CN1475211A - Compound preparation of levocarnitine and coenzyme Q10 - Google Patents
Compound preparation of levocarnitine and coenzyme Q10 Download PDFInfo
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- CN1475211A CN1475211A CNA03147716XA CN03147716A CN1475211A CN 1475211 A CN1475211 A CN 1475211A CN A03147716X A CNA03147716X A CN A03147716XA CN 03147716 A CN03147716 A CN 03147716A CN 1475211 A CN1475211 A CN 1475211A
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- levocarnitine
- compound preparation
- ubiquinone
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Abstract
A composite medicine contains levocarnitine or its physiologically receptable salt and coenzyme Q10 or its physiolgoically receptable salt.
Description
Technical field:
The present invention relates to a kind of compound medicinal formulation, particularly levocarnitine and ubiquinone
10The compound preparation that mix homogeneously forms, and the application of this compound preparation in medical treatment.
Background technology:
Levocarnitine is the essential cofactor of fatty acid metabolism, and it is the cofactor that several enzymes comprise carnitine translocase, acetylcarnitine transferase I and II.It is essential that these enzymes change acetylcarnitine into and are transferred to mitochondrion by long-chain fatty acid, thereby these materials are that to enter tricarboxylic acid cycle behind beta oxidation energy-producing.Acyl-CoA the bulk deposition that when ischemia, anoxia, in the beta oxidation process, is generated, Intramitochondrial long-chain acyl carnitine is also piled up, the free carnitine of q.s can make the acyl-CoA of accumulation enter in the mitochondrion, reduce its inhibition, make oxidative phosphorylation smooth acenine nucleotide translocase.Levocarnitine is the especially main energy source of myocardial cell of muscle cell, and many histoorgans such as brain, kidney are also mainly by the fatty acid oxidation energy supply.Be mainly used in former and secondary levocarnitine shortage at present clinically.Shock, acute, chronic cardiac insufficiency, ischemic cardiomyopathy, myocarditis, arrhythmia, angina pectoris, myocardial infarction; Chronic hepatic insufficiency, liver cirrhosis, the auxiliary treatment of chronic, acute hepatitis; Ischemic cerebrovascular, amyotrophy; Diabetes; The patient that chronic uremia is dialysed especially for a long time; Total parenteral nutrition and wound.Be used to reduce the toxicity of antitumor drug to cardiac toxicity and minimizing valproic acid.The neonate malnutrition.The bad auxiliary treatment effect of uterine contraction in puerperal.
Ubiquinone
10(cozymeO10) chemical formula is 2,3 dimethoxys-5-methyl-6-ten iso pentane two floride base benzoquinone, claims ubiquinone, ubidecarenone again.This material is the activator of a kind of Cellular respiration and cellular metabolism, by participating in the oxidative phosphorylation and adenosine triphosphate (ATP) generative process of cell, has the metabolic cardiotonic.Ubiquinone
10Have antioxidation and membrane stabilizing action, can improve myocardial metabolism.By promoting the cellular oxidation phosphorylation, improve energy metabolism of myocardial, directly antioxidation and membrane stabilizing action etc. reach protection, repair mitochondrial membrane phospholipid damaging action, thus protection myocardium, improve cardiac function.Ubiquinone
10Be mainly used in the auxiliary treatment of following disease; Cardiovascular disease is as viral myocarditis, chronic cardiac insufficiency; Hepatitis is as viral hepatitis, subacute severe hepatitis, chronic active hepatitis; The Comprehensive Treatment of cancer can alleviate some untoward reaction that radiotherapy, chemotherapy etc. cause.
