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US4666641A Expired / Lapsed US ⏱️ 0.0 years remaining

Preparation of biodegradable microcapsules based on serum albumin

Assignee: Université Paris-Sud
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Filing: 1985-06-04
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Granted: 1987-05-19
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Expires: 2005-06-04
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Abstract

Abstract The present invention relates to biodegradable microcapsules based on serum albumin, the preparation thereof and the application thereof to the release of drugs in situ. A feature of the microcapsules according to the present invention is that their wall consists of serum albumin, a portion of which is crosslinked by interfacial polymerization with the aid of an acylating bifunctional reagent, and the other, non-crosslinked portion of which is denatured by means of an alcohol.

Inventors

  • 👤 Rene Fickat
  • 👤 Simon Benita
  • 👤 Francis Puisieux

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-03 04:12
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5052; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1658; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984

Claims Analysis

Total Claims: 17
Claim 1
Independent Claim 163 words
Process for preparing microcapsules containing a pharmaceutically active substance, wherein the mcrocapsules are prepared from serum albumin by carrying out the following successive operations: (a) the serum albumin is emulsified by dispersion in an organic solvent system, by adding a pharmaceutically acceptable emulsifying agent, and stirring; (b) to the emulsion thereby obtained, maintained stirred, a crosslinking agent dissolved in the said organic solvent system is added, and stirring is maintained until the desired degree of interfacial crosslinking is obtained; (c) the microcapsules are isolated after dilution of the reaction mixture followed by a succession of stages of washing with suitable solvents and decantation stages, and the microcapsules are then subjected to several washes with alcohol and to immersion in alcohol, preferably absolute, for at least 12 hours in order to denature the non-crosslinked serum albumin, and (d) after the microcapsules are dried, the pharmaceutically active substance is incorporated therein by controlled immersion of the microcapsules in a titrated solution of the said substrate.
Claim 2
Dependent Claim 163 words
Process for preparing microcapsules containing a pharmaceutically active substance, wherein the mcrocapsules are prepared from serum albumin by carrying out the following successive operations: (a) the serum albumin is emulsified by dispersion in an organic solvent system, by adding a pharmaceutically acceptable emulsifying agent, and stirring; (b) to the emulsion thereby obtained, maintained stirred, a crosslinking agent dissolved in the said organic solvent system is added, and stirring is maintained until the desired degree of interfacial crosslinking is obtained; (c) the microcapsules are isolated after dilution of the reaction mixture followed by a succession of stages of washing with suitable solvents and decantation stages, and the microcapsules are then subjected to several washes with alcohol and to immersion in alcohol, preferably absolute, for at least 12 hours in order to denature the non-crosslinked serum albumin, and (d) after the microcapsules are dried, the pharmaceutically active substance is incorporated therein by controlled immersion of the microcapsules in a titrated solution of the said substrate.
Claim 3
Dependent Claim 74 words
Process as claimed in claim 1, wherein the microcapsules are isolated by carrying out the following successive operations: the supernatant is separated; at least one washing of the microcapsules is carried out using the said organic solvent system; 1/3 of glycerine containing approximately 25% of polysorbate and then 2/3 of water are added to the microcapsules in that order; the microcapsules are separated by sedimentation, before being washed with alcohol and immersed in alcohol.
Claim 4
Dependent Claim 12 words
Process as claimed in claim 1 wherein the emulsifying agent is phosphatidylcholine.
Claim 5
Dependent Claim 34 words
Process as claimed in claim 1 wherein the organic solvent system consists of a binary mixture of a chlorinated C 1 or C 2 hydrocarbon and a non-chlorinated C 5 to C 7 hydrocarbon.
Claim 6
Dependent Claim 19 words
Process as claimed in claim 4, wherein the organic solvent system consists of a mixture of chloroform and cyclohexane.
Claim 7
Dependent Claim 72 words
Process as claimed in claim 1 wherein the crosslinking agent is an acylating bifunctional reagent, such as a dicarboxylic acid halide or a diisocyanate, in which the two functional groups are both carried on an aromatic ring, or alternatively are separated by an aliphatic chain of 2 to 10 carbon atoms, or one of which is carried on an aromatic ring and the other on an aliphatic chain attached to the ring.
Claim 8
Dependent Claim 28 words
Process as claimed in claim 6, wherein the cross-linking agent is selected from the group consisting of succinyl dichloride, sebocoyl dichloride, terephthaloyl dichloride, toluene diisocyanate and hexamethylene diisocyanate.
Claim 9
Dependent Claim 20 words
Process as claimed in claim 1 wherein the interfacial crosslinking time is between about 30 minutes and about 90 minutes.
Claim 10
Dependent Claim 15 words
Process as claimed in claim 8, wherein the interfacial crosslinking time is about 60 minutes.
Claim 11
Dependent Claim 24 words
Process as claimed in claim 1 wherein the ratio by weight of the serum albumin to the crosslinking agent is chosen such that: ##EQU3##
Claim 12
Dependent Claim 24 words
Process as claimed in claim 10, wherein the ratio by weight of the serum albumin to the crosslinking agent is chosen such that: ##EQU4##
Claim 13
Dependent Claim 24 words
Process as claimed in claim 1 wherein the alcohol used for the operations of washing and immersion of the microcapsules consists of ethyl alcohol.
Claim 14
Dependent Claim 23 words
Process as claimed in claim 1 wherein the microcapsules are recovered in the dry state by evaporation of the washing solvent or solvents.
Claim 15
Dependent Claim 29 words
Process as claimed in claim 1 wherein, after they are separated, the microcapsules are subjected to a sterilization operation, preferably radiosterilization by application of radiation of approximately 2.5 Mrad.
Claim 16
Dependent Claim 38 words
Process as claimed in claim 1 wherein the pharmaceutically active substance adsorbed by the wall of the microcapsules consists of a watersoluble compound having a molecular weight of substantially between 300 and 600 and bearing an electrical charge.
Claim 17
Dependent Claim 20 words
Process as claimed in claim 15, wherein the pharmaceutically active substance is doxorubicin, preferably in the form of its hydrochloride.

References Cited (Backward Citations)

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US4107288A Cited
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USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1990-05-18 1990-11-17 1991-05-19 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1994-05-18 1994-11-17 1995-05-19 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1998-05-18 1998-11-17 1999-05-19 $7700.00 Window Closed / Lapsed

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