System for delivery of medical components to the lungs

Patent metadata

Field	Value
Publication number	US-11633362-B2
Application number	US-201816643682-A
Country	US
Kind code	B2
Filing date	Sep 5, 2018
Priority date	Sep 5, 2017
Publication date	Apr 25, 2023
Grant date	Apr 25, 2023

Abstract

The present invention relates generally to pharmaceutical formulations. Particularly, the present invention relates to a new delivery system for delivery of medical components to the lungs, and its utility in the fields of pharmaceutical formulation, drug delivery, medicine and diagnosis.

First claim

The invention claimed is:

1. A method of delivering at least one medical component associated with a nanoparticle to a target tissue that is a lung, tissue of a respiratory system and/or a nearby tissue and releasing the medical component into the target tissue, the method comprising intravenously administering a delivery system into the bloodstream, wherein the delivery system comprises a gas-filled microbubble, a plurality of nanoparticles and at least one medical component associated with one or more of the nanoparticles, wherein the one or more nanoparticles are not liposomes, wherein the medical component is a therapeutic agent and wherein the delivery to the target tissue and the release of the medical component is without ultrasound.

2. The method of claim 1 , wherein the plurality of nanoparticles is associated with the gas-filled microbubble.

3. The method of claim 2 , wherein the delivery system further comprises free nanoparticles and at least one medical component associated with the free nanoparticles.

4. The method of claim 1 , wherein the plurality of nanoparticles is coated with polyethylene glycol (PEG).

5. The method of claim 1 , wherein at least one of the plurality of nanoparticles further comprise at least one targeting agent.

6. The method of claim 1 , wherein the delivery system further comprises a pharmaceutically acceptable carrier.

7. The method of claim 1 , wherein the gas-filled microbubble comprises a gas selected from the group consisting of: perfluorocarbon, air, noble gases, sulfuric fluoride gases, halogens, and air-components.

8. The method of claim 1 , wherein the gas-filled microbubble further comprises a surface-active compound and/or a modifying agent.

9. The method of claim 2 , wherein the mean diameter of the gas-filled microbubbles associated with nanoparticles is in the range 0.5 to 30 μm.

10. The method of claim 1 , wherein the medical component is selected from the group consisting of: cytotoxic/cytostatic drugs, antibiotics, mucus-dissolving agents (mucolytics), anti-inflammatory drugs, a pulmonary therapeutic drug, respiratory agents, immunotherapeutic drugs, gene-modifying agents, and chemo-potentiators.

11. The method of claim 2 , wherein the plurality of nanoparticles is surface-associated with the gas-filled microbubble.

12. The method of claim 1 , wherein the nanoparticles are spherical and have a diameter of under 800 nm and wherein the microbubbles have a diameter of from 1 to 10 μm.

13. The method of claim 1 , wherein the nanoparticles are spherical and have a diameter of under 800 nm and wherein the microbubbles have a diameter of from 1 to 30 μm.

14. The method of claim 7 , wherein the air-components are selected from the group consisting of: nitrogen (N2), oxygen (O2), argon (Ar), carbon dioxide (CO2), helium (He), neon (Ne) and methane (CH4).

15. The method according to claim 1 , wherein the gas-filled microbubbles are prepared by
a. providing the nanoparticles to be loaded with the medical component;
b. adding the nanoparticles to a solution comprising a surface-active compound and/or a modifying agent;
c. adding gas to the solution comprising the nanoparticles and the surface-active compound and/or modifying agent;
d. mixing the solution comprising nanoparticles, a surface-active compound and/or a modifying agent, and gas to obtain gas-filled microbubbles.

16. The method according to claim 15 , wherein mixing occurs from 2 seconds to 60 minutes.

17. The method according to claim 15 , wherein the mixing occurs by stirring at 500 to 50,000 rpm.

18. The method according to claim 15 , wherein the surface-active substance is serum, or protein or lipid or surfactant.

19. The method of claim 16 , wherein mixing occurs from 1 to 10 minutes.

20. The method of claim 17 , wherein mixing occurs by stirring at 1000 rpm to 30,000 rpm.

21. The method of claim 1 , wherein the plurality of nanoparticles are free nanoparticles.

22. The method of claim 21 , wherein the plurality of nanoparticles is coated with polyethylene glycol (PEG).

23. The method of claim 21 , wherein at least one of the plurality of nanoparticles further comprises at least one targeting agent.

24. The method of claim 21 , wherein the delivery system further comprises a pharmaceutically acceptable carrier.

25. The method of claim 21 , wherein the gas-filled microbubble is a microbubble with nanoparticles associated on the surface.

26. The method of claim 21 , wherein the medical component is selected from the group consisting of: cytotoxic/cytostatic drugs, antibiotics, mucus-dissolving agents (mucolytics), anti-inflammatory drugs, a pulmonary therapeutic drug, respiratory agents, immunotherapeutic drugs, gene-modifying agents, chemo-potentiators.

Assignees

• Sintef Tto As

Inventors

• Mørch Yrr
• Sulheim Einar

Classifications

• A61K9/5146

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/1276 Primary

  Globules of milk; Constituents thereof · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title