FUNCTIONALIZED DRUGS AND POLYMERS THEREFROM

• US 20100152272A1
• Filed: 02/17/2010
• Published: 06/17/2010
• Est. Priority Date: 01/28/2005
• Status: Active Grant

• Current Assignee: Bezwada Biomedical, LLC
• Original Assignee: Bezwada Biomedical, LLC
• Inventors: Bezwada, Rao S.
• Granted Patent: US 8,409,559 B2
• Time in Patent Office: Days
• US Class Current: 514/420
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 31/7135 Compounds containing heavy metals
• CPC Class Codes: A61K 47/51 the non-active ingredient being a modifying agent
• CPC Class Codes: A61K 9/0058 : Chewing gums non-medicinal aspects, preparing chewing gum A23G4/00; chewing gum for care of the teeth or oral cavity, e.g. with breath freshener A61Q11/00
• CPC Class Codes: A61K 9/1647 : Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: C07C 69/734 : Ethers
• CPC Class Codes: C07C 69/92 : with etherified hydroxyl groups
• CPC Class Codes: C08G 18/3206 : aliphatic
• CPC Class Codes: C08G 18/711 : containing oxygen in addition to isocyanate oxygen
• CPC Class Codes: C08G 18/771 : oxygen
• CPC Class Codes: C08G 18/797 : containing carbodiimide and/or uretone-imine groups
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Compounds selected from:

where DRUG-OH, DRUG-COOH and DRUG-NH₂ are biologically active compounds; each X is independently selected from —CH₂COO— (glycolic acid moiety), —CH(CH₃)COO— (lactic acid moiety), —CH₂CH₂OCH₂COO— (dioxanone moiety), —CH₂CH₂CH₂CH₂CH₂COO— (caprolactone moiety), —(CH₂)_yCOO—, where y is 2-4 or 6-24 and —(CH₂CH₂O)_zCH₂COO—, where z is 2-24; each Y is independently selected from —COCH₂O— (glycolic ester moiety), —COCH(CH₃)O— (lactic ester moiety), —COCH₂OCH₂CH₂O— (dioxanone ester moiety), —COCH₂CH₂CH₂CH₂CH₂O— (caprolactone ester moiety), —CO(CH₂)_mO—, where m is 2-4 or 6-24 and —COCH₂O(CH₂CH₂O)_n— where n is between 2-24; R′ is hydrogen, benzyl or an alkyl group, the alkyl group being either straight-chained or branched; and p is 1-6. Multi-functional compounds and drug dimers, oligomers and polymers are also disclosed.

Claims

1. A compound selected from the group consisting of:

2. A compound according to claim 1 wherein each X is independently selected from the group consisting of:

—

CH₂COO—

(glycolic acid moiety),

—

CH(CH₃)COO—

(lactic acid moiety),

—

CH₂CH₂OCH₂COO—

(dioxanone moiety), and

—

CH₂CH₂CH₂CH₂CH₂COO—

(caprolactone moiety); and

each Y is independently selected from the group consisting of;

—

COCH₂O—

(glycolic ester moiety);

—

COCH(CH₃)O—

(lactic ester moiety);

—

COCH₂OCH₂CH₂O—

(dioxanone ester moiety); and

—

COCH₂CH₂CH₂CH₂CH₂O—

(caprolactone ester moiety).

4. A composition comprising two or more different species of the compound according to claim 1.

5. A cancer-preventing composition comprising an effective amount of at least one compound of claim 1, wherein DRUG-OH, DRUG-COOH and DRUG-NH₂ are cancer-preventing compounds;

a pharmaceutically acceptable excipient; and

optionally further comprising a second anti-cancer agent.

6. An anti-inflammatory composition comprising an effective amount of at least one compound of claim 1, wherein DRUG-OH, DRUG-COOH and DRUG-NH₂ have anti-inflammatory properties;

a pharmaceutically acceptable excipient; and

optionally further comprising a second anti-inflammatory agent.

7. A pain-reducing composition comprising an effective amount of at least one compound of claim 1, wherein DRUG-OH, DRUG-COOH and DRUG-NH₂ have pain-reducing properties;

a pharmaceutically acceptable excipient; and

optionally further comprising a second pain-reducing agent.

8. A bioactive composition comprising an effective amount of at least one compound of claim 1 and a pharmaceutically acceptable excipient, wherein said composition is in a form suitable for oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, or vaginal administration.

9. An antimicrobial composition comprising an effective amount of at least one compound of claim 1, wherein DRUG-OH, DRUG-COOH and DRUG-NH₂ have antimicrobial properties;

a pharmaceutically acceptable excipient; and

optionally further comprising a second antimicrobial agent.

10. A pharmaceutical composition comprising an effective amount of at least one compound of claim 1 and a pharmaceutically acceptable excipient.

11. An antioxidant composition comprising an effective amount of at least one compound of claim 1, wherein DRUG-OH, DRUG-COOH and DRUG-NH₂ have antioxidant properties;

a pharmaceutically acceptable excipient; and

optionally further comprising a second antioxidant compound.

12. A method for the treatment or prophylaxis of a cancerous disease which comprises administering to a subject in need thereof by means of controlled release drug delivery a therapeutically effective amount of at least one compound of claim 5.

13. A method for the reduction of pain which comprises administering to a subject in need thereof by means of controlled release drug delivery a therapeutically effective amount of at least on compound of claim 7.

14. A method for the treatment of inflammation which comprises administering to a subject in need thereof by means of controlled drug delivery a therapeutically effective amount of at least one compound of claim 6.

3. (canceled)

15-65. -65. (canceled)

66. A compound having the formula:

67. A compound according to claim 66 wherein each X is independently selected from the group consisting of:

—

CH₇COO—

(glycolic acid moiety),

—

CH(CH₃)COO—

(lactic acid moiety),

—

CH₇CH₇OCH₇COO—

(dioxanone moiety), and

—

CH₇CH₇CH₇CH₇CH₇COO—

(caprolactone moiety).

68. A composition comprising two or more different species of the compound according to claim 66.

69. An anti-inflammatory composition comprising an effective amount of at least one compound of claim 66;

a pharmaceutically acceptable excipient; and

optionally further comprising a second anti-inflammatory agent.

70. A pain-reducing composition comprising an effective amount of at least one compound of claim 66;

a pharmaceutically acceptable excipient; and

optionally further comprising a second pain-reducing agent.

71. A bioactive composition comprising an effective amount of at least one compound of claim 66 and a pharmaceutically acceptable excipient, wherein said composition is in a form suitable for oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, or vaginal administration.

72. A pharmaceutical composition comprising an effective amount of at least one compound of claim 66 and a pharmaceutically acceptable excipient.

73. A method for the reduction of pain which comprises administering to a subject in need thereof by means of controlled release drug delivery a therapeutically effective amount of at least one compound of claim 70.

74. A method for the treatment of inflammation which comprises administering to a subject in need thereof by means of controlled drug delivery a therapeutically effective amount of at least one compound of claim 69.