CN1562346A - Compound preparation of cyclicamp or its ramification and counteractant for free radical - Google Patents
Compound preparation of cyclicamp or its ramification and counteractant for free radical Download PDFInfo
- Publication number
- CN1562346A CN1562346A CN 200410033190 CN200410033190A CN1562346A CN 1562346 A CN1562346 A CN 1562346A CN 200410033190 CN200410033190 CN 200410033190 CN 200410033190 A CN200410033190 A CN 200410033190A CN 1562346 A CN1562346 A CN 1562346A
- Authority
- CN
- China
- Prior art keywords
- compound preparation
- free radical
- adenosine
- derivatives
- compound
- 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.)
- Pending
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A compound medicine for treating angina pectoris, myocardial infarction and heart failure and preventing peroxidizing reaction of lipoid is prepared from cyclophosphoadenoside or its derivatives and the free radical remover (reductive glutathion or CoQ10.
Description
Technical field
The invention belongs to medical technical field, relate to the compound preparation medicine of a kind of adenosine cyclophosphate class medicine and free radical scavenger.
Background technology
Adenosine cyclophosphate is a kind of important substance with physiologically active that extensively exists in human body, can regulate the multiple functional activity of cell.Second message,second messenger as hormone, performance hormonal regulation physiological function and substance metabolism effect in cell, can change function of plasma membrane, impel the calcium ion in the net agonistic muscle slurry matter to enter muscle fiber, thereby strengthen myocardial contraction, and can promote the oxidasic activity of respiratory chain, improve myocardial ischemia, alleviate coronary heart disease symptom and improve electrocardiogram, in addition, sugar, lipid metabolism, nucleic acid, proteinic synthetic adjusting etc. are played an important role.Adenosine cyclophosphate is usually used in angina pectoris, myocardial infarction, heart failure, myocarditis and cardiogenic shock during as drug use, and the cardiopalmus of improving rheumatic heart disease, symptom such as out of breath, uncomfortable in chest are had certain effect.The medicinal derivative of adenosine cyclophosphate also has meglumine adenosine cycle phosphate and Calcium Dibutyryladenosine Cyclophosph-ate, and its effect is identical with purposes and adenosine cyclophosphate.
Heart diseases such as angina pectoris, myocardial infarction, heart failure are the commonly encountered diseases and the frequently-occurring disease of serious harm human health, its pathogeny complexity, and very big to myocardial cell and heart function injury, the prognosis effect is relatively poor.The modern disease pharmacological research shows, free radical is the important root that causes the body tissue damage, especially cardiac muscle produces a large amount of free radicals during oxygen supply to attack biomacromolecule, biomembrane and other subcellular structures such as nucleic acid, protein, enzyme again at ischemia-reperfusion, thereby destroy cell and tissue, cause myocardial tissue damage.
Free radical typically refers to atom or the group that comprises unpaired electron, and the intravital free radical of people is based on oxygen-derived free radicals, and oxygen-derived free radicals is the cause of other free radical generation often.Under normal circumstances, the generation and the removing of oxygen-derived free radicals are equilibrated in the body, if for a certain reason, make the proper interior free radical that produces too much, perhaps protection in the body, removing and repair ability descend, and the metabolism of intravital free radical will be unbalance and cause the infringement of too much radical pair tissue.
Adenosine cyclophosphate and derivant thereof are better in cardiac disease curative effects such as treatment angina pectoris, myocardial infarctions, obtained clinically using widely, because the treatment of heart diseases such as angina pectoris, myocardial infarction is comprehensive, a complicated process, if in therapeutic process, can effectively remove the damage of radical pair heart, has positive meaning for the disease of rescuing the anxious property sent out of this class, raising prognosis effect.
The purpose of this invention is to provide a kind of medicine, the damage that makes it when heart diseases such as treatment angina pectoris, myocardial infarction, heart failure, can effectively remove the radical pair heart.
Summary of the invention
In order to achieve the above object, the present invention adopts adenosine cyclophosphate or derivatives thereof and free radical scavenger drug regimen, makes compound medicine, reaches the effect of collaborative onset.
