Activation of biocompatible polymers with biologicals whose binding complements are pathological effectors

• US 4,687,808 A
• Filed: 07/20/1983
• Issued: 08/18/1987
• Est. Priority Date: 08/12/1982
• Status: Expired due to Term

• Current Assignee: Kanegafuchi Chemical Industry Co. Ltd. (Kaneka Corporation)
• Original Assignee: BioSpecifics Technologies Corp. (Endo International PLC)
• Inventors: Jarrett, Robert D., McCain, G. Howard
• Primary Examiner(s): Poelak, Morton
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US06/515,949
• Time in Patent Office: 1,490 Days
• Field of Search: 604/4, 604/5, 604/6, 424/16, 424/32, 424/33, 424/35, 427/2, 525/54.1
• US Class Current: 525/54.1
• CPC Class Codes: A61K 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/6883 Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy
• CPC Class Codes: A61M 1/3687 Chemical treatment A61M1/3675 takes precedence
• CPC Class Codes: C08L 23/00 Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 39/06 Homopolymers or copolymers of N-vinyl-pyrrolidones

Abstract

Biocompatible polymers containing immobilized biologicals which retain a high specificity for binding pathological effectors or specific groups of pathological effectors are disclosed.

Claims

1. A biospecific polymer comprising:

(a) a biocompatible terpolymer support comprising glycidyl methacrylate, N-vinylpyrrolidone and hydroxyethyl methacrylate; and

(b) a biological or biologicals immobilized on said terpolymer support via chemical bonding and wherein said biological or biologicals retain their reactivity for adsorbing specific pathological effectors or specific groups of pathological effectors.

3. A biospecific polymer as claimed in claims 1 or 2 further characterized in that said terpolymer support is fixed to a mechanically stable support member.

4. A biospecific polymer as claimed in claim 3 wherein said mechanically stable support member is selected from the group consisting of polyester fiber, microporous polyolefins, cotton cloth, polystyrene, polycarbonate, polyphenylene oxide, reticulated polyurethanes and combinations thereof.

5. A biospecific polymer as claimed in claims 1 or 2 wherein said biologicals are selected from the group consisting of acetylcholine receptor proteins, histocompatibility antigens, ribonucleic acids, basement membrane proteins, immunoglobulin classes and subclasses, myeloma protein receptors, complement components, myelin proteins, hormones and their receptor components and, vitamins and their receptor components.

6. A biospecific polymer as claimed in claims 1 or 2 wherein said biological is insulin used to remove anti-insulin antibody which is associated with the autoimmune disease insulin resistance.

7. A biospecific polymer as claimed in claims 1 or 2 wherein said biological is purified gamma globulin used to remove immune components which are associated with connective tissue and proliferative diseases such as rheumatoid arthritis and carcinoma.

2. A biospecific polymer comprising:

(a) a biocompatible terpolymer support comprising glycidyl methacrylate, N-vinylpyrrolidone and hydroxyethyl methacrylate;

(b) a spacer bonded to said biocompatible terpolymer support; and

(c) a biological or biologicals immobilized on said spacer via chemical bonding and wherein said biological or biologicals retain their reactivity for adsorbing specific pathological effectors or specific groups of pathological effectors.

8. A biospecific polymer as claimed in claim 2 wherein said spacer is selected from the group consisting of 1,6-diaminohexane, glutaraldehyde, 1,4-cyclohexanedicarboxylic acid, ethylenediamine tetraacetic acid, triethylene glycol, 1,4-butanediol diglycidyl ether, methylene-p-phenyl diisocyanate, 6-aminocaproic acid, p-nitrobenzoyl chloride, 1,2-epoxy-3-(p-nitrophenoxy) propane, aminopropyltriethoxy-silane, succinic anhydride, homoapteine thiolactone and albumin.

9. A therapeutic treatment of diseases which comprises passing a diseased patient'"'"'s body fluid contact with a biospecific polymer comprising a biocompatible terpolymer support comprising glycidyl methacrylate, N-vinylpyrrolidone and hydroxyethyl methacrylate having immobilized reactive biologicals where said biologicals adsorb specific pathological effectors or groups of pathological effectors associated with said patient'"'"'s disease state and returning said body fluid to said patient.

10. A therapeutic treatment of diseases which comprises passing a diseased patient'"'"'s body fluid in contact with a biospecific polymer comprising a biocompatible terpolymer support comprising glycidyl methacrylate, N-vinylpyrrolidone and hydroxyethyl methacrylate, a spacer attached to said biocompatible terpolymer support and a biological immobilized on said spacer wherein said biologicals adsorb specific pathological effectors or specific groups of pathological effectors associated with said patient'"'"'s disease state and returning said body fluid to said patient.

13. A therapeutic treatment as claimed in claims 9, 10 or 11 wherein two or more biospecific polymers each having the same or different reactive biologicals or groups of biologicals immobilized thereon are utilized in series to remove said specific pathological effectors.

14. The therapeutic method as recited in claim 9, 10, 11 or 12 wherein the body fluid to be treated is selected from the group consisting of blood, whole blood, blood plasma, and cerebrospinal fluid.

11. A therapeutic treatment of diseases which comprises passing a body fluid which is to be administered to a patient, prior to said body fluid being administered to said patient, in contact with a biospecific polymer comprising a biocompatible terpolymer support comprising glycidyl methacrylate, N-vinylpyrrolidone and hydroxyethyl methacrylate having immobilized reactive biologicals, thereby adsorbing and removing specific pathological effectors from said body fluid, and then introducing said body fluid to said patient.

12. A therapeutic treatment of diseases which comprises passing a body fluid which is to be administered to a patient, prior to said body fluid being administered to said patient, in contact with a biospecific polymer comprising a biocompatible terpolymer support comprising glycidyl methacrylate, N-vinylpyrrolidone and hydroxyethyl methacrylate, a spacer attached to said biocompatible terpolymer support and a biological immobilized on said spacer, thereby removing specific pathological effectors from said body fluid, and then introducing said body fluid to said patient.