ZA200500517B

ZA200500517B - Anti-microbial compositions and methods of using same.

Info

Publication number: ZA200500517B
Application number: ZA200500517A
Authority: ZA
Inventors: Richard A Rosenbloom
Original assignee: The Quigley Corp
Priority date: 2002-08-06
Filing date: 2005-01-19
Publication date: 2005-11-18

Description

ANTI-MICROBIAL COMPOSITIONS AND METHODS OF USING SAME

BACKGROUND OF THE INVENTION

A. Field of the Invention

The present invention relates to anti-microbial compositions and methods of using them. More particularly, the present invention relates to anti-microbial compositions useful for treating one or more adverse effects of microbial infections, and to methods for administering the anti-microbial compositions.

B. Description of the Prior Art

Treatment of Microbial Infections

The medical literature regarding anti-microbial agents is vast and describes a number of anti-microbials including naturally occurring compounds as well as synthetic or semi-synthetic compounds produced in the laboratory. Consumers today often prefer to use naturally occurring compounds when these are available. Due to concern over side effects, which may be well documented side effects that occur in conjunction with a treatment, or possibly unknown side effects that may result from long-term use of a treatment, many consumers especially prefer anti-microbial treatments that are prepared from natural matenals, such as herbs, with a minimal amount of chemical processing.

Treatment of Inflammation

Inflammation can result from microbial infections. In modern non-herbal medicine, there are two major categories of anti-inflammatory medicines: steroidal and non-steroidal. Steroidal anti-inflammatory medicines are powerful medications, which are based on hormonal substances, such as cortisone. Steroidal medications have a stronger anti-inflammatory response than non-steroidal medicines. Steroidal medications can be taken as pills, injected into the bloodstream, or injected directly into a joint space. There are many non-steroidal anti-inflammatory medications.

Acetaminophen, aspirin, ibuprofen, and naproxen are the most commonly used non- steroidal anti-inflammatory medications.

Non-steroidal anti-inflammatory drugs have three major actions, all of which are related to inhibition of cyclo-oxygenase resulting in decreased formation of prostanoids. Firstly, an anti-inflammatory action can be achieved by reducing production of vasodilator prostaglandins (PGE2, PGI2), which means less vasodilation and, indirectly less oedema. Secondly, an analgesic effect can be achieved by reduced prostaglandin production (less sensitization of nociceptic nerve endings to the inflammatory mediators bradykinin and S-hydroxytryptamine). Thirdly, an antipyretic effect can produce an anti-inflammatory action, probably due to a decrease in the mediator PGE2 generated in response to inflammatory pyrogens, much as interleukin-1. | :

There are side effects to both of these groups of medicines. They may include, among other things, stomach upset, stomach bleeding, or ulcers, kidney problems, hearing problems and ankle swelling. Additionally, the steroidal anti-inflammatory medications can have more serious side effects including: loss of bone mass, cataracts, reduced ability to fight infection, swelling and weight gain, mood changes, high blood pressure, and problems with the bone marrow where blood cells are produced.

It is therefore an object of certain embodiments of the present invention to provide an anti-microbial composition.

It is a further object of certain embodiments of the present invention to provide an anti-microbial composition made from natural products.

It is a still further object of certain embodiments of the present invention to provide a method for treating microbial infections by administering an anti-microbial composition.

It 1s a still further object of certain embodiments of the present invention to provide a method to treat microbial infections by administering a composition made from natural products.

These and other objects of the present invention will be apparent trom the summary and detailed description of the invention, which follow.

SUMMARY OF THE INVENTION

In a first aspect, the invention provides an anti-microbial composition comprising a first ingredient obtainable from ginger, a second ingredient obtainable from green tea, and, optionally, an acceptable carrier, wherein the first ingredient is present in the anti-microbial composition in an amount effective to reduce, treat or prevent an adverse effect of microbial infection when administered to a patient prior to expected exposure to a microbe, concurrently with exposure to a microbe, or after exposure to a microbe.

In a further aspect the invention provides a method for the reduction, treatment or prevention of at least one adverse effect of microbial infection in a patient, comprising the step of administering to the patient prior to expected cxposure to a microbe, concurrently with exposure to a microbe, or after exposure to a microbe, an amount of a composition comprising a first ingredient obtainable from ginger, a second ingredient obtainable from green tea, and, optionally, an acceptable carrier.

The composition is etfective, when administered, to reduce, treat or prevent an adverse effect of microbial infection in the patient.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In a first aspect, the present invention relates to an anti-microbial composition.

