Invented by Leo J. Romanczyk, Jr., Harold H. Schmitz, Mars Inc
The Mars Inc invention works as followsThis invention discloses anti-platelet therapies or prophylaxis that include administering to the subject in need thereof, a composition containing an effective amount or derivative of a procyanidin.
Background for Anti-platelet compositions and methods
Polyphenols represent a diverse group of compounds” (Ferriera, et. al., ‘Diversity in Structure and Function of Oligomeric Flavanoids. Tetrahedron 48:10,1743-1803, 1992). Many plants contain them, and some even enter the food chain. They can be an important component of the human diet in some cases. “Although some polyphenols may not be considered nutritive, their potential health benefits have prompted interest.
For instance, quercetin (a flavonoid) has been shown to possess anticarcinogenic activity in experimental animal studies (Deshner et al., ?Quercertin and Rutin as Inhibitors of Azoxymethanol-induced Colonic Neoplasia?, Carcinogenesis, 7:1193?1196, 1991: and Kato et al., ?Inhibition of 12-O-tetradecanoylphorbol-13-acetate Induced Tumor Promotion and Ornithine Decarboxylase Activity by Quercitin: Possible Involvement of lipoxygenase Inhibition?, Carcinogenesis, 4, 1301?1305 1983). (+)-catechin, and (? (? Nobotanin (an oligomeric hydrolyzable tannin) has also been shown to possess anti-tumor activity (Okuda et al., ?Molecular Structures and Pharmacological Activities of Polyphenols?Oligomeric Hydrolyzable Tannins and Others’?Presented at the XVIth International Conference of the Groupe Polyphenols, Lisbon, Portugal, Jul. 13?16, 1992). Statistics have shown that stomach cancer deaths are significantly lower in tea-producing districts of Japan. Epigallocatechin gallate has been reported to be the pharmacologically active material in green tea that inhibits mouse skin tumors (Okuda et al, ?Molecular Structures and Pharmacological Activities of Polyphenols?Oligomeric Hydrolyzable Tannins and others. Presented at the XVIth International Conference of Groupe polyphenols in Lisbon, Portugal, 1993). Osakabe et al. (JP 7274894)?Food and drink for preventing gastric ulcers?Contains Antioxidation Substance extracted from cacao beans using hot water or ethanol? (JP 7274894?Food and Drink for Preventing Gastric Ulcers?Contains Antioxidation Substance Extracted from Cacao Beans using Hot Water or Ethanol? August 1995), have reported that antioxidant properties in cocoa bean extract (which is thought to contain epicatechin or analogous compounds) are responsible for the inhibition of gastric ulcers. Ellagic acid was also shown to have anticarcinogenic activity in different animal tumor models. (Boukharta et. al., Efficacy Of Ellagitannins And Ellagic Acid As Cancer Chemopreventive Drugs?Presented At The XVIth International Conference Of The Groupe Polyphenols Lisbon, Portugal, July. 13?16, 1992). The Kikkoman Corporation has reported the use of proanthocyanidins oligomers as antimutagens. JP 04190774A. Jul. 7, 1992). The 202nd National Meeting (Phenolic Compounds in Foods, and Their Effects On Health II) of The American Chemical Society has recently discussed the topic of phenolics in food and their modulation on tumor development in animal models. Antioxidants & cancer prevention, Huang, M. T., Ho C. T. and Lee C. Y. editors ACS Symposium Series 507 Am. Chem. Soc., Washington, D.C. 1992).
It has been discovered that cocoa and its compounds have anti-tumor or anti-cancer activity, or are antioxidants, or inhibit DNA toposomerase II enzyme activities, or is antimicrobial, or is a cyclooxygenase or lipoxygenase moderator, or is a NO-synthase or blood glucose modulator.
