Claims
- 1. Microparticles consisting essentially of (a) a biodegradable polymer having a molecular weight of 1-30 Kd, obtainable by polymerizing a polymerizable aldehyde, and (b) 0.01-2 wt % of a gas and/or liquid with a boiling point below 60.degree. C. relative to the amount of polymer, said microparticles having a diameter of 0.1 to 40 .mu.m and said aldehyde having been polymerized in the presence of said gas and/or liquid.
- 2. Microparticles according to claim 1, wherein the biodegradable polymer is a copolymer comprising a polymerizable aldehyde and a copolymerizable additive.
- 3. Microparticles according to claim 1 further containing 0-5 wt % of crosslinkers and, wherein the biodegradable polymer is crosslinked.
- 4. Microparticles according to claim 1, wherein a bio- or macromolecule is bound to said polymer.
- 5. Microparticles according to claim 4 further containing 1-95 wt % of a coupling agent based on the amount of polyaldehyde, and, wherein the bio- or macromolecule is bound to the polymer via said coupling agent.
- 6. Microparticles according to claim 1, wherein said biodegradable polymer contains 0.01-1 wt % relative to the weight of said polyaldehyde of a surfactant or a mixture of surfactants.
- 7. Microparticles according to claim 1, wherein the polymerizable aldehyde monomer is an alpha,beta-unsaturated aldehyde, an alpha-substituted acrolein derivative, and/or a dialdehyde.
- 8. Microparticles according to claim 7, wherein the .alpha.-substituted acrolein derivative is .alpha.-methylacrolein, .alpha.-chloroacrolein, .alpha.-phenylacrolein, .alpha.-ethylacrolein, .alpha.-isopropylacrolein, .alpha.-n-butylacrolein, or .alpha.-n-propylacrolein.
- 9. Microparticles according to claim 7, wherein the dialdehyde is glutaraldehyde, succinaldehyde, or a derivative thereof.
- 10. Microparticles according to claim 2, wherein the additive capable of copolymerization is .alpha.-substituted acrolein, .beta.-substituted acrolein, ethyl cyanoacrylate, methyl cyanoacrylate, butyl cyanoacrylate, hexyl cyanoacrylate, methyl methacrylate, a vinyl alcohol, an acrylic acid, a methacrylic acid, an acrylic acid chloride, a methacrylic acid chloride, acrylonitrile, methacrylonitrile, an acrylamide, a substituted acrylamide, an hydroxy methyl methacrylate, mesityl oxide, a dimethylaminoethylmethacrylate-2-vinylpyridine, and/or N-vinyl-2-pyrrolidinone.
- 11. A process for the production of microparticles according to claim 1, consisting essentially of:
- reacting, with mixing, the desired polymerizable aldehyde(s), with an aqueous solution saturated with the desired gas and/or containing the desired liquid with a boiling point below 60.degree. C., at a temperature of -5.degree. C. to +80.degree. C. and a pH of 7 to 14, within 1 minute to 24 hours, wherein the concentration of the aldehyde relative to the reaction mixture is 0.1 to 50 w/v;
- after the polymerization has finished, separating particles containing said gas or liquid below 60.degree. C. from particles not containing said gas or liquid; and
- optionally, purifying the particles containing said gas or liquid below 60.degree. C.
- 12. A process for the production of microparticles according to claim 11, further comprising:
- reacting the microparticles thus obtained with an aqueous solution which contains, relative to the mount of aldehyde, up to an equimolar amount of a coupling agent, with stirring, for up to 3 days, at temperatures of 0.degree. C. to 60.degree. C., and a pH of 3 to 9, and
- binding a bio- or macromolecule to the resultant microparticles.
- 13. A process for the production of microparticles according to claim 12, further comprising binding a bio- or macromolecule to the resultant microparticles.
- 14. A process for the production of microparticles according to claim 11, wherein the polymerizable aldehyde reactant contains a crosslinking agent in a concentration of up to 20% w/v.
- 15. A process for the production of microparticles according to claim 11, wherein the polymerizable aldehyde reactant contains a crosslinking agent in a concentration of up to 5 % w/v.