The anti-microbial composition of the present invention includes ingredients that can be obtained from ginger and green tea.

As used herein the term “flavors” includes both fruit and botanical flavors.

As used herein the term “sweeteners” includes sugars, for example, glucose, sucrose and fructose. Sugars also include high fructose com syrup solids, invert sugar, sugar alcohols including sorbitol, and mixtures thereof. Artificial sweeteners are also included within the scope of the term, “sweetener.”

As used herein, the term “acceptable” means a component that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic responses), commensurate with a reasonable risk/benefit ratio.

Further, as used herein, the term “safe and effective amount” refers to the quantity of a component, which is sufficient to yield a desired therapeutic response without undue adverse side effects (such as toxicity, irritation, or allergic responses), commensurate with a reasonable risk/benefit ratio when used in the manner described herein.

The term “inhibiting” a microbe, as used herein, is meant reducing or preventing turther growth of the microbe, and/or the elimination of some or all of the microbe from the human or animal being treated. Suitable methods for determining microbe inhibition are discussed in the examples.

All active compounds used in the present invention may be obtained trom other sources, if available. Thus, the phrase “which can be obtained from” or the phrase “which may be obtained from” is meant to encompass compounds or compositions that are obtainable from turmeric, ginger, or green tea, and therefore encompasses synthetic forms of the same compounds and/or compositions as well as the same compounds and/or compositions obtained from other sources.

Most preferably, the anti-microbial composition of the present invention includes a first ingredient obtainable from ginger and a second ingredient obtainable from green tea, in a safe and effective amount to provide one or more of the beneficial effects described herein.

The first ingredient of the anti-microbial composition of the present invention may be obtained from ginger (Zingiber officinale, also commonly called ginger root).

Native to southern Asia, ginger is a 2- to 4-foot perennial that produces grass-like leaves up to a foot long and almost an inch wide. Ginger root, as it is called in the grocery store, actually consists of the underground stem ot the plant, with its bark-like outer covering scraped off.

Chinese medical texts from the fourth century B.C.E. suggest that ginger is effective in treating nausea, diarrhea, stomachaches, cholera, toothaches, bleeding, and rheumatism. Ginger was later used by Chinese herbalists to treat a variety of respiratory conditions, including coughs and the early stages ot colds.

Ginger's modern use dates back to the early 1880s, when a scientist named D.

Mowrey noticed that ginger-filled capsules reduced his nausea during an episode of flu. Inspired by this, he performed the first double-blind study of ginger. Germany's

Commission E subsequently approved ginger as a treatment for indigestion and motion sickness. Ginger has become widely accepted as a treatment for nausea. Even some conventional medical texts suggest ginger for the treatment of the nausea and vomiting of pregnancy, although others are more cautious.

Ginger gives relief from muscular discomfort and pain. [t inhibits prostaglandin and leukotriene biosynthesis and histamine release. Thus it acts as an : anti-inflammatory as well as an antacid agent. It is a dual inhibitor of the lipoxigenase and cycloxigenase system. Ginger contains about 1 to about 4% essential oil

(oleoresin). Used alone fresh Ginger is required to be used in substantially high doses (about 50 grams daily), which is not only inconvenient but can act as an irritant to the gastric mucosa. In dry form for any significant results, about 7 to about 10 grams of dry ginger powder has to be taken daily. Such large doses of ginger are extremely 5 inconvenient for the patient and affect patient compliance on a daily basis. (See

Potwardhan, U.S. Patent No. 5,494,668.)

Ginger inhibits prostanoid synthesis and also products of 5-lipoxygenase. The potency of the ginger extract in the acute inflammation test appears to be comparable to that exhibited by acetyl salicylic acid reported in the same study. (Mascolo N. et al

Journal of Ethnopharmocology, 1989, 27, 129-140).

One of the features of inflammation is increased oxygenation of arachidonic acid, which is metabolized by two enzymic pathways--the cyclooxygenase (CO) and the 5-lipoxygenase (5-LO)-leading to the production of prostaglandins and leukotrienes respectively. It is suggested (Srivastava and Mustafa; Medical

Hypotheses, 1992, 39 342-348) that at least one of the mechanisms by which ginger shows its ameliorative effects could be related to inhibition of prostaglandin and leukotriene biosynthesis, i.e. it works as a dual inhibitor of eicosanoid biosynthesis.

Many chemical investigations have been carried out on the constituents of the essential oil of ginger. All together more than 200 different volatiles have been identified in the essential oil of ginger. The essential oil of ginger contains a mixture of various terpenes as well as some other non-terpenoid compounds.