Free radical scavenger is meant the material that can remove free radical or blocking-up free radical participation oxidation reaction, the medicine that can remove interior free yl is a lot, consider and the factor of aspects such as the physicochemical property of adenosine cyclophosphate or derivatives thereof when the compatibility, pharmacology synergism, safe medication that the selected free radical scavenger of the present invention is reduced glutathion, ubiquinone
10
Reduced glutathion (GSH) is synthetic naturally a kind of peptide in human cell's matter, form by glutamic acid, cysteine and glycine, contain sulfydryl (SH), be distributed widely in each organ of body, it is the prothetic group of Triose phosphate dehydrogenase, be again the coenzyme of aldoketonutase and triose dehydrogenase, can be by sulfydryl and intravital combined with radical, thus quicken the removing of free radical.Ubiquinone
10Being the fat-soluble quinones that extensively exists in the organism, is the activator of a kind of Cellular respiration and cellular metabolism, is important antioxidants and nonspecific immunity strengthening agent, ubiquinone
10Can provide electronics to oxygen-derived free radicals, make oxygen-derived free radicals be reduced into oxygen atom, remove the free radical that lipid peroxidation generates, protection membrane structure integrity function.In addition, ubiquinone
10Has following pharmacological action: function of resisting myocardial ischemia; Increase cardiac output, reduce Peripheral resistance, help anti-heart failure effect; Antiarrhythmic effect.
The purpose of this invention is to provide a kind of compound preparation, it is characterized in that containing adenosine cyclophosphate or derivatives thereof and reduced glutathion, wherein the quality ratio range of adenosine cyclophosphate or derivatives thereof and reduced glutathion is 1: 0.1～100.Reduced glutathion also comprises its pharmaceutically acceptable salt, as reduced glutathion sodium.
Another kind of purpose of the present invention provides a kind of compound preparation, it is characterized in that containing adenosine cyclophosphate or derivatives thereof and ubiquinone
10, wherein adenosine cyclophosphate or derivatives thereof and ubiquinone
10The quality ratio range be 1: 0.01～5.
What should specify is that among the present invention, the derivant of adenosine cyclophosphate comprises meglumine adenosine cycle phosphate and Calcium Dibutyryladenosine Cyclophosph-ate.
Compound preparation of the present invention can be an acceptable dosage form on any medicine, and as powder ampoule agent for injection, aqueous injection, oral tablet, capsule or the like, recommendering folder invention compound preparation adopts lyophilized injectable powder.
What those skilled in the art were appreciated that is, for the ease of production and processing become various dosage forms, guarantee medicine safe, effectively with factor such as stablize, compound preparation of the present invention also contains acceptable pharmaceutic adjuvant on the pharmaceutics, these pharmaceutic adjuvants are to select for use according to self physicochemical property of different pharmaceutical dosage forms and medicine, can select mannitol, sorbitol, lactose etc. for use as excipient; The pH value regulator can be selected hydrochloric acid, citric acid, sodium dihydrogen phosphate, sodium hydrogen phosphate, potassium hydroxide (sodium) etc. for use; Antioxidant can be selected sodium sulfite, sodium sulfite, vitamin C etc. for use; Solubilizing agent can be selected tween 80, polyoxyl stearate etc. for use; Metal chelating agent is selected ethylenediaminetetraacetic acid and salt thereof etc. for use.It is that the technical staff knows with conspicuous in the field of the present invention that the selection of pharmaceutic adjuvant is used.
The preparation method of compound preparation of the present invention is that those skilled in that art should know and understand, compound medicines of the present invention can be made the freeze-dried powder dosage form such as preparation technology's method according to lyophilized injectable powder, preparation technology according to aqueous injection can make water needle injection with compound medicines of the present invention, can be made as tablet for oral use or capsule according to the preparation technology of tablet or capsule.
The compound recipe combination medicament of adenosine cyclophosphate or derivatives thereof and free radical scavenger; not only can improve the symptom of heart diseases such as angina pectoris, myocardial infarction, heart failure and recover myocardial function; and can suppress the generation of lipid peroxidation; the damage and the necrosis of the cardiac muscular tissue of causing for free radical have good protective effect; especially the infringement of the free radical that myocardial ischemia-reperfusion is produced has good protective effect, and this many-sided comprehensive therapy medicine has great importance for first aid and rehabilitation, the raising prognosis of heart disease.
Verify the curative effect advantage of compound medicine of the present invention with zoopery.
