WO1988002629A1 - 2',3'-didesoxyadenosine composition - Google Patents
2',3'-didesoxyadenosine composition Download PDFInfo
- Publication number
- WO1988002629A1 WO1988002629A1 PCT/US1987/002530 US8702530W WO8802629A1 WO 1988002629 A1 WO1988002629 A1 WO 1988002629A1 US 8702530 W US8702530 W US 8702530W WO 8802629 A1 WO8802629 A1 WO 8802629A1
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- Prior art keywords
- didesoxyadenosine
- pharmaceutical composition
- component
- dosage
- subunits
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
Definitions
- This invention relates to pharmaceutical composition useful in the oral treatment of Acquired Immune Deficienc Syndrome.
- Methylmethacrylates are known as coatings fo pharmaceuticals, including Eudragit polymers of Roh Pharma. Hydroxypropylmethylcellulose is known as sustained release matrix, as disclosed first by Christenso et al., U.S. Patent 3,065,143 and again by Schor et al. U.S. Patent 4,389,393.
- a pharmaceutical compositio for the treatment of acquired immune deficiency syndrom which comprises a plurality of dosage subunits each havin at least two components including a component of 2 • ,3 ' didesoxyadenosine and an outer pharmaceutically iner component stable in acidic pH which dissolves in a basi pH, whereby upon oral administration of said pharmaceutica composition the 2' ,3 '-didesoxyadenosine is not exposed t gastrointestinal fluids until the small intestine.
- the 2' ,3 '-didesoxyadenosine is permitted to remain free of degradation that apparently takes place in the stomach fluids by blocking contact of the 2',3'- didesoxyadenosine with the stomach fluids through said outer pharmaceutically inert component stable in acidic pH.
- a plurality of dosage subunits each having at least three components including a component of 2' ,3 '-didesoxyadenosine sandwiched between pharmaceutically inert layers, at least the outer one of which is stable in acidic pH and which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2',3*-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine.
- a nonpareil seed As an inner layer remote from the gastrointestinal fluids may be mentioned a nonpareil seed.
- a capsule containing said plurality of dosage subunits.
- a compressed tablet containing said plurality of dosage subunits, the matrix of said tablet disintegrating in the gastrointestinal tract to yield said plurality of dosage subunits.
- a pharmaceutical composition for the oral treatment of acquired immune deficiency syndrome which comprises a component of 2 ',3'- didesoxyadenosine and a barrier component to shield the 2* ,3 *-didesoxyadenosine from the gastrointestinal fluids until said pharmaceutical composition passes into the small intestine, said barrier component being substantially impervious to degradation in a fluid other than a basic medium, whereby upon introduction into the gastrointestinal tract beyond the stomach said 2' ,3'-didesoxyadenosine is released.
- a sustained release composition for the introduction of 2 ', 3 ' -didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3'- didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3'-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, said dosage subunits releasing said 2 ' ,3 '-didesoxyadenosine only over a prolonged period of time.
- a sustained release composition for the introduction of 2' ,3'-didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3'- didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which only erodes in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, at least some of said dosage subunits including an outer core of a slowly erodible polymeric material, whereby a sustained release of 2',3'-didesoxyadenosine is achieved.
- a sustained release composition for the introduction of 2',3'- didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3 '-didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, said dosage subunits being contained in a matrix of a polymer which only gradually exposes said dosage subunits to the environment of the gastrointestinal tract.
- the polymer is a hydroxypropylmethylcellulose, with a tablet made up of from about 60 to 95 percent, and preferably 80 to 92 percent by weight of said dosage subunits and from about 5 to about 40 percent, and preferably from about 8 to about 20 percent of the hydroxypropylmethyl-cellulose.
- a hydroxypropylmethylcellulose suitable for the present invention may be mentioned Methocel K15M (Dow Chemical Co., Midland, Michigan) and Methocel K4M (Dow Chemical Co., Midland, Michigan) .
- a total adult daily dosage which is spread out over three to five administrations per day, or twice daily in the sustained release aspect of the present invention comprises from about 2 to about 1O00 mg per day, preferably about 25 to about 750 mg per day, and still more preferably about 10 to 250 mg per administration.
- Nonpareil seeds (20 to 30 mesh) are wetted with polyvinylpyrrolidone solution using Kollidon 30 (BASF, mw 30,000) which has been first dissolved in isopropanol in a coating pan with repeated dustings of 2' ,3'- didesoxyadenosine (about ten to twenty times) to build up a 2 ' ,3'-didesoxyadenosine-coated nonpareil seed.
