JP2006117704A5

JP2006117704A5 -

Info

Publication number: JP2006117704A5
Application number: JP2006025034A
Authority: JP
Filing date: 2006-02-01
Publication date: 2007-11-29

Claims

Look containing cyclodextrin may contain PGE1 or PGE1 cyclodextrin clathrate thereof, to a dosage form further comprising Nde including maltose, lyophilized moisture content of less than about 1.5 wt%;
However, (1) per lyophilized product preparation, PGE1 which may contain cyclodextrin, or PGE1 cyclodextrin inclusion compound as PGE1, 20 μg and maltose 40-60 mg, No moisture content, 0.1 to 0.8% by weight, substantially unchanged after storage at 60 ° C. for 1 week, and 98.5 remaining PGE1 after storage at 60 ° C. for 1 month % Or more and decomposition products (I)

And / or degradation products (II)

Is substantially not detected by liquid chromatography, or the production rate of the decomposition product (I) is 0.05% or less and the production rate of the decomposition product (II) is 0.15% or less. Formulation, and
(2) A formulation comprising 500 μg of PGE1 containing PGE1 which may contain cyclodextrin or PGE1 cyclodextrin inclusion compound and 50 to 150 mg of maltose per lyophilized product, and containing citric acid In addition, the water content is 0.1 to 0.8% by weight, the shape is not substantially changed after storage at 60 ° C. for 1 week, and the residual rate of PGE1 is 98.5% or more after storage at 60 ° C. for 1 month. And the decomposition product (I)

And / or degradation products (II)

Is substantially not detected by liquid chromatography, or the production rate of the decomposition product (I) is 0.05% or less and the production rate of the decomposition product (II) is 0.15% or less. Excluding formulation.

The lyophilized product according to claim 1, wherein the drug is an α-cyclodextrin inclusion compound of PGE1.

The freeze-dried product according to claim 1 , which is a freeze-dried product prepared by adding maltose as an aqueous maltose solution having a pH of about 4.7 to about 6.3.

Against PGE1 of 1 part by weight, the lyophilizate according to claim 1 maltose is from about 50 to about 10000 parts by weight.

The lyophilized product according to claim 4 , wherein maltose is about 500 to about 10,000 parts by weight with respect to 1 part by weight of PGE1.

The freeze-dried product according to claim 5 , wherein maltose is about 2000 to about 3000 parts by weight with respect to 1 part by weight of PGE1.

The freeze-dried product according to claim 4 , wherein the maltose is about 50 to about 500 parts by weight with respect to 1 part by weight of PGE1.

The lyophilized product according to claim 7 , wherein maltose is about 100 to about 300 parts by weight with respect to 1 part by weight of PGE1.

The freeze-dried product according to claim 1 filled in a vial.

The freeze-dried product according to claim 1, wherein the moisture content is about 1.0% by weight or less.

1 lyophilizate per the PGE1 about 20 [mu] g, and maltose containing about 40 to about 60mg, lyophilized according to claim 1 moisture content of about 0.05 to about 1.0 wt%.

1 lyophilizate per the PGE1 about 500 [mu] g, and maltose containing about 50 to about 150mg, lyophilized according to claim 1 moisture content of about 0.05 to about 1.0 wt%.

Decomposition product (I) after storage at about 60 ° C. for about 1 month

And / or degradation products (II)

The freeze-dried product according to claim 9, 11 or 12 , which has a quality that is substantially not detected.

Decomposition product (I) after storage at about 60 ° C. for about 1 month

And / or degradation products (II)

Or but not substantially detected, the production rate is greater than about 0.05% of degradation products (I), production rate of decomposition products (II) is a quality of less than about 0.15% claim 9 11 or 12 freeze-dried product.

The freeze-dried product according to claim 9, 11 or 12 , which has a quality that does not substantially change in shape after storage at about 60 ° C for about 1 week.

The freeze-dried product according to claim 9, 11 or 12 , wherein the residual rate of PGE1 is about 98.5% or more after storage at about 60 ° C for about 1 month.

(A) freezing the aqueous solution containing the PGE1 or PGE1 cyclodextrin inclusion compound optionally containing cyclodextrin at about −50 to about −30 ° C., (b) at a degree of vacuum of about 5 to about 20 Pascal. The temperature is raised to about −20 to 20 ° C. and vacuum dried at that temperature, and (c) the temperature is raised to about 25 to 55 ° C. and secondarily dried at that temperature. Of producing a freeze-dried product.

The freeze-dried product according to claim 1 obtained by the production method according to claim 17 .

The freeze-dried product according to claim 1, which is a prophylactic and / or therapeutic agent for chronic arterial occlusion, peripheral blood circulation disorder, arterial tube-dependent congenital heart disease and / or spinal canal stenosis.

PGE1 optionally containing cyclodextrin, or PGE1 cyclodextrin inclusion compound, and lyophilized having a pH of about 4.3 to about 5.1 comprising maltose having a pH of about 4.7 to about 6.3 Aqueous solution.