WO2005072253A2

WO2005072253A2 - An improved herbal therapeutic composition for treating cardiovascular diseases

Info

Publication number: WO2005072253A2
Application number: PCT/US2005/001924
Authority: WO
Inventors: Chaim Jeremiah Lieberman
Original assignee: Advanced Plant Pharmaceuticals, Inc.
Priority date: 2004-01-21
Filing date: 2005-01-21
Publication date: 2005-08-11
Also published as: WO2005072253A3

Abstract

A therapeutic herbal composition useful in lowering cholesterol, and treating arthritis, blood pressure and Alzheimer’s disease. The composition includes trigonella foenum-graecum seed, Syzygium aromaticum fruit, Allilum sativum bulb, Cinnamonmum zyelanicum bark, Saussurea costus root and Alfalfa which includes an effective amount of sodium chloride to promote the digestibility and storage stability of the compositions, have been shown effective in reducing cholesterol.

Description

An Improved Herbal Therapeutic Composition for Treating Cardiovascular Diseases

BACKGROUND OF THE INVENTION 1. Field of the Invention The subject invention relates generally to a therapeutic herbal composition, and in particular to an herbal composition which includes Trigonellafoenum- graecum seed, Syzygium aromaticum fruit, Allilum sativum bulb, Cinnamonmum zyelanicum bark, Saussurea costus root and Alfalfa. This therapeutic herbal composition is formed from a synergistic combination of herbs which are useful in lowering cholesterol, and treating arthritis, blood pressure and Alzheimer's disease. It is also useful as a bitters tonic.

2. Description of the Related Art Although the use of various herbs have been described in related areas, the synergistic combination of the subject invention has never previously been described.

Japanese Patent Publication No. 4,005,237 teaches the combination of Cinnamomum sieboldii and Allium sativum for superoxide scavenging in the treatment of inflammatory disorders. German Patent Publication No. 3,724,341 teaches the use of Cinnamomum ∑eylanicum as an anti-inflammatory agent which exerts a synergistic anti-inflammatory effect in combination with Pumica granitum cortex, Cardamon zingiberaceie fruit and Piper longum fruit.

PCT Application PCT/US94/02184, published as WO 94/18994, is directed to a therapeutic herbal composition formed from Trigonellafoenum-graecum seed, Syzygium aromaticum fruit, Allilum sativum bulb, Cinnamonmum zyelanicum bark, Saussurea costus root, and Euphorbia lathyris.

U.S. Patent No. 5,707,631 discloses an oral therapeutic composition comprising Trigonellafoenum-graecum seed, Syzygium aromaticum fruit, Allilum sativum bulb, Cinnamonmum zyelanicum bark, Saussurea costus root, Euphorbia lathyris, and sodium chloride. None of the above references teaches an herbal composition of the present invention.

SUMMARY OF THE INVENTION The subject invention provides a therapeutic composition which comprises Trigonellafoenum-graecum seed, Syzygium aromaticum fruit, Allilum sativum bulb, Cinnamonmum zyelanicum bark, Saussurea costus root, and Alfalfa in amounts effective to produce a physiological benefit. Preferably, the composition further comprises an amount of sodium chloride, more preferably sea salt, which is effective to promote the digestibility (palatability) and storage stability of the therapeutic composition.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 illustrates the assay results of cholesterol efflux to HDL, where 20 μg/ml HDL protein was used for efflux assay, 0.5, 1.0, 2.0, and 4.0 μL of a cholesterol reducing agent sold under the U.S. registered trademark LO-CHOL which is also referred to herein as "Lochol". The amounts of Lochol extract were used in the pretreatment, 3μM of TO compound was used as positive control.

Figure 2 illustrates the assay results of cholesterol efflux to apoA-I where 15μg/ml apoA-I protein was used for efflux assay, 0.5, 1.0, 2.0, and 4.0μL of Lochol extract were used in the pretreatment, 3μM of TO compound was used as positive control. DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS The term "effective concentration" or "effective amount" is used to describe an amount or concentration of an active agent or composition according to the present invention which is used in the present invention to produce an intended result. In the case of the present invention, effective concentrations are generally concentrations which are effective in reducing cholesterol, treating arthritis, blood pressure and Alzheimer's disease, which may include concentrations of the active agent which prevent these conditions as well. The term effective concentration or amount subsumes the administration of a pharmaceutically active agent according to the present invention for a period consistent with the realization of the intended result. Effective amounts of the compounds which are used according to the present invention include amounts which comprise approximately 500 mg to 3000 mg, more preferably about 1150 mg twice daily. These amounts of herbal product produce an effective concentration range in human body fluids, i.e., blood, plasma, and serum.

