US4540602A
Expired / Lapsed
US
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Process for the preparation of activated pharmaceutical compositions
Assignee: Freund Corp
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Filing: 1982-09-20
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Granted: 1985-09-10
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Expires: 2002-09-20
Abstract
Abstract Disclosed is a process for the preparation of an activated pharmaceutical composition containing a solid drug that is scarcely soluble in water, the pharmaceutical composition being characterized in that, when it is administered orally, the drug is readily absorbed to attain its high blood concentration quickly. This process is carried out by providing a solid drug that is scarcely soluble in water, dispersing the drug in water in the presence of a water-soluble high-molecular substance to form a disperse system containing the drug in the form of finely divided particles substantially not greater than 10 mu in diameter, and then removing the water from the disperse system.
Inventors
- 👤 Shimesu Motoyama
- 👤 Satashi Sato
- 👤 Seiichi Umeda
- 👤 Hirotsune Yasumi
- 👤 Emiko Suto
- 👤 Yuko Takasaka
- 👤 Takuichi Tsujino
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:23
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5036; A61K9/5042; A61K9/5047; A61K9/14; A61K9/5031
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
131 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a low-boiling hydrophobic organic solvent; (2) dissolving the solid drug in said low-boiling hydrophobic organic solvent; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular weight substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 2
Dependent Claim
131 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a low-boiling hydrophobic organic solvent; (2) dissolving the solid drug in said low-boiling hydrophobic organic solvent; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular weight substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 3
Dependent Claim
160 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a low-boiling hydrophobic organic solvent selected from the group consisting of chloroform, methylene chloride, trichloroethylene, trichloroethane, carbon tetrachloride, benzine, n-hexane, benzene, toluene, ethyl ether, isopropyl ether, methyl ethyl ketone, ethyl acetate and mixtures thereof; (2) dissolving the solid drug in said low-boiling hydrophobic organic solvent; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular weight substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hyroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 4
Dependent Claim
160 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a low-boiling hydrophobic organic solvent selected from the group consisting of chloroform, methylene chloride, trichloroethylene, trichloroethane, carbon tetrachloride, benzine, n-hexane, benzene, toluene, ethyl ether, isopropyl ether, methyl ethyl ketone, ethyl acetate and mixtures thereof; (2) dissolving the solid drug in said low-boiling hydrophobic organic solvent; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular weight substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hyroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 5
Dependent Claim
147 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a hydrophobic organic solvent which is a mixture of a low-boiling hydrophobic organic solvent and a non-volatile hydrophobic organic solvent; (2) dissolving the solid drug in said mixture of hydrophobic organic solvents; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular weight substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 6
Dependent Claim
147 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a hydrophobic organic solvent which is a mixture of a low-boiling hydrophobic organic solvent and a non-volatile hydrophobic organic solvent; (2) dissolving the solid drug in said mixture of hydrophobic organic solvents; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular weight substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 7
Dependent Claim
197 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a hydrophobic organic solvent which is a mixture of a low-boiling hydrophobic organic solvent selected from the group consisting of chloroform, methylene chloride, trichloroethylene, trichloroethane, carbon tetrachloride, benzine, n-hexane, benzene, toluene, ethyl ether, isopropyl ether, methyl ethyl ketone and ethyl acetate and a non-volatile hydrophobic organic solvent selected from the group consisting of glycerides, liquid paraffin, squalane, squalene, lecithin, pristane, low-HLB sorbitan fatty acid esters and low-HLB sucrose fatty acid esters; (2) dissolving the solid drug in said mixture of hydrophobic organic solvents; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 8
Dependent Claim
197 words
A process for the preparation of an activated pharmaceutical composition containing a solid drug in the form of finely divided particles substantially not greater than 10 microns in diameter, which comprises the steps of: (1) providing a solid drug that is scarcely soluble in water and is soluble in a hydrophobic organic solvent which is a mixture of a low-boiling hydrophobic organic solvent selected from the group consisting of chloroform, methylene chloride, trichloroethylene, trichloroethane, carbon tetrachloride, benzine, n-hexane, benzene, toluene, ethyl ether, isopropyl ether, methyl ethyl ketone and ethyl acetate and a non-volatile hydrophobic organic solvent selected from the group consisting of glycerides, liquid paraffin, squalane, squalene, lecithin, pristane, low-HLB sorbitan fatty acid esters and low-HLB sucrose fatty acid esters; (2) dissolving the solid drug in said mixture of hydrophobic organic solvents; (3) emulsifying the resulting solution in water in the presence of a water-soluble, high-molecular substance selected from the group consisting of hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, carboxymethyl cellulose sodium salt, alpha-starch, hydroxypropyl starch, pullalan, gum arabic, tragacanth gum, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone and mixtures thereof; and (4) then removing the dispersion medium from the so-formed disperse system.
Claim 9
Dependent Claim
21 words
The process according to claim 1, 2, 3 or 4, wherein the water-soluble, high-molecular substance is dissolved in water before emulsification.
Claim 10
Dependent Claim
65 words
The process according to claim 1, 2, 3 or 4, wherein the solid drug that is scarcely soluble in water and is soluble in a hydrophobic organic solvent is selected from the group consiting of ajmaline, isopropyl antipyrine, quinine ethylsulphate, ethenzamide, erythromycin, erthyromycin fatty acid ester, kitasamycin, chlorpropamide, chlormezanone, cortisone acetate, diazepam, digitoxin, cyclophosphamide, spironolactone, nalidixic acid, amobarbital, indomethacin, jasamycin, nifedipine, ubidecarenone and chloramphenicol palmitate.
Claim 11
Dependent Claim
31 words
The process according to claim 1, 2, 3 or 4, wherein the step of removing the dispersion medium from the disperse system is carried out by evaporation as rapidly as possible.
Claim 12
Dependent Claim
30 words
The process according to claim 1, 2, 3 or 4, wherein the step of removing the dispersion medium from the disperse system is carried out by spray-drying the disperse system.
Claim 13
Dependent Claim
38 words
The process according to claim 1, 2, 3 or 4, wherein the step of removing the dispersion medium from the disperse system is carried out by spraying the disperse system onto an excipient in a fluid-bed spray granulator.
Claim 14
Dependent Claim
37 words
The process according to claim 1, 2, 3 or 4, wherein after removal of the dispersion medium, further comprises the step of forming the resulting activated pharmaceutical composition into subtle granules, granules, tablets, sugar-coated tablets or suppositories.
References Cited (Backward Citations)
US2650895A
Cited
US2805977A
Cited
US2875130A
Cited
US2897119A
Cited
US3056728A
Cited
US3493652A
Cited
US3594326A
Cited
US3445563A
Cited
US3565559A
Cited
US3577514A
Cited
US3691090A
Cited
US3960757A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-09-09 | 1989-03-11 | 1989-09-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-09-09 | 1993-03-11 | 1993-09-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-09-09 | 1997-03-11 | 1997-09-10 | $7700.00 | Window Closed / Lapsed |