COMPOSITION TO BE USED FOR STRENGTHENING THE IMMUNE SYSTEM IN HUMAN AND ANIMAL TO ACQUIRE PAN-IMMUNITY

Abstract

The disclosure concerns a composition for strengthening the immunity system to acquire pan-immunity, for the prevention and treatments of infectious and other diseases with immunological components, including eliminating cancer cells. The administration of the composition can be by oral, parenteral or non-parenteral routes, local injection, topical application, or in combinations thereof, and the administration of the composition as adjuvant potentiator in various therapies/treatments uses the aforenamed routes. The composition contains, as active ingredients, an extract of Allium species and an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species.

Claims

1. A composition to be used for strengthening the immunity system in a human subject or an animal subject, the composition comprising as active ingredients an extract of Allium species and an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species.

2. A composition for strengthening the immunity system according to claim 1, wherein the extract of Paullinia species and/or the extract of Theobroma species are atomized.

3. A composition for strengthening the immunity system according to claim 1, said wherein the composition comprises from 20% to 80% by weight of the extract of Allium species, from 1.5% to 20% by weight of the extract of Citrus species, from 0.05% to 5.0% by weight of the extract of Paullinia species, and from 0.05% to 5.0% by weight of the extract of Theobroma species based on the total weight of the four active ingredients.

4. A composition for strengthening the immunity system according to claim 1, said wherein the extract of Allium species comprises an extract of Allium cepa, the extract of Citrus species comprises an extract of Citrus limon, the extract of Paullinia species comprises an extract of Paullinia cupana, and the extract of Therobroma species comprises an extract of Therobroma cacao, and wherein the composition comprises from 60% to 70% by weight of the extract of Allium cepa, from 7% to 12% by weight of the extract of Citrus limon, from 0.08% to 0.20% by weight of the extract of Paullinia cupana, and from 0.06% to 0.18% by weight of the extract of Theobroma cacao based on the total weight of the four active ingredients.

5. A composition for strengthening the immunity system according to claim 1, wherein the extract of Allium species comprises an extract of Allium cepa, the extract of Citrus species comprises an extract of Citrus limon, the extract of Paullinia species comprises an extract of Paullinia cupana, and the extract of Therobroma species comprises an extract of Therobroma cacao, and wherein the composition comprises from 32% to 45% by weight of the extract of Allium cepa, 6% to 12% of the extract of Citrus limon, 2% to 3% of the extract of Paullinia cupana, 0.25% to 3.2% of an hydroalcoholic extract of the extract of Theobroma cacao.

6. A composition for strengthening the immunity system according to claim 1, wherein the composition further comprises as excipients from 1.0% to 8.0% by weight of sodium chloride and from 10% to 40% by weight of glycerine based on the total weight of the composition.

7. A composition for strengthening the immunity system according to claim 1, to be used to acquire pan-immunity.

8. A composition for strengthening the immunity system according to claim 1, to be used to acquire pan-immunity and to prevent and to treat infectious and other immune-related diseases that are due to dysfunction of immune system including eliminating cancer cells.

9. A composition for strengthening the immunity system according to claim 1, to be used as an adjuvant potentiator in various therapies or treatments.

10. A composition for strengthening the immunity system according to claim 1, in an appropriate form to be administrated by parenteral, non-parenteral, oral, local, topical routes, or in combinations thereof.

11. A supplemental immunity composition comprising: greater than or equal to about 20 wt. % to less than or equal to about 80 wt. % of an Allium species extract; greater than or equal to about 1.5 wt. % to less than or equal to about 20 wt. % of a Citrus species extract; greater than or equal to about 0.05 wt. % to less than or equal to about 5 wt. % of a Paullinia species extract; greater than or equal to about 0.05 wt. % to less than or equal to about 5 wt. % of a Theobroma species extract; greater than or equal to about 1 wt. % to less than or equal to about 8 wt. % of sodium chloride; and greater than or equal to about 10 wt. % to less than or equal to about 40 wt. % of glycerine.

12. The supplemental immunity composition of claim 11, wherein the Allium species extract comprises an Allium cepa extract.

13. The supplemental immunity composition of claim 11, wherein the Citrus species extract comprises a Citrus limon extract.

14. The supplemental immunity composition of claim 11, wherein the Paullinia species extract comprises a Paullinia cupana extract.

15. The supplemental immunity composition of claim 11, wherein the Theobroma species extract comprises a Theobroma cacao extract.

16. The supplemental immunity composition of claim 11, wherein at least one of the Paullinia species extract and the Theobroma species extract is atomized.

17. A method for strengthening the immunity system in subject, the method comprising: administering to the subject a supplemental immunity composition comprising: an extract of Allium species; an extract of Citrus species; an extract of Paullinia species; and an extract of Theobroma species.

