EP1305013A1 - Preparation antioxydante protegeant contre les affections vasculaires et son utilisation - Google Patents
Preparation antioxydante protegeant contre les affections vasculaires et son utilisationInfo
- Publication number
- EP1305013A1 EP1305013A1 EP01944968A EP01944968A EP1305013A1 EP 1305013 A1 EP1305013 A1 EP 1305013A1 EP 01944968 A EP01944968 A EP 01944968A EP 01944968 A EP01944968 A EP 01944968A EP 1305013 A1 EP1305013 A1 EP 1305013A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- ldl
- preparation
- terpinene
- preparation according
- oxidation
- 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- Withdrawn
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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- 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)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- 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
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Definitions
- the invention relates to a preparation with vascular protective and antioxidant activity and its use.
- Hypercholesterolaemia in particular an increased fraction carrying the chorus (low density lipoprotein, LDL) and the oxidative change in LDL in the blood and in the endothelial lesions of the arterial vessels are important causal factors for the development of atherosclerosis.
- Atherosclerosis is a gradual disease with lipid deposits in the arterial vascular system of humans over decades.
- This disease can lead to occlusion of the coronary arteries (heart attack) due to growing plaques (lipid deposits inside the vessels) or lesions.
- plaques lipid deposits inside the vessels
- lesions lipid deposits inside the vessels
- a loosening plaque can cause a cerebral artery (stroke) to close.
- stroke cerebral artery
- atherosclerosis also develops in the other parts of the circulatory system.
- LDL oxidation quantitatively plays the most important role in the development of atherosclerosis
- Lipoproteins are macromolecular complexes of protein and lipid that are characterized by physico-chemical parameters such as salt density and ultracentrifugation. on and characterized by special proteins (apolipoproteins).
- the lipoproteins circulate in the blood and enable the transport and transfer of water-insoluble fats such as cholesterol, neutral fat (triglycerides) and phospholipids, depending on their hydrated
- VLDL Very Low Density Lipoproteins
- LDL Low Density Lipoproteins
- HDL High Density Lipoproteins
- LDL is the main transport molecule for cholesterol and cholesterol esters in the blood plasma. It consists of a lipid core surrounded by a shell of phospholipids and unesterified cholesterol. A protein molecule (Apo B-100) is embedded in the shell.
- Biological oxidation of LDL cholesterol occurs in part in the blood plasma, which is possible due to activated oxygen species with the formation of radicals. Further oxidation takes place in atherosclerotic plaque additionally through endothelial cells (the inner layer of an artery, also called intima) and through smooth muscle cells (the middle layer of an artery, media). About lipid peroxidation
- the preparation contains an ethereal oil or terpinene containing terpinene.
- Essential oils of citrus fruits, in particular lemons, are preferably used which contain ⁇ -terpinene as a natural component.
- essential oils When using essential oils to produce the preparation according to the invention, it can also be used in a form enriched with terpinene.
- the preparation additionally contains ⁇ -tocopherol (vitamin E) and / or coenzyme Q (Q 10 ).
- vitamin E ⁇ -tocopherol
- Q 10 coenzyme Q
- LDL in vitro oxidation of LDL is a common model for checking various substances for their antioxidative properties, since by pre-incubating the plasma with (especially lipophilic) test substances, these can be enriched in the LDL in vitro (McLean and Hagaman, 1989, Biochemistry 28 (1); 321-327, Esterbauer et al, 1991b, Am. J. Clin. Nutr. 53, 315S-321S). After enrichment, their influence on the oxidizability of the LDL can be examined.
- Peroxyl radicals can be formed a relatively stable tertiary radical, which is also mesomerized at least via a double bond.
- the protection of the LDL from oxidation by lemon oil or by the ⁇ -terpinene contained therein is based on its ability to react with lipid peroxyl radicals and thus on the one hand to interrupt the chain reaction of lipid peroxidation and on the other hand to delay protein oxidation.
- the preparation according to the invention can be used meaningfully in various areas.