The present invention, therefore, provides a cocoa extract that is substantially pure and compounds derived from it. The extract or compounds are preferably polyphenol(s), e.g. polyphenols enriched with cocoa-procyanidins, such as polyphenols derived from at least one cocoa-procyanidin chosen from (?) The extract or compounds preferably contain polyphenol(s), such as polyphenol(s) enriched with cocoa procyanidin(s), such as at least one cocoa procyanidin selected from (?)
The present invention provides a composition that is anti-tumor or anti-cancer, antioxidant, DNA toposomerase II inhibitor or antimicrobial or cyclooxygenase or lipoxygenase or NO-synthase or blood or glucose modulator. It comprises a substantially pure extract or compound from cocoa or synthetic polyphenols such as polyphenols enriched with procyanidins and a carrier suitable for pharmaceutical, veterinary, food science or other applications. The cocoa extract or compound preferably contains cocoa procyanidins. The cocoa compounds or extracts are preferably obtained through a process that involves reducing cocoa to powder, defatting it, and extracting the active compound(s).
The present invention also comprises a method of treating a patient who is in need of treatment by an anti-tumor or anti-cancer agent, an antioxidant, DNA toposomerase II inhibitor or antimicrobial or cyclooxygenase or lipoxygenase moderator, an NO or no-synthase, or blood or glucose modulator. This includes administering to the patients a composition that contains an effective amount of a substantially purified cocoa extract, compound The cocoa extract can be cocoa polyphenol(s), and is obtained preferably by reducing cacao beans to powder, defatting it, and extracting and purifying the active compound(s).
No? “Anti-cancer or anti-tumor, or anti-tumor, or anti-tumor, or antioxidant, DNA toposomerase II inhibitor, antimicrobial cyclooxygenase or lipoxygenase, or cyclooxygenase or lipoxygenase moderator” “NO-synthase, blood or in vivo sugar modulating activities or compositions containing the invention cocoa polyphenols and procyanidins may be prepared according to standard techniques known by those with expertise in pharmaceutical or food science.
The compositions may be co-administered or sequentially administered with other antineoplastic, anti-tumor or anticancer agents, antioxidants, DNA topoisomerase II enzyme inhibiting agents, or cyclooxygenase and/or lipoxygenase, blood or in vivo glucose or NO or NO-synthase modulating agents, or with those that reduce or alleviate the ill effects of antineoplastic, antitumor The compositions may be administered in conjunction with or in sequence with other anti-tumor agents, antioxidants or DNA topoisomerase enzyme inhibitors. They can also be administered in conjunction with cyclooxygenase or lipoxygenase or blood or in-vivo glucose, NO or N-synthase-modulating agents or agents that reduce or alleviate the ill effects caused by antineoplastic agents.
Furthermore, the invention comprises a kit in which the active cocoa is provided. The kit may include a separate container that contains a carrier, diluent, or excipient. The kit can also include an additional anti-cancer, anti-tumor or antineoplastic agent, antioxidant, DNA topoisomerase II enzyme inhibitor or antimicrobial, or cyclo-oxygenase and/or lipoxygenase, NO or NO-synthase or blood or in vivo glucose modulating agent and/or an agent which reduces or alleviates ill effects of antineoplastic, anti-tumor or anti-cancer agents, antioxidant, DNA topoisomerase II enzyme inhibitor or antimicrobial, or cyclo-oxygenase and/or lipoxygenase, NO or NO-synthase or blood or in vivo glucose modulating agents for co- or sequential-administration. The additional agent can be in separate containers or mixed with the cocoa extract. The kit may also include instructions on how to mix or combine ingredients, and/or administer the product.
A cocoa polyphenol-containing composition, which is useful for modulating inflammatory pathways in a mammal, for maintaining vascular health, and as an antibacterial treatment, comprising a cocoa ingredient containing the cocoa polyphenols and optionally a carrier, diluent, or excepient. Compositions can be used as food, dietary supplements, or pharmaceuticals. “The food or dietary supplements can be in the form of a powder, an elixir or beverage (i.e. ethanol extract).
