Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1999-06-30
2001-08-14
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S469000, C424S486000, C424S497000, C424S498000, C424S502000
Reexamination Certificate
active
06274174
ABSTRACT:
RELATED APPLICATIONS
This application claims the benefit of priority under 35 U.S.C. §371 to Patent Convention Treaty (PCT) International Application Ser. No: PCT/JP98/04910, filed on Oct. 29, 1998, which claims benefit of priority to JP 314591/1997, filed Oct. 31, 1997. The aforementioned applications are explicitly incorporated herein by reference in their entirety and for all purposes.
TECHNICAL FIELD
The present invention relates to a process for processing alginic acid, which has conventionally been used as a thickening agent, a gelatinizing agent and a stabilizing agent in the fields of foods, pharmaceuticals and cosmetics, into a water-insoluble spherical microparticle aggregate applicable to other new fields including chemical industries and agriculture as well as the above-mentioned conventional fields; and an aggregate of multivalent metal alginate microparticles produced by the process. In particular, the present invention relates to an aggregate of multivalent metal alginate microparticles which is suitable as a carrier of a controlled-release preparation and a process for producing the aggregate. More specifically, the present invention relates to a controlled-release preparation which comprises aggregates of multivalent metal alginate microparticles as a carrier and a slightly soluble medicament having a slow dissolution rate carried on the aggregates and which can release the medicament rapidly in the upper part of the small intestine, and a process for producing the controlled-release preparation.
BACKGROUND ART
In the conventional pharmaceutical preparations for oral administration which contains a slightly soluble medicament, the medicament shows a small dissolution rate in the digestive tract. Therefore, the amount of the dissolved medicament per a certain time of period is small, the absorption of the medicament through the digestive tract is delayed, and the amount of the medicament absorbed through the digestive tract per hour becomes small, resulting in slow absorption in a living body and a low bioavailability. In these situations, improvement in solubility of the slightly soluble medicament has been desired for effective manifestation of the efficacy and the quick-acting nature of the medicament.
As examples of the methods previously proposed for improving the solubility of a slightly soluble medicament, Japanese Patent No. 2516524 discloses a method for reducing the particle size of and amorphizing a slightly soluble, crystalline medicament (e.g., nifedipine, indomethacin); and Japanese Patent Application Laid-open Publication No. 54-2316 discloses a method for preparing powders or granules from solid dispersions comprising nifedipine and polyvinylpyrrolidone, which comprises dissolving nifedipine and polyvinylpyrrolidone in an organic solvent (e.g., methanol) to give a solution and then removing the organic solvent therefrom.
Among the commercially available nifedipine preparations, a preparation in which poly(ethylene glycol) is used to form a solid dispersion of nifedipine is “Adalat” (Bayer); and a preparation in which nifedipine is dissolved in an organic solvent and coated on lactose is “Sepamit” (Kanebo, Ltd.).
As a example of amorphization, Japanese Patent Publication No. 54-29565 discloses a method comprising adding a plurality of medicaments including a slightly soluble base medicament into a &bgr;-1,4-glucane and co-ground the medicaments. In this method, the &bgr;-1,4-glucane used is a microcrystalline cellulose “Avicel” (a trade name, Asahi Chemical Industry Co., Ltd.); examples of the slightly soluble base medicament are phenacetin, phenoxymethyl penicillin and phenobarbital; examples of the other medicaments simultaneously used with the base medicament are slightly soluble cortisone acetate, soluble tetracycline hydrochloride and water-soluble pyridoxine hydrochloride; the grinding apparatus for co-grinding of the medicaments is one having mechanisms for mechanically crushing and grinding the medicaments into a microcrystalline form, such as a ball mill; and the co-grinding is continued until the crystalline substances cause no diffraction peak specific to the crystalline substances, that is, from several hours to 10-odd hours which is required for complete amorphization.
Methods for preparing a solid dispersion of nifedipine with an organic solvent are disclosed in Japanese Patent Application Laid-open No. 54-2316 (supra) and Japanese Patent Publication No. 3-7645.
A method for improving the dissolution rate of a slightly soluble medicament is disclosed in Japanese Patent Publication No. 5-66364 in which a slightly soluble medicament and a water-soluble polymer are fed to a twin-roll mill (which is equipped with horizontal two rolls which rotate in opposing directions to each other) through a gap between the rolls while rotating the rolls, and kneaded by the rotation of the rolls.
A method for preparing an easy-absorbable nifedipine preparation which is stable to moisture is disclosed in Japanese Patent Publication No. 3-28404, by which it becomes possible to improve the dissolution properties, particular dissolution rate, of nifedipine in water and, thereby, to produce a preparation stable to moisture compared to the conventional solid solution powdery preparations containing polyvinylpyrrolidone.
This method comprises the steps of granulating a pharmaceutical additive (e.g., lactose) and a water-soluble binder (e.g., polyvinylpyrrolidone) to give a water-soluble fine particulate carrier, spraying a solution of nifedipine and either hydroxypropylmethylcellulose or methylcellulose in a solvent (e.g., ethanol) on the carrier, and then drying the sprayed carrier. The nifedipine preparation provided by this method is one in which nifedipine is coated in the form of a solid dispersion. The preparation thus produced is easy-to-dissolve or easy-to-absorb and is stable to moisture.
A medicament complex comprising a base medicament hardly soluble to water (e.g., phenacetin) which is carried on the surface of a modified starch (e.g., pregelatinized starch), is disclosed in Japanese Patent Publication No. 7-47548. In this patent publication, it is described that the dissolution rate of the base medicament of the medicinal complex is increased as determined by the dissolution test (the second solution, pH 6.8) of the base medicament performed in accordance with the paddle method described in the Japanese Pharmacopoeia Tenth Edition, and thereby the solubility of the base medicament is improved.
A method for improving the dissolution properties of a crystalline medicament that is intestinally slightly soluble to the intestinal juice is disclosed in Japanese Patent Application Laid-open No. 6-227969. This method comprises the steps of dissolving an enteric polymer (e.g., calboxymethylethylcellulose; a product of FREUND INDUSTRIAL CO., LTD.) with a mixed solvent of methylene chloride and ethanol to give a solution, dispersing indomethacin particles (mean particle diameter: 10 &mgr;m) or mefenamic acid particles (mean particle diameter: 27 &mgr;m) in air as the crystalline medicament particles slightly soluble to the intestinal juice, spraying the above-prepared solution to the particles to adhere the enteric polymer on the particles, and drying the particles.
A method for improving the dissolution properties of a crystalline medicament slightly soluble to water is disclosed in Japanese Patent Application Laid-open No. 7-112928. This method comprises the steps of dissolving nifedipine (mean particle diameter: 20 &mgr;m) into ethanol to give a solution, spraying the solution to a hydrophilic substance (e.g., lactose; mean particle diameter: 5-10 &mgr;m) to make carry the medicament (i.e., nifedipine) on the hydrophilic substance, granulating the medicament-carried hydrophilic substance together with a water-soluble polymer (e.g., hydroxypropyl cellulose) as a binder.
Alginate gel beads are disclosed in Japanese Patent Application Laid-open No. 2-167220, where a sustained-release preparation is described in which a basic medicament (e.g., nifedipine)
Hom-ma Takeshi
Myo Nagayoshi
Nanbu Hironobu
Sato Takaya
Fish & Richardson P.C.
Nisshinbo Industries Inc.
Page Thurman K.
Tran S.
LandOfFree
Aggregates of spherical multivalent metal alginate... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Aggregates of spherical multivalent metal alginate..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Aggregates of spherical multivalent metal alginate... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2460553