18. The method of claim 17, wherein the supplemental immunity composition comprises: greater than or equal to about 20 wt. % to less than or equal to about 80 wt. % of the Allium species extract; greater than or equal to about 1.5 wt. % to less than or equal to about 20 wt. % of the Citrus species extract; greater than or equal to about 0.05 wt. % to less than or equal to about 5 wt. % of the Paullinia species extract; and greater than or equal to about 0.05 wt. % to less than or equal to about 5 wt. % of the Theobroma species extract.

19. The method of claim 17, wherein the supplemental immunity composition further comprises: greater than or equal to about 1 wt. % to less than or equal to about 8 wt. % of sodium chloride; and greater than or equal to about 10 wt. % to less than or equal to about 40 wt. % of glycerine.

20. The method of claim 17, wherein the Allium species extract comprises an Allium cepa extract, the Citrus species extract comprises a Citrus limon extract, the Paullinia species extract comprises a Paullinia cupana extract, and the Theobroma species extract comprises a Theobroma cacao extract.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] FIG. 1: VWRA of placebo-mice was greatly reduced, and reached the lowest running distance at day 3 post-irradiation. Mice recovered gradually over the next several days, returning to the initial running distance measured in the pre-irradiation period.

[0027] FIG. 2: Average cumulative distance run during post-irradiation by “the composition” group (“Drug”) was 17% greater than Placebo group. “The composition” group mice returned to daily running distance baseline after 7 days; placebo mice returned to baseline running distance 12 days after irradiation.

[0028] FIG. 3: As in the described model, a decrease in voluntary wheel speed is most pronounced during the late hours of the active phase (i.e. dark cycle). The average post-irradiation running speed was systematically greater in the “the composition” group (“Drug”) versus placebo group, in every section of the active phase.

[0029] FIG. 4: As in the described model, a decrease in voluntary wheel distance is most pronounced during the late hours of the active phase (i.e. dark cycle). The average post-irradiation running distance was systematically greater in the “the composition” group (“Drug”) versus placebo group, in every section of the active phase.

[0030] FIG. 5: Both “the composition” and Placebo were given in a 1% saccharin solution. Volume of solution consumed by mice in “the composition” group (“Drug”) was less than mice in Placebo group, before and after irradiation.

[0031] FIG. 6: The mean group body weight showed that there was no difference in body weight between mice in Placebo group and mice in “the composition” group (“Drug”).

DETAILED DESCRIPTION

[0032] It has been discovered that the administration by oral route, or parenteral route, or local injection, or a combination thereof, of a composition containing as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species, has a novel and previously unknown effect for strengthening the immune system in human and animal in order to acquire pan-immunity.

[0033] A composition comprising the ingredients mentioned hereafter was administered topically to human subjects with abnormal conditions in terms of inflammation. It was observed that, the composition significantly improved the inflammatory skin condition thanks to the anti-inflammatory function of the composition.

[0034] The present invention proposes a method for the improvement/strengthening of the immune system; comprising the administration by oral, parenteral, topical application, or local injection, and/or as adjuvant potentiator in various therapies/treatments, or in combination, of a composition containing as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species.

[0035] In particular, the present invention concerns a method for strengthening immunity system; comprising the administration by oral route, or parenteral route, or topical application, or injection, or a combination thereof, of a composition containing as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species. Among the methods for strengthening immunity system to acquire pan-immunity, according to the invention, those which are of more particular interest are the methods in which the preferred composition contains from 20% to 80% by weight of an extract of Allium species, from 1.5% to 20% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species and from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients. According to an embodiment, the composition comprises from 20% to 80% by weight of an extract of Allium species, from 1.5% to 20% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, from 1.0% to 8.0% by weight of Sodium chloride and from 10% to 40% by weight of glycerine, based on the total weight of the composition.

[0036] Among the methods for strengthening the immunity system, 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 (local or systemic), but also as an adjuvant potentiator in therapies/treatments for strengthening the immunity system to acquire pan-immunity. The compositions contain from 20% to 80% by weight of an extract of Allium species, from 1.5% to 20% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species and from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, based on the weight of the four active ingredients.

[0037] According to an embodiment, the compositions contain from 20% to 80% by weight of an extract of Allium species, from 1.5% to 20% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species and from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients. According to an embodiment, the composition comprises from 20% to 80% by weight of an extract of Allium species, from 1.5% to 20% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, from 1.0% to 8.0% by weight of Sodium chloride and from 10% to 40% by weight of glycerine, based on the total weight of the composition.

[0038] 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.

[0039] The term genus citrus refers particularly to the family Rutaceae, especially Citrus limon.

