EP2209483A2 - Combinaison de baisse de pression sanguine comprenant ipp et/ou vpp - Google Patents

Combinaison de baisse de pression sanguine comprenant ipp et/ou vpp

Info

Publication number
EP2209483A2
EP2209483A2 EP08848815A EP08848815A EP2209483A2 EP 2209483 A2 EP2209483 A2 EP 2209483A2 EP 08848815 A EP08848815 A EP 08848815A EP 08848815 A EP08848815 A EP 08848815A EP 2209483 A2 EP2209483 A2 EP 2209483A2
Authority
EP
European Patent Office
Prior art keywords
blood pressure
compound
peptide
preferably selected
vpp
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.)
Withdrawn
Application number
EP08848815A
Other languages
German (de)
English (en)
Inventor
Van Der Lucas Cyril Gerard Heyden
Joris Kloek
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.)
DSM IP Assets BV
Original Assignee
DSM IP Assets BV
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 DSM IP Assets BV filed Critical DSM IP Assets BV
Priority to EP08848815A priority Critical patent/EP2209483A2/fr
Publication of EP2209483A2 publication Critical patent/EP2209483A2/fr
Withdrawn legal-status Critical Current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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a novel blood pressure lowering composition.
  • Hypertension commonly referred to as "high blood pressure” or HTN, is a medical condition in which the blood pressure is chronically elevated. While it is formally called arterial hypertension, the word “hypertension” without a qualifier usually refers to arterial hypertension. Hypertension can be classified as either essential (primary) or secondary. Essential hypertension indicates that no specific medical cause can be found to explain a patient's condition. Secondary hypertension indicates that the high blood pressure is a result of (i.e. secondary to) another condition, such as kidney disease or certain tumors (especially of the adrenal gland). Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysm, and is a leading cause of chronic renal failure. Even moderate elevation of arterial blood pressure leads to shortened life expectancy. At severely high pressures, mean arterial pressures 50% or more above average, a person can expect to live no more than a few years unless appropriately treated, (source:
  • antihypertensives compounds which are used to treat hypertension, will have a positive effect for only a certain percentage of people using the hypertensives.
  • ACE angiotensin converting enzyme
  • inhibiting peptides are found to be effective for about two third of people with high blood pressure, which amount corresponds with many prescription drugs.
  • the present invention discloses a novel blood pressure lowering composition which has an effect on at least four fifth of the people in need of such a composition.
  • the composition of the invention comprises: a peptide which has an ACE inhibiting effect; and at least one compound which can be extracted or purified from a natural source, this compound is preferably selected from the group consisting of CoQIO, grape seed extract, resveratrol, EGCG, Vitamin D, Pufa, GABA, Lycopene, Hawthorne, hydroxytyrosol or is preferably selected on anti-oxidative action of the polyphenols present in grape seed extract or isolate.
  • Prefered peptides are IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro).
  • I or Ne is isoleucine.
  • V or VaI is Valine.
  • P or Pro is proline.
  • the present invention also relates to a method of producing the composition of the invention by bringing together the peptide which is IPP and/or VPP and the at least one compound which can be extracted or purified from a natural source,this compound is preferably selected from the group consisting of CoQIO, grape seed extract, resveratrol, EGCG, Vitamin D, Pufa, GABA, Lycopene, Hawthorne, hydroxytyrosol or is preferably selected on anti-oxidative action of the polyphenols present in grape extract or isolate.
  • this compound is preferably selected from the group consisting of CoQIO, grape seed extract, resveratrol, EGCG, Vitamin D, Pufa, GABA, Lycopene, Hawthorne, hydroxytyrosol or is preferably selected on anti-oxidative action of the polyphenols present in grape extract or isolate.
  • the invention relates to the use of a peptide which has an ACE inhibiting effect; and - at least one compound which can be extracted or purified from a natural source, this compound which can be extracted or purified from a natural source, this compound is preferably selected from the group consisting of CoQI O, grape seed extract, resveratrol, EGCG, Vitamin D, Pufa, GABA, Lycopene, Hawthorne, hydroxytyrosol or is preferably selected on anti-oxidative action of the polyphenols present in grape seed extract or isolate in a food, feed, neutraceutical or dietary supplement or for the preparation of a food, feed, neutraceutical or dietary supplement.
  • the peptide is preferably IPP or VPP.
  • this use relates to ACE inhibition effect or for blood pressure lowering.
