Method For The Management Of Cancer And Cancer Treatment-Related Comorbidities

Abstract

A method for the management of cancer and treatment of cancer comorbidities, including but not limited to cancer-related fatigue, cachexia, anorexia, pain, anemia, asthenia, depression, muscle weakness, nausea, vomiting, skin, and skin appendages adverse reactions; the method including the administration by the conventional and non-conventional oral, topical, parenteral routes and intra-tumoral injection, or in combination thereof, or the administration as adjuvant potentiator in other therapies using the forenamed routes, of a composition containing as active ingredient an extract of Allium species, which contains querceting, an extract of Citrus species and an extract of Pauffinia species and an extract of Theobroma species.

Claims

1. A method for managing cancer and for treating at least one cancer comorbidity selected from the group consisting of cachexia, anorexia, pain, anemia, asthenia, depression, muscle weakness, nausea, vomiting, adverse skin reactions, adverse skin appendages reactions, and a combination thereof in a subject in need thereof, the method comprising: administering to the subject, by an oral route, a topical route, a parenteral route, an intra-tumoral injection, or a combination thereof, a composition comprising as active ingredients an extract of Allium species comprising quercetin, an extract of Citrus species, an extract of Pauffinia species, and an extract of Theobroma species.

2. The method according to claim 1, wherein the composition contains the extract of the Allium species comprising quercetin, the extract of the Citrus species, an atomized extract of the Pauffinia species and an atomized extract of the Theobroma species.

3. The method according to claim 1, wherein the composition comprises: from 30% to 93% by weight of the extract of the Allium species comprising quercetin, from 3% to 33% by weight of the extract of the Citrus species, from 0.10% to 2.5% by weight of the atomized extract of the Paullinia species, and from 0.10% to 2.5% by weight of the atomized extract of the Theobroma species, wherein the percentages are based on the total weight of the four active ingredients.

4. The method according to claim 1, wherein the at least one cancer comorbidity comprises pain, depression, muscle weakness, adverse skin reactions, adverse skin appendages reactions, or a combination thereof.

5. The method according to claim 1, wherein the extract of Allium species is an extract of Allium cepa.

6. The method according to claim 1, wherein the extract of Citrus species is an extract of Citrus lemon.

7. The method according to claim 1, wherein the extract of Pauffinia species is an extract of Pauffinia cupana.

8. The method according to claim 1, wherein the extract of Theobroma species is an extract of Theobroma cacao.

9. The method according to claim 1, wherein the composition comprises: approximately 87% by weight of an extract of Allium cepa comprising quercetin; approximately 12% by weight of an extract of Citrus lemon; approximately 0.5% by weight of an extract of Pauffinia cupana; and approximately 0.5% by weight of an extract of Theobroma cacao, wherein the percentages are based on the total weight of the four active ingredients.

10. A method for managing cancer and for treating at least one cancer comorbidity in a subject in need thereof, the method comprising: administering to the subject a composition comprising an extract of Allium species, an extract of Citrus species, an extract of Pauffinia species, and an extract of Theobroma species.

11. The method according to claim 10, wherein the extract of Allium species comprises quercetin.

12. The method according to claim 10, wherein the administering is performed orally, topically, or parenterally.

13. The method according to claim 10, wherein at least one of the extract of Pauffinia species or the extract of Theobroma species is atomized.

14. The method according to claim 10, wherein the composition comprises: from 30% to 93% by weight of the extract of the Allium species; from 3% to 33% by weight of the extract of the Citrus species; from 0.10% to 2.5% by weight of the extract of the Pauffinia species; and from 0.10% to 2.5% by weight of the extract of the Theobroma species, wherein the percentages are based on the total weight of the extract of Allium cepa, the extract of Citrus lemon, the extract of Pauffinia cupana, and the extract of Theobroma cacao.

15. The method according to claim 10, wherein the composition consists of the extract of Allium species, the extract of Citrus species, the extract of Pauffinia species, and the extract of Theobroma species.