[0040] The term extract (atomized or not) of Paullinia species refers particularly to extracts and native extracts obtained from all species of the genus Paullinia (family Sapindaceae), especially Paullinia cupana (Guarana).

[0041] The term extract (atomized 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.

[0042] The most preferred compositions used according to the invention are: those containing approximately 66% by weight of an extract of Allium cepa, approximately 9% by weight of an extract of Citrus limon, approximately 0.11% by weight of an extract (atomized or not) of Paullinia cupana and approximately 0.11% 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, an extract of Citrus species and an extract of Paullinia 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 ingredients an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species.

[0043] In order to obtain a measurable effect on the strengthening of the immunity system to acquire pan-immunity, it is necessary to perform the administration of the compositions chronically. 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 or liquid solution. For example, the composition can be orally administered in human, twice daily, with 5 ml each intake.

[0044] The present invention also concerns a composition containing as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species for use in strengthening the immunity system in order to acquire pan-immunity, by oral, parenteral, other above-mentioned routes, and/or as adjuvant potentiator in various therapies/treatments, or in combination thereof. According to an embodiment of the invention the composition for use in strengthening the immunity system in order to acquire pan-immunity contains an extract of Allium species, an extract of Citrus species and an extract (atomized or not) of Paullinia species and an extract (atomized or not) of Theobroma species. According to a further embodiment of the invention the composition for use in strengthening the immunity system in order to acquire pan-immunity, contains from 20% to 80% by weight of an extract of Allium species, from 1.5% to 20% by weight of an extract of Citrus species, from 0.05% to 5.0% by weight of an extract (atomized or not) of Paullinia species and from 0.05% to 5.0% by weight of an extract (atomized or not) of Theobroma species, based on the total weight of the four active ingredients.

EXAMPLES OF COMPOSITIONS/TREATMENTS

Example 1

[0045] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0046] an extract of Allium cepa (containing quercetin): 71% [0047] an extract of Citrus limon: 1.7% [0048] an atomised extract of Paullinia cupana: 4.5% [0049] an atomised extract of Theobroma cacao: 4.8%

Example 2

[0050] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0051] an extract of Allium cepa (containing quercetin): 60.50% [0052] an extract of Citrus limon: 5.25% [0053] an atomised extract of Paullinia cupana: 2.5% [0054] an atomised extract of Theobroma cacao: 2.3%

Example 3

[0055] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0056] an extract of Allium cepa (containing quercetin): 52.50% [0057] an extract of Citrus limon: 6.20% [0058] an atomised extract of Paullinia cupana: 1% [0059] an atomised extract of Theobroma cacao: 1%

Example 4

[0060] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0061] an extract of Allium cepa (containing quercetin): 48.50% [0062] an extract of Citrus limon: 20.5% [0063] an atomised extract of Paullinia cupana: 1.5% [0064] an atomised extract of Theobroma cacao: 1.35%

Example 5

[0065] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0066] an extract of Allium cepa (containing quercetin): 45.50% [0067] an extract of Citrus limon: 20% [0068] an atomised extract of pulverized Paullinia cupana: 0.75% [0069] an atomised extract of Theobroma cacao: 0.65%

Example 6

[0070] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0071] an extract of Allium cepa (containing quercetin): 31.50% [0072] an extract of Citrus limon: 18% [0073] an atomised extract of Paullinia cupana: 0.15% [0074] an atomised extract of pulverized Theobroma cacao: 0.18%

Example 7

[0075] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0076] an extract of a species of the genus Allium belonging to the family Liliaceae other than Allium cepa: 30.50% [0077] an extract of Citrus limon: 3.20% [0078] an extract of Paullinia cupana: 0.06% [0079] an atomised extract of Theobroma cacao: 0.05%

Example 8

[0080] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0081] an extract of Allium cepa: 30.50% [0082] an extract of Citrus limon: 3.20% [0083] an atomised extract of Paullinia cupana: 0.06% [0084] an extract of Theobroma cacao: 0.05%

Example 9

[0085] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0086] an extract of Allium cepa: 35.50% [0087] an extract of Citrus limon: 3.80% [0088] an atomised extract of Paullinia cupana: 0.03% [0089] an atomised extract of Theobroma cacao: 0.03%

Example 10

[0090] The mice have received, every day by oral route, a treatment with a composition having, independently from the excipients, the following composition: [0091] an extract of Allium cepa 36.45% [0092] an extract of Citrus limon: 10% [0093] an extract of Paullinia cupana: 2.5% [0094] an hydroalcoholic extract of Theobroma cacao : 1.35%
The excipients used in the above examples are from 1.0% to 8.0% by weight of sodium chloride and from 10% to 40% by weigh of glycerine, based on the total weight of the composition.