The left bundle branch of utilization ligation rat arteria coronaria causes myocardial infarction model, model success rat is divided into four groups at random: (1). model control group: wait the capacity normal saline by rat body weight;
(2). compound recipe meglumine adenosine cycle phosphate glutathion group: give this compound medicine 230mg/kg body weight by rat body weight, the quality proportioning of meglumine adenosine cycle phosphate and reduced glutathion is 1: 6.67 in this compound medicine;
(3). compound recipe meglumine adenosine cycle phosphate ubiquinone
10Group: give this compound medicine 33mg/kg body weight by rat body weight, the quality proportioning of meglumine adenosine cycle phosphate and reduced glutathion is 1: 0.11 in this compound medicine;
(4). meglumine adenosine cycle phosphate group: give 30mg/kg body weight by rat body weight.
Below respectively organize in model success back 5min and give relative medicine respectively by femoral vein.
Data determination: (1). the mensuration of superoxide dismutase SOD and malonaldehyde MDA: the ligation arteria coronaria is after 4 hours, and the sacrificed by exsanguination rat is got ventricular muscles, makes ice normal saline tissue homogenate, and is centrifugal, gets the content that supernatant is measured SOD enzymatic activity and MDA;
(2). the mensuration of myocardial infarct size: the ligation arteria coronaria is after 4 hours, and the sacrificed by exsanguination rat is taken out its heart immediately, and cardiac muscle is carried out TTC dyeing, separates infarcted region in the myocardium sheet, calculates the infarcted myocardium wet weight and accounts for the percentage ratio of chamber weight in wet base whole-heartedly.Record experimental data following (n=8, x ± s):
| Group | SOD/U.mg -1Protein | MDA/nmol.mg -1Protein | Myocardial infarct size |
| Matched group | 55.8±7.8 | ?22.8±1.9 | ?24.8±2.3 |
| Compound recipe meglumine adenosine cycle phosphate glutathion group | 84.9±11.3 | ?8.2±2.2 | ?9.5±1.8 |
| Compound recipe meglumine adenosine cycle phosphate ubiquinone 10Group | 79.0±9.4 | ?10.9±2.5 | ?14.7±1.1 |
| The meglumine adenosine cycle phosphate group | 69.8±9.6 | ?15.2±2.4 | ?17.9±0.9 |
By above data as can be seen, two kinds of medicines of compound preparation of the present invention, drug effect for the rat heart muscle infarction all is better than using separately meglumine adenosine cycle phosphate, compare with matched group, no matter be SOD activity, content that reduces lipid peroxide that improves cardiac muscular tissue and the scope that reduces myocardial infarction, all have significant effect.
The specific embodiment
Several embodiment with following further illustrate compound preparation of the present invention by its preparation process, but do not represent the embodiment limitation of the present invention.
Embodiment 1. injection adenosine cyclophosphate glutathione freeze-dried powder injections
Prescription: adenosine cyclophosphate 20g
Reduced glutathion 300g
Water for injection 2500ml
Mannitol is an amount of
The pH value regulator is an amount of
Sodium sulfite is an amount of
Sodium ethylene diamine tetracetate is an amount of
Tween 80 is an amount of
Get above recipe quantity by lyophilized injectable powder preparation technology, can be prepared into the lyophilized powder compound injection of 1000 bottles of injections, contain adenosine cyclophosphate 20mg and reduced glutathion 300mg in every bottle of medicine.The quality proportioning of adenosine cyclophosphate and reduced glutathion is 1: 15.
Embodiment 2. meglumine cyclic adenosine for injecta glutathione freeze-dried powder injections
Similarly, adenosine cyclophosphate among the embodiment 1 is replaced with its derivant meglumine adenosine cycle phosphate and the change recipe quantity, also can make meglumine cyclic adenosine for injecta glutathione freeze-dried powder injection, make to contain meglumine adenosine cycle phosphate 30mg and reduced glutathion 200mg in every bottle of medicine.The quality proportioning of meglumine adenosine cycle phosphate and reduced glutathion is 1: 6.67.