The term "sea salt" is used to describe preferred salt which is used in the present invention to promote the digestibility and storage stability of compositions according to the present invention. Although any source of sodium chloride may be used in the present invention, provided that the amount of sodium chloride represents approximately 1% to about 20% by weight, more preferably about 3% to about 5% by weight of the final composition, salt obtained by the evaporation of salt water obtained from the ocean or sea, and in particular the Dead Sea, is preferred. Although numerous sources of salt are proposed for use in the present invention, one supplier of the preferred Dead Sea salt is Modin BAM, Israel.

The subject invention will now be described in terms of its preferred embodiments. These embodiments are set forth to aid in the understanding of the subject invention, but are not to be construed as limiting.

One preferred composition in accordance with the present invention is described in Table I.

Table I

Material Wt % of wt. Trigonella foenum-graecum 500 mg 43.5% Syzygium aromaticum fruit 100 mg 8.5% Allilum sativum bulb 100 mg 8.5% Cinnamonnum zyelanicum 100 mg 8.5% Saussurea costus root 100 mg 8.5% Alfalfa 250 mg 22.5%

Total: 1150 mg

The composition supplies the physiologically important chemicals listed in Table II.

Table II

Choline Calcium Phosphorous Iron Magnesium Sodium Potassium Zinc Vitamin A Niacin Riboflavin Esterins Ascorbic Acid Lecithin Phytosterols Tryptophane Beta Carotene Colchicine

The biological active components include choline and inositol.

The above herbs are typically dried and ground to a fine powder. All weights are expressed in milligrams and all percentages are by weight of the essential elements in the composition. The composition is typically an intimate mixture of powders. However, extracted herbs may also be used.

The composition as described above is thereafter combined with an amount of sodium chloride, in amounts effective to render the product more palatable and storage stable. Sea salt is a particularly preferred component containing sodium chloride which may be advantageously added to the present compositions. Sea salt obtained from the Dead Sea is particularly preferred. It is an unexpected result that the inclusion of sodium chloride in amounts ranging from about 1.0% to about 20%, more preferably about 3% to about 5% by weight of the composition comprising the above-described six herbal components will produce a particularly effective and palatable composition exhibiting good digestibility and storage stability (i.e., for periods of at least one month, more preferably at least about six months, and even 1 year or longer). While not being limited by way of theory, it is believed that the inclusion of salt within the above-described weight ranges maintains and/or enhances the activity of the composition and instills favorable characteristics of digestibility and storage stability to the compositions by decreasing the hygroscopic character of the herbal mixture in the absence of the salt.

Administration is typically oral, with administration being via, e.g., a capsule. For example, an 1150 mg capsule of the herbal composition of the present invention can be administered to a patient several times daily, e.g., twice daily. The dosage of course may vary depending on body weight and other conditions readily determinable to those skilled in the art who have read the present application.

In addition to the above herbs, various pharmaceutically acceptable additives, excipients, and fillers, such as ash, may be present.

The following study was done to examine the effect of the composition in accordance with the present invention on cholesterol efflux from macrophages. The preferred composition in accordance with the present invention as listed in Table 1 in combination with 3% by weight of sea salt is used in the following study

(hereinafter referred to as "Lochol extract").

There are two major pathways for cholesterol efflux from macrophages. They are:

1. Cholesterol efflux from macrophages to lipid-poor apolipoproteins, mainly, apoliproprotein A-I (apoA-I), facilitated by ATP -banding cassetter transport Al (ABCA1). 2. HDL-mediated cholesterol efflux which is mainly ABCA1 independent.