16. The method according to claim 10, wherein the at least one cancer comorbidity is cancer-related fatigue, cachexia, anorexia, pain, anemia, asthenia, depression, muscle weakness, nausea, vomiting, adverse skin reactions, adverse skin appendages reactions, or a combination thereof.

17. A method for managing cancer and for treating at least one cancer comorbidity in a subject in need thereof, the method comprising: administering to the subject a composition comprising: from 30% to 93% by weight of an extract of Allium cepa comprising quercetin; from 3% to 33% by weight of an extract of Citrus lemon; from 0.10% to 2.5% by weight of an extract of Pauffinia cupana; and from 0.10% to 2.5% by weight of an extract of Theobroma cacao, wherein the percentages are based on the total weight of the extract of Allium cepa, the extract of Citrus lemon, the extract of Pauffinia cupana, and the extract of Theobroma cacao.

18. The method according to claim 17, wherein the composition comprises: approximately 87% by weight of the extract of Allium cepa comprising quercetin; approximately 12% by weight of the extract of Citrus lemon; approximately 0.5% by weight of the extract of Pauffinia cupana; and approximately 0.5% by weight of the extract of Theobroma cacao.

19. The method according to claim 17, wherein the composition consists of the extract of Allium cepa comprising quercetin, the extract of Citrus lemon, the extract of Pauffinia cupana; and the extract of Theobroma cacao.

20. The method according to claim 17, wherein the administering comprises administering the composition to the subject daily for at least 6 months.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 corresponds to the curves of the mean body weight (in grams) measured at different times.

[0015] FIG. 2 corresponds to the curves of the mean tumor volume (in mm.sup.3) measured at different times.

DETAILED DESCRIPTION

[0016] In particular, the present invention concerns a method for the management of cancer and treatment of cancer comorbidities, including but not limited to cancer-related fatigue, cachexia, anorexia, pain, anemia, asthenia, depression, impaired cognitive function, loss of appetite, muscle weakness, nausea, vomiting, arthritis, organ damage, including but not limited to radiation-induced burns, heart disorders due to cardiotoxicity by chemo- and radiotherapy, hypertension, thromboembolism, occasional chest pain, difficulty in breathing, shortness of breath, dizziness, fainting, pallor (pale skin or lips), headaches, difficulty in concentrating, insomnia, difficulty in staying warm, bleeding problems, nail damages, and skin appendages adverse reactions, exampled by irritation and dry skin, sore and dry ulcerated mouths; comprising the administration by oral route, topical, or parenteral route, intra-tumoral injection, or a combination thereof, of a composition containing as active ingredient an extract of Allium species, which may contain quercetin, an extract of Citrus species and an extract of Pauffinia species and an extract of Theobroma species. Among the methods for the management of t cancer and treatment of cancer comorbidities, according to the invention, those which are of more particular interest are the methods in which the preferred oral composition contains from 30% to 93% by weight of an extract of Allium species, which contains quercetin, from 3% to 33% by weight of an extract of Citrus species, from 0.10% to 2.5% by weight of an extract (atomized or not) of Pauffinia species and from 0.10% to 2.5% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients.

[0017] According to an embodiment, the composition comprises from 30% to 93% by weight of an extract of Allium species, which contains quercetin, from 3% to 33% by weight of an extract of Citrus species, from 0.10% to 2.5% by weight of an extract (atomized or not) of Pauffinia species, from 0.10% to 2.5% by weight of an extract (atomized or not) of Theobroma species, from 0.5% to 3.0% by weight of Sodium chloride and from 25% to 50% by weight of Glycerin, based on the total weight of the composition. Among the methods for the management of cancer and treatment of cancer comorbidities, those which are the more preferred interest are the methods in which the compositions are used not only as conventional oral composition, composition for injection, topical application, but also as an adjuvant potentiator in for the management of cancer and its treatment-related comorbidities. The compositions contain from 30% to 93% by weight of an extract of Allium species, which contains quercetin, from 3% to 33% by weight of an extract of Citrus species, from 0.10% to 2.5% by weight of an extract (atomized or not) of Pauffinia species and from 0.10% to 2.5% by weight of an extract (atomized or not) of Theobroma species, based on the weight of the four active ingredients.

