Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2001-01-11
2003-08-05
Wilson, James O. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S084000, C536S095000, C536S124000
Reexamination Certificate
active
06602995
ABSTRACT:
RELATED APPLICATION
This application claims priority and is related to Japanese Application No. 2000-005167, filed Jan. 14, 2000.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention generally relates to a process for the production of low-substituted hydroxypropyl cellulose that is added for the purpose of imparting disintegration properties or binding properties during the manufacture of preparations in the fields of medicines, foods and the like. More particularly, it relates to a method for the formation of neutralization-precipitated particles of low-substituted hydroxypropyl cellulose in a purification step.
2. Description of the Related Art
In solid preparations for use in the fields of medicines, foods and the like, those composed of principal components alone have problems in that, when they are administered as medicines, they may not be satisfactorily disintegrated to such an extent as to exhibit a sufficient drug effect or in that, when they are formed into tablets or granules, they may fail to retain their form owing to poor binding properties. In such cases, disintegration properties or binding properties can be imparted by adding low-substituted hydroxypropyl cellulose to preparations.
Besides low-substituted hydroxypropyl cellulose, additives used for this purpose include carboxymethylcellulose calcium, crosslinked carboxymethylcellulose sodium, crosslinked polyvinyl pyrrolidone, carboxymethylstarch and the like. However, low-substituted hydroxypropyl cellulose has the advantage that it is nonionic and hence less liable to changes in properties due to reaction with ionic drugs or the like.
This advantage is utilized, for example, in a process wherein a powder of low-substituted hydroxypropyl cellulose is dry-blended with a drug and other pharmaceutical excipients, and the resulting blend is formed into tablets; and in a process wherein a powder of low-substituted hydroxypropyl cellulose is granulated by kneading with water or an aqueous solution of a water-soluble binder, and the resulting granules are molded.
Low-substituted hydroxypropyl cellulose may be produced as the reaction product of an alkali cellulose with propylene oxide. This can be done, for example, by soaking pulp in an aqueous solution of sodium hydroxide, pressing it to yield an alkali cellulose, and reacting the alkali cellulose with propylene oxide, or by dispersing powdered pulp in an organic solvent (e.g., isopropyl alcohol, tert-butyl alcohol or hexane), adding an aqueous solution of sodium hydroxide thereto so as to yield an alkali cellulose, and adding propylene oxide thereto and reacting it with the alkali cellulose.
Low-substituted hydroxypropyl cellulose is soluble in aqueous alkaline solutions, and sodium hydroxide used as a catalyst remains in the reaction product. In conventional processes, this reaction product is dissolved in water, and the remaining alkali is neutralized with an acid to form neutralization-precipitated particles of low-substituted hydroxypropyl cellulose.
In order to remove the salt formed in this step and other impurities, the neutralization-precipitated particles are washed with water or hot water. The washed material is pressed to remove water, dried, and pulverized to yield a final product of low-substituted hydroxypropyl cellulose.
Moreover, in conventional processes for the production of low-substituted hydroxypropyl cellulose, the reaction product is dissolved in water by means of a horizontal kneader or a vertical mixer and then neutralized by the addition of an acid to form neutralization-precipitated particles of low-substituted hydroxypropyl cellulose. In these processes, a long time is required to dissolve low-substituted hydroxypropyl cellulose. Furthermore, if the addition rate of an acid during neutralization is unduly high, coarse particles are formed to interfere with uniform neutralization. In a subsequent washing step, it is difficult to decrease the ash content of such coarse particles.
SUMMARY OF THE INVENTION
The present invention has been made in view of the above-described circumstances, and an object of the present invention is to provide a process for the production of low-substituted hydroxypropyl cellulose wherein, in the formation of low-substituted hydroxypropyl cellulose particles, a granular material obtained by granulating the reaction product is neutralized with an acid to form neutralization-precipitated particles of low-substituted hydroxypropyl cellulose which can reduce the treating time as compared with conventional processes and, moreover, permit its ash content to be easily decreased in a subsequent washing step.
As a result of intensive investigations carried out with a view to accomplishing the above object, the present inventors have now found that, in the formation of neutralization-precipitated particles of low-substituted hydroxypropyl cellulose, an improvement in treating capacity and hence a reduction in production cost can be achieved by granulating the reaction product of an alkali cellulose with a hydroxypropylating agent and neutralizing the resulting granular material with an acid. The present invention has been completed on the basis of this finding.
Accordingly, the present invention provides a method for the formation of neutralization-precipitated particles of low-substituted hydroxypropyl cellulose wherein a granular material obtained by granulating the reaction product is neutralized with an acid.
When a granular material obtained by granulating the reaction product is neutralized with an acid in the production of low-substituted hydroxypropyl cellulose and, more particularly, in the formation of neutralization-precipitated particles of low-substituted hydroxypropyl cellulose, the treating time can be reduced as compared with conventional processes. Moreover, the neutralization-precipitated particles obtained according to the present invention have a narrow particle size distribution and hence a low water content after washing, so that they exhibit excellent efficiency in ash extraction. Thus, there can be formed neutralization-precipitated particles of low-substituted hydroxypropyl cellulose which permit its ash content to be easily decreased in a subsequent washing step and thereby causes a reduction in the production cost of the product.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention will be more specifically described hereinbelow.
In the low-substituted hydroxypropyl cellulose of the present invention, the number of moles of the hydroxypropoxyl substituent group per mole of the glucose unit (C
6
H
10
O
5
) is preferably in the range of 0.1 to 0.5. If the number of moles of the hydroxypropoxyl substituent group is less than 0.1, the resulting product may not exhibit the desired binding properties. If it is greater than 0.5, the resulting product may not exhibit the desired disintegration properties and, therefore, the resulting preparations (e.g., molded tablets) may have an unduly long disintegration time.
In the present invention, the reaction product of an alkali cellulose with a hydroxypropylating agent may be obtained according to any of various well-known techniques. This can be done, for example, by soaking raw pulp in a 10-50 wt % aqueous solution of sodium hydroxide, pressing it to yield an alkali cellulose, and reacting the alkali cellulose with a hydroxypropylating agent (e.g., propylene oxide) at 20-90° C. for about 2-8 hours; or by dispersing powdered pulp in an organic solvent (e.g., isopropyl alcohol, tert-butyl alcohol or hexane), adding an aqueous solution of sodium hydroxide thereto so as to yield an alkali cellulose, and adding a hydroxypropylating agent (e.g., propylene oxide or propylene chlorohydrin) thereto and reacting it with the alkali cellulose.
In the present invention, the reaction product of an alkali cellulose with a hydroxypropylating agent is fed to a granulating machine, in which the reaction product is tumbled or consolidated to yield a granular material of the reaction product. Then, neutralization-precipitated particles of
Maruyama Naosuke
Umezawa Hiroshi
Shin-Etsu Chemical Co. , Ltd.
White Everett
Wilson James O.
LandOfFree
Method for the formation of low-substituted hydroxypropyl... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for the formation of low-substituted hydroxypropyl..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for the formation of low-substituted hydroxypropyl... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3123728