WO2013117007A1 - Composition renfermant des phytostérols et du kudzu pour les maladies cardiovasculaires - Google Patents

Composition renfermant des phytostérols et du kudzu pour les maladies cardiovasculaires Download PDF

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Publication number
WO2013117007A1
WO2013117007A1 PCT/CN2012/071016 CN2012071016W WO2013117007A1 WO 2013117007 A1 WO2013117007 A1 WO 2013117007A1 CN 2012071016 W CN2012071016 W CN 2012071016W WO 2013117007 A1 WO2013117007 A1 WO 2013117007A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
accordance
kudzu
phytosterols
cholesterol
Prior art date
Application number
PCT/CN2012/071016
Other languages
English (en)
Inventor
Youyou ZHAO
Weiguo Zhang
Ying Xia
Qiutao GAO
Olivier Ballevre
Peter J VAN BLADEREN
Hua Bai
Original Assignee
Nestec S.A.
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 Nestec S.A. filed Critical Nestec S.A.
Priority to PCT/CN2012/071016 priority Critical patent/WO2013117007A1/fr
Priority to PCT/EP2013/052605 priority patent/WO2013117733A1/fr
Priority to CN201380008698.5A priority patent/CN104105494A/zh
Publication of WO2013117007A1 publication Critical patent/WO2013117007A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/488—Pueraria (kudzu)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention generally relates to the field of health and wellness.
  • the present invention addresses hypercholesterolemia and disorders associated therewith.
  • the present invention describes a composition comprising phytosterols and kudzu for use in the treatment, alleviation or prevention of disorders associated with hypercholesterolemia .
  • Cardiovascular Diseases are the leading cause of death and disability globally. More people are severely affected annually by CVDs than from any other cause. From a WHO report, an estimated 17.3 million people died from CVDs in 2008, representing 30% of all global deaths. Of these deaths, an estimated 7.3 million were due to coronary heart disease and 6.2 million were due to stroke. By 2030, almost 23.6 million people will die from CVDs, mainly from heart disease and stroke. These are projected to remain the single leading causes of death. Kudzu and phytosterols are well known to have beneficial health effects, however, both individual ingredients have their limitations.
  • Kudzu originated in China and was brought to the United States from Japan in the late 1800s. It is distributed throughout much of eastern United States and is most common in the southern part of the continent. Kudzu has been traditionally used in China to treat alcoholism, diabetes, gastroenteritis, and deafness.
  • the most abundant isoflavone of kudzu is puerarin (daidzein 8-C-glucoside) . Its compound also contains daidzein, daidzin (daidzei 7-O-glucoside) and other isoflavones.
  • puerarin lowered apolipoprotein (ApoBlOO) secretion in liver cells but not intestinal cell line (Lee JS, etal . , BMC Complement Altern Med. 2002 Dec 16;2:12. Epub 2002).
  • Phytosterols are known to be able to reduce blood concentrations of total and LDL cholesterol by reducing cholesterol absorption in the gut.
  • a daily intake of around 2.4 g of plant sterols (or its saturated form, stands) is associated with ci.n 8 "6 reduction of blood total cholesterol concentrations.
  • phytosterols have unwanted side effects. For example, they inhibit alpha and beta carotene absorption.
  • Beta carotene is an important source of Vitamin A. Vitamin A is essential for growth and development.
  • the present inventors were surprised to see that the subject matter of the independent claim achieves the objective of the present invention.
  • the subject matter of the dependant claims further develops the central idea of the present invention.
  • the inventors have found in a hamster model that - when administered together - kudzu and phytosterols act synergistically and allow reducing blood lipids and blood levels of LDL cholesterol statistically significantly, while keeping the individual dosages of phytosterols and kudzu sufficiently low to avoid unwanted side effects and discomfort
  • the present invention relates in part to a composition comprising phytosterols and kudzu for use in the treatment, alleviation or prevention of disorders associated with hyperlipidemia and/or hypercholesterolemia.
  • the present invention also relates to the use of phytosterols and kudzu in the preparation of a composition for treating, alleviating or preventing disorders associated with hyperlipidemia and/or hypercholesterolemia.
