US4780321A
Expired / Lapsed
US
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Microcapsules having mixed walls formed of reticulated polyholosides and proteins and process for preparation thereof
Assignee: Centre National de la Recherche Scientifique
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Filing: 1986-08-07
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Granted: 1988-10-25
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Expires: 2006-08-07
Abstract
Abstract A process for preparing microcapsules containing a pharmaceutically active substance of a water soluble nature is provided, which involves dissolving a mixture containing at least one water soluble polyholoside or water soluble derivative of a polyholoside, at least one protein, and the pharmaceutically active substance in an alkaline aqueous solution having a pH preferably above 10, the solution being emulsified by dispersion within an immiscible organic solvent, by addition of an emulsifier of the water in oil type and by stirring. Thereafter, a reticulation agent dissolved in the same immiscible organic solvent is added to the previously obtained emulsion being stirred, and the stirring is continued until interfacial reticulation is achieved. The microcapsules are then isolated by diluting the reaction mixture with solvent, or a mixture of solvents and then centrifugation or decantation.
Inventors
- 👤 Marie Christine Levy
- 👤 Bertrand Gourdier
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 07:29
CPC Classifications
B; B01; B01J; B01J13/00; B01J13/02; B01J13/06; B01J13/14; B01J13/16; A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5036; A61K9/5042; A61K9/5047; A61K9/5052; A61K9/5089; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
164 words
A process for preparation of microcapsules having mixed walls containing pharmaceutically active substance, of a water soluble nature comprising: (i) dissolving a mixture containing at least one water soluble polyhoside or water-soluble derivative of a polyhoside, at least one protein, and the pharmaceutically active substance in an alkaline aqueous solution having a pH preferably above 10, said solution being emulsified by dispersion within an immiscible organic solvent, by addition of an emulsifier of the water in oil type and by stirring; (ii) adding a reticulation agent dissolved in said immiscible organic solvent to the emulsion thus obtained, which is being stirred, continuing said stirring until interfacial reticulation achieved, and (iii) isolating the microcapsules by diluting the reaction mixture by means of a solvent or an adequate mixture of solvents followed by decantation, centrifugation, or a combination thereof, wherein the properties of lysis and gastric resistance are improved relative to microcapsules which are made by the same method and contain only protein or only carbohydrate.
Claim 2
Dependent Claim
164 words
A process for preparation of microcapsules having mixed walls containing pharmaceutically active substance, of a water soluble nature comprising: (i) dissolving a mixture containing at least one water soluble polyhoside or water-soluble derivative of a polyhoside, at least one protein, and the pharmaceutically active substance in an alkaline aqueous solution having a pH preferably above 10, said solution being emulsified by dispersion within an immiscible organic solvent, by addition of an emulsifier of the water in oil type and by stirring; (ii) adding a reticulation agent dissolved in said immiscible organic solvent to the emulsion thus obtained, which is being stirred, continuing said stirring until interfacial reticulation achieved, and (iii) isolating the microcapsules by diluting the reaction mixture by means of a solvent or an adequate mixture of solvents followed by decantation, centrifugation, or a combination thereof, wherein the properties of lysis and gastric resistance are improved relative to microcapsules which are made by the same method and contain only protein or only carbohydrate.
Claim 3
Dependent Claim
46 words
A process according to claim 1, wherein the water-soluble polyholoside or water-soluble derivative of polyholoside is selected from the group consisting of water-soluble natural polyholosides, polyholosides made water-soluble by treatment with acid or alkaline solution or by chemical grafting of hydrophilic lateral chains, and mixtures thereof.
Claim 4
Dependent Claim
39 words
A process according to claim 2, wherein said water-soluble polyholoside or water-soluble derivative of polyholoside is selected from the group consisting of alkali-cellulose, soluble starch, dextrans of low molecular weight, hydroxypropyl cellulose, gum arabic, gum guar and mixtures thereof.
Claim 5
Dependent Claim
11 words
A process according to claim 1, wherein said protein is casein.
Claim 6
Dependent Claim
11 words
A process according to claim 1, wherein said protein is gelatin.
Claim 7
Dependent Claim
41 words
A process according to claim 1, wherein the organic solvent used during the emulsification stage is a water-immiscible solvent of a density substantially between 0.7 and 1.1, which solvent permits the dissolution of the reticulation agent used during said step (ii).
Claim 8
Dependent Claim
34 words
A process according to claim 1, wherein the emulsifier used during the emulsification stages is a surfactant agent, preferably of a non-ionic type, that permits the preparation of an emulsion of a water-in-oil type.
Claim 9
Dependent Claim
32 words
A process according to claim 1, wherein said immiscible organic solvent is a binary mixture of a C 1 -C 2 chlorinated hydrocarbon and of a non-chlorinated C 5 -C 7 hydrocarbon.
Claim 10
Dependent Claim
67 words
A process according to claim 1, wherein the reticulation agent is an acylating bifunctional reagent selected from the group consisting of carboxylic diacid halides and diisocyanates where the two functional groups are both carried by an aromatic cycle or separated by an aliphatic chain containing from 2 to 10 carbon atoms, or one is carried by an aromatic cycle and the other by a juxtanuclear aliphatic chain.
Claim 11
Dependent Claim
28 words
A process according to claim 9, wherein the reticulation agent is selected from the group consisting of succinyl dichloride, sebacoyl dichloride, terephthaloyl dichloride, toluene diisocyanate and hexamethylene diisocyanate.
Claim 12
Dependent Claim
28 words
A process according to claim 9, wherein the reticulation agent is added to the reaction mixture dissolved in the same organic solvent used during the first emulsification stage.
Claim 13
Dependent Claim
26 words
A process according to claim 1, wherein the concentration of the reticulation agent in said organic solvent changes from saturation to a concentration of about 0.1M.
Claim 14
Dependent Claim
37 words
A process according to claim 12, wherein the solution of reticulation agent is added to the emulsion at the rate of a volume substantially equal to the volume of solvent used for the preparation of said emulsion.
Claim 15
Dependent Claim
33 words
A process according to claim 1, wherein the microcapsules are recovered in dry state either by evaporation of the washing solvent or solvents or by lyophilization of the suspension of microcapsules in water.
Claim 16
Dependent Claim
10 words
A microcapsule prepared according to the process of claim 1.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-10-25 | 1992-04-25 | 1992-10-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-10-25 | 1996-04-25 | 1996-10-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-10-25 | 2000-04-25 | 2000-10-25 | $7700.00 | Window Closed / Lapsed |