Each histoorgan activity energy needed of human body relies on biological oxidation to provide, and wherein in the biological oxidation, oxidation of fatty acids is the main source that provides of energy sometimes.Fatty acid oxidation is divided three phases: (1) activation (carrying out in Cell sap); (2) beta oxidation (in mitochondrion); (3) tricarboxylic acid cycle (in mitochondrion).(P) and with a part activation of fatty acid is acyl-CoA to two energy-rich phosphate bonds of the every consumption of activation stage.Acyl-the CoA that in Cell sap, generates.Must be along under the assistance of carnitine, just can change over to through the catalysis of carnitine acyltransferase and to enter tricarboxylic acid cycle in the mitochondrion.Cause the ATP level to descend in ischemia, anoxia, cell membrane and subcellular fraction membrane permeability raise, and the acyl-CoA of accumulation can cause membrane structure and change, film phase disintegrate and cause cell death.In addition, during anoxia based on sugared anerobic glycolysis, accumulations such as fatty acid cause acidosis, ion imbalances, aqtocytolysis death, the free carnitine of q.s can make the acyl-CoA of accumulation enter in the mitochondrion, reduces its inhibition to acenine nucleotide translocase, makes oxidative phosphorylation smooth.Therefore, replenish a certain amount of levocarnitine and can make in the fatty acid oxidation process, make activation--〉this process of beta oxidation finishes smoothly.After entering beta oxidation, acyl-CoA is through the activation dehydrogenation of dehydrogenase, and the hydrogen that takes off in respiratory chain, is finished beta oxidation with electron transport through the transmission of several carriers, enters tricarboxylic acid cycle again and exhaustive oxidation, and discharges big energy.In electron transport, ubiquinone
10Be most important a kind of hydrogen carrier,, therefore be fat-soluble because it has very long hydrocarbon side chain, and he not with protein binding, molecule is less, so ubiquinone
10Mobile big in being imbued with the mitochondrial inner membrane of lipid, the sample that can shuttle back and forth between the different components of respiratory chain moves and transmits electronics and proton.Therefore, replenish a certain amount of ubiquinone
10The beta oxidation process is finished smoothly, thereby finished oxidation of fatty acids smoothly, discharge big energy.
Levocarnitine and ubiquinone
10As two kinds of important coenzyme in the fatty acid oxidation process, divided at present and else made the medicine listing, the discovery that the present invention is surprised, both are merged use, make compound medicinal formulation, have complementary effect, so the present invention proposes two kinds of materials are formed a kind of new compound preparation, curative effect is single with levocarnitine or ubiquinone
10Significantly improve, have synergism, produced beyond thought effect.And with respect to replenishing levocarnitine and coenzyme Q10 in clinical at twice, this compound preparation is easy to use, economical and practical.
Summary of the invention:
The invention provides a kind of pharmaceutical composition, the active component of said preparation is a: levocarnitine or its physiologically acceptable salt and b: ubiquinone
10Or its physiologically acceptable salt.
Described levocarnitine and ubiquinone
10Or its physiologically acceptable salt is meant, can be free form, also can be the form of their various physiologically acceptable salt.As alkali metal salt, alkali salt or acid salt etc., also can make the form of their inner salt or ester, and the form of any its active derivant of reservation.Compositions of the present invention is removed above-mentioned two kinds of compositions, also can add pharmaceutically acceptable auxiliary element medicine acceptable carrier, described medicine acceptable carrier comprises, solubilizing agent, cosolvent, antiseptic, filler, disintegrating agent, fluidizer, diluent and any adjuvant that needs when making pharmaceutical preparation, these can be: water, the Tweens material, starch, sucrose, fructose, lactose, mannitol, sorbitol, benzoic acid, sodium benzoate, benzyl alcohol, ethanol, the spans material, cellulose and derivant thereof, gelatin, polyvinylpyrrolidone, Polyethylene Glycol, Pulvis Talci, magnesium stearate etc.