- Kollidon 30 BASF, mw 30,000
- Alcohol dissolved Kollidone 90 (BASF, mw 90,000) is used as a wetting agent for nonpareil seeds (20 to 30 mesh) in a coating pan with repeated dustings of 2 ' ,3'- didesoxyadenosine (about ten to twenty times) to build up a
- EXAMPLE III The 2' ,3 '-didesoxyadenosine-coated nonpareil seeds of Example I are introduced into a Wurster column (Glatt) and coated with a methylmethacrylate in a solvent, using 50 gm Eudrigit L (Rohm Phar a) in a solvent mixture of 250 cc acetone and 250 cc isopropanol. After coating in the Wurster column, the total weight of 2' ,3'-didesoxyadenosine as a percentage of 2',3 '-didesoxyadenosine plus coating is 45%. The dosage subunits dissolve readily in the small intestine.
- EXAMPLE IV 2',3 '-Didesoxyadenosine-coated nonpareil seeds of Example I are introduced into a Wurster column (Glatt) and coated with a methylmethacrylate in a solvent, using 25 gm Eudrigit L (Rohm Pharma) , 25 gm Eudragit RS (Rohm Pharma) in a solvent mixture of 250 cc acetone and 250 cc isopropanol. After coating in the Wurster column, the total weight of 2 ',3 '-didesoxyadenosine as a percentage of 2 ',3'-didesoxyadenosine plus coating is 45%. The inclusion of the Eudrigit RS retards dissolution of the dosage subunits to permit a sustained delivery of the 2 ',3'- didesoxyadenosine into the bloodstream of the patient.
- EXAMPLE V 2',3'-Didesoxyadenosine-coated nonpare
- Capsules are made of a plurality of dosage subunits of Example III to make up 250 mg 2 ' ,3 '-didesoxyadenosine per capsule.
- the capsules dissolve in the gastrointestinal tract upon oral administration, and each of the dosage subunits releases 2 ',3 '-didesoxyadenosine in the small intestine, to provide 2',3'-didesoxyadenosine to the bloodstream.
- Sustained release capsules are made of a plurality of dosage subunits of Example IV to make up 250 mg 2 ',3'- didesoxyadenosine per capsule.
- the capsules dissolve in the gastrointestinal tract upon oral administration, and each of the dosage subunits releases 2',3'- didesoxyadenosine in the small intestine, to provide 2 ',3'- didesoxyadenosine to the bloodstream of the subject.
- Tablets of a total weight of 330 mg are produced by mixing and then compressing together in a ratio of 10:1 of the dosage subunits of Example II and hydroxypropylmethylcellulose (Methocel K15M, Dow Chemical
- the sustained release tablet of this example provides an advantage over the other dosage forms in that the dosage subunits are only gradually exposed to the environment of the gastrointestinal fluids, whereby 2' ,3'- didesoxyadenosine is introduced into the bloodstream over a prolonged period of time.
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
A pharmaceutical composition for the oral treatment of acquired immune deficiency syndrome which comprises a plurality of dosage subunits each having at least two components including a component of 2',3'-didesosxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2',3'-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine.
Description
2* 3'-DIDESOXYADENOSINE COMPOSITION
BACKGROUND OF THE INVENTION This invention relates to pharmaceutical composition useful in the oral treatment of Acquired Immune Deficienc Syndrome.
2 ' , 3 ' -didesoxyadenosine is a known compound Methylmethacrylates are known as coatings fo pharmaceuticals, including Eudragit polymers of Roh Pharma. Hydroxypropylmethylcellulose is known as sustained release matrix, as disclosed first by Christenso et al., U.S. Patent 3,065,143 and again by Schor et al. U.S. Patent 4,389,393.
DESCRIPTION OF THE INVENTION In accordance with a first aspect of the presen invention there is provided a pharmaceutical compositio for the treatment of acquired immune deficiency syndrom which comprises a plurality of dosage subunits each havin at least two components including a component of 2 • ,3 ' didesoxyadenosine and an outer pharmaceutically iner component stable in acidic pH which dissolves in a basi pH, whereby upon oral administration of said pharmaceutica composition the 2' ,3 '-didesoxyadenosine is not exposed t gastrointestinal fluids until the small intestine. Acquired immune deficiency syndrome was found by a prio researcher to be treated in vitro, but not in vivo, wit 2 ', 3 '-didesoxyadenosine. According to the presen invention, the 2' ,3 '-didesoxyadenosine is permitted to remain free of degradation that apparently takes place in the stomach fluids by blocking contact of the 2',3'- didesoxyadenosine with the stomach fluids through said outer pharmaceutically inert component stable in acidic pH.
