Ono Pharmaceutical Co., Ltd.

Akio Nishiura

Yoshiki Sakai

Teppei Ogata

Kaoru Kobayashi

Kousuke Tani

Toru Maruyama

Takayuki Maruyama

Tohru Kambe

Takuya Seko

Hideyuki Yoshida

Shin-ichi Hamano

Nobutaka Abe

Shinsei Fujimura

Hikaru Sugihara

Ryoji Matsumoto

Yoshiharu Kimura

Toshihiko Nagase

Soonih Kim

Yoshihiko Nakai

Tetsuo Obitsu

Kazuya Abe

Kiyoto Sakata

Shin-Ichi Hamano

The present invention provides a compound of which active |form| is represented by a formula (A). and which can be injected into a joint cavity which is an affected part of disorders and can be accumulated in the joint cavity to exert the pharmacological effect thereof in a sustained manner, for the purpose of ameliorating cartilage disorders without developing any side effect. A compound according to the present invention, which is represented by a formula (I): (wherein all of symbols are as defined in the description), is a compound that can achieve the above-mentioned purpose. This compound does not exhibit any side effect on the cardiovascular system even when the compound is administered in an effective amount for exhibiting a cartilage regeneration activity, and is therefore extremely useful as a safe and effective preventive and/or therapeutic agent for cartilage disorders. Since a suspension produced using this compound can be injected without requiring the incision of the affected part, it can reduce the burden on patients, and is extremely useful as a medicinal agent.

Compound for treating cartilage disorders

It relates to an endogenous repair factor production accelerator which comprises one or at least two selected from prostaglandin (PG) I2 agonist, EP2 agonist and EP4 agonist. Since prostaglandin (PG) I2 agonist, EP2 agonist or EP4 agonist has various endogenous repair factor production accelerating action, angiogenesis acceleration action and stem cell differentiation induction action, it is useful as preventive and/or therapeutic agents for ischemic organ diseases (e.g., arteriosclerosis obliterans, Buerger disease, Raynaud disease, myocardial infarction, angina pectoris, diabetic neuropathy, spinal canal stenosis, cerebrovascular accidents, cerebral infarction, pulmonary hypertension, bone fracture, Alzheimer disease, etc.) and various cell and organ diseases.

Endogeneous repair factor production accelerators

It relates to an endogenous repair factor production accelerator which comprises one or at least two selected from prostaglandin (PG) 12 agonist, EP2 agonist and EP4 agonist. Since prostaglandin (PG) 12 agonist, EP2 agonist or EP4 agonist has various endogenous repair factor production accelerating action, angiogenesis acceleration action and stem cell differentiation induction action, it is useful as preventive and/or therapeutic agents for ischemic organ diseases (e.g., arteriosclerosis obliterans, Buerger disease, Raynaud disease, myocardial infarction, angina pectoris, diabetic neuropathy, spinal canal stenosis, cerebrovascular accidents, cerebral infarction, pulmonary hypertension, bone fracture, Alzheimer disease, etc.) and various cell and organ diseases.

Endogeneous repair factor production promoters

An adhesive preparation which has a pressure-sensitive adhesive layer comprising two components, i.e., a C1-4 alcohol ester of 4-{[2-((1R,2R,3R)-3-hydroxy-2-{(1E,3S)-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-5-osocyclopentyl)ethyl]sulfanyl}butanoic acid and a silicone-based pressure-sensitive adhesive. This is an effective and safe preparation which is stable, shows little change in skin permability and release a drug not rapidly but continuously.

Adhesive preparation

A pharmaceutical composition for topical administration for prevention and/or treatment of diseases associated with decrease in bone mass comprising an EPagonist as an active ingredient. An EPagonist, in which includes a compound possessing prostaglandin skeleton as a representative, possesses promoting action on bone formation, so it is useful for prevention and/or treatment of diseases associated with decrease in bone mass (bone diseases such as primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss and bone necrosis, postoperative osteogenesis, alternative therapy for bone grafting).

Pharmaceutical composition for treatment of diseases associated with decrease in bone mass comprising EP4 agonist as active ingredient

Endogenous repair factor production accelerator

The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EPagonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn's disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget's disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.

8-azaprostaglandin derivatives and medical use thereof

Prostaglandin E.sub.1 ester derivatives of the formula (I): ##STR1## wherein the R' groups are the same as each other and are C4-12 alkyl; or cyclodextrin clathrates thereof, liposome formulations containing them, and pharmaceutical compositions containing them, as active ingredient. The compounds of formula (I) have the effect of increasing blood flow and are useful for the prevention and/or treatment of peripheral circulatory disorder, decubitus, or skin ulcers, or for the maintenance of blood flow.

Prostaglandin derivatives

Prostaglandin E, ester derivatives of the formula (I): ##STR1## wherein R is (i) --CH.sub.2 CH.sub.2 --O--CO--R.sup.1

A polyurethane (I) of 1000 to 100,000 in average molecular weight, comprising plural segments, which are each structural units of A-B, A-C and A-D of the formulae: ##STR1## the proportion of the said segments of A-B, A-C and A-D, i.e. x:y:z is in the molar ratio 0.01 to 0.8:0 to 0.80:0 to 0.99, provided that the sum of x, y and z is 1.0; each segment being produced by combining with repeat units of A, B, C and D of the formulae: ##STR2## wherein R.sup.1 is a skeleton of a diisocyanate and the three R.sup.1 's in each of segments A-B, A-C and A-D can be the same or different; aza is a group of the formula: ##STR3## wherein Y.sup.1 and Y.sup.2 which can be the same or different, are oxygen, imino(--NH--) or a group of the formula:

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Mishima-gun, Japan

Akio Nishiura