  • the peptide and the compound which can be extracted or purified from a natural source have together a synergetic effect on blood pressure lowering.
  • the present invention also relates to a method of treatment of a person in need of a blood pressure lowering effect which comprises administering to said person the composition of the invention.
  • the peptide having an ACE inhibiting effect may be produced according to any known process. It may be isolated from a protein source, it may be made by chemically or enzymatically hydrolyzing a protein or may be produced synthetically. Preferably the peptide is produced by hydrolysing a suitable protein and is part of a hydrolysate. The hydrolysate may optionally be purified to increase the peptide content in the hydrolysate.
  • Substrates for enzymatic hydrolysis include whole milk, skimmed milk, acid casein, rennet casein, acid whey products or cheese whey products. Other substrates for enzymatic hydrolysis are collagen based animal proteins such as gelatine as well as bones or fish-bones.
  • vegetable substrates like wheat gluten, milled barley and protein fractions obtained from, for example, soy, rice or corn are suitable substrates.
  • milk or milk derived protein such as casein or whey, is used.
  • the compound extracted from a natural source can be;
  • EPA and DHA may modulate the signaling intracellular Ca 2+ ion, which leads vascular muscles to dilate.
  • Other postulated mechanisms include shifting of the TxA 2 / TxA 3 balance in favor of TXA 3 and at the cost of the vasoconstrictive TxA 2 ; Altering prostaglandin synthesis; enhancing cell membrane fluidity, leading to altered ion channel activity.
  • GABA Gamma-amino-butyric acid
  • GABA administered at moderate doses does not cross the blood-brain barrier, its effects on blood pressure are considered to take place via peripheral mechanisms. Based on studies in rats, the most likely mechanism appears to be attenuation of sympathetic neurotransmission through blockade of GABA 6 receptors at sympathetic nerve terminals or ganglionic sites. However, binding of GABA to peripheral benzodiazepine receptors has been described and may account for part of GABA's hypotensive effect as well.
  • Grape seed extract (including Resveratrol) An abstract in the Faseb Journal (The FASEB Journal. 2007;21 :750.33) from the University of California at Davis has reported that blood pressure in subjects with pre- hypertension dropped by 8 / 6 mmHg for systolic and diastolic blood pressure after taking grape seed extract (300 mg).
  • Mechanism of action for grape seed extract the primary mechanism of action underlying the putative blood pressure lowering responses would lie in the anti-oxidative action of the polyphenols. This antioxidant effect would improve the bioavailability of the endogenous vasodilator nitric oxide (NO).
  • Tomato extract (lycopene) Only one study has been published on blood pressure lowering properties of tomato extract in humans, but it appears to be a well-designed study with robust effects (-10 mmHg decrease in a placebo controlled study. Egelhard , Am Heart J. 2006). Mechanism of action For tomato extract the primary mechanism of action underlying the putative blood pressure lowering responses would lie in the anti-oxidative action of the polyphenols. This antioxidant effect would improve the bioavailability of the endogenous vasodilator nitric oxide (NO). Some in vitro studies have suggested an ACE-inhibitory action of a number of polyphenols, but this effect has not been substantiated in humans.
  • Hawthorne has shown a trend towards blood pressure reduction in one study (Phytother Res. 2002 Feb;16(1 ):48-54.)
  • protein hydrolysate hydrolysate or hydrolysed protein is meant the product that is formed by enzymatic hydrolysis of the protein, an enriched hydrolysate being a fraction of the protein hydrolysate for example enriched in selected peptides or wherein peptides or polypeptides have been removed from the hydrolysate. So an enriched hydrolysate is preferably a mixture of peptides (or a peptide mixture).
  • the peptide mixture of the invention is therefore a mixture of at least two, preferably at least three, more preferably at least four peptides. More preferably the mixture comprises a peptide population of which more than 50%, preferably even more than 60%, and most preferably more than 75% of the peptides present have a molecular weight below 500 Da.
  • the protein hydrolysate used in the present invention has a DH of between 7 and 50, preferably a DH of between 10 and 40 and most preferably between 15 and 30.
  • a “peptide” or “oligopeptide” is defined herein as a chain of at least two amino acids that are linked through peptide bonds.
  • the terms “peptide” and “oligopeptide” are considered synonymous (as is commonly recognized) and each term can be used interchangeably as the context requires.
