を防止する役割を果たす。フィブリン
糊は、例えば、ボルヒールの商標により化学及血清療法
研究所より販売されている。[0016] Fibrin glue is widely used for the purpose of adhering and closing tissues during surgery. For example, it is applied to the cerebral dura mating part, the suture part after gastrectomy, the hepatic transection end part, the intestinal anastomosis part, the anastomosis part of blood vessels and nerves, the eardrum formation part, etc.
By producing fibrin on the coated surface and solidifying,
It plays a role in preventing leakage of body fluids and blood. Fibrin glue is sold by the Institute of Chemotherapy and Serum Therapy, for example, under the trademark Bolheal.
【００１７】本発明の炎症性腸疾患の術後の再発および
ケロイド形成の抑制に有効な薬剤を調製するには、サイ
トカイン並びにロイコトリエンの産生を抑制する薬剤の
溶液を用いて上記ボルヒールの中のフィブリノゲンもし
くはトロンビンを溶解し配合すればよい。また、付加的
にステロイド剤を本願発明の薬剤に共存させることも好
ましい態様である。量比については、例えば、ウリナス
タチン０.５万単位〜５０万単位、好ましくは１０万単
位〜２０万単位とプレドニゾロン１mg〜５０mg，好まし
くは１０mg〜２０mgをフィブリン糊３ml製剤に混合する
ことが好ましい。In order to prepare a drug effective for suppressing the postoperative recurrence of inflammatory bowel disease and keloid formation of the present invention, a solution of the drug for suppressing the production of cytokines and leukotrienes is used and the fibrinogen in the above-mentioned Volhiel is used. Alternatively, thrombin may be dissolved and blended. Further, it is also a preferred embodiment that a steroid drug is additionally allowed to coexist with the drug of the present invention. Regarding the quantitative ratio, for example, it is preferable to mix urinastatin 0.550,000 to 500,000 units, preferably 100,000 to 200,000 units with prednisolone 1 mg to 50 mg, preferably 10 mg to 20 mg in a fibrin glue 3 ml preparation.
【００１８】本発明の炎症性腸疾患の術後の再発および
ケロイド形成の抑制に有効な薬剤の使用は、例えば炎症
性腸疾患の回腸肛門吻合術後に残存する直腸粘膜を含む
吻合部周辺に塗布、または噴霧すればよい。また、炎症
性サイトカイン並びにロイコトリエンが過剰に産生され
る自己免疫疾患、腸型ベーチェット、ＳＬＥ(システミ
ック ループス エリテマトーデス)腸炎、もしくはケ
ロイド体質による吻合部狭窄、皮膚ケロイド形成などに
も同様な使用方法で有用性が期待される。 さらに、術
前・術後にサイトカイン産生抑制剤を単独で、もしくは
ステロイドを併用して静脈内もしくは動脈内に投与する
ことで本願発明の薬剤の効果を助長することも期待でき
る。The use of the drug of the present invention effective for suppressing the postoperative recurrence of inflammatory bowel disease and keloid formation is carried out, for example, in the vicinity of the anastomosis part including the rectal mucosa remaining after the ileoanal anastomosis for inflammatory bowel disease. It may be applied or sprayed. Also useful for autoimmune diseases in which inflammatory cytokines and leukotrienes are excessively produced, enteric Behcet, SLE (systemic lupus lupus erythematosus) enteritis, anastomotic stenosis due to keloid constitution, and skin keloid formation. Sex is expected. Furthermore, it is expected that the effect of the drug of the present invention can be promoted by administering the cytokine production inhibitor alone or in combination with steroid before and after the operation intravenously or intraarterially.
【００１９】[0019]
【発明の効果】 本発明の炎症性腸疾患の術後の再発お
よびケロイド形成の抑制に有効な薬剤は、サイトカイン
並びにロイコトリエンの産生を抑制する薬剤を徐放する
ことができ、かつ炎症性腸疾患の術後再発やケロイド形
成の抑制にすぐれた効果を有する製剤である。EFFECTS OF THE INVENTION The drug effective for suppressing the postoperative recurrence of inflammatory bowel disease and keloid formation of the present invention is capable of sustained release of the drug for suppressing the production of cytokines and leukotrienes, and the inflammatory bowel disease. It is a preparation that has an excellent effect on the suppression of postoperative recurrence and keloid formation.
