Adjuvant immunotherapy for the preventive, curative or palliative treatment of chronic systemic diseases such as cancer, of clinical manifestations associated with diseases like cachexia and correction of adverse effects of drugs such as immunosuppression, neutropenia and lymphopenia, comprising the association or combination of a biological response modifier specially selected and other substances with antineoplastic action and/or other treatments

• US 9,295,682 B2
• Filed: 12/15/2009
• Issued: 03/29/2016
• Est. Priority Date: 12/15/2009
• Status: Active Grant

• Current Assignee: Iseu Da Silva Nunes
• Original Assignee: Iseu Da Silva Nunes
• Inventors: Nunes, Iseu da Silva
• Primary Examiner(s): Xiao, Yan
• Application Number:
  US13/516,628
• Publication Number:
  US 20120251441A1
• Time in Patent Office: 2,296 Days
• Field of Search: 424/85.2, 424/278.1
• US Class Current: 1/1
• 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 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention comprises a new combination or association of pharmacologically active substances and/or non-drug treatments for cancer. According to the present invention, the combination or association of substances and/or non-drug treatments is used to treat cancer, clinical problems associated to cancer and adverse side effects related to substances and/or treatments used to fight this illness. The components of the combination or association of substances, the biological response modifier (proteic aggregate of ammonium and magnesium phospholinoleate-palmitoleate anhydride) and at least one substance and/or treatment with antineoplastic properties can be jointly or simultaneously or consecutively or sequentially administered in an appropriate form, according to their chemical properties, and with the use of the most suitable procedures, and also in the most therapeutically effective dose and use.

Claims

1. A compound for use in a method of treatment of lung cancer, including precancerous lesions, and adverse events caused by said cancer or anti-cancer agents and treatments, including cancer cachexia, lymphopenia, neutropenia and febrile neutropenia of said cancer, the compound comprising in combination:

(a) an immunomodulator, wherein the immunomodulator is a proteic aggregate of ammonium and magnesium phospholinoleate-palmitoleate anhydride, with molecular weight of 320.000 Dalton, having of 11.6±

4.0% of total lipids (22.7±

5.0% of palmitoleic acid, 42.9±

2.0% of linoleic acid, 32.0±

3.0% of oxidated linoleic acid), 20.1±

0.9% of magnesium ions, 10.0±

3.3% of ammonium ions, 45.2+2.7% of phosphate, and 0.49±

0.01% of proteins, and

(b) at least one anti-cancer agent suitable for treating said cancer, said agent providing synergistic effects without additional toxicity when used with the immunomodulator, wherein the anti-cancer agent is cytokines (interleukin-2 (IL-2), interleukin 12(IL-12), interferon alpha, interferon alpha-2a, peginterferon alpha-2a, interferon alpha-2b, peginterferon alpha-2b, interferon alpha-n1, interferon alphacon-1, interferon beta, interferon beta-1a, interferon beta-1 b, tumor necrosis factor (TNF)), wherein the anti-cancer treatment is selected from the group consisting of;

surgical procedures (surgery, cryosurgery, electrocauterization, surgery associated to polarized light or laser with the use of photosensitizing substances, removal of lesions by chemical abrasion, removal of lesions by electrocauterization, endoscopic ablation, endoscopic radiofrequency ablation with the use of balloon catheter) transplantation of bone marrow cells, systemic and localized radiotherapy, and combinations thereof.

2. The compound according to claim 1, wherein the at least one anti-cancer agent is cytokines.

3. The compound according to claim 1, wherein the amino acid content in the proteic aggregate is:

Asp 7.19%, Thr 3.56%, Ser 7.56%, Glu 8.53%, Pro 0.5%, Gly 9.69%, Ala 7.46%, Val 1.0%, Met 4.38%, Isoleu 2.54%, Leu 3.03%, Tyr 0.5%, Phe L0%, His 2.83%, Lys 3.56%, Trp 1.3%, and Arg 35.2%.

4. The compound for use according to claim 1, wherein the cancer cachexia is selected from the group consisting of:

primary cancer cachexia and secondary cancer cachexia.

5. A method of treating a subject with lung cancer, the method comprising administering a therapeutically effective amount of the compound of claim 1 to a said subject;

wherein the anti-cancer agent or treatment is suitable for treating said cancer.

6. The method according to claim 5, wherein the immunomodulator and the anti-cancer agents or treatments to be associated to the immunomodulator, is performed jointly, simultaneously, consecutively or sequentially, in a procedure judged effective against said cancer.

7. The method according to claim 5 or 6, wherein the anti-cancer agent or treatment is suitable for treating the cancer lesion.

8. A method of treating cancer cachexia in a subject with lung cancer, the method comprising administering to the subject an effective amount of the compound according to claim 1.

9. The compound according to claim 1 wherein said synergistic effects are selected from the group consisting of potentiating therapeutic effects, increasing the time period of therapeutic effects, using smaller doses of anti-cancer agents, using higher doses of anti-cancer agents, recovering the effectiveness of the immune system, recovering of primary and secondary cachexia, recovering of neutropenia, febrile neutropenia and lymphopenia and a shorter period of treatment.

10. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition according to claim 1, further comprising a component selected from the group consisting of:

an excipient, a suspension, a transporter, a stabilizers and combinations thereof.

12. The pharmaceutical composition according to claim 11, wherein the composition is a preparation selected from the group consisting of:

an aqueous solution, a solid form solution, a microencapsulation, and liposomes.

13. The pharmaceutical composition according to claim 12, wherein the composition is present in an injectable form, or is present in an oral form.

14. Use of proteic aggregate of ammonium and magnesium phospholinoleate-palmitoleate anhydride, as a fixed component for the manufacture of new drugs with at least one other pharmacologically active compound or substance select among the compounds of claim 2.