Medical emulsion for lubrication and delivery of drugs

• US 20010051595A1
• Filed: 06/21/2001
• Published: 12/13/2001
• Est. Priority Date: 09/23/1997
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Dillard, David H., Rauker, Robert M., Lyons, Robert T., Bluni, Scott T., Fieggen, Bruce
• Granted Patent: US 6,391,832 B2
• Time in Patent Office: Days
• US Class Current: 508/491
• CPC Class Codes: A61B 17/320758 with a rotating cutting instrument, e.g. motor driven A61B17/320725, A61B17/32075 and A61B17/320783 take precedence; for removing intra-ocular material A61F9/00763; endoscopic rotatable cutting instruments A61B17/32002
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61P 23/00 Anaesthetics
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

A medical lubricant suitable for injection into the blood stream of a patient. The lubricant is suitable for use with rotating equipment such as atherectomy drive shafts moving within sheaths and over guide wires and other minimally invasive medical devices introduced into a patient through a catheter like instrument. The lubricant is an oil-in-water emulsion including a surfactant, a co-surfactant, and a pH buffer. The lubricant can further include a cryogenic agent and a pH adjusting agent. One lubricant includes olive oil as an emulsified oil, egg yolk phospholipid as a surfactant, sodium deoxycholate as a co-surfactant, glycerin as a cryogenic agent, L-histidine as a pH buffer, and is pH adjusted using sodium hydroxide. The lubricant can also include a therapeutic agent. The lubricant can withstand freeze/thaw cycles as well as saline dilution, heating, and shear stress without significant creaming, separation, or unacceptable increases in oil droplet size. Compared to saline, the lubricant provides significantly increased lubrication efficiency for rapidly moving parts.

Claims

1. A medical lubricant oil emulsion comprising a mixture of:

an oil;

a surfactant;

a co-surfactant;

a pH buffer;

wherein when said pH buffer is an amino acid buffer and said amino acid buffer has a concentration of less than 0.20 g/100 mL emulsion; and

water.

2. A medical lubricant as recited in

claim 1

, wherein said oil comprises at least 60% mixed triglycerides of mono-unsaturated oleic acid, said surfactant is a phospholipid, said co-surfactant is a bile salt, and said pH buffer is an amino acid buffer having a concentration of less than 0.20 g/100 mL emulsion.

3. A medical lubricant as recited in recited in

claim 2

, wherein said oil is a vegetable oil.

4. A medical lubricant as recited in

claim 3

, wherein said vegetable oil is selected from the group of refined oils consisting of almond oil, coconut oil, corn oil, cotton seed oil, marine oil, olive oil, palm kernel oil, peanut oil, safflower oil, sesame oil, soybean oil, sunflower oil, and physical or interesterified mixtures thereof.

5. A medical lubricant as recited in recited in

claim 4

, wherein said vegetable oil is purified olive oil comprised of at least 60% mixed triglycerides of mono-unsaturated oleic acid.

6. A medical lubricant as recited in

claim 2

, wherein said phospholipid is selected from the group consisting of soy bean and egg yolk phospholipids.

7. A medical lubricant as recited in

claim 2

, wherein said phospholipid is egg yolk phospholipid.

8. A medical lubricant as recited in

claim 2

, wherein said bile salt is selected from the group of salts of bile acids consisting of cholic acid, deoxycholic acid, glycocholic acid, taurocholic acid, and mixtures thereof.

9. A medical lubricant as recited in

claim 8

, wherein said bile salt is sodium deoxycholate.

10. A medical lubricant as recited in

claim 2

, wherein said amino acid buffer is selected from the group consisting of alanine, aspartic acid, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, valine, and mixtures thereof.

11. A medical lubricant as recited in

claim 10

, wherein said amino acid buffer is L-histidine.

12. A medical lubricant as recited in

claim 2

, further comprising a cryogenic agent.

13. A medical lubricant as recited in

claim 12

, wherein said cryogenic agent is glycerin.

14. A medical lubricant as recited in

claim 2

, further comprising a heavy metal chelator.

15. A medical lubricant as recited in

claim 14

, wherein said chelator includes a physiologically acceptable salt of ethylenediamine tetracetic acid (EDTA).

16. A medical lubricant oil emulsion comprising:

an oil;

a phospholipid;

a bile salt,

a cryogenic agent;

an amino acid buffer having a concentration of less than 0.20 g/100 mL emulsion; and

water.

17. A medical lubricant as recited in

claim 16

, wherein said lipid emulsion has a mean droplet size less than about 5 micro meters.

18. A medical lubricant as recited in

claim 16

, wherein said lipid emulsion has a mean droplet size less than about 1 micrometer.