- the preparation can be used as a medicament, nutritional supplement and / or as a dietary agent, which may contain further active ingredients, safe additives and / or auxiliaries as required.
- Fig. 3 Delay in the formation of conjugated dienes in LDL by enriching them with ⁇ -terpinene, ⁇ -tocopherol and reduced coenzyme Q (Qio): an unexpected effect
- the lag phase provides information about the oxidizability of the LDL; a longer lag phase means greater resistance to oxidation. It was examined whether the enrichment of the LDL with lemon oil or ⁇ -terpinene can protect the LDL from Cu (II) -induced oxidation. As Fig. 1 shows, the formation of conjugated dienes in LDL is significantly extended by enriching them with lemon oil.
- LDL Due to the 37 tryptophan residues in the ApoB-100, LDL shows fluorescence in the UV range.
- the oxidation of HDL or LDL with Cu (II) is accompanied by a decrease in the tryptophan residues (Reyftmann et al., 1990, Biochim. Biophys. Acta 1042, 159-167), this can be followed by measuring the fluorescence.
- the fluorescence drops within a few seconds, which is due to quenching effects caused by copper. Then the fluorescence decreases more or less linearly, in a second phase the fluorescence quickly decreases.
- the time until the transition from the slow to the faster phase can be defined as the lag phase, as with diene conjugation. (G hassleauf et. Al., 1995, Biochim. Biophys. Acta 1256, 221-232).
- the faster decrease in fluorescence begins approximately at the same time as the propagation phase of diene conjugation and is probably due to the reaction of products of lipid peroxidation with tryptophan residues. In this test system, too, it was examined whether the enrichment of the LDL with lemon oil or ⁇ -terpinene on the Cu (II) -induced loss of tryptophan fluorescence.
- the preparation according to the invention can be processed into any dosage forms. It can serve as a medicine, nutritional supplement or as a dietetic. Diluted, it can be administered, for example, as a liquid in the form of a juice or in the form of a drop. Furthermore, liquids such as whey or solids such as fiber or cereals can also be added.
- the preparation according to the invention can contain harmless natural or synthetic additives or auxiliaries, such as binders, disintegrants, lubricants, release agents, solvents, stabilizers, colorants and taste correctants.
- auxiliaries which can be used according to the invention are
- Binders such as starch, alginates, gelatin, sugar, locust bean gum, cellulose derivatives such as cellulose ether and polymers such as polyvinylpyrrolidone;
- Disintegrants such as starch and starch ether
- Lubricants and separating agents such as talc, stearates, such as calcium and magnesium stearate, magnesium and calcium carbonate, cellulose, magnesium oxide, colloidal silica, silicates, such as sodium, magnesium, calcium and aluminum silicate, separating flours, such as bread flour, Cereal skin, potato rolling, buckwheat and wood flour and locust bean gum; Deschn solvent, such as water, alcohol and solutions of Bin ⁇ ;
- Stabilizers such as fats, oils, flavorings and strength ⁇ derivatives
- Colorants such as natural and synthetic dyes permitted under food and pharmaceutical law Fe and pigments, for example carotene, sugar color, betanine and lycopene; and
- flavorings such as spices, salts, sweeteners and flavorings.
- auxiliaries mentioned above are particularly suitable for tableting and granulating.