Pharmaceutical preparation of the present invention can be made the acceptable dosage form of any medicine.Preferably injection and oral liquid also can be other dosage forms, as: tablet, capsule, granule, electuary, infusion solutions, freeze-dried powder etc.Can contain levocarnitine or its physiologically acceptable salt 0.05-5.0g in the per unit preparation, ubiquinone
10Or its physiologically acceptable salt 1mg-100mg.Preferably the dosage of per unit preparation can contain levocarnitine or its physiologically acceptable salt 1.0-2.0g, ubiquinone
10Or its physiologically acceptable salt 10mg-25mg.Described unit formulation is meant that each preparation unit is as every tablet of tablet, every capsules, every injection, every bottle of oral liquid etc.In use also can refer to each taking dose, be levocarnitine or its physiologically acceptable salt 1.0-2.0g as each use amount, ubiquinone
10Or its physiologically acceptable salt 10mm-25mg.For pharmaceutical preparation, can add the medicine acceptable carrier, can not add yet, take by weighing a certain amount of active component, mix homogeneously is made compound preparation according to the galenic pharmacy routine techniques.
Because ubiquinone
10Dissolubility is relatively poor in water, therefore, when preparation compound injection of the present invention and oral liquid, needs to add a certain amount of solubilizing agent, to guarantee ubiquinone in injection or the oral liquid
10Can dissolve fully.Solubilizing agent commonly used is tween 20, Tween-40, Tween-60, tween 80, Arlacel-80, polyoxyl stearate etc.
The present invention has compared when using different solubilizing agent, the stability of this compound liquid preparation.Single during with Tweens or spans, medicinal liquid can keep clear and bright in a short time, but room temperature placed three months, and medicinal liquid is muddy gradually so that precipitate occurs, thereby has influenced the quality of product, brings certain difficulty to clinical practice, improves the use amount of solubilizing agent, with ubiquinone
10With solubilizing agent by 1: 2-1: 40 (weight) are mixed, and along with the increase of solubilizing agent consumption, can prolong the clear and bright time of solution, but increasing of solubilizing agent consumption reduces the safety of injection, therefore, single with Tweens or spans solubilizing agent, the preparation injection there is certain insecurity.
Polyoxyethylene stearate (40) ester (Polyoxyl 40 stearate) also is a kind of surfactant commonly used, uses more extensive in suppository, liquid preparation.There are bibliographical information polyoxyl stearate and Tweens to share and improve ubiquinone
10The stability of injection, therefore the present invention adopts tween to mix use by a certain percentage with polyoxyethylene stearate (40) ester, the stability that compares the liquid preparation of preparation in 1: 1,2: 1,4: 1,8: 1, found that and use tween 80: polyoxyethylene stearate (40) ester (1: 1) is done solubilizing agent, the liquid preparation of being prepared was at room temperature placed 2 years, did not all have muddy the appearance.Dimension the present invention adopts tween 80: polyoxyethylene stearate (40) ester (1: 1) disposes the compound recipe solution do solubilizing agent.
Because ubiquinone
10To photaesthesia, meet light and easily decompose; To the oxygen sensitivity, easily oxidative degradation.Therefore, final injection or oral liquid need fill in the inflated with nitrogen brown bottle, to guarantee stability of formulation.
Preparation of the present invention, curative effect are single with levocarnitine or ubiquinone
10Significantly improve, have synergism, and easy to use, economical and practical.
The specific embodiment:
Below in conjunction with embodiment the present invention is described in detail:
Embodiment 1:
Prescription:
Ubiquinone
1020g
Levocarnitine 1000g
Water for injection 5000ml
Tween 80: an amount of technology of polyoxyethylene stearate (40) ester (1: 1): get recipe quantity levocarnitine 1000g, ubiquinone
1020g, an amount of solubilizing agent, add 5000ml water for injection, regulate pH value to 3.0-5.5 with an amount of 0.1mol/L hydrochloric acid solution, fully mix, filtration, fill is filled nitrogen brown bottle (every bottle of 5ml) and is promptly got compound injection of the present invention.