  • hyperlipidemia disorders associated with hyperlipidemia and/or hypercholesterolemia are well known to those of skill in the art (see for example Bhatnagar D. et al . , BMJ 2008 ; 337 : a993, herewith incorporated by reference) .
  • hypercholesterolemia is one of the major causes of atherosclerosis or coronary heart diseases.
  • Hyperlipidemia is characterized by abnormally elevated levels of any or all lipids and/or lipoproteins in the blood.
  • cardiovascular disorders are a group of disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, deep vein thrombosis and pulmonary embolism, etc.
  • Cerdiovascular disorders generally refers to any disease that affects the cardiovascular system, and in particular refers to those disorders related to atherosclerosis (arterial disease) . These conditions usually have similar causes, mechanisms, and treatments.
  • Atherosclerosis is the buildup of fatty deposits (such as cholesterol) called plaque on the inside walls of arteries. By the time that heart problems are detected, atherosclerosis is usually quite advanced, having progressed for decades.
  • the main cause of atherosclerosis is yet unknown, it is a syndrome affecting arterial blood vessels, a chronic inflammatory response in the walls of arteries, caused largely by the accumulation of macrophages and promoted by low-density lipoproteins (LDL, plasma lipoproteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL) . It is commonly referred to as a hardening or furring of the arteries. This is caused by the formation of multiple plaques within the arteries.
  • LDL low-density lipoproteins
  • HDL functional high density lipoproteins
  • Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. Hyperlipidemias may also be classified directly into which types of lipids are elevated, that is hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of Lipoprotein (a) may also be classified as a form of hyperlipidemia. Today, people make great efforts to keep their cholesterol levels low. Typical measures to reduce cholesterol levels are reducing dietary cholesterol intake, administration of certain medications, and rarely other treatments even including surgery. The present invention now provides a convenient dietary way to reduce cholesterol levels.
  • composition of the present invention may be used for lowering the plasma total cholesterol level, in particular the plasma level of LDL cholesterol.
  • a low LDL cholesterol concentration reduces the risk of cardiovascular disorders.
  • composition of the present invention is administered in a caloric restriction regimen and/or to subject which exercise aerobically regularly.
  • Typical cardiovascular disorders that can be prevented, ameliorated or treated with the composition of the present invention may be selected from the group consisting of artherosclerosis , myocardinal infarction, coronary heart disease, stroke, peripheral vascular diseases or combinations thereof .
  • compositions of the present invention may also be for use in treating or preventing high blood triglyceride levels and/or disorders linked thereto.
  • One major field of public concern is heart health.
  • the compositions of the present invention may be for use in promoting heart health and/or in treating, alleviating or preventing an impaired heart health.
  • compositions are administered in an amount sufficient to at least partially cure or arrest the symptoms of a disease and/or its complications. An amount adequate to accomplish this is defined as "a therapeutically effective dose”. Amounts effective for this purpose will depend on a number of factors known to those of skill in the art such as the severity of the disease and the weight and general state of the patient.
  • compositions according to the invention are administered to a patient susceptible to or otherwise at risk of a particular disease in an amount that is sufficient to at least partially reduce the risk of developing a disease.
  • a prophylactic effective dose Such an amount is defined to be "a prophylactic effective dose”.
  • the compositions of the present invention are effective following a dose-response curve. They may be administered in a therapeutically effective dose or a prophylactic effective dose. Skilled artesians will be able to determine such dosages appropriately.
  • composition of the present invention may be to be administered in a daily dose corresponding to at least 0.6 g, 3 g, or 6 g kudzu and at least 15 mg, 50 mg, or lOOmg phytosterols per kg body weight per day.
  • the composition of the present invention may comprise at least 0.3 g kudzu and at least 15 mg phytosterols per kg body weight per day.