【００２０】以下に、実施例を挙げて本発明を具体的に
説明する。The present invention will be specifically described below with reference to examples.
【００２１】[0021]
【実施例】実施例 １ ミラクリッド(ウリナスタチン)５万単位を４０mMカルシ
ウム液３mlに溶解した。この溶液に、さらにトロンビン
７５０単位を溶解し、ミラクリッドを含むトロンビン溶
液を得た。別に、フィブリノゲン２４０mgを蒸留水３ml
に溶解し、フィブリノゲン溶液を得た。このミラクリッ
ド含有トロンビン溶液１mlとフィブリノゲン溶液１mlを
混合し、ミラクリッド含有フィブリンゲル２mlを作製し
た。このミラクリッド含有フィブリンゲル２mlを生理食
塩液１００ml中に入れ、室温に放置し、経時的に生理食
塩液中のミラクリッドの活性を測定した。測定は、トリ
プシンと被検体を混合後に残存するトリプシン活性を合
成基質を用いて測定することにより行った。その結果、
放置後１００時間にフィブリンゲル中のミラクリッドの
８６％が徐放された(図１参照のこと)。EXAMPLES Example 1 50,000 units of milacrid (urinastatin) were dissolved in 3 ml of 40 mM calcium solution. Further, 750 units of thrombin was dissolved in this solution to obtain a thrombin solution containing miracled. Separately, 240 mg of fibrinogen was added to 3 ml of distilled water.
To obtain a fibrinogen solution. 1 ml of this miracled-containing thrombin solution and 1 ml of a fibrinogen solution were mixed to prepare 2 ml of miracled-containing fibrin gel. 2 ml of this miracled-containing fibrin gel was placed in 100 ml of physiological saline and allowed to stand at room temperature, and the activity of miracled in the physiological saline was measured over time. The measurement was performed by measuring the trypsin activity remaining after mixing trypsin and the test substance using a synthetic substrate. as a result,
At 100 hours after standing, 86% of miraculid in fibrin gel was gradually released (see FIG. 1).
【００２２】実施例 ２ プレドニゾロン(プレドニン)５０mgを蒸留水５mlに溶解
した。この溶液に、さらにトロンビン１２５０単位を溶
解し、プレドニゾロンを含むトロンビン溶液を得た。別
に、フィブリノゲン４００mgを１０００u/mlアプロチニ
ン液５mlに溶解し、フィブリノゲン溶液を得た。このプ
レドニゾロン含有トロンビン溶液１mlとフィブリノゲン
溶液１mlを混合し、プレドニゾロン含有フィブリンゲル
２mlを作製した。このプレドニゾロン含有フィブリンゲ
ル２mlを生理食塩液１００ml中に入れ、室温に放置し、
経時的に生理食塩液中のプレドニゾロンの量を測定し
た。測定は、プレドニゾロンに帰属される２４７nmの吸
収極大を利用して行った。その結果、放置後１２時間に
フィブリンゲル中のプレドニゾロンの約８０％が徐放さ
れた(図２参照のこと)。 Example 2 50 mg of prednisolone (predonin) was dissolved in 5 ml of distilled water. Further, 1250 units of thrombin was dissolved in this solution to obtain a thrombin solution containing prednisolone. Separately, 400 mg of fibrinogen was dissolved in 5 ml of 1000 u / ml aprotinin solution to obtain a fibrinogen solution. 1 ml of this thrombin solution containing prednisolone and 1 ml of a fibrinogen solution were mixed to prepare 2 ml of fibrin gel containing prednisolone. 2 ml of this prednisolone-containing fibrin gel was placed in 100 ml of physiological saline and left at room temperature.