The active compounds of ginger which may be employed in the present invention include, but are not limited to, 1,8-cineole, 10-dehydrogingerdione, 10- gingerol, 6-gingerdione, 6-gingerol, 6-shogaol, 8-B-17-epoxy-A-trans-12-ene-15,16- diol, 8-gingerol, 8-shogaol, 9-oxo-nerolidol, acetaldehyde, acetic acid, alanine, a- linolenic-acid, a-linolenic acid, a-phellandrene, a-piene, a-terpinene, a-terpineol, a- zingiberene, ar-curcumene, arginine, ascorbic acid, asparagine, p-bisabolol, 3- carotene, P-elemene, B-eudesmol, B-ionone, -myrcene, B-phellandrene, B-pinene, B- selinene, B-sesquiphellandrene, B-sitosterol, B-thujone, bornyl-acetate, boron, caffeic acid, calcium, camphene, camphor, capric acid, caprylic acid, capsaicin, caryophyllene, chavicol, chlorogenic acid, chromium, citral, citronellal, citronellal, cobalt, copper, cumene, curcumin, cystine, delphinidin, d-cadinene, elemol, ethyl acetate, ethyl-myristate, famesal, farnesene, ferulic acid, furfural, y-aminobutyric acid,

v-terpinene, geranial, geraniol, geranyl-acetate, gingerenone, glutamic acid, glycine, hexahydrocurcumin, histidine, isogingerenone-B, isoleucine, kaempferol, lecithin, : limonene, linoleic acid, magnesium, manganese, methionine, mufa, myrecene, myricetin, myristic acid, neral, nerol, nerolidol, niacin, nickel, oleic acid, oxalic acid, p-coumaric acid, p-cymene, p-hydroxy-benzoic acid, palmitic acid, pantothenic acid, paradol, patchoulic alcohol, phenylalanine, quercetin, riboflavin, selenium, shikimic- acid, terpinen-4-ol, thiamin, tryptophan, vanillic acid, vanillin, zinc, and zingerone.

Also, mixtures ot two or more of these active compounds may be employed.

The first ingredient of the composition of the present invention, which may be obtained from ginger, can be incorporated in the anti-microbial composition of the present invention in many different forms including extracts such as ginger powder extracts, ginger fluid extracts, ginger powder including ginger root powder, and one or more active compounds of ginger, parts of, or whole ginger plants, tinctures thereof, and mixtures thereof. Preferably, the first ingredient of the anti-microbial composition of the present invention is selected from ginger extract, and ginger root powder. :

Each gram of the anti-microbial composition of the present invention preferably contains about 30 mg to about 150 mg of ginger root powder. Most preferably, each gram of the anti-microbial composition contains about 50 mg to about 110 mg of ginger root powder. These ranges use, as a baseline, the use of

Ginger Root Powder, ex. Stryka Botanics in the ingested formulation and Ginger

Extract K (Aquaresin Ginger), ex. Kalsec, Inc. ot Kalamazoo, Michigan in the spray formulation.

The amounts of various ingredients are given herein in terms of one form of the ingredient, i.e. ginger root powder. If that ingredient is present in another form, then the amount to be employed is that amount which will provide the same amount of the one or more active compounds as the amount of that ingredient given herein.

For example, if a tincture of ginger is employed, the amount of the tincture employed will be the amount that provides the same amounts of one or more active compounds as would be provided by the amounts of ginger root powder specified above. This applies to all ingredients for which the amounts are given herein for one particular form of that ingredient.

The second ingredient of the anti-microbial composition of the present invention may be obtained trom green tea. The second ingredient obtained from green tea may have an antioxidant effect.

Green tea is the dried leaves and leaf buds of the shrub Camellia sinensis. It is mainly produced in China and Japan. Dried tea leaves are composed mainly of phytochemicals known as polyphenols (about 36%), principally flavonols (including catechins), flavonoids, and flavondiols. The leaves also contain plant alkaloids (about 4%), including caffeine, theobromine and theophylline. Much of the research on green tea has been focused on its potential to prevent cancer. Research suggests that the polyphenols in green tea are responsible for a chemopreventive effect (E. Kaegi,

Canadian Medical Association Journal, 1998, 158: 1033-35).

The pharmacological activities of green tea are mainly due to its active compounds. The active compounds of green tea usctul in the present invention include, but are not limited to, flavonols, catechins, flavonoids, flavondiols, plant alkaloids, caffeine, theobromine, theophylline, phenolic acids, proteins, carbohydrates, and minerals.

