Combinatorial therapies for the treatment of neoplasias using the opioid growth factor receptor

• US 8,003,630 B2
• Filed: 08/25/2006
• Issued: 08/23/2011
• Est. Priority Date: 02/26/2004
• Status: Active Grant

• Current Assignee: Pennsylvania State University
• Original Assignee: Penn State Research Foundation
• Inventors: McLaughlin, Patricia J., Smith, Jill P., Zagon, Ian S.
• Primary Examiner(s): SZNAIDMAN, MARCOS L
• Application Number:
  US11/510,682
• Publication Number:
  US 20070053838A1
• Time in Patent Office: 1,824 Days
• Field of Search: 424/1.69, 424/649, 514/34, 514/109
• US Class Current: 514/183
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/525 Isoalloxazines, e.g. riboflavins, vitamin B2
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/33 derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
• CPC Class Codes: A61K 41/00 : Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 51/00 : Preparations containing radioactive substances for use in therapy or testing in vivo
• CPC Class Codes: A61N 5/10 : X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to pharmaceutical compositions for treating neoplasias in an animal or human comprised of a carrier and therapeutically effective amounts of at least one chemotherapeutic agent along with the biotherapeutic endogenous pentapeptide Met-enkephalin, referred to as opioid growth factor. Also provided are methods of treating neoplasias in an animal or human in need of such treatment, comprising the administration to the animal or human therapeutically effective amounts of a pharmaceutical composition comprised of a carrier and therapeutically effective amounts of at least one neoplasia-treating agent, such as a chemotherapeutic agent or radiation, along with opioid growth factor.

Claims

1. A method for treating pancreatic cancer characterized by an opioid growth factor receptor in a patient in need of such treatment, comprising:

administering to said patient a combination regimen of gemcitabine and opioid growth factor capable of increasing the kill rate of pancreatic cancer cells and improving quality of life greater than achieved with the gemcitabine or opioid growth factor alone, wherein said regimen includes 120 mg/kg body weight of gemcitabine and 10 mg/kg body weight of opioid growth factor.

2. The method of claim 1, wherein the opioid growth factor is administered daily and the gemcitabine is administered every three days.

3. The method of any one of claims 1 and 2, wherein the gemcitabine is administered intravenously over a period of between about 10 to 60 minutes.

4. The method of claim 2, wherein the method is continued for a period of at least 3 weeks.

5. The method of any one of claims 2 and 4, wherein the opioid growth factor is administered simultaneously with the gemcitabine.

6. The method of claim 1 wherein the opioid growth factor is administered sequentially with the gemcitabine.

7. The method of claim 1, wherein the gemcitabine or opioid growth factor is administered parenterally, intravenously, intramuscularly, intraperitoneally, subcutaneously, by implanted osmotic pump or by transdermal patch.

8. A method of increasing the anti-neoplastic effects of gemcitabine comprising the step of introducing into pancreatic cancer cells from 120 mg/kg body weight of gemcitabine in combination with from 10 mg/kg body weight of opioid growth factor.

9. The method of claim 8, wherein the anti-neoplastic effects observed with said combination are greater than the anti-neoplastic effects of the gemcitabine alone.

10. A method of killing pancreatic cancer cells characterized by an opioid growth factor receptor in a patient in need of such treatment, comprising:

administering to said patient from 120 mg/kg body weight of gemcitabine and from 10 mg/kg body weight of opioid growth factor, wherein the anti-neoplastic effects observed with said combination are greater than the anti-neoplastic effects of the gemcitabine alone.