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WO1996019218A1 - Compositions de tocopherols et de tocotrienols - Google Patents

Compositions de tocopherols et de tocotrienols Download PDF

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Publication number
WO1996019218A1
WO1996019218A1 PCT/US1995/016848 US9516848W WO9619218A1 WO 1996019218 A1 WO1996019218 A1 WO 1996019218A1 US 9516848 W US9516848 W US 9516848W WO 9619218 A1 WO9619218 A1 WO 9619218A1
Authority
WO
WIPO (PCT)
Prior art keywords
approximately
natural
tocopherols
tocotrienols
tocotrienol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1995/016848
Other languages
English (en)
Inventor
James P. Clark
Manfred S. Dunker
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Henkel Corp
Original Assignee
Henkel Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Henkel Corp filed Critical Henkel Corp
Priority to US08/849,978 priority Critical patent/US6358997B1/en
Priority to AU46882/96A priority patent/AU4688296A/en
Publication of WO1996019218A1 publication Critical patent/WO1996019218A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E

Definitions

  • the present invention relates to pharmaceutical compositions comprising a combination of natural tocotrienols and natural tocopherols useful as a dietary supplement which exert a protective action on the cardiovascular system.
  • This invention is also directed to a method for preventing treating hypercholesteremia and/or hyperlipidemia by the administration of natural tocotrienols and natural tocopherols.
  • Vitamin E generally refers to the group of compounds (tocol and tocotrienol derivatives) which exhibit qualitatively the biological activity of alpha- tocopherol. They are fat soluble, closely related chemical compounds found in vegetable oils, such as wheat germ oil, rice oil, soy bean oil and the like. Alpha-tocopherol has the greatest biological activity per unit weight while its isomers beta, gamma, delta, epsilon, zeta and eta-tocopherols have vitamin E activity to a lesser extent.
  • the tocopherols and their esters such as tocopherol acetate, tocopherol palmitate, tocopherol succinate and the like are normally water-insoluble.
  • vitamin and multivitamin preparations which include vitamin E as a dietary supplement optionally along with other vitamins and trace elements.
  • vitamin E as a dietary supplement
  • other vitamins and trace elements For a discussion of these preparations, see, Remington's Pharmaceutical Sciences. Eighteenth Edition (1990), Mack Publishing Company pp. 1008-1009 and Handbook of Nonprescription Drugs. Ninth Edition (1990), published by the American Pharmaceutical Association, pp. 447-527.
  • Tocotrienols have been implicated in the suppression of cholesterolgenesis and arterial thrombosis by inhibition of platelet thromboxane formation. See, for example, the disclosure in U.S. Patent 5,157,132 and the references disclosed therein.
  • Tocopherols (Vitamin E) which comprise alpha, beta, gamma and delta tocopherols are essential for normal reproduction, normal development of muscles, normal resistance of erythrocytes to hemolysis and perhaps most importantly are believed to act as an antioxidant.
  • Beta-carotene has also been suggested as useful in reducing undesirable vascular events in patients with chronic stable angina. See Gaziano et al., "Beta Carotene Therapy for Chronic Stable Angina,” Circulation. 82:111, Abstract No. 0796 (1990).
  • the present inventors have surprisingly discovered a method for protecting the mammalian body against high blood levels of cholesterol and/or lipids by the ingestion of natural tocotrienols and natural tocopherols, thereby reducing the risk of the development of cardiovascular disease.
  • the art has never appreciated nor suggested such a method for the use of those natural products.
  • tocotrienol obtained from palm oil is preferred because of its low cost and ready availability.
  • the naturally occurring tocotrienols are predominantly the d-isomer.
  • the natural tocopherols useful in the practice of the present invention include all the naturally occurring tocopherols, i.e., alpha, beta, gamma and delta as well as the corresponding esters, such as the succinate.
  • the present invention is directed to a method for preventing or treating the harmful effects of high serum cholesterol and/or lipid levels in a mammal, including humans.
  • natural tocotrienols and natural tocopherols are administered preferably daily to exert a protective action on the cardiovascular system of the body against high levels of cholesterol and lipids.
  • the active agents are administered in an oral dosage form with each dose typically containing approximately 200 to approximately 400 mg tocotrienols and approximately 150 to approximately 500 mg tocopherols per unit dose.
  • Preferred Embodiments of the Invention Disease prevention through management of blood serum lipids and cholesterol is an accepted clinical approach.
  • the present inventors have surprisingly now found a method whereby the body of a mammal, including humans is protected against high levels of cholesterol and/or lipid thereby lowering the risk of cardiovascular disease.