The amount of prednisolone in physiological saline was measured over time. The measurement was performed using the absorption maximum of 247 nm attributed to prednisolone. As a result, about 80% of prednisolone in the fibrin gel was gradually released 12 hours after standing (see FIG. 2).
【００２３】実施例 ３ 患者(２６才、男性)は、交通事故外傷により腹膜炎を起
こし、緊急手術で穿孔部腸管の切除を行なうも、吻合部
再発、外瘻形成、さらに皮膚ケロイドの形成を認め、ク
ローン病と診断された。その後、ミラクリッドとステロ
イドの動注療法により炎症を鎮静化せしめ、経過観察中
であったが再手術となった。再手術時に腸管病変部の切
除を行ない、吻合部にミラクリッド２０万単位とプレド
ニン１０mgを含むフィブリン糊を腸管吻合部に塗布し
た。術後、内視鏡を用いた経過観察を行なっているが、
３カ月経過するも吻合部再発及びケロイド形成を認めて
いない。 Example 3 A patient (26 years old, male) suffered from peritonitis due to trauma from a traffic accident, and although the intestinal tract at the perforation site was excised by emergency surgery, recurrence of the anastomotic site, external fistula formation, and formation of a skin keloid were observed. , Was diagnosed with Crohn's disease. After that, the inflammation was subsided by intracranial infusion therapy with miracled and steroids, and she was re-operated although she was still under observation. At the time of reoperation, the intestinal lesion was excised, and fibrin glue containing 200,000 units of miracled and 10 mg of predonin was applied to the anastomosis site. After the operation, follow-up observation using an endoscope is performed.
No recurrence of anastomosis or keloid formation was observed after 3 months.
─────────────────────────────────────────────────────
─────────────────────────────────────────────────── ───
【手続補正書】[Procedure amendment]
【提出日】平成７年１２月２０日[Submission date] December 20, 1995
【手続補正１】[Procedure amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】図面の簡単な説明[Correction target item name] Brief description of drawings
【補正方法】追加[Correction method] Added
【補正内容】[Correction contents]
【図面の簡単な説明】[Brief description of drawings]
【図１】 本願発明の炎症性腸疾患の術後吻合部再発お
よびケロイド形成抑制剤からのミラクリッド（ウリナス
タチン）の除放効果を示す図である。FIG. 1 is a graph showing the effect of miracrid (urinastatin) release from a keloid formation inhibitor on postoperative anastomotic site recurrence of inflammatory bowel disease of the present invention.
【図２】 本願発明の炎症性腸疾患の術後吻合部再発お
よびケロイド形成抑制剤からのプレドニゾロンの除放効
果を示す図である。FIG. 2 is a graph showing the effect of prednisolone release from a keloid formation inhibitor on postoperative anastomotic site recurrence of inflammatory bowel disease of the present invention.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 31/56 Ａ６１Ｋ 31/56 ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification code Internal reference number FI technical display area A61K 31/56 A61K 31/56
Claims (3)
の産生を抑制する薬剤を含有するフィブリン糊からなる
炎症性腸疾患の術後吻合部再発およびケロイド形成を抑
制する薬剤。1. A drug for suppressing postoperative anastomosis recurrence and keloid formation of inflammatory bowel disease, which comprises fibrin glue containing a drug for suppressing the production of inflammatory cytokines and leukotrienes.
生抑制剤がウリナスタチン、メシル酸ガベキサート、メ
シル酸ナファモスタット、メシル酸カモスタット、サラ
ゾスルファピリジン、５ＡＳＡ、メトロニダゾール、プ
ラノトールより選択される請求項１記載の炎症性腸疾患
の術後吻合部再発およびケロイド形成を抑制する薬剤。2. The inflammatory bowel according to claim 1, wherein the cytokine and leukotriene production inhibitor is selected from ulinastatin, gabexate mesylate, nafamostat mesilate, camostat mesilate, salazosulfapyridine, 5ASA, metronidazole, and planotol. A drug that suppresses postoperative anastomotic recurrence of disease and keloid formation.
