Claims
- 1. A process for making porous particles of biologically active molecules from particles having a diameter of approximately 10 to 90 micrometers comprising:providing a solution of biologically active molecules selected from the group consisting of carbohydrates, nucleotides, inorganic compounds, synthetic organic molecules, polypeptides, and lipids, in a solvent that can be removed by lyophilization; atomizing the solution into a liquified gas selected from the group consisting of nitrogen, argon, and oxygen in a vessel to produce frozen particles containing biologically active molecules in combination with the solvent; removing the gas from the vessel containing the frozen particles; removing the solvent from the particles by lyophilization to produce porous particles having a diameter of between approximately 10 and 90 microns, suspending the porous particles in a non-solvent for the biologically active molecules, and fragmenting by exposure to dispersive energy with continuous cooling the suspension of particles until particles having diameters of approximately 0.1 to 10 micrometers and containing at least 70% of their original biological activity are produced.
- 2. The process of claim 1 further comprising selecting an aqueous solvent and adjusting the pH, ionic strength, and concentrations of dissolved biologically active molecules in the solution.
- 3. The process of claim 2 wherein volatile salts which can be removed using lyophilization are used to buffer the solution.
- 4. The process of claim 1 wherein the solution is atomized through an ultrasonic nozzle.
- 5. The process of claim 1 further comprising suspending the 10 to 90 micrometer diameter porous particles in a polymer-solvent solution selected from the group consisting of poly(lactic acid)/methylene chloride, poly(lactic-co-glycolic acid)/ethyl acetate and ethylene-vinyl acetate copolymer/methylene chloride.
- 6. The process of claim 1 further comprising removing the 0.1 to 10 micrometer particles from the non-solvent.
- 7. The process of claim 1 further comprising incorporating the 0.1 to 10 micrometer particles in a polymeric matrix.
- 8. Particles of biologically active molecules having a diameter of between approximately 0.1 and 10 micrometers, containing molecules having greater than 90% of the activity of the molecules in solution prior to forming the particles, wherein the particles are produced by;providing a solution of biologically active molecules selected from the group consisting of carbohydrates, nucleotides, inorganic compounds, synthetic organic molecules, polypeptides, lipids, in a solvent that can be removed by lyophilization; atomizing the solution into a liquified gas in a vessel to produce frozen particles having diameters between 10 and 90 micrometers containing biologically active molecules in combination with the solvent; removing the gas from the vessel containing the frozen particles; removing the solvent from the particles by lyophilization to produce porous particles; suspending the porous particles in a non-solvent for the biologically active molecules; and fragmenting the porous particles into particles having diameters of approximately 0.1 to 10 micrometers.
- 9. The porous particles of claim 8 further comprising a polymeric matrix.
- 10. The porous particles of claim 9 wherein the polymeric matrix is formed of poly(lactic acid), poly(lactic-co-glycolic acid), ethylene-vinyl acetate, copolymers and blends thereof.
Parent Case Info
This is a continuation of application Ser. No. 07/759,604 filed on Sep. 13, 1991now abandoned, which is a continuation of application Ser. No. 07/345,684 filed on May 1, 1989, now abandoned.
US Referenced Citations (6)
Foreign Referenced Citations (1)
Number |
Date |
Country |
2 077 693 |
Jun 1981 |
GB |
Non-Patent Literature Citations (1)
Entry |
Himberger, D., et al., “Low-temperature Acoustic System for Inducing Nonthermal Ultrasonic Damage on Biological Targets” Rev. Sci. Instrum. 57(8), pp. 1681-1683 (Aug. 1986). |
Continuations (2)
|
Number |
Date |
Country |
Parent |
07/759604 |
Sep 1991 |
US |
Child |
08/006682 |
|
US |
Parent |
07/345684 |
May 1989 |
US |
Child |
07/759604 |
|
US |