  • Natural tocotrienols and natural tocopherols are derived from vegetable oils. Soy oil is the most widely used source. Sunflower, corn, peanut, rapeseed and cottonseed oils may also be used.
  • vitamin E Natural tocotrienol and natural tocopherols are very different from that produced by chemical synthesis, i.e., synthetic "vitamin E.” While the definition of vitamin E is not consistent, for the purposes of the present invention, vitamin E refers to both tocotrienols and tocopherols.
  • Synthetic vitamin E is a mixture of eight different stereoisomers, only one of which is molecularly equivalent to natural vitamin E. The other seven stereoisomers have a lower biological activity. The mammalian body prefers the natural stereoisomer.
  • Natural vitamin E is recognized as having 36 percent greater potency than synthetic vitamin E. Recent studies suggest that natural vitamin E is probably twice as effective as synthetic vitamin E.
  • Natural vitamin E also remains in the body much longer than synthetic vitamin E.
  • the seven synthetic stereoisomers are secreted into the bile and then into the intestine for removal from the body.
  • the natural vitamin E stereoisomer on the other hand, is returned to the bloodstream in the form of low density lipoproteins.
  • Any natural tocopherol or tocotrienol, its ester or compounds convertible to either tocopherols or their esters are suitable for use in the practice of the present invention.
  • the daily administration of approximately 100 mg to approximately 1000 mg of natural tocopherols and approximately 100 mg to approximately 1000 mg natural tocotrienols exhibit a protective effect against high levels of cholesterol and lipid thereby preventing or treating the subsequent development of coronary heart disease.
  • the dosage of naturally occurring tocotrienol is preferably in the range of approximately 150 mg to approximately 500 mg, more preferably approximately 200 mg to approximately 400 mg.
  • the dosage of naturally occurring tocopherol administered to a mammal, including humans, in need of such prevention or treatment is preferably approximately 150 mg to approximately 500 mg per oral dose.
  • the present inventors' method is cost effective since it avoids expense medication to lower elevated level cholesterol and/or lipid.
  • compositions of the present invention can be made by conventional compounding procedures known in the pharmaceutical art, that is, by mixing the active substances with edible pharmaceutically acceptable non-toxic inert, solid or liquid carriers and/or excipients suitable for systemic administration and conventionally used in oral dosage forms. Additionally, edible, non-toxic pharmaceutically acceptable stabilizers usually used as stabilizers in oral dosage forms or edible, non-toxic pharmaceutically acceptable salts thereof can be included in the compositions of the present invention. All the above carriers, excipients and stabilizers are intended to include only those suitable for oral administration and all are conventional and known to the pharmaceutical compounding art.
  • the natural tocotrienols and the natural tocopherols are formulated with an inert pharmaceutically acceptable carrier, suitable for oral administration.
  • Typical solid dosage forms include for example soft gelatin capsules, hard gelatin capsules, tablets, powders, chewable tablets and the like.
  • Typical liquid dosage forms include emulsions, elixirs and the like.
  • Soft gelatin capsules are preferred in the practice of the present invention.
  • These formulations are prepared in accordance with known techniques in the art.
  • the natural tocotrienols and natural tocopherols are mixed with a fixed oil, such as peanut oil. The resulting mixture is optionally blended and dispensed in gelatin capsules.
  • the natural tocotrienols and natural tocopherols are preferably combined in the same oral dosage form, however, two separate dosage forms, one of each tocotrienol and tocopherol can be administered in two separate dosage forms.
  • the patient ingests the capsule preferably daily to obtain the benefit of the administration of the natural tocotrienols and natural tocopherols.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques contenant des tocotriénols naturels et des tocophérols naturels. On décrit également un procédé pour la prévention ou le traitement chez les mammifères des effets néfastes de niveaux élevés de cholestérol et/ou de lipides dans le sérum. Ce procédé consiste à administrer par voie orale entre 100 mg environ et 1000 mg environ de tocotriénols naturels et entre 100 mg environ et 1000 mg environ de tocophérols naturels à un patient ou à un mammifère ayant besoin d'un tel traitement préventif ou curatif.
PCT/US1995/016848 1994-12-22 1995-12-22 Compositions de tocopherols et de tocotrienols Ceased WO1996019218A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US08/849,978 US6358997B1 (en) 1995-12-22 1995-12-22 Tocopherol and tocotrienol compositions
AU46882/96A AU4688296A (en) 1994-12-22 1995-12-22 Tocopherol and tocotrienol compositions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US36269394A 1994-12-22 1994-12-22
US08/362,693 1994-12-22