  • a “polypeptide” is defined herein as a chain containing more than 30 amino acid residues. All (oligo)peptide and polypeptide formulas or sequences herein are written from left to right in the direction from amino- terminus to carboxy-terminus, in accordance with common practice.
  • a protein is defined as used herein as the non-hydrolyzed protein. Moreover, especially when protein is discussed in general, protein can also mean the total of polypeptides, peptides and free amino acids.
  • Free amino acids are amino acids that are not joined to another amino acid by a peptide bound. "Amino acids” might be used on several occasions in this specification also meaning “free amino acids”. Preferably the amount of free amino acids in the composition of the invention is less than 5 wt% of the total protein.
  • nutraceutical denotes the usefulness in both the nutritional and pharmaceutical field of application.
  • novel nutraceutical compositions comprising the composition of the invention can find use as supplement to food and beverages and as pharmaceutical formulations or medicaments for enteral or parenteral application which may be solid formulations such as capsules or tablets, or liquid formulations, such as solutions, suspensions or emulsions.
  • dietary supplement denotes a product taken by mouth that contains a compound or mixture of compounds intended to supplement the diet.
  • the compound or mixture of compounds in these products may include: vitamins, minerals, herbs or other botanicals and amino acids.
  • Dietary supplements can also be extracts or concentrates, and may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders.
  • nutraceutical denotes the usefulness in both the nutritional and pharmaceutical field of application.
  • the nutraceutical compositions according to the present invention may be in any form that is suitable for administrating to the animal body including the human body, especially in any form that is conventional for oral administration, e.g. in solid form such as (additives/supplements for) food or feed, food or feed premix, tablets, pills, granules, dragees, capsules, and effervescent formulations such as powders and tablets, or in liquid form such as solutions, emulsions or suspensions as e.g. beverages, pastes and oily suspensions. Controled (delayed) release formulations incorporating the hydrolysates according to the invention also form part of the invention.
  • solid form such as (additives/supplements for) food or feed, food or feed premix, tablets, pills, granules, dragees, capsules, and effervescent formulations such as powders and tablets, or in liquid form such as solutions, emulsions or suspensions as e.g. beverages, pastes and oily suspension
  • a multi-vitamin and mineral supplement may be added to the nutraceutical compositions of the present invention to obtain an adequate amount of an essential nutrient, which is missing in some diets.
  • the multi-vitamin and mineral supplement may also be useful for disease prevention and protection against nutritional losses and deficiencies due to lifestyle patterns.
  • beverage which can be used for the supplementation of the composition of the invention can be in the form of beverage, such as sports drinks, energy drinks or other soft drinks, or any other suitable nutrient preparation.
  • a sports drink is a beverage which is supposed to rehydrate athletes, as well as restoring electrolytes, sugar, and other nutrients. Sports drinks are usually isotonic, meaning they contain the same proportions of nutrients as found in the human body.
  • Energy drinks are beverages which contain (legal) stimulants, vitamins (especially B vitamins) and minerals with the intent to give the user a burst of energy.
  • Common ingredients include caffeine, guarana (caffeine from the Guarana plant), taurine, various forms of ginseng, maltodextrin, inositol, carnitine, creatine, glucuronolactone and ginkgo biloba. Some may contain high levels of sugar, or glucose. Many such beverages are flavored and/or colored.
  • a soft drink is a drink that does not contain alcohol, as opposed to hard drinks, that do. In general, the term is used only for cold beverages. Hot chocolate, tea, and coffee are not considered soft drinks. The term originally referred exclusively to carbonated drinks, and is still commonly used in this manner.(http://en.wikipedia.org/wiki/Soft_drink).
  • An endoprotease is defined herein as an enzyme that hydrolyses peptide bonds in a polypeptide in an endo-fasion and belongs to the group EC 3.4.
  • the endoproteases are divided into sub-subclasses on the basis of catalytic mechanism. There are sub- subclasses of serine endoproteases (EC 3.4.21 ), cysteine endoproteases (EC 3.4.22), aspartic endoproteases (EC 3.4.23), metalloendoproteases (EC 3.4.24) and threonine endoproteases (EC 3.4.25).
  • Exoproteases are defined herein as enzymes that hydrolyze peptide bonds adjacent to a terminal ⁇ -amino group (“aminopeptidases”), or a peptide bond between the terminal carboxyl group and the penultimate amino acid (“carboxypeptidases”).