  • composition of the present invention may comprise at least 3 g kudzu and at least 50 mg phytosterols per kg body weight per day.
  • composition of the present invention may comprise at least 6 g kudzu and at least 100 mg phytosterols per kg body weight per day.
  • the dosages should be kept at a reasonably low level.
  • the dosages of kudzu may not exceed 6 g per kg body weight per day and the dosage of phytosterols may not exceed 40 mg per kg body weight per day.
  • Kudzu may be provided in any form suitable for administration to humans or animals.
  • kudzu may be provided as fresh kudzu root, kudzu leaves, kudzu flowers, dried kudzu, or as an extract thereof.
  • Typical phytosterols that may be used for the purpose of the present invention may be selected from the group consisting of plant sterols, stands, or combinations thereof.
  • Phytosterols may be provided as chemically pure compounds. As such they may be purified from plant sources or synthesized chemically. This allows a very precise dosing.
  • phytosterols from natural sources or extracts thereof.
  • the phytosterols may be dietary phytosterols. They may be provided as vegetable oils, nuts, cereal products, vegetables, fruit, berries or as extracts thereof.
  • the composition may be any composition that is suitable for human or animal consumption.
  • the composition may be selected from the group consisting of a food product, a drink, a functional food, a nutraceutical , a food additive, a nutritional formula, and a pet food product.
  • composition of the present invention may be to be administered to adults or the elderly.
  • a subject shall be considered as "elderly" if it has surpassed the first half of its average expected lifespan in its country of origin, preferably, if it has surpassed the first two thirds of the average expected lifespan in its country of origin, more preferably if it has surpassed the first three quarters of the average expected lifespan in its country of origin, most preferred if it has surpassed the first four fifths of the average expected lifespan in its country of origin.
  • composition of the present invention may be to be administered to people above the age of 45, 50, 55, 60, 65, 70, 75 or 80 years.
  • composition of the present invention may be to be administered to humans or animals, for example companion animals such as cats or dogs.
  • NIH and NCEP for fasting HDL levels and risk for heart disease a level of less than 40 mg/dL HDL cholesterol for men and less than 50 mg/dL HDL cholesterol for women causes a heightened risk for heart disease.
  • An HDL cholesterol level of 60-50 mg/dL for women and of 60-40 mg/dL for men is considered normal .
  • composition of the present invention may be to be administered to people with a fasting HDL cholesterol level of below 60 mg/dL, of below 50 mg/dL or of below 40 mg/dL .
  • the American Heart Association, NIH, and NCEP have also provided a set of guidelines for fasting LDL-Cholesterol levels and risk for heart disease.
  • a fasting LDL-Cholesterol level of 100 to 129 mg/dL corresponds to a near optimal LDL level, corresponding to higher rates for developing symptomatic cardiovascular disease events .
  • a fasting LDL-Cholesterol level of 130 to 159 mg/dL corresponds to a borderline high LDL level, corresponding to higher rates for developing symptomatic cardiovascular disease events .
  • a fasting LDL-Cholesterol level of 160 to 199 mg/dL corresponds to a high LDL level, corresponding to much higher rates for developing symptomatic cardiovascular disease events
  • a fasting LDL-Cholesterol level of above 200 mg/dL corresponds to a very high LDL level, corresponding to highest increased rates of symptomatic cardiovascular disease events.
  • the composition of the present invention may be to be administered to people with a fasting LDL cholesterol level of above 100 mg/dL, of above 130 mg/dL, of above 160 mg/dL or of above 200 mg/dL.
  • the composition of the present invention may be consumed briefly before, with or briefly after the consumption of a high-fat or high LDL cholesterol meal.
  • a meal shall be considered high in fat if it contains more than 60%, more than 80% or more than 100% of the daily recommended fat intake.
  • a meal shall be considered high in LDL cholesterol if it contains more than 60%, more than 80% or more than 100% of the daily recommended LDL cholesterol intake.
  • the composition may be to be administered in the time frame from 1 hour before to 1 hour after a high fat and/or high LDL cholesterol meal.
  • TC Blood total cholesterol
  • K Kudzu Root
  • PS Plant Sterol