Embodiment 2:
Prescription:
Ubiquinone
1040g
Levocarnitine 2000g
Water for injection 10000ml
Tween 80: an amount of technology of polyoxyethylene stearate (40) ester (1: 1): get recipe quantity levocarnitine 1000g, ubiquinone
10, an amount of solubilizing agent, add 10000ml water for injection, regulate pH value to 3.0-5.5 with an amount of 0.1mol/L hydrochloric acid solution, fully mix, filtration, fill is filled nitrogen brown bottle (every bottle of 10ml) and is promptly got compound oral liquid of the present invention.
Claims (10)
1, a kind of compound medicinal formulation is characterized in that, the active component of said preparation is a: levocarnitine or its physiologically acceptable salt and b: ubiquinone
10Or its physiologically acceptable salt.
2, the compound preparation of claim 1 is any pharmaceutically acceptable dosage form.
3, the compound preparation of claim 1 is a liquid preparation.
4, the compound preparation of claim 1, the amount that contains levocarnitine or its physiologically acceptable salt in every dose is 0.05-5.0g, ubiquinone
10Or the amount of its physiologically acceptable salt is 1mg-100mg.
5, the compound preparation of claim 1, the amount that contains levocarnitine or its physiologically acceptable salt in every dose is 1.0-2.0g, ubiquinone
10Or the amount of available salt is 10mg-25mg on its physiology.
6, the compound preparation of claim 1 also contains and makes the needed carrier of preparation.
7, the compound preparation of claim 1, its active component accounts for the 0.1-99.9% of total formulation weight amount, makes the 0.1-99.9% that the needed carrier of preparation accounts for the total formulation weight amount.
8, the compound preparation of claim 3 is oral liquid or injection.
9, claim 6 and 8 compound preparation, described carrier comprises solubilizing agent, is selected from the mixed solution of tween and polyoxyethylene stearate (40) ester.
10, the compound preparation of claim 9, solubilizing agent are the blended homogeneous phase solution of weight ratio that tween 80 and polyoxyethylene stearate (40) ester were pressed 1: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA03147716XA CN1475211A (en) | 2003-06-24 | 2003-06-24 | Compound preparation of levocarnitine and coenzyme Q10 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA03147716XA CN1475211A (en) | 2003-06-24 | 2003-06-24 | Compound preparation of levocarnitine and coenzyme Q10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1475211A true CN1475211A (en) | 2004-02-18 |
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ID=34156164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA03147716XA Pending CN1475211A (en) | 2003-06-24 | 2003-06-24 | Compound preparation of levocarnitine and coenzyme Q10 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766590B (en) * | 2010-02-01 | 2011-11-16 | 北京康比特体育科技股份有限公司 | Combination for protecting peroxide injury of myocardium |
| CN102552923A (en) * | 2012-01-31 | 2012-07-11 | 辽宁思百得医药科技有限公司 | Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method |
| WO2019119445A1 (en) * | 2017-12-22 | 2019-06-27 | 邦泰生物工程(深圳)有限公司 | Nadh compound, and formulation and application thereof |
-
2003
- 2003-06-24 CN CNA03147716XA patent/CN1475211A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766590B (en) * | 2010-02-01 | 2011-11-16 | 北京康比特体育科技股份有限公司 | Combination for protecting peroxide injury of myocardium |
| CN102552923A (en) * | 2012-01-31 | 2012-07-11 | 辽宁思百得医药科技有限公司 | Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method |
| WO2019119445A1 (en) * | 2017-12-22 | 2019-06-27 | 邦泰生物工程(深圳)有限公司 | Nadh compound, and formulation and application thereof |
| ES2786774R1 (en) * | 2017-12-22 | 2020-10-16 | Bontac Bio Eng Shenzhen Co Ltd | Composition for coenzyme compound NADH, preparation and application thereof. |
| US10894059B2 (en) | 2017-12-22 | 2021-01-19 | Bontac Bio-Engineering (Shenzhen) Co., Ltd | NADH compound composition, and preparation and use thereof |
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