The second ingredient which may be obtained from green tea, can be included in the anti-microbial composition in the form of green tea powder, green tea extracts such as green tea powder extracts, green tea fluid extracts, and one or more active compounds of green tea, part of, or whole green tea plants, green tea leaves, tinctures thereof, or mixtures thereof. Preferably, the second ingredient of the anti-microbial composition of the present invention is selected from green tea leaves, green tea powder and green tea extract. More preferably, the second ingredient of the anti- microbial composition of the present invention is green tea extract.

Each gram of the anti-microbial composition of the present invention preferably contains about 5 mg to about 20 mg of green tea extract. Most preferably, each gram of the anti-microbial composition contains about 7 mg to about 15 mg of green tea extract. These ranges use, as a baseline, the use of Green Tea, ex. Stryker

Botanics in the ingested formulation and Green Tea Extract, ex. Phytoway, Inc.,

ChanSha, P.R. China, in the spray formulation.

Also preferably, the anti-microbial composition of the present invention includes, as an optional ingredient, one or more ingredients obtainable from turmeric,

in a sate and effective amount to provide one or more of the beneficial effects ~ described herein. :

Turmeric (Curcuma longa), or Haldi in Hindi, is used very widely as medicine as well as a common ingredient in Indian cooking. The rhizome of turmeric is used In medicine and food as a fine powder.

Anti-inflammatory effects of curcumin isolated from Curcuma longa were reported in Srimal and Dhawan, Pharmacology of Diferuloyl Methane, a Non- steroidal Anti-inflammatory Agent, J. Pharm. Pharmac., 25:447-452 (1973).

Sigmficant anti-inflammatory activity for curcumin, comparable with phenylbutazone and hydrocortisone, was observed by Arora et al. (Indian Journal of Medical

Research, 1971, 59, 1289-1291). Curcumin, an alkaloid (diferuloyl methane) isolated from the alcoholic extract of turmeric, has been shown to be a potent anti- inflammatory agent. Further work on anti-inflammatory and anti-arthritic activity has also been carried out by Thatte et al. (Indian Journal of Pharmacology, 1986, 18 (1), 19-21). Turmeric has been found to have significant anti-inflammatory activity both in acute and chronic models. The therapeutic dose of turmeric, for optimal activity if used alone, is reported to be in the range of about S to about 10 grams of dry powder daily (Patwardhan, U.S. Patent No. 5,494,668). This dosage level, however, can produce a feeling of nausea.

Curcumin not only has anti-inflammatory properties but also has anti-oxidant, anti-tumor and other valuable properties. When used in low concentrations, curcumin can inhibit nitric oxide synthase (NOS) and, therefore, inhibit nitnic oxide production.

For example, Brouet et al. (Biochem. Biophys. Res. Commun., 1995, Jan. 17; 206 (2); 533-40) have reported that NOS activity in soluble extracts of macrophages activated for 6-24 hours in the presence of curcumin (10 microM) was significantly lower that that of macrophages activated without curcumin. Northern-blot and immunoblotting analyses demonstrated that significantly reduced levels of the mRNA and 130-k Da protein of inducible NOS were expressed in macrophages activated with curcumin, compared to those without curcumin activation. Inhibition ot NOS induction was maximal when curcumin was added together with lipopolysaccharide (LPS) and interteron-gamma (IFN-gamma) and decreased progressively as the interval between curcumin and LPS/IFN-gamma was increased to 18 hours.

Claims

WHAT IS CLAIMED IS:

1. An anti-microbial composition comprising: a first ingredient obtainable from ginger; a second ingredient obtainable from green tea; and an acceptable carrier; wherein the first and second ingredients are present in the anti-microbial composition in an amount which, when combined, is effective to reduce, treat or prevent an adverse effect of microbial infection when administered to a patient prior to expected exposure to a microbe, concurrently with exposure to a microbe, or after exposure to a microbe.

2. The anti-microbial composition of claim 1, wherein the first ingredient is selected from ginger powder extract, ginger fluid extract, ginger powder, at least a part of a whole plant of ginger, a ginger tincture, one or more compounds contained in ginger, and mixtures thereof; and the second ingredient is selected from green tea powder, green tea powder extract, green tea fluid extract, at least a part of a whole plant of green tea, tinctures of green tea, one or more compounds contained in green tea, and mixtures thereof.

3. The anti-microbial composition of claim 1, wherein the first ingredient comprises ginger root powder and the second ingredient comprises green tea extract.

4. The anti-microbial composition of claim 3, wherein each gram of the composition contains about 5 mg to about 20 mg of green tea extract.

