Teijin Limited

Hiroyuki Kawashima

Yoshinobu Hashimoto

Toru Takeshita

Yoshiki Suzuki

Kiyoshi Bannai

Sachio Ishimoto

Seiji Kurozumi

Takao Niki

Minoru Hayashi

Masuo Morisaki

Nobuo Ikekawa

This is a bone formation stimulant containing vitamin D.sub.3 or its derivative and acetylsalicylic acid or its formaceutically permissible salt. The present bone formation stimulant is used to cure or prevent the diseases caused by the deficiency of vitamin D or related diseases by dosing human beings or animals with it.

Bone formation stimulant

Novel 1.alpha.,3.beta.-dihydroxy-24-oxocholesta-5,7-diene and the hydroxyl group-protected derivatives thereof. Said novel 1.alpha.-hydroxy-24-oxovitamin D.sub.3 and said novel intermediates are also useful as the intermediates of 1.alpha.,24-dihydroxyvitamin D.sub.3. 1.alpha.,3.beta.-Dihydroxy-24-oxocholesta-5,7-diene and the hydroxyl group-protected derivatives thereof are prepared from fucosterol via 1.alpha.,3.beta.-diprotected hydroxy-24(24)-ethylenedioxycholest-5-ene. 1.alpha.-hydroxy-24-oxovitamin D.sub.3 is prepared by irradiation with ultraviolet rays to 1.alpha.,3.beta.-dihydroxy-24-oxocholesta-5,7-diene or a hydroxyl group-protected derivatives thereof, isomerization using heat energy, and, when necessary, elimination of the protecting groups.

Novel 1.alpha.-hydroxy-24-oxovitamin D.sub.3, its preparing process and

Novel 1.alpha., 24-dihydroxycholecalciferol and derivatives thereof which are useful with reduced side-effects for the treatment of abnormal metabolism of calcium and phosphorus caused by liver failure, renal failure, gastrointestinal tract failure and parathyroid failure, and related bone diseases. Preparation of the novel 1.alpha., 24-dihydroxycholecalciferol and their derivatives starts from 1.alpha., 24-dihydroxycholesterol prepared by reacting 1.alpha., 2.alpha.-epoxy-24-keto-cholesta-4,6-dien-3-one with an alkali metal and a proton donor in the presence of liquid ammonia or a liquid amine. Reaction of the 1.alpha., 24-dihydroxycholesterol with an allylic brominating agent, followed by contacting with a dehydrobrominating agent, affords 1.alpha.,3.beta., 24-trihydroxycholesta-5,7-diene derivative, which can then be converted to 1.alpha., 24-dihydroxycholocalciferol by ultraviolet irradiation in a organic solvent, followed by isomerization. Processes are also provided for separating 1.alpha., 24-dihydroxycholesterol into an (S)-epimer and an (R)-epimer, and also for separating at least one of 1.alpha., 3.beta., 24(S)-and 1.alpha., 3.beta., 24(R)-trihydroxycholesta-5,7-dienes from trihydroxycholesta-4,6-diene.

Novel 1.alpha.,24-dihydroxycholecalciferol compositions, novel

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Hino, Japan

Hiroyuki Kawashima