Briefly, during the experiments, THP-1 cells were differentiated into human macrophage-like cells by treatment with PMA for 72 hours. Then the cells were labeled with [³H] cholesterol in 1% fetal bovine serum and RPMI-1640 cell culture media in the presence or absence of the indicated amount of Lochol extract or To compound (9-cis-retinoic acid and 22-hydroxyl cholesterol). To compound is liver X receptor (LXR) activator that increases ABCA1 and ABCG1/G4 expression and increases cholesterol efflux to apoA-I and HDL. Following 24 hour cell labeling and treatment, cells were washed three times and the indicated amount of apoA-I or HDL was added and incubated with cells for 5 hours for the cholesterol efflux assay. The percentage cholesterol efflux was determined as the count in media divided by the count in media plus cellular count (total) and then multiplied by 100.

Table 3 lists the assay results of the present study. Figure 1 illustrates the assay results of cholesterol efflux to HDL, where 20 μg/ml HDL protein was used for efflux assay, 0.5, 1.0, 2.0, and 4.0 μL of Lochol extract were used in the pretreatment, 3μM of TO compound was used as positive control. Figure 2 illustrates the assay results of cholesterol efflux to apoA-I where 15 μg/ml apoA-I protein was used for efflux assay, 0.5, 1.0, 2.0, and 4.0μL of Lochol extract were used in the pretreatment, 3 μM of TO compound was used as positive control. Figures 1-2 and Table III show the beneficial effects of the herbal composition in accordance with the present invention in lowering LDL and increasing HDL levels. Thus, while there have been shown and described and pointed out fundamental novel features of the present invention as applied to preferred embodiments thereof, it will be understood that various omissions and substitutions and changes in the form and details of the compositions described and illustrated, and of the methods described may be made by those skilled in the art without departing from the spirit of the present invention. Substitutions of elements from one described embodiment to another are also fully intended and contemplated. It is the intention, therefore, to be limited only as indicated by the scope of the claims which follow.

Table III

Sample Media Celluar Total % Mean

Cotrol-HDL-1 5568 43974 49542 11.2 11.2

Cotrol-HDL-2 5408 44716 50124 10.8

Cotrol-HDL-3 5694 43699 49393 11.5

Lochol 0.5 μL 5170 46068 51238 10.1 9.6

Lochol 0.5 μL 5452 50910 56362 9.7

Lochol 0.5 μL 5441 54515 59956 9.1

Lochol 1 μL 5356 52054 57410 9.3 9.1

Lochol 1 μL 5343 54957 60300 8.9

Lochol 1 μL 5623 55573 61196 9.2

Lochol 2 μL 4302 41942 46244 9.3 9.4

Lochol 2 μL 4775 46802 51577 9.3

Lochol 2 μL 4994 47104 52098 9.6

Lochol 4 μL 4277 37124 41041 10.3 10.1

Lochol 4 μL 4302 38784 43086 10.0

Lochol 4 μL 4418 39355 43773 10.1

To 3μM HDL-1 6716 41040 47756 14.1 13.3

To 3μM HDL-2 6475 44242 50717 12.8

To 3μM HDL-3 6961 45811 52772 13.2

Control-apoAI- -1 3879 44367 48246 8.0 8.1

Control-apoAL -2 3948 44897 48845 8.1

Control- apoAI- -3 329 11 340

Lochol 0.5 μl 3479 48234 51713 6.7 7.3

Lochol 0.5 μl 4092 50457 54549 7.5

Lochol 0.5 μl 4215 51245 55460 7.6

Lochol 1 μl 3733 52093 55826 6.7 6.3

Lochol 1 μl 3646 52418 56064 6.5

Lochol 1 μl 3262 53433 56695 5.8

Lochol 2 μl 2658 43832 46490 5.7 6.0

Lochol 2 μl 2884 42728 45612 6.3

Lochol 2 μl 2841 43811 46722 6.1

Lochol 4 μl 2628 40763 43391 6.1 5.8

Lochol 4 μl 2789 43716 46505 6.0

Lochol 4 μl 2404 42217 44621 5.4

To μMapoAI-1 6172 48180 54352 11.4 10.8

To 3μM apoAI :-2 5473 46747 52220 10.5

To 3μM apoAI -3 5609 47574 53813 10.5

Claims

1. A composition comprising Trigonellafoenum-graecum seed, Syzygium aromaticum fruit, Allilum sativum bulb, Cinnamonmum zyelanicum bark, Saussurea costus root, and Alfalfa in amounts effective to produce a physiological benefit.

