Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2002-05-03
2004-05-04
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S553000, C514S555000
Reexamination Certificate
active
06730702
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a novel agent for prophylaxis or treatment of inflammatory bowel diseases, more particularly an agent for prophylaxis or treatment of inflammatory bowel diseases which comprises as an active ingredient sulfodehydroabietic acid or a pharmaceutically acceptable salt thereof, and a use of said active ingredient in preparation of an agent for prophylaxis or treatment of inflammatory bowel diseases, and further relates to a method for prophylaxis or treatment of inflammatory bowel diseases.
BACKGROUND ART
Inflammatory bowel diseases include intractable inflammatory diseases of large and small intestines which are caused by various nosogenesis, for example, ulcerative colitis which is a cryptogenic diffuse non-specific inflammation wherein mucosa on the large intestine is mainly invaded and erosion and ulcer are formed, or Crohn's disease which is a cryptogenic non-specific granulomatous inflammatory disease accompanied by fibrosis or ulcer. In addition, the lesion of the intestine in Behçet's disease which is a chronic systemic inflammatory disease is also included.
The nosogenesis of ulcerative colitis, Crohn's disease, or Behçet's disease has not been clarified yet, but their immunological mechanisms have recently attracted a lot of attentions. In the medication of these inflammatory bowel diseases, immunosupressants, steroids, salazosulfapyridine, etc. have been used, but they cannot exhibit sufficient effects in certain patients. Besides, they should be improved with respect to side effects, and under these circumstances, it has been desired to develop a medicament being more effective and having a high safety.
On the other hand, sulfodehydroabietic acid or a salt thereof has been known to exhibit an inhibitory activity of acid secretion or pepsin secretion, etc., and to be useful as an agent for prophylaxis or treatment of peptic ulcer (gastric ulcer, duodenal ulcer) or gastritis (JP-A-58-77814, JP-A-63-165361, JP-A-2-167258). It is considered that peptic ulcer (gastric ulcer, duodenal ulcer) or gastritis and inflammatory bowel diseases are different in not only their lesion regions, but also their nosogenesis is quite different. In the nosogenesis of peptic ulcer such as gastric ulcer and duodenal ulcer, the digestion by gastric juice cannot be left out of consideration. In the medication of these diseases, a medicament exhibiting an inhibitory activity of acid secretion such as a histamine H2 receptor antagonist or a proton pump inhibitor is mainly used in the medication of peptic ulcer and gastritis. On the other hand, an immunosupressant, a steroid, a salazosulfapyridine, etc. is mainly employed in the medication of inflammatory bowel diseases, which is quite different from the medication of peptic ulcer or gastritis.
It has not been known at all that sulfodehydroabietic acid or a salt thereof is useful in the prophylaxis or treatment of inflammatory bowel diseases.
DISCLOSURE OF INVENTION
An object of the present invention is to provide a novel agent being useful in the prophylaxis or treatment of inflammatory bowel diseases.
During the studies on a novel remedy for inflammatory bowel diseases, the present inventors have found that sulfodehydroabietic acid disclosed in JP-A-58-77814, JP-A-63-165361, etc. or a pharmaceutically acceptable salt thereof exhibits an excellent effect in the prophylaxis or treatment of inflammatory bowel diseases, and have accomplished the present invention.
That is, the present invention provides an agent for prophylaxis or treatment of inflammatory bowel diseases, which comprises as an active ingredient sulfodehydroabietic acid (chemical name: (+)-(1R,4aS,10aR)-1,2,3,4,4a,9,10,10a-octadehydro-1,4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic acid) of the following formula (I):
or a pharmaceutically acceptable salt thereof.
The present invention also relates to a use of said sulfodehydroabietic acid (I) or a pharmaceutically acceptable salt thereof in preparation of an agent for prophylaxis or treatment of inflammatory bowel diseases.
Moreover, the present invention provides a method for prophylaxis or treatment of inflammatory bowel diseases which comprises administering said sulfodehydroabietic acid (I) or a pharmaceutically acceptable salt thereof orally or parenterally to a patient being suffering from an inflammatory bowel disease.
BEST MODE FOR CARRYING OUT THE INVENTION
The active ingredient of the present agent for prophylaxis or treatment of inflammatory bowel diseases, sulfodehydroabietic acid of the formula (I) or a pharmaceutically acceptable salt thereof, is a known compound, and can be prepared, for example, by the methods disclosed in JP-A-58-77814, JP-A-63-165361, JP-A-2-167258, or by a modified method thereof.
The pharmaceutically acceptable salt of sulfodehydroabietic acid of the formula (I) includes, for example, a salt with an alkali metal (e.g., sodium, lithium, potassium, etc.), a salt with an alkaline earth metal (e.g., magnesium, calcium, etc.), and a salt with a metal such as aluminum. Among them, the preferable salt is a sodium salt of sulfodehydroabietic acid, especially a monosodium salt or a disodium salt thereof, and the most preferable salt is sulfodehydroabietic acid monosodium salt. Sulfodehydroabietic acid monosodium salt is more advantageous than disodium salt thereof as being less hygroscopic and being more stable (JP-A-63-165361). Besides, a pharmaceutically acceptable salt of sulfodehydroabietic acid may exist as well in the form of a hydrate thereof, and the hydrate of sulfodehydroabietic acid monosodium salt may be, for example, pentahydrate thereof, i.e., sulfodehydroabietic acid monosodium salt pentahydrate. The monosodium salt pentahydrate of sulfodehydroabietic acid of the formula (I) (chemical name: (+)-(1R,4aS,10aR)-1,2,3,4,4a,9,10,10a-octahydro-1,4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic acid 6-sodium salt pentahydrate) has been known as Ecabet sodium.
According to the study of the present inventors, sulfodehydroabietic acid (I) or a pharmaceutically acceptable salt thereof of the active ingredient is hardly absorbed at the gut, and when it is administered orally, it can efficiently reach to the inferior gut and can adhere to the mucosa of the lesion site, and exhibit the pharmacological effects thereof so that the efficacy thereof is extremely excellent. In addition, sulfodehydroabietic acid (I) or a pharmaceutically acceptable salt thereof of the active ingredient shows few side effects, and the safety thereof is extremely high.
The agent for prophylaxis or treatment of inflammatory bowel diseases of the present invention is effective on the lesion of the intestine (including fistula) in Crohn's disease, the lesion of the intestine in Behçet's diseases, ulcerative colitis, hemorrhagic rectal ulcer, ileum pouchitis, etc.
Besides, since sulfodehydroabietic acid (I) or a pharmaceutically acceptable salt thereof of the active ingredient of the present invention can cure the lesion of the gut without causing a stenosis, it may also be useful in the prophylaxis of the stenosis of the gut, especially in the prophylaxis of the stenosis of the intestine accompanying with inflammatory bowel diseases. When surgically treating a patient of an inflammatory bowel disease, an artificial anus may be constructed, but in said patient, such an inflammation may occasionally spread to the periphery of the artificial anus. The sulfodehydroabietic acid (I) or a pharmaceutically acceptable salt thereof of the active ingredient of the present invention is also effective in the inflammation of artificial anus periphery.
The sulfodehydroabietic acid (I) or a pharmaceutically acceptable salt thereof of the active ingredient of the present invention may be administered either orally or rectally, and further can be administered directly into the intestine through an artificial anus in a patient having one, or can directly be applied in the inflammation of the periphery of ane artificial anus.
The pres
Kono Toru
Nomura Masafumi
Fay Zohreh
Kwon Brian-Yong S.
Tanabe Seiyaku Co. Ltd.
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