19. A medical lubricant as recited in

claim 16

, wherein said oil has a concentration of between about 5 and about 40 g/100 mL emulsion,

said phospholipid includes egg yolk phospholipid and has a concentration of between about 0.3 and about 3 g/100 mL emulsion,

said bile salt has a concentration of between about 0.04 and about 4.0 g/100 mL emulsion,

said cryogenic agent is selected from the group consisting of refined propylene glycol and glycerin and has a concentration between about 1 and about 30 g/100 mL emulsion, and

said amino acid buffer has a concentration of between about 0.01 and about 0.19 g/100 mL emulsion.

20. A medical lubricant as recited in

claim 19

, wherein said oil includes olive oil and has a concentration of between about 15 and about 25 g/100 mL emulsion,

said phospholipid has a concentration of between about 0.6 and about 1.8 g/100 mL emulsion,

said bile salt includes sodium deoxycholate and has a concentration of between about 0.2 and about 0.8 g/100 mL emulsion,

said cryogenic agent includes glycerin and has a concentration between about 2 and about 20 g/100 mL emulsion, and

said amino acid buffer includes L-histidine and has a concentration of between about 0.05 and 0.19 g/100 mL emulsion.

21. A medical lubricant oil emulsion comprising:

refined olive oil;

egg yolk phospholipid;

sodium deoxycholate;

glycerin;

L-histidine having a concentration of less than 0.20 g/mL emulsion; and

water for injection.

22. A medical lubricant as recited in

claim 21

, further comprising disodium EDTA and sodium hydroxide.

23. A medical lubricant oil emulsion comprising a mixture of:

an oil;

a surfactant;

a co-surfactant;

a pH buffer;

a therapeutic agent; and

water.

24. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one anti-thrombogenic agent chosen from heparin, heparin derivatives, urokinase and dextro-phenylalanine-proline-arginine chloromethylketone.

25. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one anti-proliferative agent chosen from enoxaprin, angiopeptin, a monoclonal antibody capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid.

26. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one anti-inflammatory agent chosen from dexamethasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine.

27. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one antineoplastic/antiproliferative/anti-mitotic agent chosen from paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine, epothilones, endostatin, angiostatin, and thymidine kinase inhibitors.

28. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one anesthetic agents chosen from lidocaine, bupivacaine, and ropivacaine.

29. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one anti-coagulant chosen from dextro-phenylalanine-proline-arginine chloromethylketone, an arginine-glycine-aspartic acid peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors, and tick antiplatelet peptides.

30. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one vascular cell growth promoter chosen from growth factor inhibitors, growth factor receptor antagonists, transcriptional activators of genes encoding vascular cell growth promoter proteins, and translational activators of mRNAs encoding vascular cell growth promoter proteins.

31. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one vascular cell growth inhibitor chosen from growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors of genes encoding vascular cell growth inhibitors, translational repressors of mRNAs encoding vascular cell growth inhibitors, DNA replication inhibitors, vascular cell growth inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, and bifunctional molecules consisting of an antibody, and a cytotoxin.

32. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent is selected from the group consisting of cholesterol-lowering agents, vasodilating agents, and agents which interfere with endogenous vascoactive mechanisms.

33. A medical lubricant as recited in

claim 23

, wherein said therapeutic agent comprises at least one agent chosen from a substantially purified genetic material, a substantially purified protein, and cells.

34. A medical lubricant as recited in

claim 33

, wherein said genetic material comprises at least one polynucleotide chosen from anti-sense DNA, anti-sense RNA, DNA coding for an anti-sense RNA, DNA coding for a tRNA, DNA coding for a rRNA, and DNA coding for a protein.

35. A medical lubricant as recited in

claim 33

, wherein said cells are human cells that are of autologous or allogeneic origin.

36. A medical lubricant as recited in

claim 33

, wherein said cells are xenogeneic non-human cells.

37. A medical lubricant as recited in

claim 33

, wherein said therapeutic agent comprises at least one protein chosen from acidic fibroblast growth factors, basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor α

and β

, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α

, hepatocyte growth factor, insulin like growth factor, and bone morphogenic proteins.

38. A medical lubricant as recited in

claim 33

, wherein said genetic material comprises at least one DNA encoding a protein chosen from acidic fibroblast growth factors, basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor α

and β

, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor α

, hepatocyte growth factor, insulin like growth factor, and bone morphogenic proteins.

39. A method of lubricating an intravascular device comprising:

preparing a patient for a medical procedure;

inserting into the patient a medical device in need of lubrication;

infusing a medical lubricant into the patient during said insertion or during operation of said medical device, said medical lubricant oil emulsion comprising;

olive oil;

an egg yolk phospholipid;

a bile salt;

an amino acid buffer;

a therapeutic agent; and

water.

40. A method according to

claim 39

wherein the medical procedure is atherectomy, the medical device is an intravascular device, capable of differentially removing intravascular deposits from the walls of an artery;

and the therapeutic agent comprises a cell proliferation inhibitor that provides an anti-restenosis effect.

41. A method according to

claim 39

wherein the medical procedure is myocardial revascularization, the medical device is a myocardial revascularization device, and the therapeutic agent comprises an agent that promotes angiogenesis.