- the preparation according to the invention can be added to the desired product in any manufacturing step.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Vascular Medicine (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Nutrition Science (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10038640A DE10038640A1 (de) | 2000-07-28 | 2000-07-28 | Präparat mit gefäßschützender und antioxidativer Wirkung sowie dessen Verwendung |
DE10038640 | 2000-07-28 | ||
PCT/DE2001/002082 WO2002009685A1 (fr) | 2000-07-28 | 2001-05-28 | Preparation antioxydante protegeant contre les affections vasculaires et son utilisation |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1305013A1 true EP1305013A1 (fr) | 2003-05-02 |
Family
ID=7651698
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01944968A Withdrawn EP1305013A1 (fr) | 2000-07-28 | 2001-05-28 | Preparation antioxydante protegeant contre les affections vasculaires et son utilisation |
Country Status (18)
Country | Link |
---|---|
US (1) | US20040047922A1 (fr) |
EP (1) | EP1305013A1 (fr) |
JP (1) | JP2004513077A (fr) |
CN (1) | CN1444475A (fr) |
AU (1) | AU2001267324A1 (fr) |
BR (1) | BR0112663A (fr) |
CA (1) | CA2411907A1 (fr) |
CZ (1) | CZ2003194A3 (fr) |
DE (2) | DE10038640A1 (fr) |
EE (1) | EE200300044A (fr) |
MX (1) | MXPA03000718A (fr) |
NO (1) | NO20030412L (fr) |
NZ (1) | NZ523185A (fr) |
PL (1) | PL364992A1 (fr) |
RU (1) | RU2003105695A (fr) |
SK (1) | SK872003A3 (fr) |
WO (1) | WO2002009685A1 (fr) |
ZA (1) | ZA200210123B (fr) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6616942B1 (en) | 1999-03-29 | 2003-09-09 | Soft Gel Technologies, Inc. | Coenzyme Q10 formulation and process methodology for soft gel capsules manufacturing |
WO2003041632A2 (fr) | 2001-11-14 | 2003-05-22 | Texas Tech University | Système d'administration de médicament sous forme d'auto-nanoémulsion à base eutectique |
KR20060082791A (ko) * | 2003-06-25 | 2006-07-19 | 찰스 에르윈 | 코엔자임 q10의 전달을 증가시키기 위한 화학적 배합물 및방법 |
US20080089877A1 (en) * | 2003-08-14 | 2008-04-17 | Udell Ronald G | Super Absorption Coenzyme Q10 |
US8124072B2 (en) | 2003-09-29 | 2012-02-28 | Soft Gel Technologies, Inc. | Solubilized CoQ-10 |
US8105583B2 (en) * | 2003-09-29 | 2012-01-31 | Soft Gel Technologies, Inc. | Solubilized CoQ-10 |
US7169385B2 (en) | 2003-09-29 | 2007-01-30 | Ronald G. Udell | Solubilized CoQ-10 and carnitine |
US8343541B2 (en) | 2007-03-15 | 2013-01-01 | Soft Gel Technologies, Inc. | Ubiquinol and alpha lipoic acid compositions |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1343561A (en) * | 1972-03-23 | 1974-01-10 | Hisamitsu Pharmaceutical Co | Substances for use in the treatment of gallstones |
US4246287A (en) * | 1979-10-26 | 1981-01-20 | International Flavors & Fragrances Inc. | Flavoring with fenchyl ethyl ether |
JPS60172925A (ja) * | 1984-02-17 | 1985-09-06 | Kao Corp | 胆石溶解剤 |
JPS60204722A (ja) * | 1984-03-28 | 1985-10-16 | Junichi Iwamura | 高脂血症改善・予防剤 |
ATE117665T1 (de) * | 1990-11-14 | 1995-02-15 | Oreal | Amphiphile, nichtionische derivate des glycerins sowie die entsprechenden zwischenprodukte, verfahren zu ihrer herstellung und diese enthaltende zusammensetzungen. |
AU659625B2 (en) * | 1991-01-18 | 1995-05-25 | Clilco, Ltd. | Lice-repellant compositions |
JPH08275728A (ja) * | 1995-04-06 | 1996-10-22 | New Aqua Gijutsu Kenkyusho:Kk | Dha油を主成分とする食用油 |
US5891465A (en) * | 1996-05-14 | 1999-04-06 | Biozone Laboratories, Inc. | Delivery of biologically active material in a liposomal formulation for administration into the mouth |
EP1021177A4 (fr) * | 1997-02-04 | 2002-05-15 | John V Kosbab | Compositions et procedes destines a la prevention et au traitement de maladies degeneratives vasculaires |
