Tumescent drug delivery

• US 10,322,083 B2
• Filed: 04/17/2017
• Issued: 06/18/2019
• Est. Priority Date: 06/25/2004
• Status: Active Grant

• Current Assignee: HK Pharma, Co.
• Original Assignee: HK Pharma, Co.
• Inventors: Klein, Jeffrey Alan
• Primary Examiner(s): Ramachandran, Umamaheswari
• Application Number:
  US15/489,225
• Publication Number:
  US 20170216198A1
• Time in Patent Office: 792 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/546 containing further heterocyclic rings, e.g. cephalothin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 25/007 Side holes, e.g. their profiles or arrangements; Provisions to keep side holes unblocked
• CPC Class Codes: A61M 5/14 Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

A method of subcutaneous delivery of a drug or a therapeutic agent to a subject comprising administering to said subject a mass of fluid of a tumescent composition comprising: (a) the drug or the therapeutic agent; (b) a vasoconstrictor; and (c) a pharmaceutically acceptable carrier, wherein a relatively large total amount of the drug is isolated from systemic circulation in the subject because only drug in an outer boundary of the mass of fluid is the available for absorption, whereas a portion of the drug located within a central portion of the mass of fluid is virtually isolated from the systemic circulation by virtue of profound capillary vasoconstriction, wherein epinephrine-induced vasoconstriction dramatically slows systemic absorption of the drug or therapeutic agent, and wherein the mass of fluid is a reservoir that delivers the drug or the therapeutic agent to the subject with pharmacokinetics that are analogous to a slow-release oral tablet or a slow constant intravenous (IV) Infusion.

Claims

1. A method of subcutaneous delivery of a drug or a therapeutic agent to a subject to treat a localized condition, the method comprising:

(a) preparing a liquid composition consisting of the drug or the therapeutic agent dissolved in a tumescent solution, wherein the tumescent solution consists of a local anesthetic, a vasoconstrictor and a pharmaceutically acceptable carrier, and

(b) delivering a mass of the liquid composition subcutaneously to a localized tissue in the subject, wherein the drug or the therapeutic agent treats the localized condition in the localized tissue,

wherein a concentration of the drug or the therapeutic agent subcutaneously delivered exceeds a concentration of the drug or the therapeutic agent that can be safely achieved by intravenous delivery, and wherein an amount of the drug or the therapeutic agent located at an outer boundary of the mass of fluid and available for absorption is less than an amount of the drug or the therapeutic agent located within a central portion of the mass of fluid and virtually isolated from the systemic circulation by virtue of capillary vasoconstriction,

wherein the localized condition is selected from the group consisting of a tumor, surgical site infection, chronic post-operative pain, risk of deep vein thrombosis, risk of post-operative thromboembolism and a burn wound.

2. The method of claim 1, wherein the vasoconstrictor component comprises epinephrine.

3. The method of claim 2, wherein the concentration of epinephrine is approximately 0.2 to 1.5 mg per L.

4. The method according to claim 1, wherein the drug or the therapeutic agent is an antibiotic.

5. The method of claim 4, wherein the antibiotic component comprises cefazolin.

6. The method of claim 4, wherein the antibiotic component comprises a mixture of two or more antibiotics.

7. The method of claim 1, wherein the composition further comprises an anti-inflammatory agent.

8. The method of claim 1, wherein the local anesthetic comprises lidocaine.

9. The method of claim 8, wherein the concentration of lidocaine is approximately 1,500 mg to 2,500 mg per L of solution.

10. The method according to claim 1 wherein the drug or therapeutic agent is a chemotherapeutic agent.

11. The method according to claim 1, used in the context of an emergency resuscitation where insertion of an IV catheter into a vein cannot be readily achieved.

12. The method according to claim 1, the subject is treated for an acute trauma or burn wound in a civilian or a military situation wherein access for intravenous delivery of fluids is not possible.

13. The method according to claim 1, wherein the subject is an obese patient in which finding an accessible vein for IV access is difficult.

14. The method of claim 1, comprising making an incision through the skin into the subcutaneous tissue of the patient and/or removal of subcutaneous tissue from the patient.

15. The method according to claim 1, wherein the mass of fluid comprising the tumescent composition is administering into a subcutaneous fat compartment.

16. The method according to claim 1, wherein the mass of fluid comprising the tumescent composition is administered to the subject by tumescent delivery to a subcutaneous compartment of a surgical site in a subject undergoing a surgical procedure, wherein a risk of surgical site infection in the subject is thereby reduced.

17. The method of claim 1, wherein the chemotherapy agent comprises adriamycin.

18. The method of claim 1, wherein the angiogenesis inhibitor comprises angiostatin.

19. A method of subcutaneous delivery of a drug or a therapeutic agent to a subject to treat a localized condition, the method comprising:

(a) providing a liquid composition consisting of the drug or the therapeutic agent dissolved in a tumescent solution, wherein the tumescent solution consists of a vasoconstrictor and a pharmaceutically acceptable carrier, and

(b) delivering a mass of the liquid composition subcutaneously to a localized tissue in the subject, wherein the drug or the therapeutic agent treats the localized condition in the localized tissue,

wherein a concentration of the drug or the therapeutic agent subcutaneously delivered exceeds a concentration of the drug or the therapeutic agent that can be safely achieved by intravenous delivery, and wherein an amount of the drug or the therapeutic agent located at an outer boundary of the mass of fluid and available for absorption is less than an amount of the drug or the therapeutic agent located within a central portion of the mass of fluid and virtually isolated from the systemic circulation by virtue of capillary vasoconstriction, and

wherein the localized condition is selected from the group consisting of a tumor, surgical site infection, chronic post-operative pain, risk of deep vein thrombosis, risk of post-operative thromboembolism and a burn wound.