[0018] According to an embodiment, the compositions contain from 30% to 93% by weight of an extract of Allium cepa, from 3% to 33% by weight of an extract of Citrus lemon, from 0.10% to 2.5% by weight of an extract (atomized or not) of Pauffinia species and from 0.10% to 2.5% by weight of an extract (atomized or not) of Theobroma species, based on the weight of the four active ingredients. According to an embodiment, the composition contains from 30% to 93% by weight of an extract of Allium species, which contains quercetin, from 3% to 33% by weight of an extract of Citrus species, from 0.10% to 2.5% by weight of an extract (atomized or not) of Pauffinia species, from 0.10% to 2.5% by weight of an extract (atomized or not) of Theobroma species, from 0.5% to 3.0% by weight of Sodium chloride and from 25% to 50% by weight of Glycerin, based on the total weight of the composition.

[0019] The term extract of Allium species refers particularly to extracts and native extracts obtained from all species of the genus Allium (family Liliaceae) and especially Allium cepa, which may contain quercetin. The term extract of Citrus species refers particularly to extracts and native extracts obtained from all species of the genus Citrus (family Rutaceae) and especially Citrus lemon. The term extract (atomised or not) of Pauffinia species refers particularly to extracts and native extracts obtained from all species of the genus Pauffinia (family Sapindaceae) and especially Pauffinia cupana. The term extract (atomised or not) of Theobroma species refers particularly to aqueous-alcoholic extracts and native extracts obtained from all species of the genus Theobroma (family Malvaceae) and especially Theobroma cacao.

[0020] The most preferred compositions used according to the invention are: those containing approximately 87% by weight of an extract of Allium cepa, which contains quercetin, approximately 12% by weight of an extract of Citrus lemon, approximately 0.5% by weight of an extract (atomized or not) of Pauffinia cupana and approximately 0.5% by weight of an extract (atomized or not) of Theobroma cacao, based on the total weight of the four active ingredients. According to the invention, the composition is chronically administered in a mixture containing as active ingredient an extract of Allium species, which contains quercetin, an extract of Citrus species and an extract of Pauffinia species and an extract of Theobroma species. According to an embodiment of the invention the composition is administered daily during a period of several months or longer with a composition containing as active ingredient an extract of Allium species, which contains quercetin, an extract of Citrus species and an extract of Pauffinia species and an extract of Theobroma species.

[0021] In order to obtain a measurable effect on the management of cancer and treatment of cancer comorbidities, it is necessary to perform the administration of the compositions chronically, preferably during at least 6 months. When using the compositions obtained according to the invention, doses may vary within relatively wide limits and must be set according to the person being treated and the condition concerned. Pharmaceutical compositions normally contain from 0.4 to 1000 mg, preferably from 2 to 400 mg, of active ingredients as defined above, in the form of dry extract.

[0022] The present invention also concerns a composition containing as active ingredient an extract of Allium species, which contains quercetin, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species for use in the management of cancer and for the treatment of cancer comorbidities, including but not limited to cancer-related fatigue, cachexia, anorexia, pain, anemia, asthenia, depression, muscle weakness, nausea, vomiting, skin, and skin appendages adverse reactions; by both conventional and non-conventional routes, and/or as adjuvant potentiator in cell therapies, or topical route, or parenteral route, or intra-tumoral injection, or in combination thereof. According to an embodiment of the invention the composition for use in the management of cancer and for the treatment of cancer comorbidities contains an extract of Allium species, which contains quercetin, an extract of Citrus species and an extract (atomized or not) of Pauffinia species and an extract (atomized or not) of Theobroma species. According to a further embodiment of the invention the composition for use in the management of cancer and for the treatment of cancer comorbidities, contains from 30% to 93% by weight of an extract of Allium species, which contains quercetin, from 3% to 33% by weight of an extract of Citrus species, from 0.10% to 2.5% by weight of an extract (atomized or not) of Pauffinia species and from 0.10% to 2.5% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients.

