Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Utility Patent
1997-11-07
2001-01-02
Tsang, Cecilia (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C548S541000, C548S550000
Utility Patent
active
06169108
ABSTRACT:
TECHNICAL FIELD
This apply is a 371 at PCT/JP96/00485 filed Mar. 1, 1996.
The present invention relates to a method for preparing pyrrolidinylacetamide derivatives as anhydrous crystals which are suitable as pharmaceutical bulk powders. More specifically, the present invention relates to a method for preparing anhydrous crystals of pyrrolidinylacetamide derivatives which are substantially free from hygroscopicity when stored under a highly humid condition for a long period of time.
BACKGROUND ART
The compound represented by the following formula:
[N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide; referred to as Compound (1) hereinafter in the specification] has been expected to be a cognition-enhancing agent (see, the Japanese Patent Unexamined Publication (KOKAI) No. (Hei) 6-65197/1994). An anhydrous crystal of Compound (1) can be prepared from a hydrous crystal of said compound.
In the course of preparations of the anhydrous crystals of the aforementioned compound, the inventors of the present invention have encountered significant differences in hygroscopicity among the lots of anhydrous crystals, and found that the differences were due to the existence of several sorts of anhydrous crystals having distinguishable hygroscopic rates. In addition, they first found that a main cause of resulting the crystals with different hygroscopic rates was attributable to drying conditions for preparing anhydrous crystals by drying the hydrate.
In order to maintain constant quality of pharmaceutical preparations, it is desired to use anhydrous crystals substantially free from hygroscopicity as bulk powders. However, substantially non-hygroscopic anhydrous crystals of the aforementioned compound have not yet been known to date.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide an anhydrous crystal of the aforementioned compound that is substantially free from hygroscopicity. Another object of the present invention is to provide a novel method for preparation that can produce the anhydrous crystal in a large scale with excellent reproducibility.
The inventors of the present invention conducted various researches to achieve the foregoing objects, and as a result, they found that an anhydrous crystal substantially free from hygroscopicity can be obtained by drying a hydrous crystal of Compound (1) under a specific reduced pressure with heating. The present invention was achieved on the basis of this finding.
The present invention thus provides an anhydrous crystal of a compound represented by the general formula: R
2
—CH
2
CONH—R
1
wherein R
1
represents a substituted or non-substituted pyridyl group or substituted or non-substituted phenyl group; and R
2
represents a substituted or non-substituted 2-oxo-1-pyrrolidinyl group, characterized in that said crystal is substantially free from hygroscopicity. According to a preferred embodiment of the present invention, there is provided the aforementioned crystal which gains 1% or less weight increase when stored at a temperature of 25° C. for 30 day under a relative humidity of 83%.
According to another aspect of the present invention, there is provided a method for preparing the aforementioned crystal which comprises the step of drying a crystal of the compound represented by the above formula at a temperature of 80° C. or above under reduced pressure. According to preferred embodiments of this invention, there are provided the aforementioned process wherein a hydrous crystal of the above compound is dried; the aforementioned process wherein water content of the hydrous crystal is 20% or less; the aforementioned process wherein the drying step is carried out at a temperature between the range of from 110 to 120° C.; and the aforementioned process wherein reduced pressure of 50 mmHg or lower is applied.
REFERENCES:
patent: 4341790 (1982-07-01), Betzing et al.
patent: 5461157 (1995-10-01), Kamihara et al.
patent: 574952 (1993-12-01), None
patent: 6-65197 (1994-03-01), None
Kitaoka Hiroaki
Ono Makoto
Sato Yukio
Terada Tatsuya
Daiichi Pharmaceutical Co. Ltd.
Greenblum & Bernstein P.L.C.
Sackey Ebenezer
Tsang Cecilia
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