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Botany (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Biotechnology (AREA)
  • Hematology (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention se rapporte à une composition renfermant des phytostérols et du kudzu destinée à être utilisée dans le traitement, la diminution ou la prévention des troubles associés à l'hypercholestérolémie et/ou l'hyperlipidémie.
PCT/CN2012/071016 2012-02-10 2012-02-10 Composition renfermant des phytostérols et du kudzu pour les maladies cardiovasculaires WO2013117007A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/CN2012/071016 WO2013117007A1 (fr) 2012-02-10 2012-02-10 Composition renfermant des phytostérols et du kudzu pour les maladies cardiovasculaires
PCT/EP2013/052605 WO2013117733A1 (fr) 2012-02-10 2013-02-08 Kudzu et stérols végétaux et leurs effets sur les maladies cardiovasculaires
CN201380008698.5A CN104105494A (zh) 2012-02-10 2013-02-08 葛和植物固醇及它们对心血管疾病的作用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2012/071016 WO2013117007A1 (fr) 2012-02-10 2012-02-10 Composition renfermant des phytostérols et du kudzu pour les maladies cardiovasculaires

Publications (1)

Publication Number Publication Date
WO2013117007A1 true WO2013117007A1 (fr) 2013-08-15

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PCT/CN2012/071016 WO2013117007A1 (fr) 2012-02-10 2012-02-10 Composition renfermant des phytostérols et du kudzu pour les maladies cardiovasculaires
PCT/EP2013/052605 WO2013117733A1 (fr) 2012-02-10 2013-02-08 Kudzu et stérols végétaux et leurs effets sur les maladies cardiovasculaires

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PCT/EP2013/052605 WO2013117733A1 (fr) 2012-02-10 2013-02-08 Kudzu et stérols végétaux et leurs effets sur les maladies cardiovasculaires

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104352665A (zh) * 2014-11-04 2015-02-18 王慧 气血两虚型风湿性心脏病补益心脾制剂及制备方法
GB2518027A (en) * 2013-05-15 2015-03-11 Weiquan Li Chinese medicine composition for lowering lipid and protecting liver as well as preparation method and application thereof

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WO2014015467A1 (fr) * 2012-07-23 2014-01-30 Nestec S. A. Composition comprenant des phytostérols et du kudzu et son utilisation dans le traitement, l'atténuation ou la prévention de troubles métaboliques

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JP2008214191A (ja) * 2005-04-27 2008-09-18 Toyo Shinyaku:Kk 肝中脂質蓄積抑制剤
KR100816052B1 (ko) * 2006-04-28 2008-03-21 주식회사 삼양제넥스 수중 분산된 식물스테롤에스테르 함유 조성물
KR101177508B1 (ko) * 2010-01-29 2012-08-28 고려대학교 산학협력단 폐경기 여성건강 예방 및 치료용 칡 추출물 조성물

Non-Patent Citations (8)

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DONG, Y ET AL.: "Advances in Studies on Chemical Components of Pueraria DC.", FOOD & MACHINERY., vol. 21, no. 6, November 2005 (2005-11-01), pages 85 *
HUANG, C.L. ET AL.: "Effects of Radix Puerariae Decoction of the different dose on the Blood-lipid Levels of Hyperlipidemia.", JOURNAL OF SHANXI COLLEGE OF TRADITIONAL CHINESE MEDICINE., vol. 8, no. 4, August 2007 (2007-08-01), pages 15 *
LIU, H.Y. ET AL.: "Effects of Puerarin on the Levels of PGIZ and TXA2 in Plasma of Rats with Hyperlipidemia.", JOURNAL OF THIRD MILITARY MEDICAL UNIVERSITY., vol. 26, no. 11, June 2004 (2004-06-01), pages 967 *
PAN L.H. ET AL.: "Advance in Research on Cardiovascular Effects of Soybean Function Factors.", FOOD SCIENCE., vol. 26, no. 8, August 2005 (2005-08-01), pages 447 *
PENG, S.J. ET AL.: "Studies on Effects ofPuerarin on the Blood-lipid Levels of Rats.", LISHIZHEN EDICINE AND MATERIA MEDICA., vol. 17, no. 12, December 2006 (2006-12-01), pages 2516 *
QUAN, J. ET AL.: "Advances in Studies on Soybean Function Components. Soybean Bulletin.", ADVANCES IN STUDIES ON SOYBEAN FUNCTION COMPONENTS. SOYBEAN BULLETIN., May 2004 (2004-05-01), pages 28 *
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2518027A (en) * 2013-05-15 2015-03-11 Weiquan Li Chinese medicine composition for lowering lipid and protecting liver as well as preparation method and application thereof
GB2518027B (en) * 2013-05-15 2016-06-08 Li Weiquan Chinese medicine composition for lowering lipid and protecting liver as well as preparation method and application thereof
CN104352665A (zh) * 2014-11-04 2015-02-18 王慧 气血两虚型风湿性心脏病补益心脾制剂及制备方法

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