In a preferred aspect, there is provided a plurality of dosage subunits each having at least three components
including a component of 2' ,3 '-didesoxyadenosine sandwiched between pharmaceutically inert layers, at least the outer one of which is stable in acidic pH and which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2',3*-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine. As an inner layer remote from the gastrointestinal fluids may be mentioned a nonpareil seed. In a still further embodiment of this aspect of the invention there is provided a capsule containing said plurality of dosage subunits. As an alternative embodiment, there is provided a compressed tablet containing said plurality of dosage subunits, the matrix of said tablet disintegrating in the gastrointestinal tract to yield said plurality of dosage subunits.
In accordance with a second aspect of the present invention there is provided a pharmaceutical composition for the oral treatment of acquired immune deficiency syndrome which comprises a component of 2 ',3'- didesoxyadenosine and a barrier component to shield the 2* ,3 *-didesoxyadenosine from the gastrointestinal fluids until said pharmaceutical composition passes into the small intestine, said barrier component being substantially impervious to degradation in a fluid other than a basic medium, whereby upon introduction into the gastrointestinal tract beyond the stomach said 2' ,3'-didesoxyadenosine is released.
In a third aspect of the present invention there is provided a sustained release composition for the introduction of 2 ', 3 ' -didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3'-
didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3'-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, said dosage subunits releasing said 2 ' ,3 '-didesoxyadenosine only over a prolonged period of time.
In accordance with this third aspect of the present invention there is provided a sustained release composition for the introduction of 2' ,3'-didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3'- didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which only erodes in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, at least some of said dosage subunits including an outer core of a slowly erodible polymeric material, whereby a sustained release of 2',3'-didesoxyadenosine is achieved.
In an alternate embodiment, there is provided a sustained release composition for the introduction of 2',3'- didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3 '-didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, said dosage subunits
being contained in a matrix of a polymer which only gradually exposes said dosage subunits to the environment of the gastrointestinal tract. In one embodiment, the polymer is a hydroxypropylmethylcellulose, with a tablet made up of from about 60 to 95 percent, and preferably 80 to 92 percent by weight of said dosage subunits and from about 5 to about 40 percent, and preferably from about 8 to about 20 percent of the hydroxypropylmethyl-cellulose. As a hydroxypropylmethylcellulose suitable for the present invention may be mentioned Methocel K15M (Dow Chemical Co., Midland, Michigan) and Methocel K4M (Dow Chemical Co., Midland, Michigan) .
A total adult daily dosage which is spread out over three to five administrations per day, or twice daily in the sustained release aspect of the present invention, comprises from about 2 to about 1O00 mg per day, preferably about 25 to about 750 mg per day, and still more preferably about 10 to 250 mg per administration.
EXAMPLE I Nonpareil seeds (20 to 30 mesh) are wetted with polyvinylpyrrolidone solution using Kollidon 30 (BASF, mw 30,000) which has been first dissolved in isopropanol in a coating pan with repeated dustings of 2' ,3'- didesoxyadenosine (about ten to twenty times) to build up a 2 ' ,3'-didesoxyadenosine-coated nonpareil seed.
EXAMPLE II
Alcohol dissolved Kollidone 90 (BASF, mw 90,000) is used as a wetting agent for nonpareil seeds (20 to 30 mesh) in a coating pan with repeated dustings of 2 ' ,3'- didesoxyadenosine (about ten to twenty times) to build up a
2' ,3 '-didesoxyadenosine-coated nonpareil seed.
EXAMPLE III The 2' ,3 '-didesoxyadenosine-coated nonpareil seeds of Example I are introduced into a Wurster column (Glatt) and
coated with a methylmethacrylate in a solvent, using 50 gm Eudrigit L (Rohm Phar a) in a solvent mixture of 250 cc acetone and 250 cc isopropanol. After coating in the Wurster column, the total weight of 2' ,3'-didesoxyadenosine as a percentage of 2',3 '-didesoxyadenosine plus coating is 45%. The dosage subunits dissolve readily in the small intestine.