The cocoa polyphenols may be synthesized or derived from cocoa ingredients. They are present in cocoa products. They can be extracted either from cocoa nibs or cocoa beans. The cocoa procyanidins can be monomers or oligomers. “The oligomers range from dimers to octadecamers.
When extracting cocoa polyphenols from cocoa beans or cocoa nibs (or cocoa fractions), chocolate liquor, defatted cocoa powder, or defatted solid cocoa, a solvent that dissolves cocoa polyphenols must be used. Solvents that are suitable include water, alcohol, methanol acetone or ethyl-acetate mixtures. The preferred solvents are water-acetone or methanol mixtures. It is best to use slightly acidified water as a solvent. In some cases, the extract can be purified. For example, by removing the caffeine or theobromine. It is then purified further by gel permeation and/or liquid chromatography. The extract can be divided into monomeric or oligomeric fractions during high pressure liquid-chromatography. These fractions must contain at least 50% of monomers and/or specific oligomers. The fractions containing monomers, lower oligomers up to and including tetramers contain 90-95% of the weight of that particular oligomeric fragment.
The above composition can be used to modulate a mammalian inflammatory path by inhibiting COX, modulating production of eicosanoids, endothelin and reducing thrombosis. It also modulates oxidative stress in order to reduce vascular disease and associated inflammatory disorders. Modulating oxidative stress by, for instance, preventing (LDL oxidation) is another way that the composition above can modulate mammalian inflammation pathways and vascular disease.
The products comprising the cocoa polyphenol-containing composition are preferably in forms suitable for oral delivery, such as tablets, capsules, pills, concentrates, powders, liquids, or food ingredients, food additives or dietary supplements. The tablet may comprise an effective amount of the cocoa polyphenol-containing composition and optionally a carrier, such as sorbitol, lactose, cellulose, or dicalcium phosphate. The capsule may comprise a gelatin capsule containing a predetermined dosage of the cocoa polyphenol-containing composition. Oral delivery products may also contain dietary supplements such as calcium nitrate (nitrate of calcium), magnesium stearate (stearate of magnesium), vitamins and minerals.
The compositions containing cocoa extract or sub-fractions of it, or mixtures of them, further include a liquid carrier or solid carrier suitable for food, supplements, or pharmaceuticals.” These products can include food and beverages, as well as capsules, tablets, and pressed powder formulations. The following definitions are provided to help clarify what is disclosed in this application:
As used in this article, a “food” is a material consisting primarily of protein, carbohydrate and/or fat. A material primarily composed of carbohydrate, protein and/or lipids, and used by an organism for growth, repair, vital processes, and energy. Minerals, vitamins and condiments can be added to foods. Merriam-Webster’s Collegiate Dictionary 10th Edition 1993.
As used in this article, a “pharmaceutical” is a drug. A medicinal drug. Merriam-Webster’s Collegiate Dictionary 10th Edition 1993.
As used in this document, a “Food Supplement” is a product that contains or bears one or more of the following dietary ingredients: a vitamin, nutrient mineral, herb or other botanical substance, amino acid. A product that contains one or more of these dietary ingredients (other than tobacco), is intended to be used to supplement a diet. These include a vitamin, mineral, herb, botanical or amino acid. Merriam-Webster’s Collegiate Dictionary 10th Edition 1993. Supplement is used on the labels of food products. The term “supplement” is used to describe nutrients that have been added at a level greater than 50% higher than the U.S. RDA. Whitney, Cataldo, and Rolfes. 525).
The compositions containing cocoa extracts or sub-fractions of them, or mixtures of them, are useful for inhibiting COX and LOX activities, increasing nitric oxygen production, reducing platelet aggregation and thrombosis. They also reduce blood pressure, reduce thrombosis and inhibit excessive proliferation of vascular muscle. Chronic inflammation is also responsible for diseases such as arthritis, edema and gingivitis, peridontitis and bowel disease.
The structure of monomers containing procyanidins is:
Click here to view the patent on Google Patents.