Christopher J Rhodes

US Patent:

6428771, Aug 6, 2002

Filed:

May 15, 1995

Appl. No.:

08/441378

Inventors:

Solomon S. Steiner - Mt. Kisco NY
Robert Feldstein - Dobbs Ferry NY
Huiling Lian - Yonkers NY
Christopher A. Rhodes - Stamford CT
Gregory S. Shen - Hartsdale NY

Assignee:

Pharmaceutical Discovery Corporation - Elmsford NY

International Classification:

A61K 912

US Classification:

424 45, 424 46, 424489

Abstract:

Drug delivery to the pulmonary system has been achieved by encapsulation of the drug to be delivered in microparticles having a size range between 0. 5 and ten microns, preferably in the range of two to five microns, formed of a material releasing drug at a pH of greater than 6. 4. In a preferred embodiment, the drug delivery system is based on the formation of diketopiperazine microparticles which are stable at a pH of 6. 4 or less and unstable at pH of greater than 6. 4, or which are stable at both acidic and basic pH, but which are unstable at pH between about 6. 4 and 8. Other types of materials can also be used, including biodegradable natural and synthetic polymers, such as proteins, polymers of mixed amino acids (proteinoids), alginate, and poly(hydroxy acids). In another embodiment, the microparticles have been modified to effect targeting to specific cell types and to effect release only after reaching the targeted cells.

US Patent:

8394414, Mar 12, 2013

Filed:

Nov 12, 2003

Appl. No.:

10/706243

Inventors:

Solomon S. Steiner - Mt. Kisco NY, US
Robert Feldstein - Yonkers NY, US
Huiling Lian - Yonkers NY, US
Christopher A. Rhodes - Ellicott City MD, US
Gregory S. Shen - Hartsdale NY, US

Assignee:

MannKind Corporation - Valencia CA

International Classification:

A61K 9/16

US Classification:

424493, 424489, 424490

Abstract:

Drug delivery to the pulmonary system has been achieved by encapsulation of the drug to be delivered in microparticles having a size range between 0. 5 and ten microns, preferably in the range of two to five microns, formed of a material releasing drug at a pH of greater than 6. 4. In a preferred embodiment, the drug delivery system is based on the formation of diketopiperazine microparticles which are stable at a pH of 6. 4 or less and unstable at pH of greater than 6. 4, or which are stable at both acidic and basic pH, but which are unstable at pH between about 6. 4 and 8. Other types of materials can also be used, including biodegradable natural and synthetic polymers, such as proteins, polymers of mixed amino acids (proteinoids), alginate, and poly(hydroxy acids). In another embodiment, the microparticles have been modified to effect targeting to specific cell types and to effect release only after reaching the targeted cells.

US Patent:

20030017211, Jan 23, 2003

Filed:

Aug 2, 2002

Appl. No.:

10/211215

Inventors:

Solomon Steiner - Mount Kisco NY, US
Robert Feldstein - Yonkers NY, US
Huiling Lian - Yonkers NY, US
Christopher Rhodes - Ellicott City MD, US
Gregory Shen - Hartsdale NY, US

Assignee:

Pharmaceutical Discovery Corporation

International Classification:

A61K048/00
A61K038/28
A61K031/727
A61K009/50
A61K009/14

US Classification:

424/499000, 424/501000, 514/002000, 514/003000, 514/044000, 514/056000, 424/046000

Abstract:

Drug delivery to the pulmonary system has been achieved by encapsulation of the drug to be delivered in microparticles having a size range between 0.5 and ten microns, preferably in the range of two to five microns, formed of a material releasing drug at a pH of greater than 6.4. In a preferred embodiment, the drug delivery system is based on the formation of diketopiperazine microparticles which are stable at a pH of 6.4 or less and unstable at pH of greater than 6.4, or which are stable at both acidic and basic pH, but which are unstable at pH between about 6.4 and 8. Other types of materials can also be used, including biodegradable natural and synthetic polymers, such as proteins, polymers of mixed amino acids (proteinoids), alginate, and poly(hydroxy acids). In another embodiment, the microparticles have been modified to effect targeting to specific cell types and to effect release only after reaching the targeted cells.