EXAMPLE IV 2',3 '-Didesoxyadenosine-coated nonpareil seeds of Example I are introduced into a Wurster column (Glatt) and coated with a methylmethacrylate in a solvent, using 25 gm Eudrigit L (Rohm Pharma) , 25 gm Eudragit RS (Rohm Pharma) in a solvent mixture of 250 cc acetone and 250 cc isopropanol. After coating in the Wurster column, the total weight of 2 ',3 '-didesoxyadenosine as a percentage of 2 ',3'-didesoxyadenosine plus coating is 45%. The inclusion of the Eudrigit RS retards dissolution of the dosage subunits to permit a sustained delivery of the 2 ',3'- didesoxyadenosine into the bloodstream of the patient. EXAMPLE V
Capsules are made of a plurality of dosage subunits of Example III to make up 250 mg 2 ' ,3 '-didesoxyadenosine per capsule. The capsules dissolve in the gastrointestinal tract upon oral administration, and each of the dosage subunits releases 2 ',3 '-didesoxyadenosine in the small intestine, to provide 2',3'-didesoxyadenosine to the bloodstream.
EXAMPLE VI Sustained release capsules are made of a plurality of dosage subunits of Example IV to make up 250 mg 2 ',3'- didesoxyadenosine per capsule. The capsules dissolve in the gastrointestinal tract upon oral administration, and each of the dosage subunits releases 2',3'- didesoxyadenosine in the small intestine, to provide 2 ',3'-
didesoxyadenosine to the bloodstream of the subject.
EXAMPLE VII
Tablets of a total weight of 330 mg are produced by mixing and then compressing together in a ratio of 10:1 of the dosage subunits of Example II and hydroxypropylmethylcellulose (Methocel K15M, Dow Chemical
Co. , Midland Michigan) .
The sustained release tablet of this example provides an advantage over the other dosage forms in that the dosage subunits are only gradually exposed to the environment of the gastrointestinal fluids, whereby 2' ,3'- didesoxyadenosine is introduced into the bloodstream over a prolonged period of time.
Claims
1. A pharmaceutical composition for the oral treatment of acquired immune deficiency syndrome which comprises a plurality of dosage subunits each having at least two components including a component of 2 ',3'-didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine.
2. A pharmaceutical composition of claim 1 for the oral treatment of acquired immune deficiency syndrome which comprises a plurality of dosage subunits each having at least three components including a component of 2' ,3 '- didesoxyadenosine sandwiched between pharmaceutically inert layers, at least the outer one of which is stable in acidic pH and which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2',3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine.
3. A 2* ,3'-didesoxyadenosine pharmaceutical composition of claim 1 for the oral treatment of acquired immune deficiency syndrome which is a capsule containing said plurality of dosage subunits.
4. A pharmaceutical composition of claim l which is a compressed tablet containing said plurality of dosage subunits, the matrix of said tablet disintegrating in the gastrointestinal tract to yield said plurality of dosage subunits.
5. A pharmaceutical composition for the oral treatment of acquired immune deficiency syndrome which comprises a component of 2 ', 3 '-didesoxyadenosine and a barrier component to shield the 2' ,3'-didesoxyadenosine from the gastrointestinal fluids until said pharmaceutical composition passes into the small intestine, said barrier component being substantially impervious to degradation in a fluid other than a basic medium, whereby upon introduction into the gastrointestinal tract beyond the stomach said 2' ,3'-didesoxyadenosine is released.
6. A sustained release composition for the introduction of 2r,3 •-didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3 '-didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3*-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, said dosage subunits releasing said 2 ',3 '-didesoxyadenosine only over a prolonged period of time.
7. A sustained release composition for the introduction of 2',3 '-didesoxyadenosine into the bloodstream of a patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3 '-didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which only erodes in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2' ,3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, at least some of said dosage subunits including an outer core of a slowly erodible polymeric material, whereby a sustained release of 2* ,3 '-didesoxyadenosine is achieved.
8. A sustained release composition for the introduction of 2',3 '-didesoxyadenosine into the bloodstream of a ' patient suffering from acquired immune deficiency syndrome over a period of at least eight hours which comprises a plurality of dosage subunits each having at least two components including a component of 2' ,3 '-didesoxyadenosine and an outer pharmaceutically inert component stable in acidic pH which dissolves in a basic pH, whereby upon oral administration of said pharmaceutical composition the 2',3 '-didesoxyadenosine is not exposed to gastrointestinal fluids until the small intestine, said dosage subunits being contained in a matrix of a polymer which only gradually exposes said dosage subunits to the environment of the gastrointestinal tract.