US5925335A (en) * | 1997-06-12 | 1999-07-20 | C.S. Bioscience Inc. | Dental formulation |
DE19915102A1 (de) * | 1999-04-01 | 2000-10-05 | Pohl Boskamp Gmbh Chem Pharma | Verwendung von Limonen zur Behandlung oxidativer Zellschädigungen |
US20020048551A1 (en) * | 1999-04-06 | 2002-04-25 | Keller Brian C. | Delivery of biologically active material in a liposomal formulation for administration into the mouth |
-
2000
- 2000-07-28 DE DE10038640A patent/DE10038640A1/de not_active Withdrawn
-
2001
- 2001-05-28 AU AU2001267324A patent/AU2001267324A1/en not_active Abandoned
- 2001-05-28 DE DE10192998T patent/DE10192998D2/de not_active Expired - Fee Related
- 2001-05-28 MX MXPA03000718A patent/MXPA03000718A/es not_active Application Discontinuation
- 2001-05-28 WO PCT/DE2001/002082 patent/WO2002009685A1/fr not_active Application Discontinuation
- 2001-05-28 US US10/311,730 patent/US20040047922A1/en not_active Abandoned
- 2001-05-28 SK SK87-2003A patent/SK872003A3/sk not_active Application Discontinuation
- 2001-05-28 RU RU2003105695/15A patent/RU2003105695A/ru not_active Application Discontinuation
- 2001-05-28 NZ NZ523185A patent/NZ523185A/en unknown
- 2001-05-28 CN CN01813403A patent/CN1444475A/zh active Pending
- 2001-05-28 EE EEP200300044A patent/EE200300044A/xx unknown
- 2001-05-28 EP EP01944968A patent/EP1305013A1/fr not_active Withdrawn
- 2001-05-28 CZ CZ2003194A patent/CZ2003194A3/cs unknown
- 2001-05-28 PL PL01364992A patent/PL364992A1/xx not_active Application Discontinuation
- 2001-05-28 BR BR0112663-6A patent/BR0112663A/pt not_active Application Discontinuation
- 2001-05-28 JP JP2002515238A patent/JP2004513077A/ja active Pending
- 2001-05-28 CA CA002411907A patent/CA2411907A1/fr not_active Abandoned
-
2002
- 2002-12-13 ZA ZA200210123A patent/ZA200210123B/xx unknown
-
2003
- 2003-01-27 NO NO20030412A patent/NO20030412L/no not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO0209685A1 * |
Also Published As
Publication number | Publication date |
---|---|
AU2001267324A1 (en) | 2002-02-13 |
PL364992A1 (en) | 2004-12-27 |
MXPA03000718A (es) | 2003-06-04 |
NZ523185A (en) | 2005-07-29 |
CZ2003194A3 (cs) | 2003-05-14 |
WO2002009685A1 (fr) | 2002-02-07 |
DE10038640A1 (de) | 2002-02-14 |
EE200300044A (et) | 2004-10-15 |
BR0112663A (pt) | 2003-06-24 |
CN1444475A (zh) | 2003-09-24 |
ZA200210123B (en) | 2003-05-27 |
DE10192998D2 (de) | 2003-01-16 |
RU2003105695A (ru) | 2004-06-27 |
NO20030412D0 (no) | 2003-01-27 |
CA2411907A1 (fr) | 2002-12-05 |
US20040047922A1 (en) | 2004-03-11 |
JP2004513077A (ja) | 2004-04-30 |
NO20030412L (no) | 2003-02-11 |
SK872003A3 (en) | 2003-06-03 |
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Legal Events
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
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17P | Request for examination filed |
Effective date: 20021121 |
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AK | Designated contracting states |
Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
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AX | Request for extension of the european patent |
Extension state: LT LV |
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17Q | First examination report despatched |
Effective date: 20040121 |
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Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
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RIC1 | Information provided on ipc code assigned before grant |
Ipc: A61P 9/14 20060101ALI20051229BHEP Ipc: A61K 36/00 20060101ALI20051229BHEP Ipc: A61K 31/01 20060101AFI20051229BHEP |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 20060427 |