2. The composition of claim 1 further comprising an amount of sodium chloride effective to substantially promote the digestibility and storage stability of the composition.

3. The composition of claim 2 wherein the amount of sodium chloride is from about 1 to about 20 weight percent of the composition.

4. The composition of claim 2 wherein the amount of sodium chloride is from about 3 to about 5 weight of the composition.

5. The composition according to claim 1, wherein the Trigonellafoenum-graecum seed is present in an amount of from about 5 to about 95 weight percent of the composition, Syzygium aromaticum fruit is present in an amount of from 1 about to about 50 weight percent of the composition, Allilum sativum bulb is present in an amount from about 1 to about 50 weight percent of the composition, Cinnamonmum zyelanicum bark is present in an amount from about 1 to about 50 weight percent of the composition, Saussurea costus root is present in an amount from about 1 to about 50 weight percent of the composition, and Alfalfa is present in an amount from about 1 to about 90 weight percent of the composition.

6. The composition according to claim 1, wherein the Trigonellafoenum-graecum seed is present in an amount of about 43.5 weight percent of the composition, Syzygium aromaticum fruit is present in an amount of about 8.5% weight percent of the composition, Allilum sativum bulb is present in an amount of about 8.5 weight percent of the composition, Cinnamonmum zyelanicum bark is present in an amount of about 8.5 weight percent of the composition, Saussurea costus root is present in an amount of about 8.5 weight percent of the composition, and Alfalfa is present in an amount of about 22.5% by weight of the composition.

7. The composition of claim 6 further comprising about 3% by weight of sea salt.

8. The composition according to claim 1 further comprising a pharmaceutically acceptable additive, excipient or filler.

9. The composition according to claim 8 wherein said additive is ash.

10. A capsule comprising the composition of claim 1.

11. The capsule according to claim 10, wherein the Trigonellafoenum-graecum seed is present in an amount of about 500 mg, Syzygium aromaticum fruit is present in an amount of about 1 OOmg, Allilum sativum bulb is present in an amount of about 100 mg, Cinnamonmum zyelanicum bark is present in an amount of about 100 mg, Saussurea costus root is present in an amount of about 100 mg, and Alfalfa is present in an amount of about 250 mg.

12. The capsule of claim 10 further comprising about 3% by weight of sea salt.

13. A composition comprising Trigonellafoenum-graecum seed, Syzygium aromaticum fruit, Allilum sativum bulb, Cinnamonmum zyelanicum bark, Saussurea costus root, and Alfalfa in amounts effective to produce a physiological benefit in combination with about 1% to about 20% by weight of sodium chloride.

14. The composition according to claim 13, wherein the Trigonella foenum-graecum seed is present in an amount of from about 5 to about 95 weight percent of the composition, Syzygium aromaticum fruit is present in an amount of from about 1 to about 50 weight percent of the composition, Allilum sativum bulb is present in an amount from about 1 to about 50 weight percent of the composition, Cinnamonmum zyelanicum bark is present in an amount from about 1 to about 50 weight percent of the composition, Saussurea costus root is present in an amount from about 1 to about 50 weight percent of the composition, Alfalfa is present in an amount from about 1 to about 90 weight percent of the composition, and said sodium chloride is included as sea salt.

15. The composition according to claim 13, wherein the Trigonellafoenum-graecum seed is present in an amount of about 43.5% by weight of the composition, Syzygium aromaticum fruit is present in an amount of about 8.5% by weight of the composition, Allilum sativum bulb is present in an amount of about 8.5% by weight of the composition, Cinnamonmum zyelanicum bark is present in an amount of about 8.5% by weight of the composition, Saussurea costus root is present in an amount of about 8.5% by weight of the composition, and Alfalfa is present in an amount of about 22.5% by weight of the composition, said sea salt being included in an amount of about 3% to about 5% by weight of said composition.

16. The composition according to claim 13 further comprising a pharmaceutically acceptable additive, excipient, or filler.

17. The composition according to claim 16 wherein said additive is ash.

18. A capsule comprising the composition of claim 13.