5. The anti-microbial composition of claim 4, wherein each gram of the composition contains about 30 mg to about 150 mg of ginger root powder.

6. The anti-microbial composition of claim 3, wherein each gram of the composition contains about 7 mg to about 15 mg of green tea extract. AMENDED SHEET

7. The anti-microbial composition of claim 6, wherein each gram of the composition contains about 50 mg to about 110 mg of ginger root powder.

8. The anti-microbial composition of claim 1, further comprising an ingredient obtainable from turmeric.

9. The anti-microbial composition of claim 8, wherein the ingredient obtainable from turmeric is selected from the group consisting of turmeric powder extract, turmeric fluid extract, turmeric extract, one or more curcuminoid compounds, one or more other compounds contained in turmeric, turmeric powder, at least a part of a whole plant of turmeric, a turmeric tincture, and mixtures thereof.

10. The anti-microbial composition of claim 9, wherein the ingredient obtainable from turmeric comprises turmeric extract.

11. The anti-microbial composition of claim 10, wherein each gram of the composition comprises from about 5 mg to about 20 mg of turmeric powder extract.

12. The anti-microbial composition of claim 10, wherein each gram of the composition comprises from about 7 mg to about 15 mg of turmeric powder extract.

13. The anti-microbial composition of claim 1, further comprising resveratrol.

14. An anti-microbial composition comprising: turmeric extract; ginger root powder; a green tea extract; and an acceptable carrier; wherein the ginger root powder, green tea extract and turmeric extract are present in the anti-microbial composition in an amount which, when combined, is effective to reduce, treat or prevent an adverse effect of microbial infection when administered to a patient prior to expected exposure to a microbe, concurrently with exposure to a microbe, or after exposure to a microbe. AMENDED SHEET

15. The anti-microbial composition of claim 14, further comprising resveratrol.

16. The anti-microbial composition of claim 14, wherein each gram of the composition contains about 5 mg to about 20 mg of green tea extract, about 30 mg to about 150 mg of ginger root powder, and about 5 mg to about 20 mg of turmeric powder extract.

17. Use of composition comprising a first ingredient obtainable from ginger; a second ingredient obtainable from green tea; and an acceptable carrier; for the manufacture of a medicament fort the reduction, treatment or prevention of at least one adverse effect of microbial infection.

18. Use as claimed in claim 17, wherein the microbial infection is selected from the group consisting of herpes virus, HIV virus, AIDS virus, streptococcus bacterium, influenza virus, rhinovirus, and respiratory syncytial virus.

19. Use as claimed in any one of claims 17 or 18, wherein the medicament is in a form selected from a tablet, a capsule, a lozenge, a troche, a hard candy, a chewable composition, and a dental product.

20. Use as claimed in any one of claims 17-19, wherein the medicament is a nasal spray or a throat spray.

21. Use as claimed in any one of claims 17-20, wherein the first ingredient is selected from ginger powder extract, ginger fluid extract, ginger powder, at least a part of a whole plant of ginger, a ginger tincture, one or more compounds contained in ginger, and mixtures thereof; and AMENDED SHEET the second ingredient is selected from green tea powder, green tea powder extract, green tea fluid extract, at least a part of a whole plant of green tea, tinctures of green tea, one or more compounds contained in green tea, and mixtures thereof.

22. Use as claimed in any one of claims 17-21, wherein the first ingredient comprises ginger root powder and the second ingredient comprises green tea extract.

23. Use as claimed in any one of claims 17-22, wherein each gram of the composition contains about 5 mg to about 20 mg of green tea extract, and about 30 mg to about 150 mg of ginger root powder.

24. Use as claimed in any one of claims 17-23, further comprising an ingredient obtainable from turmeric. :

25. Use as claimed in any one of claims 17-24, wherein the ingredient obtainable from turmeric is selected from turmeric powder extract, turmeric fluid extract, turmeric extract, one or more curcuminoid compounds, one or more other compounds contained in turmeric, turmeric powder, at least a part of a whole plant of turmeric, a turmeric tincture, and mixtures thereof.

26. Use as claimed in any one of claims 17-25, wherein the ingredient obtainable from turmeric comprises turmeric extract.

27. Use as claimed in any one of claims 17-26, wherein the composition contains about 5 mg to about 20 mg of turmeric powder extract.

28. Use as claimed in any one of claims 17-27, wherein the composition further comprises resveratrol.

29. A composition of claim | or 14, substantially as herein described and exemplified.

30. Use of claim 17, substantially as herein described and exemplified. AMENDED SHEET