記載の炎症性腸疾患の術後吻合部再発およびケロイド形
成を抑制する薬剤。3. The method according to claim 1, which further contains a steroid drug.
A drug for suppressing postoperative anastomotic recurrence and keloid formation of the inflammatory bowel disease described.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21284695A JP3919836B2 (en) | 1995-07-28 | 1995-07-28 | Postoperative anastomotic site recurrence and keloid formation inhibitor of inflammatory bowel disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21284695A JP3919836B2 (en) | 1995-07-28 | 1995-07-28 | Postoperative anastomotic site recurrence and keloid formation inhibitor of inflammatory bowel disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0940579A true JPH0940579A (en) | 1997-02-10 |
| JP3919836B2 JP3919836B2 (en) | 2007-05-30 |
Family
ID=16629307
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21284695A Expired - Lifetime JP3919836B2 (en) | 1995-07-28 | 1995-07-28 | Postoperative anastomotic site recurrence and keloid formation inhibitor of inflammatory bowel disease |
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| Country | Link |
|---|---|
| JP (1) | JP3919836B2 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998005358A1 (en) * | 1996-08-02 | 1998-02-12 | Shionogi & Co., Ltd. | Sustained release preparations for injection containing gabexate mesylate |
| WO2001097872A1 (en) * | 2000-06-22 | 2001-12-27 | Austin Sam L | Bioadhesive compositions and methods of preparation and use |
| US7229633B2 (en) * | 2000-06-22 | 2007-06-12 | Spinal Restoration, Inc. | Biological bioadhesive compositions and methods of preparation and use |
| JP2007538002A (en) * | 2004-01-20 | 2007-12-27 | ニュートリション セラピューティックス，インコーポレイテッド | Methods of using punicic acid to improve immune response and prevent metabolic disorders |
| US8258188B2 (en) | 2004-01-20 | 2012-09-04 | Josep Bassaganya-Riera | Method of using punicic acid to enhance immune response and prevent metabolic disorders |
| WO2022192195A1 (en) * | 2021-03-09 | 2022-09-15 | Ensysce Biosciences Inc. | Modified release compositions of nafamostat and methods of using same |
-
1995
- 1995-07-28 JP JP21284695A patent/JP3919836B2/en not_active Expired - Lifetime
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998005358A1 (en) * | 1996-08-02 | 1998-02-12 | Shionogi & Co., Ltd. | Sustained release preparations for injection containing gabexate mesylate |
| WO2001097872A1 (en) * | 2000-06-22 | 2001-12-27 | Austin Sam L | Bioadhesive compositions and methods of preparation and use |
| JP2004513676A (en) * | 2000-06-22 | 2004-05-13 | オースティン，サム，エル | Bioadhesive composition and its production and use |
| AU2001273623B2 (en) * | 2000-06-22 | 2006-06-08 | Spinal Restoration, Inc. | Bioadhesive compositions and methods of preparation and use |
| US7229633B2 (en) * | 2000-06-22 | 2007-06-12 | Spinal Restoration, Inc. | Biological bioadhesive compositions and methods of preparation and use |
| US7235255B2 (en) * | 2000-06-22 | 2007-06-26 | Spinal Restoration, Inc. | Biological bioadhesive compositions and methods of preparation and use |
| JP2007538002A (en) * | 2004-01-20 | 2007-12-27 | ニュートリション セラピューティックス，インコーポレイテッド | Methods of using punicic acid to improve immune response and prevent metabolic disorders |
| US8258188B2 (en) | 2004-01-20 | 2012-09-04 | Josep Bassaganya-Riera | Method of using punicic acid to enhance immune response and prevent metabolic disorders |
| US8822543B2 (en) | 2004-01-20 | 2014-09-02 | Nutrition Therapeutics, Inc. | Method of using punicic acid to enhance immune response and prevent metabolic disorders |
| WO2022192195A1 (en) * | 2021-03-09 | 2022-09-15 | Ensysce Biosciences Inc. | Modified release compositions of nafamostat and methods of using same |
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|---|---|
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