- 16. A process for the production of microparticles according to claim 11, wherein the reaction mixture contains a surfactant in a concentration of from 0.01 to 10% w/v.
- 17. A process for the production of microparticles according to claim 11, wherein the desired gas is passed through the reaction mixture.
- 18. Microparticles according to claim 7, wherein the .alpha.,.beta.-unsaturated aldehyde is acrolein, crotonaldehyde, or propynoicaldehyde.
- 19. A pharmaceutical composition comprising microparticles according to claim 1 and a pharmaceutically acceptable adjuvant.
- 20. A method of obtaining an ultrasonic image comprising administering to a patient microparticles of claim 1 and taking an ultrasonic image of the patient.
- 21. Microparticles of claim 2, wherein the surfactant is polyethylene oxide; a carboxylic acid salt; a polyoxyethylene fatty acid ester; sodium dioctyl sulfosuccinate; polyglutaraldehyde sodium hydrogen sulfite adduct; polyethylene glycol, a polyoxyethylene polyoxypropylene, sodium oleate, or polyoxyethylene stearate.
- 22. Microparticles of claim 1, wherein the gas or highly volatile liquid is ammonia, air, helium, neon, argon, xenon, krypton, a sulfur halide, sulfur hexalfluoride, nitrogen, carbon oxides, oxygen, hydrogen, methane, ethane, propane, butane, pentane, neopentane, isopentane, cyclopentane, ethylene, propylene, acetylene, 3,3-dimethyl-1-butyne, 2,3-pentadiene, 2-methyl-2-butene, 2-methyl-1,3-butadiene, 2-butyne, 2-methyl-1-butene, 3-methyl-1-butene, methylene chloride, 1,1-dichloroethylene, isopropyl chloride, dibromodifluoromethane, bromomethane, dimethyl ether, diethyl ether, a fluorinated ether, dimethylaminoacetone, propylene oxide, N-ethylmethylamine, N-ethyldimethylamine, and/or furan.
- 23. Microparticles of claim 5, wherein said coupling agent is hydroxylamine, butylamine, allylamine, ethanolamine, trishydroxymethylaminomethane, 3-amino-1-propanesulfonic acid, 5-aminovaleric acid, 8-aminooctanoic acid, D-glucosamine hydrochloride, aminogalactose, aminosorbitol, aminomannitol, diethylaminoethylamine, an aniline, sulfonyl acid amide, choline, N-methylglucamine, piperazine, 1,6-hexanediamine, urea, hydrazine, glycine, alanine, lysine, serine, valine, leucine, a peptide, a protein, albumin, human serum albumin, polylysine, gelatin, a polyglycolamine, an aminopolyalcohol, a dextran sulfate with amino groups, N-aminopolyethylene glycol (HO-PEG-NH.sub.2), N,N"-diaminopolyethylene glycol (NH.sub.2 -PEG-NH.sub.2), an antibody, an immunoglobulin, PEG linker asparaginic acid, PEG linker glutaminic acid, PEG linker DTPA, PEG linker EDTA, 1,3-propanediol, glycerol, or pentaerythritol.
- 24. Microparticles of claim 1, wherein said biomolecule is a monoclonal antibody.
- 25. A pharmaceutical composition according to claim 19, wherein the concentration of microparticles is 1 microgram to 100 mg per ml the composition.
Priority Claims (1)
Number |
Date |
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40 04 430.0 |
Feb 1990 |
DEX |
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Parent Case Info
This application is a continuation of application Ser. No. 08/095,500, filed Jul. 26, 1993, now abandoned, which is a continuation of application Ser. No. 07/653,792, filed Feb. 11, 1991, now abandoned.
US Referenced Citations (12)
Foreign Referenced Citations (2)
Number |
Date |
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0324938 |
Jul 1989 |
EPX |
06978 |
Aug 1989 |
WOX |
Continuations (2)
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Number |
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Parent |
95500 |
Jul 1993 |
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Parent |
653792 |
Feb 1991 |
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