US4871716A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Magnetically responsive, hydrophilic microspheres for incorporation of therapeutic substances and methods of preparation thereof
Assignee: University of Florida
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Filing: 1986-12-03
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Granted: 1989-10-03
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Expires: 2006-12-03
Abstract
Abstract Novel magnetically responsive hydrophilic protein or polypeptide microspheres prepared by dispersing an aqueous solution or dispersion of protein or polypeptide and particulate magnetically responsive material in an organic solvent solution of a high molecular weight polymer to form a stabilized dispersion of microspheres and cross-linking said microspheres with a polyfunctional cross-linking agent.
Inventors
- 👤 William E. Longo
- 👤 Richard A. McCluskey
- 👤 Eugene P. Goldberg
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 04:03
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/51; A61K9/5107; A61K9/5115; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/1658; A61K9/1682; A61K9/1694; A61K9/513; A61K9/5146; A61K9/5161; A61K9/5169; A61K9/5192; Y; Y10; Y10S; Y10S436/00; Y10S436/829; Y10S930/00; Y10S930/01; Y10S930/29; Y10S977/00; Y10S977/70; Y10S977/788; Y10S977/832; Y10S977/838; Y10T; Y10T436/00; Y10T436/24
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
132 words
A method of preparing novel hydrophilic, magnetically responsive microspheres consisting essentially of cross-linked protein or polypeptide particulate and a magnetically responsive material comprising (a) providing a dispersion of an aqueous solution or dispersion of polypeptide or protein microspheres and a particulate magnetically responsive material in an organic, substantially water immiscible solvent solution of a high molecular weight polymer, said organic solvent being substantially a non-solvent for said microspheres and said polymer solution stabilizing the dispersion of microspheres and magnetically responsive material, (b) incorporating a polyfunctional cross-linking agent for said protein or polypeptide in said dispersion, and (c) allowing said cross-linking agent to react with said protein or polypeptide microspheres for a time sufficient to cross-link at least a portion of the microspheres, thereby providing magnetically responsive microspheres containing free reactive functional groups.
Claim 2
Independent Claim
132 words
A method of preparing novel hydrophilic, magnetically responsive microspheres consisting essentially of cross-linked protein or polypeptide particulate and a magnetically responsive material comprising (a) providing a dispersion of an aqueous solution or dispersion of polypeptide or protein microspheres and a particulate magnetically responsive material in an organic, substantially water immiscible solvent solution of a high molecular weight polymer, said organic solvent being substantially a non-solvent for said microspheres and said polymer solution stabilizing the dispersion of microspheres and magnetically responsive material, (b) incorporating a polyfunctional cross-linking agent for said protein or polypeptide in said dispersion, and (c) allowing said cross-linking agent to react with said protein or polypeptide microspheres for a time sufficient to cross-link at least a portion of the microspheres, thereby providing magnetically responsive microspheres containing free reactive functional groups.
Claim 3
Dependent Claim
19 words
The method of claim 1 including the step of separating said cross-linked protein or polypeptide microspheres from said dispersion.
Claim 4
Dependent Claim
10 words
The method of claim 1 wherein said protein is albumin.
Claim 5
Dependent Claim
12 words
The method of claim 3 wherein said albumin is human serum albumin.
Claim 6
Dependent Claim
12 words
The method of claim 3 wherein said albumin is bovine serum albumin.
Claim 7
Dependent Claim
29 words
The method of claim 1 or 2 wherein said organic solvent solution of high molecular weight polymer is a solution of polymethylmethacrylate in a mixture of toluene and chloroform.
Claim 8
Dependent Claim
25 words
The method of claim 1 or 2 wherein said organic solvent solution of high molecular weight polymer is a solution of polyoxyethylene-polyoxypropylene copolymer in chloroform.
Claim 9
Dependent Claim
27 words
The method of claim 1 or 2 wherein said organic solvent solution of high molecular weight polymer is a solution of cellulose acetate butyrate in ethylene dichloride.
Claim 10
Dependent Claim
25 words
The method of claim 1 or 2 wherein said organic solvent solution of high molecular weight polymer is a solution of bisphenol polycarbonate in chloroform.
Claim 11
Dependent Claim
27 words
The method of claim 1 or 2 wherein the concentrations of high molecular weight polymer in organic solvent is from about 1% to about 40%, by weight.
Claim 12
Dependent Claim
38 words
The method of claim 1 or 2 wherein said stabilized dispersion of protein or polypeptide microspheres is formed by dispersing an aqueous solution of said protein or polypeptide in said organic solvent solution of high molecular weight polymer.
Claim 13
Dependent Claim
26 words
The method of claim 1 or 2 wherein said microspheres have an average size in the range of from about 0.05 microns to about 500 microns.
Claim 14
Dependent Claim
14 words
The method of claim 1 or 2 wherein said cross-linking agent is a dialdehyde.
Claim 15
Dependent Claim
11 words
The method of claim 13 wherein said cross-linking agent is glutaraldehyde.
Claim 16
Dependent Claim
14 words
The method of claim 1 or 2 wherein said cross-linking agent is a diisocyanate.
Claim 17
Dependent Claim
14 words
The method of claim 15 wherein said diisocyanate is 2,4-tolylene diisocyanate or 1,6-diisocyanate hexane.
Claim 18
Dependent Claim
12 words
The method of claim 1 wherein said magnetically responsive material is magnetite.
Claim 19
Dependent Claim
12 words
The product produced according to the method of claim 1 or 2.
Claim 20
Dependent Claim
10 words
The product produced according to the method of claim 3.
Claim 21
Dependent Claim
41 words
The method of claim 1 including the step of reacting reactive functional groups of said cross-linked microspheres with a first substance containing at least one functional group reactive therewith to form a covalent bond between said cross-linked microspheres and said substance.
Claim 22
Dependent Claim
21 words
The method of claim 20 wherein said first substance is a biologically active substance suitable for administration to a biological system.
Claim 23
Dependent Claim
27 words
The method of claim 20 wherein said substance contains at least one additional functional group which is non-reactive with the reactive functional groups of said cross-linked microspheres.
Claim 24
Dependent Claim
30 words
The method of claim 22 wherein said at least one additional functional group is reacted with a second substance containing a functional group reactive therewith to form a bond therebetween.
Claim 25
Dependent Claim
21 words
The method of claim 23 wherein said second substance is a biologically active substance suitable for administration to a biological system.
Claim 26
Dependent Claim
12 words
The method of claim 20 wherein said magnetically responsive material is magnetite.
Claim 27
Dependent Claim
10 words
The product produced according to the method of claim 20.
Claim 28
Dependent Claim
10 words
The product produced according to the method of claim 21.
Claim 29
Dependent Claim
10 words
The product produced according to the method of claim 22.
Claim 30
Dependent Claim
10 words
The product produced according to the method of claim 23.
Claim 31
Dependent Claim
10 words
The product produced according to the method of claim 24.
Claim 32
Dependent Claim
10 words
The product produced according to the method of claim 25.
Claim 33
Dependent Claim
34 words
A composition in unit dosage form adapted for administration to a biological system comprising a biologically effective amount of the product of any of claims 26 to 31 and a biologically acceptable carrier therefor.
Claim 34
Independent Claim
24 words
A method of administering a biologically active substance to a biological system comprising administering thereto the product of any of claims 26 to 31.
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) | 1992-10-02 | 1993-04-03 | 1993-10-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-10-02 | 1997-04-03 | 1997-10-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-10-02 | 2001-04-03 | 2001-10-03 | $7700.00 | Window Closed / Lapsed |