US Patent:

60714972, Jun 6, 2000

Filed:

Apr 24, 1997

Appl. No.:

8/847352

Inventors:

Solomon S. Steiner - Mt. Kisco NY
Robert Feldstein - Dobbs Ferry NY
Huiling Lian - Yonkers NY
Christopher A. Rhodes - Stamford CT
Gregory S. Shen - Hartsdale NY

Assignee:

Pharmaceutical Discovery Corporation - Elmsford NY

International Classification:

A61K 912

US Classification:

424 45

Abstract:

Drug delivery to the pulmonary system has been achieved by encapsulation of the drug to be delivered in microparticles having a size range between 0. 5 and ten microns, preferably in the range of two to five microns, formed of a material releasing drug at a pH of greater than 6. 4. In a preferred embodiment, the drug delivery system is based on the formation of diketopiperazine microparticles which are stable at a pH of 6. 4 or less and unstable at pH of greater than 6. 4, or which are stable at both acidic and basic pH, but which are unstable at pH between about 6. 4 and 8. Other types of materials can also be used, including biodegradable natural and synthetic polymers, such as proteins, polymers of mixed amino acids (proteinoids), alginate, and poly(hydroxy acids). In another embodiment, the microparticles have been modified to effect targeting to specific cell types and to effect release only after reaching the targeted cells.

US Patent:

55764363, Nov 19, 1996

Filed:

Mar 2, 1994

Appl. No.:

8/204559

Inventors:

R. Tyler McCabe - South Salem NY
Christopher A. Rhodes - Stamford CT
Bruce F. DeCosta - Yonkers NY

Assignee:

Pharmaceutical Discovery Corporation - Elmsford NY

International Classification:

C07D27112

US Classification:

546156

Abstract:

Conjugates of fluorescent labels with specific, selective, and high affinity ligands for receptors have been synthesized and used to directly measure binding to receptors.

US Patent:

57122695, Jan 27, 1998

Filed:

Jan 24, 1995

Appl. No.:

8/377667

Inventors:

R. Tyler McCabe - South Salem NY
Bryan R. Wilson - Tuxedo NY
Christopher A. Rhodes - Stamford CT

Assignee:

Pharmaceutical Discovery Corporation - Elmsford NY

International Classification:

A61K 3155
C07D47104

US Classification:

514220

Abstract:

Muscarinic M. sub. 2 receptor ligands are described which are suitable for the treatment of neurological disorders, and which may be administered with minimal side-effects. A method of synthesis of these compounds is also described.

US Patent:

55038522, Apr 2, 1996

Filed:

Sep 1, 1994

Appl. No.:

8/299842

Inventors:

Solomon S. Steiner - Mount Kisco NY
Christopher A. Rhodes - Stamford CT
Gregory S. Shen - Hartsdale NY
R. Tyler McCabe - Yorktown NY

Assignee:

Pharmaceutical Discovery Corporation - Elmsford NY

International Classification:

A61K 916
A61K 950

US Classification:

424493

Abstract:

Drug delivery systems have been developed based on the formation of diketopiperazine (or analogs) microparticles. In the preferred embodiment the microparticle is stable at low pH and disintegrates at physiological pH, and is particularly useful for oral drug delivery. In other embodiments, the microparticles are stable at high pH and disintegrate at neutral or basic pH, or are stable at neutral pH and disintegrate at high or low pH. In the most preferred embodiment the microparticles are formed in the presence of the drug to be delivered, for example, insulin, felbamate, calcitonin or heparin. The diketopiperazine synthetic intermediates are preferably formed by cyclodimerization to form diketopiperazine derivatives at elevated temperatures under dehydrating conditions, functionalized on the side chains, and then precipitated with drug to be incorporated into microparticles.