Teijin Limited

Kenji Ishimaru

Hideki Tsuruta

Toru Takeshita

Osamu Nishikawa

Kimihiko Hamamoto

Yataro Ichikawa

Tsutomu Kiriyama

Itaru Yamamoto

Michiyuki Tokashiki

Noriaki Sasaki

Takami Arai

Michio Yamamoto

Jun-ichi Oshida

Michiyuki Takashiki

Yoshitaka Sakamoto

A method of culturing animal cells, which comprises (A) subjecting living animal cells to suspension culture in a culture tank, (B) withdrawing a portion of a suspension culture fluid containing the living animal cells from the culture tank, (C) supplying the withdrawn suspension culture fluid to a centrifugal separating device which is operated under specific conditions and separating the living animal cells from the suspension culture fluid, (D) withdrawing the separated living animal cells from the centrifugal separating device, and (E) recycling at least a portion of the withdrawn living animal cells to the culture tank for the step (A).

Method of culturing animal cells

A method for treating synthetic pulp particles, which includes treating a slurry of synthetic pulp particles having a Schopper-Riegler freeness of more than 30.degree.SR by a concentration provided with a rotary filter bed to lower the freeness not more than 30.degree.SR, water-washing the synthetic pulp particles in the state where the freeness is not more than 30.degree.SR, and dispersing the synthetic pulp particles in water to restore the freeness to more than 30.degree.SR.

Method for treating synthetic pulp particles, and pulp particles

An apparatus for cell culture by perfusion comprising a cell culture tank for suspension culture, said cell culture tank having a suspension cell culture zone, a cell settling zone, an opening for discharging a spent culture medium from the settling zone and an opening for supplying a culture medium to the suspension culture zone, the suspension culture zone and the setting zone being separated by a partition therebetween in a manner to communicate with each other in the lower portion of the settling zone, and the settling zone being formed between the side wall of the cell culture tank and the partition. Another type of apparatus for cell culture having a unit in which main culturing and settling are carried out in a cell settling zone, and a multiunit cell culture apparatus having at least two culturing units which are stacked longitudinally are also described. A method for culturing cells by perfusion in the culture apparatus which comprises withdrawing a substantially cell-free culture medium from the settling zone and introducing a fresh culture medium into the suspension culture zone.

Culture apparatus and method

The present invention relates to novel vitamin D.sub.3 derivatives which have a carboxyl group or its ester group at the 22-position, processes for the preparation thereof, and antigens, which comprise said vitamin D.sub.3 derivative and an immunogenic carrier material, to be used for the preparation of antibodies for enzymeimmunoassay or radioimmunoassay and antibodies obtained therefrom. The determination of such activated vitamin D.sub.3 compounds as 25-hydroxy vitamin D.sub.3, 24, 25-dihydroxy vitamin D.sub.3, etc. can be made satisfactorily according to the present invention.

Vitamin D.sub.3 derivatives, process for preparation thereof, and

The present invention relates to a novel process for the preparation of active-type vitamin D.sub.3 compounds and their intermediates. In accordance with the present invention, a large amount of an active-type vitamin D.sub.3 compounds, for example 1.alpha.-hydroxycholecalciferol, 1.alpha.,25-dihydroxycholecalciferol and the like, is efficiently prepared with high industrial advantages by a novel processes, which comprises (i) reacting hydroxycholesta-5-enes having the hydroxyl groups protected with lower alkoxycarbonyl group as a starting material with allylic brominating agent and dehydrobrominating agent to prepare the corresponding hydroxycholesta-5,7-dienes, (ii) exposing the hydroxycholesta-5,7-dienes to ultraviolet irradiation or to a combination of the irradiation with thermal isomerization to obtain a mixture of the unreacted hydroxycholesta-5,7-dienes and previtamin D.sub.3 compounds or a mixture of the unreacted hydroxycholesta-5,7-dienes and the protected active-type vitamin D.sub.3 compounds, (iii) separating the mixture into the unreacted hydroxycholesta-5,7-dienes and previtamin D.sub.3 compounds or the protected active-type vitamin D.sub.3 compounds, (iv) recycling the unreacted hydroxycholesta-5,7-dienes as reuse and (v) thermally isomerizing the remaining compounds and/or splitting off the protective groups. The process for the preparation of active-type vitamin D.sub.3 compounds, in the present invention, is of very high industrial value, capable of carrying out by simple operation and adaptable to large scale commercial production.

Process for the preparation of active-type vitamin D.sub.3 compounds

A process for producing a steroid compound having an oxo group in the side chain, which comprises condensing an acid halide having a steroid skeleton with an organozinc compound at the halocarbonyl group of the acid halide in an inert organic medium in the presence of a catalytic amount of an ether capable of forming a complex with the organozinc compound, and if desired, hydrolyzing the product. The process produces the steroid compound at a high yield, and often at an almost quantitative yield. The steroid compound is an important intermediate for the production of vitamin D.sub.3 analogs such as active forms of vitamin D.sub.3. In one preferred embodiment, an industrially advantageous process from the standpoint of operation is provided.

Process for producing steroid compounds having an oxo group in the side

This invention relates to novel 25-hydroxy-24-oxocholestane derivatives and a process for preparing them. The novel 25-hydroxy-24-oxocholestane derivatives of this invention can easily be converted to 24,25-dihydroxycholecalciferol or 1.alpha.,24,25-trihydroxycholecalciferol which is known as useful for medicine controlling the calcium metabolism of warm-blooded animals. Moreover, 25-hydroxy-24-oxocholestane derivatives can be converted to novel 25-hydroxy-24-oxocholecalciferol expressed by the following formula ##STR1## and novel 1.alpha.,25-dihydroxy-24-oxocholecalciferol of the formula ##STR2## which are useful for medicine. The new 25-hydroxy-24-oxocholestane derivatives in the present invention are very useful as the intermediates for the synthesis of a variety of active vitamin D.sub.3.

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Iwakuni, Japan

Kenji Ishimaru