Adhesive drug delivery composition

• US 6,387,408 B1
• Filed: 04/13/1998
• Issued: 05/14/2002
• Est. Priority Date: 11/08/1988
• Status: Expired due to Fees

• Current Assignee: West Pharmaceutical Services Drug Delivery & Clinical Research Centre Ltd
• Original Assignee: West Pharmaceutical Services Drug Delivery & Clinical Research Centre Ltd
• Inventors: Illum, Lisbeth, Williams, Paul, Caston, Antony James
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Sheikh, Humera N.
• Application Number:
  US09/059,646
• Time in Patent Office: 1,492 Days
• Field of Search: 424/489, 424/464, 424/465, 424/881, 424/150.1, 424/139.1, 424/184.1, 424/185.1, 424/197.11, 424/234.1, 424/450, 424/490, 424/492, 424/496, 424/499, 424/426, 424/497, 424/491, 530/327
• US Class Current: 424/489
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61K 9/5052 Proteins, e.g. albumin
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Adhesive material from the fimbriae (esp. Type 1) of bacteria or synthetic analogues or fragments thereof is combined with a drug to provide for attachment to the gut of a mammal, thereby prolonging the transit time of the drug through the gut.

The 28 kDa polypeptide from E. coli Type 1 fimbriae is the preferred adhesive material (“adhesin”). The drug is presented in a carrier such as albumin, a polylactide/glycolide copolymer or alginate microcapsules. The adhesin may be incorporated in the carrier during preparation thereof, adsorbed onto the carrier after preparation, or covalently linked thereto, for example with carbodiimide.

Claims

1. A drug delivery composition comprising

particles comprising a drug and a bacterial bioadhesive material binding via a sugar residue, lectin-mediated process to the small intestine of a mammal,

wherein the bioadhesive material is incorporated on the surface of the particles either by coating or covalent binding.

2. A composition according to claim 1 wherein the drug is present as a plurality of particles.

3. A composition according to claim 2 wherein the particles have an average diameter of 20 microns or less.

4. A composition according to claim 2 or 3 wherein the bacterial bioadhesive material is covalently attached to the drug particles.

6. A composition according to claim 1 or 5 wherein the bacterial bioadhesive material is found in the Type 1 adhesin of E. coli.

7. A composition according to claim 6 wherein the bacterial bioadhesive material comprises a 28 kDa polypeptide of E. coli adhesins.

8. A process for preparing a composition according to claim 1 or 5 comprising combining a drug, a carrier incorporating the drug and a bacterial bioadhesive material binding to the small intestine of a mammal via a sugar residue, lectin-mediated process, wherein the bacterial bioadhesive material is incorporated on the surface of the carrier.

18. The composition of claim 1 wherein the bioadhesive material is a surface adhesin polypeptide of a bacterium.

19. The composition of claim 1 wherein the bioadhesive material is a fimbria or portion thereof from E. coli.

20. The composition of claim 1 wherein the particles are formed of a polymer selected from the group consisting of polystyrene, polymethylmethacrylate, albumin, gelatin, dextran, alginate, polylactide, polyglycolide, copolymers of polylactide glycolide, polyhydroxybutyrate and polyanhydride microspheres.

23. The composition according to claim 2 wherein the bacterial bioadhesive material is found in the Type 1 adhesin of E. coli.

24. The composition according to claim 3 wherein the bacterial bioadhesive material is found in the Type 1 adhesin of E. coli.

25. The composition according to claim 4 wherein the bacterial bioadhesive material is found in the Type 1 adhesin of E. coli.

5. A drug delivery composition for sustained release of a drug in the gastrointestinal tract comprising:

liposomes or an emulsion having incorporated therein;

at least one drug, and

a bacterial bioadhesive material binding to the small intestine of a mammal via a sugar residue, lectin-mediated process, wherein the bioadhesive material is linked to a lipid entrapped in the liposomes or emulsion, and wherein the liposomes or emulsion are bound to the small intestine by the bioadhesive material to permit sustained release of the drug to the gastrointestinal tract of a mammal.

26. The composition according to claim 5 wherein the bacterial bioadhesive material is found in the Type 1 adhesin of E. coli.

9. A method of treating a mammal comprising administering orally to the mammal a therapeutically effective amount of a drug delivery composition comprising polymeric particles, having incorporated therein a drug and having coupled to the surface a bacterial bioadhesive material binding to the small intestine of a mammal via a sugar residue, lectin-mediated process for a period of time permitting controlled release of the drug to the gastrointestinal tract of the mammal.

10. The method of claim 9 wherein the bioadhesive material is covalently attached to the particles.

11. The method of claim 9 wherein the bioadhesive material is a surface adhesin polypeptide of a bacterium.

12. The method of claim 10 wherein the bioadhesive material is a fimbriae or portion thereof from E. coli.

13. The method of claim 9 wherein the particles consist of a polymeric drug.

14. The method of claim 9 wherein the drug is selected from the group consisting of cephalosporins, chlorthiazide, isosorbide and frusemide.

15. The method of claim 9 wherein the drug is selected from the group consisting of insulin, growth hormone, calcitonin, interferon and tumor necrosis factor.

16. The method of claim 9 wherein, after the particles are adhered to the small intestine, the drug is released from the particles and absorbed in the upper regions of the small intestine.

17. The method of claim 9 wherein, after the particles are adhered to the small intestine, the drug is released from the particles and absorbed in the colon.

21. A method of treating a mammal comprising administering orally to the mammal a therapeutically effective amount of a drug delivery composition comprising

liposomes or an emulsion having incorporated therein at least one drug, and

a bacterial bioadhesive material binding via a sugar residue lectin-mediated process to the small intestine, which is linked to a lipid entrapped in the liposomes or emulsion, and which adheres to the small intestine for a period of time permitting controlled release of the drug.

22. The method of claim 21 wherein the bacterial bioadhesive material is a fimbria or portion thereof from E. coli.