9. A sustained release composition of claim 8 wherein said polymer is a hydroxypropylmethylcellulose.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US919,358 | 1978-06-26 | ||
| US91935886A | 1986-10-16 | 1986-10-16 | |
| US2511887A | 1987-03-12 | 1987-03-12 | |
| US025,118 | 1987-03-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1988002629A1 true WO1988002629A1 (en) | 1988-04-21 |
Family
ID=26699316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1987/002530 Ceased WO1988002629A1 (en) | 1986-10-16 | 1987-10-02 | 2',3'-didesoxyadenosine composition |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1988002629A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0495270A1 (en) * | 1987-09-23 | 1992-07-22 | William Dr. Drell | Azaribine composition |
| EP0524579A1 (en) * | 1991-07-22 | 1993-01-27 | Bristol-Myers Squibb Company | Improved oral dosing formulations of dideoxy purine nucleosides |
| EP1079809A4 (en) * | 1998-05-22 | 2001-11-07 | Bristol Myers Squibb Co | Enteric coated pharmaceutical composition and method of manufacturing |
| US6607747B2 (en) | 1998-05-22 | 2003-08-19 | Bristol-Myers Squibb Company | High drug load acid labile pharmaceutical composition |
| US8337892B1 (en) * | 1999-07-26 | 2012-12-25 | Ethypharm | Low-dose tablets and preparation method |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0032562A1 (en) * | 1980-01-12 | 1981-07-29 | Dr. Karl Thomae GmbH | Dipyridamol retard-forms and process for their preparation |
| WO1984002843A1 (en) * | 1983-01-26 | 1984-08-02 | Egyt Gyogyszervegyeszeti Gyar | Process for the preparation of sustained release pharmaceutical compositions having a high active ingredient content |
| EP0136464A2 (en) * | 1983-08-24 | 1985-04-10 | BIORESEARCH S.p.A. | Therapeutic compositions for oral use containing stable S-Adenosy1-L-Methionine salts |
| EP0206497A2 (en) * | 1985-05-15 | 1986-12-30 | The Wellcome Foundation Limited | Therapeutic nucleosides and their preparation |
-
1987
- 1987-10-02 WO PCT/US1987/002530 patent/WO1988002629A1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0032562A1 (en) * | 1980-01-12 | 1981-07-29 | Dr. Karl Thomae GmbH | Dipyridamol retard-forms and process for their preparation |
| WO1984002843A1 (en) * | 1983-01-26 | 1984-08-02 | Egyt Gyogyszervegyeszeti Gyar | Process for the preparation of sustained release pharmaceutical compositions having a high active ingredient content |
| EP0136464A2 (en) * | 1983-08-24 | 1985-04-10 | BIORESEARCH S.p.A. | Therapeutic compositions for oral use containing stable S-Adenosy1-L-Methionine salts |
| EP0206497A2 (en) * | 1985-05-15 | 1986-12-30 | The Wellcome Foundation Limited | Therapeutic nucleosides and their preparation |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0495270A1 (en) * | 1987-09-23 | 1992-07-22 | William Dr. Drell | Azaribine composition |
| EP0524579A1 (en) * | 1991-07-22 | 1993-01-27 | Bristol-Myers Squibb Company | Improved oral dosing formulations of dideoxy purine nucleosides |
| US5880106A (en) * | 1991-07-22 | 1999-03-09 | Bristol-Myers Squibb Company | Oral dosing formulations of dideoxy purine nucleosides |
| EP1079809A4 (en) * | 1998-05-22 | 2001-11-07 | Bristol Myers Squibb Co | Enteric coated pharmaceutical composition and method of manufacturing |
| US6607747B2 (en) | 1998-05-22 | 2003-08-19 | Bristol-Myers Squibb Company | High drug load acid labile pharmaceutical composition |
| JP2006022115A (en) * | 1998-05-22 | 2006-01-26 | Bristol Myers Squibb Co | Method for producing enteric-coated pharmaceutical composition |
| US7122207B2 (en) | 1998-05-22 | 2006-10-17 | Bristol-Myers Squibb Company | High drug load acid labile pharmaceutical composition |
| CZ300497B6 (en) * | 1998-05-22 | 2009-06-03 | Bristol-Myers Squibb Company | Pharmaceutical composition, its spheronized core and the method of preparation of nuclei and pharmaceutical composition |
| US8337892B1 (en) * | 1999-07-26 | 2012-12-25 | Ethypharm | Low-dose tablets and preparation method |
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