EXAMPLE OF THE TREATMENT

[0023] The patients have received, every day by oral, topical, parenteral routes, or intra-tumoral injection, alone or in combination, a treatment containing: [0024] an extract of Allium cepa (containing querceting): 87.04% [0025] an extract of Citrus lemon: 11.96% [0026] an atomised extract of Paullinia cupana: 0.50% [0027] an atomised extract of Theobroma cacao: 0.50% (hereafter composition A).

[0028] Ohis lotion has been prepared as indicated in example 1 of patent application WO 2008/113912. Composition A which is a mixture of four natural ingredients has been reported to beneficially affect defects in abnormal cell apoptosis, as well as in inflammatory processes. This has indicated that composition A is capable of affecting positively in the management of the above-mentioned cancer and cancer treatment related comorbidities.

Example 1

[0029] Study of the composition, containing as active ingredient an extract of Allium species, which contains quercetin, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species, on its anti-inflammatory effect via inhibiting TNF alpha-induced expression of pro-inflammatory molecules: ICAM-1, E-selectin and Interleukin 8, as summarized Table 2a, 2b and 2c).

TABLE-US-00001 TABLE 1 The tested compositions Compound Ingredient in total % wt A Allium Cepa 50.0 Citrus 50.0 B Allium Cepa 87.5 Citrus 12.5 C Allium Cepa 87.0 Citrus 12.0 Guarana dry extract 0.5 Cacao dry extract 0.5 Control Medium

TABLE-US-00002 TABLE 2a The effects of compositions on the expression of adhesion molecule ICAM-1 (CD54) on the surface of endothelial cells (HUVECs) % Increase (+) Non-treated TNF-treated % Reduction () cells measured cells measured compared to Composition by sABC* by sABC* control Medium 3 172 386 181 (control) A 2 061 296 561 23% B 1 947 297 444 23% C 1 664 254 171 34% *specific Antibody Bound per Cell

TABLE-US-00003 TABLE 2b The effects of compositions on the expression of adhesion molecule E-selectin/ELAM-1 (CD62E) on the surface of endothelial cells (HUVECs) % Increase (+) Non-treated TNF-treated % Reduction () cells measured cells measured compared to Composition by sABC* by sABC* control Medium Non detectable 3 074 (control) A 251 4 235 +38% B 186 3 447 +12% C 65 1 648 46% *specific Antibody Bound per Cell

TABLE-US-00004 TABLE 2c The effects of compositions on the expression of cytokine Interleukin 8 (IL-8) by endothelial cells (HUVECs) % Increase (+) Non-treated TNF-treated % Reduction () cells measured cells measured compared to Composition by sABC* by sABC* control Medium 1 164 5 406 (control) A 1 067 6 274 +16% B 1 015 5 563 +3% C 887 4 827 11% *specific Antibody Bound per Cell

Example 2

[0030] Study on the anti-tumor activity of a new composition using nude mice carrying subcutaneous human tumor of type KB. FIG. 1 illustrates the curves of the average weight of nude mice bearing subcutaneous human tumor type KB. Mice were randomized at Day 7 and received a daily injection of 100 l composition solution (THI) of 0.3% and 1.0% respectively for five consecutive days.

[0031] In FIG. 1, x-axis represents time (days); y-axis represents average weight of nude mice (g). Blue (curve 2): control vehicle; Pink (curve 3): composition (THI) of 0.3%; Yellow (curve 1): composition (THI) of 1%. No significant weight changes were observed.

[0032] FIG. 2 illustrates the curves of the mean tumor volume of nude mice bearing subcutaneous human tumor type KB. Mice were randomized at Day 7 and received a daily injection of 100 l composition solution (THI) of 0.3% and 1.0% respectively for five consecutive days. In FIG. 2, x-axis represents time (days); y-axis represents average tumor volume of nude mice (mm3). Blue (curve 2): control vehicle; Pink (curve 3): composition (THI) of 0.3%; Yellow (curve 1): composition (THI) of 1%. No significant weight changes were observed. Composition (THI) 0.3% show anti-tumor effect compared to control.