EXPERIMENTAL RESULTS

[0095] The results are obtained by using the above compositions within the ranges in the examples 1 to 10. For all the above compositions, the tests performed on mice have surprisingly shown a strengthening of their immunity system significantly demonstrated according to a mode of evidence known in the art, as explained above, measured by their increased wheel running capacity in comparison with the level of their immunity system before intake of the composition.

[0096] This indicates that the composition according to the present invention is capable of positively influencing and strengthening the immunity system.

[0097] Our studies have shown that a composition comprising the ingredients mentioned hereafter enabled significant improvement of health conditions related to strengthened and good function of immune system.

Example 1: Wheel Running Activity

[0098] The study outcome summary is presented below in Table 1 and FIGS. 1-6.

TABLE-US-00001 TABLE 1 Outcome of study on the composition to improve immunologic status in a mouse model, that is shown by enhanced Voluntary Wheel Running Activity (VWRA) FIG. Topic Study on “the composition” (see FIG.) Experimental 20 mice irradiated (800 cGy) setting 10 taking “the composition” 10 taking Placebo 1 Irradiation VWRA of Placebo mice reached the lowest and VWRA amount of VWRA 3 days post-irradiation. Mice recovered gradually over the next several days, until returned to baseline running distance of pre- irradiation period. 2 Effect of “the Average cumulative distance run during post- composition” irradiation by “the composition” group was 17% on VWRA greater than Placebo group. after Statistically significant difference in several time- irradiation points. “The composition” group mice returned to daily running baseline distance after 7 days. Placebo mice returned to baseline running distance 12 days after irradiation. 3 Speed by 4 As previously observed in the model, a decrease hours in voluntary wheel running speed was most increment pronounced during the late hours of the active during of the phase (i.e. dark cycle). active phase The post-irradiation running speed was (dark cycle) systematically greater in “the composition” group versus Placebo group, in every section of the active phase. Statistically significant difference in several time- points. 4 Distance by Distance was systematically greater in “the 4 hours composition” group versus Placebo group, in increment every section of the active phase. during of the Statistically significant difference in several time- active phase points. (dark cycle) As observed in the model, decreases in voluntary wheel running distance were most pronounced during the late hours of the active phase. 5 Solution Volume of solution consumed by mice in “the consumption composition” group was less than mice in Placebo group, before and after irradiation. Statistically significant difference in several time- points. 6 Body weight There was no difference in body weight between mice in Placebo group and mice in “the composition” group. Other No overt co-morbidities, such as anemia, physiological anhedonia (assessed by saccharine preference &behavioral testing), change in weight, etc., were observed. observation

Example 2: Immunity-Improving/Immunomodulatory/Anti-Inflammatory Effect

[0099] The study outcome summary is presented below in Tables 2-4. The composition within the ranges in the examples 1 to 10, containing as active ingredient an extract of Allium species, an extract of Citrus species and an extract of Paullinia species and an extract of Theobroma species, was used to perform the study on its immunity-improving/immunomodulatory/anti-inflammatory effect via down-regulation of TNF alpha-induced expression of pro-inflammatory molecules: Interleukin-8, ICAM-1 and E-selectin, as summarized in Table 2-4.

TABLE-US-00002 TABLE 2 The effects of “composition” on the expression of cytokine Interleukin-8 (IL-8) by endothelial cells (HUVECs) Non-treated TNF-treated % Increase (+) cells cells % Reduction (−) measured by measured by compared to Composition sABC* sABC* control Medium (control) 1 164 5 406 Composition   887 4 827 −11% *specific Antibody Bound per Cell

TABLE-US-00003 TABLE 3 The effects of “composition” on the expression of adhesion molecule E-selectin/ELAM-1 (CD62E) on the surface of endothelial cells (HUVECs) Non-treated TNF-treated % Increase (+) cells cells % Reduction (−) measured by measured by compared to sABC* sABC* control Medium (control) Non detectable 3 074 Composition 65 1 648 −46% *specific Antibody Bound per Cell

TABLE-US-00004 TABLE 4 The effects of “composition” on the expression of adhesion molecule ICAM-1 (CD54) on the surface of endothelial cells (HUVECs) TNF-treated % Increase (+) Non-treated cells cells % Reduction (−) measured by measured by compared to sABC* sABC* control Medium (control) 3 172 386 181 Composition 1 664 254 171 −34% *specific Antibody Bound per Cell

[0100] Hence, the above study shows that a composition according to the invention enabled modulation of the over-reaction of immune response through anti-inflammation. Consequently, the composition improved health condition as a result of good functioning of the strengthened immune system. Thus, a composition according to the invention provides a method for strengthening the immune system for good immune functions and finally acquire pan-immunity.