  • composition according to the invention has a bland or neutral taste and an improved solubility under acid conditions and can be used as basis for other beverages such as sport drinks or soft drinks or health drinks or fermented products.
  • bland taste of a composition or product of the invention is meant that the bitterness level of a 3 wt% protein in water sample, is similar to or lower than a level of 15 mg/litre of quinine sulphate dissolved in destilled water and tasted at a temperature of 14°C.
  • the quantity of enzyme required to achieve the desired degree of hydrolysis depends upon the enzyme used.
  • the enzyme dosage and incubation conditions are optimised in such a way so that the majority of the casein protein fraction is dissolved in the aqueous phase of the reaction after incubation periods of typically 6 to 20 hours.
  • majority is meant that under pH 4, less than 20%, preferably less than 10%, more preferably less than 5% of the protein present in the casein fraction can be precipitated upon centrifugation for 10 minutes at 2000 g.
  • the enzyme inactivation step which can be used after the hydrolysis can be a heat treatment which comprises heating to a temperature of at least 85°C for at least 10 minutes. If higher temperatures or more extreme pH values are used, shorter periods may be feasible. Such heat treatment is preferably carried out at an acidic pH value, preferably between 3 and 7.
  • the enzyme inactivation treatment can be done for both fractions seperately or can be done after that the fractions are mixed to form the composition of the invention.
  • each hydrolysate or the mixture of both hydrolysates can be filtered using an ultrafilter, a microfilter, diatomaceous earth, fiberglass filters or using cross-flow filtration. Complete enzyme inactivation can be confirmed by a dye-gelatin test.
  • the filtered final hydrolysate(s) can be treated with activated charcoal or with nanofiltration, ion exchange or electro dialysis to remove a surplus of salts.
  • the filtered hydrolysate(s) can be pasteurised or sterilised and, if required, further concentrated by drying techniques such as evaporation, nano filtration, spray drying, fluidized bed drying or combinations thereof.
  • drying techniques such as evaporation, nano filtration, spray drying, fluidized bed drying or combinations thereof.
  • the obtained product is in a granular form.
  • the hydrolyzed casein protein containing fraction can be concentrated and dried.
  • the dried product can be redissolved in the hydrolyzed whey protein containing fraction to obtain the desired protein concentration and protein ratio and then, if required, centrifuged or filtered and pasteurised or sterilised to obtain the product according to the invention.
  • the product can be subjected to additional enzyme treatments such as lactases or can be fermented with different types of starter cultures or can be combined with all kinds of ingredients such as oils, fats, emulsifyers, carbohydrates, fruit concentrates, flavours, colorants, alcohol, carbon dioxide, thickeners, acidulants, antioxidants, herbs or herb extracts, health promoting compounds like vitamins or provitamins or bioactive or tryptophane containing peptides or amino acids to formulate a product which is in line with the marketing needs.
  • Degree of Hydrolysis such as lactases or can be fermented with different types of starter cultures or can be combined with all kinds of ingredients such as oils, fats, emulsifyers, carbohydrates, fruit concentrates, flavours, colorants, alcohol, carbon dioxide, thickeners, acidulants, antioxidants, herbs or herb extracts, health promoting compounds like vitamins or provitamins or bioactive or tryptophane containing peptides or amino acids to formulate a product which is in line with the marketing needs.
  • the degree of hydrolysis is the extent to which peptide bonds are broken by the enzymatic hydrolysis reaction.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Fodder In General (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La présente invention porte sur une composition comprenant un peptide qui est IPP et/ou VPP ; et au moins un composé qui peut être extrait ou purifié à partir d'une source naturelle. Ce composé est, de préférence, choisi dans le groupe constitué par CoQ10, un extrait de pépins de raisin, le resveratrol, GEGC, la vitamine D, Pufa, GABA, le lycopène, Hawthorne, l'hydroxytyrosol ou est, de préférence, choisi sur une action anti-oxydante des polyphénols présents dans un extrait ou un isolat de pépins de raisin.
EP08848815A 2007-11-14 2008-11-10 Combinaison de baisse de pression sanguine comprenant ipp et/ou vpp Withdrawn EP2209483A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08848815A EP2209483A2 (fr) 2007-11-14 2008-11-10 Combinaison de baisse de pression sanguine comprenant ipp et/ou vpp