Publications (1)

Publication Number Publication Date
WO1996019218A1 true WO1996019218A1 (fr) 1996-06-27

Family

ID=23427142

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/016848 Ceased WO1996019218A1 (fr) 1994-12-22 1995-12-22 Compositions de tocopherols et de tocotrienols

Country Status (2)

Country Link
AU (1) AU4688296A (fr)
WO (1) WO1996019218A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7012092B2 (en) 1999-11-30 2006-03-14 Mel Rich Formulation and delivery method to enhance antioxidant potency of Vitamin E
US7329688B2 (en) * 2002-12-17 2008-02-12 Soft Gel Technologies, Inc. Natural vitamin E compositions with superior antioxidant potency
US7452549B2 (en) 2000-10-24 2008-11-18 Nestec S.A. Synergistic antioxidant combination of delta tocols and polyphenols
US7872042B2 (en) * 2004-05-14 2011-01-18 Rubin Berish Y Use of tocotrienols for elevating IKBKAP gene expression and treating Familial Dysautonomia

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5393776A (en) * 1990-09-14 1995-02-28 Bristol-Myers Squibb Company Tocotrienol analogs in the treatment of hypercholesterolemia and hyperlipidemia

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5393776A (en) * 1990-09-14 1995-02-28 Bristol-Myers Squibb Company Tocotrienol analogs in the treatment of hypercholesterolemia and hyperlipidemia

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MEDLINE ABSTRACTS, issued 1991, TAN D.T. et al., "Effect of A Palm-Oil-Vitamin E Concentrate on the Serum and Lipoprotein Lipids in Humans", Abstract No. 91189080; & AM. J. CLIN. NUTR., Volume 53, (4 Suppl), 1027s-1030s. *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7012092B2 (en) 1999-11-30 2006-03-14 Mel Rich Formulation and delivery method to enhance antioxidant potency of Vitamin E
US7015245B2 (en) 1999-11-30 2006-03-21 Melvin Rich Formulation to enhance antioxidant potency of Vitamin E
US8013013B2 (en) 1999-11-30 2011-09-06 Soft Gel Technologies, Inc. Formulation and delivery method to enhance antioxidant potency of vitamin E
US8110600B2 (en) 1999-11-30 2012-02-07 Soft Gel Technologies, Inc. Formulation and delivery method to enhance antioxidant potency of vitamin E
US7452549B2 (en) 2000-10-24 2008-11-18 Nestec S.A. Synergistic antioxidant combination of delta tocols and polyphenols
US7329688B2 (en) * 2002-12-17 2008-02-12 Soft Gel Technologies, Inc. Natural vitamin E compositions with superior antioxidant potency
US7449491B2 (en) 2002-12-17 2008-11-11 Soft Gel Technologies, Inc. Natural vitamin E compositions with superior antioxidant potency
AU2003301069B2 (en) * 2002-12-17 2010-11-18 Soft Gel Technologies, Inc. Natural vitamin E compositions with superior antioxidant potency
US7989493B2 (en) 2002-12-17 2011-08-02 Soft Gel Technologies, Inc. Natural vitamin E compositions with superior antioxidant potency
US7872042B2 (en) * 2004-05-14 2011-01-18 Rubin Berish Y Use of tocotrienols for elevating IKBKAP gene expression and treating Familial Dysautonomia

Also Published As

Publication number Publication date
AU4688296A (en) 1996-07-10

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