Method of administration of chemotherapy to tumors

• US 4,558,690 A
• Filed: 01/26/1982
• Issued: 12/17/1985
• Est. Priority Date: 01/26/1982
• Status: Expired due to Fees

• Current Assignee: University of Scranton The An Institution of Higher Education of PA
• Original Assignee: University of Scranton
• Inventors: Joyce, Patrick J.
• Primary Examiner(s): Cohen, Lee S.
• Application Number:
  US06/343,011
• Time in Patent Office: 1,421 Days
• Field of Search: 128/1.3, 128/1.5, 128/804, 128/1 R, 604/20, 604/21, 604/890, 604/891, 424/32, 424/33, 424/78, 424/81
• US Class Current: 128/898
• CPC Class Codes: A61F 2007/0089 Chemotherapy developing heat
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

An improved method of administration of microspheres of cytotoxic chemicals to tumor sites without effect on non tumor tissue is disclosed. The method comprises injection of chemotherapeutic agents coated with a thermoplastic polymer having a melting point above normal body temperature (in a melting point range of about 40°-46° C.) accompanied by dielectric radio-frequency localized heating of the tumor to elevate its interior temperature above the melting point of the encapsulating thermoplastic polymer. The tumor is partially necrosed and sensitized by the R.F. nonionizing radiation bombardment and the entry of the chemotherapy agent triggered by the removal of the protective coat of thermoplastic polymer.

A preferred embodiment of the invention is a dose of 30 mg of methotrexate (A-methopterin) in the form of spherical microscapsules having an average of 200-800 microns diameter and a polymer of polystearyl acrylate encapsulating coating of an average thickness of 1-50 microns. This dose is injected into the tumor and released by a 30-60 minute irradiation of the tumor by 175-200 watts of R.F. non-ionizing radiation at a frequency of 13.56 megahertz from a set of capacitive plates positioned on opposite sides of the impregnated tumors. The tumor temperature is elevated to a threshold temperature of 43° C. which is the melting point and release point of the encapsulated acrylic resin. The temperature of the rest of the organism outside the tumor remains at 39°-40° C. which is below the release temperature of the resin.

Claims

1. A method for treatment of tumors of animals and humans which comprises:

(a) elevating the temperature of the tumor with exposure to a nonionizing radiofrequency field to partially necrose and attenuate its cells,

(b) injecting intratumorally and extracellularly into the tumor interstices a therapeutic dose of a tumoricidal agent encapsulated with a polymeric coating of a biologically inert thermoplastic resin characterized as having a melting point higher than the temperature of the surrounding body tissue and within the elevated temperature range of the tumor,

(c) activating the tumoricidal agent by heating the same within the tumor interstices above the melting point of the encapsulating resin so as to release the same within the tumor interstices without exposing the remaining normal body tissue to the effects of the agent.

2. A method according to claim 1 wherein the tumoricidal agent employed has an encapsulating thermoplastic polymer coating which melts within a temperature range of 40°

-46°

C.

3. A method according to claim 2 wherein the tumoricidal agent encapsulated is methotrexate and the encapsulating thermoplastic polymer is an acrylate resin having a melting point of 43°

C.

4. A method according to claim 3 wherein the encapsulating thermoplastic polymer employed is polystearyl acrylate.

5. A method for the administration of biologically active pharmaceuticals into a neoplasm of a mammal to reduce systemic side effects thereof which comprises:

(a) introducing intratumorally and extracellularly into the interstices of the neoplasm within the segment of the mammal to be treated a therapeutic dose of microcapsules of a biologically active pharmaceutical which has been precoated with a releasable polymeric encapsulating resin coating which has a melting point range extending from 40°

-46°

C. and which until the coating is removed is substantially inert biologically,

(b) removing this polymeric encapsulating resin coating from the pharmaceutical to release the active agent within the cellular interstices by radiofrequency heating the microcapsules above the melt temperature of the encapsulating resin.

6. A method according to claim 5 wherein the heating is of a small organ or segment of the body capable of having its temperature elevated to a level of at least 40°

C. for a period of time sufficient to elevate the temperature of the microcapsules above the melting point of their encapsulating resin.

7. A method according to claim 5 wherein the polymeric encapsulating resin coating removed is an acrylate polymer and the biologically active pharmaceutical is a cytotoxic cancericidal composition.

8. A method for treatment of tumors of mammals which comprises:

(a) preheating the tumor to be treated and elevating its temperature above body temperature,

(b) administering a therapeutic dose of a tumoricidal agent encapsulated with a coating having a melting point higher than the temperature of the surrounding nontumor body tissue and within the elevated temperature range of the tumor into the interstices of the tumor and

(c) activating the tumoricidal agent by heating the same within the tumor interstices to a temperature above the melting point of its encapsulated coating.

9. A method for the administration of biologically active pharmaceuticals into a neoplasm of a mammal to reduce systemic side effects thereof which comprises:

(a) introducing intratumorally and extarcellularly into the interstices of the neoplasm within the segment of the mammal to be treated a therapeutic dose of microcapsules of a biologically active pharmaceutical substrate which has been precoated with a releasable encapsulating coating of lauric acid or esters of lauric acid which have a melting point range extending from 40°

-46°

C. and which will until the coating is removed remain substantially inert biologically;

(b) removing this coating from the pharmaceutical substrate to release the active agent within the interstices by radiofrequency heating of the microcapsules above the melt temperature of the coating.