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP07120625 2007-11-14
EP08848815A EP2209483A2 (fr) 2007-11-14 2008-11-10 Combinaison de baisse de pression sanguine comprenant ipp et/ou vpp
PCT/EP2008/065242 WO2009062914A2 (fr) 2007-11-14 2008-11-10 Nouvelle composition à effet hypotenseur

Publications (1)

Publication Number Publication Date
EP2209483A2 true EP2209483A2 (fr) 2010-07-28

Family

ID=39272173

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08848815A Withdrawn EP2209483A2 (fr) 2007-11-14 2008-11-10 Combinaison de baisse de pression sanguine comprenant ipp et/ou vpp

Country Status (4)

Country Link
EP (1) EP2209483A2 (fr)
JP (1) JP2011504464A (fr)
CN (1) CN101909645A (fr)
WO (1) WO2009062914A2 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103127045B (zh) * 2013-02-05 2014-10-29 新疆优康来生物科技开发有限公司 一种含有γ-氨基丁酸和番茄红素的组合物及其制备方法
CN107375897A (zh) * 2017-08-15 2017-11-24 普维食品发展（上海）有限公司 一种辅助降血压的组合物及其用途
CN109380728B (zh) * 2018-10-17 2022-03-22 汤臣倍健股份有限公司 一种具有辅助降血压功效的组合物及保健食品
CN111919963B (zh) * 2020-07-10 2021-06-01 青岛农业大学 一种从小麦面筋蛋白中酶法制备富含ipp和vpp水解物的方法
CN114010773A (zh) * 2021-10-26 2022-02-08 江苏协合转化医学研究院有限公司 一种降血压且无副作用的组合物配方及其制备工艺和用途

Family Cites Families (5)

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Publication number Priority date Publication date Assignee Title
JP4727770B2 (ja) * 1997-09-26 2011-07-20 カルピス株式会社 尿中カテコールアミン低下、尿中ノルアドレナリン低下、尿中ドーパミン低下及びＦｉｓｃｈｅｒ比低下の少なくとも１つの軽減剤
JP2002241305A (ja) * 2001-02-14 2002-08-28 Yakult Honsha Co Ltd 高血圧症予防・治療剤
WO2005011660A1 (fr) * 2003-07-29 2005-02-10 Abbott Laboratories Utilisation de vitamine d pour reguler a la baisse le systeme renine-angiotensine-aldosterone
US20050143356A1 (en) * 2003-12-08 2005-06-30 Vanderbilt University Selective inhibition of cyclooxygenase 1 in the treatment of diabetic nephropathy
US20100166859A1 (en) * 2006-01-16 2010-07-01 Luppo Edens Novel nutraceutical compositions and use thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009062914A2 *

Also Published As

Publication number Publication date
WO2009062914A2 (fr) 2009-05-22
JP2011504464A (ja) 2011-02-10
WO2009062914A3 (fr) 2009-11-05
CN101909645A (zh) 2010-12-08

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