Embodiment 3. meglumine adenosine cycle phosphate ubiquinones
10Injection
Prescription: meglumine adenosine cycle phosphate 45g
Ubiquinone
105g
Water for injection adds to 5000ml
The pH value regulator is an amount of
Sodium sulfite is an amount of
Tween 80 is an amount of
Polyoxyl stearate is an amount of
Get above recipe quantity by aqueous injection preparation technology, can be prepared into 1000 bottles of injection, adopt brown medicine bottle fill and inflated with nitrogen.Contain meglumine adenosine cycle phosphate 45mg and ubiquinone in every bottle of medicine
105mg.Meglumine adenosine cycle phosphate and ubiquinone
10The quality proportioning be 1: 0.11.
Claims (6)
1. a compound preparation is characterized in that containing adenosine cyclophosphate or derivatives thereof and reduced glutathion, and wherein the quality ratio range of adenosine cyclophosphate or derivatives thereof and reduced glutathion is 1: 0.1～100.
2. a compound preparation is characterized in that containing adenosine cyclophosphate or derivatives thereof and coenzyme Q10, wherein the quality ratio range of adenosine cyclophosphate or derivatives thereof and coenzyme Q10 be 1: 0.01～5.
3. a kind of compound preparation according to claim 1 is characterized in that reduced glutathion also comprises its pharmaceutically acceptable salt.
4. according to claim 1 and 2 described a kind of compound preparations, it is characterized in that the derivant of adenosine cyclophosphate comprises meglumine adenosine cycle phosphate and Calcium Dibutyryladenosine Cyclophosph-ate.
5. according to any one is described in the claim 1 to 4, this compound preparation can be an acceptable dosage form on any medicine.
6. according to any one is described in the claim 1 to 5, this compound preparation also contains acceptable pharmaceutic adjuvant on the pharmaceutics.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410033190 CN1562346A (en) | 2004-04-05 | 2004-04-05 | Compound preparation of cyclicamp or its ramification and counteractant for free radical |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410033190 CN1562346A (en) | 2004-04-05 | 2004-04-05 | Compound preparation of cyclicamp or its ramification and counteractant for free radical |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1562346A true CN1562346A (en) | 2005-01-12 |
Family
ID=34481324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410033190 Pending CN1562346A (en) | 2004-04-05 | 2004-04-05 | Compound preparation of cyclicamp or its ramification and counteractant for free radical |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1562346A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101897948A (en) * | 2010-07-16 | 2010-12-01 | 浙江大学 | Application of S-nitroso glutathione |
| CN104161769A (en) * | 2014-08-16 | 2014-11-26 | 广州一品红制药有限公司 | Cyclic adenosine monophosphate-containing composition and applications thereof |
-
2004
- 2004-04-05 CN CN 200410033190 patent/CN1562346A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101897948A (en) * | 2010-07-16 | 2010-12-01 | 浙江大学 | Application of S-nitroso glutathione |
| CN101897948B (en) * | 2010-07-16 | 2013-03-13 | 浙江大学 | Application of S-nitroso glutathione |
| CN104161769A (en) * | 2014-08-16 | 2014-11-26 | 广州一品红制药有限公司 | Cyclic adenosine monophosphate-containing composition and applications thereof |
| CN104161769B (en) * | 2014-08-16 | 2016-01-20 | 广州一品红制药有限公司 | A kind of compositions containing adenosine cyclophosphate and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1227011C (en) | Method of treating adenosine depletion | |
| CA2061270C (en) | Method and composition for treating reperfusion injury | |
| US5712259A (en) | NADH and NADPH pharmaceuticals for treating chronic fatigue syndrome | |
| CN1191061C (en) | Medical compsns. | |
| CN116370444B (en) | Application of coenzyme Q10 in preparation of medicine for preventing and treating aortic dissection | |
| US5744157A (en) | Preparation for maintaining and/or increasing muscular power and body cell mass | |
| US20070264370A1 (en) | Composition and methods for the treatment of joint pain using Angelica gigas Nakai extract and powder as combined with Glucosamine Sulfate, or Chondroitin Sulfate and HCL, or MSM, or aspirin, or Celedrin, and as combinations thereof in powder, pill, capsule, spray, liquid, and gelcap form | |
| JPH04506667A (en) | Thyroid hormone cardiac therapy | |
| CN1562346A (en) | Compound preparation of cyclicamp or its ramification and counteractant for free radical | |
| JPH0639377B2 (en) | Myopathic or muscular dystrophy therapeutic agent containing alkanoyl L-carnitine as an active ingredient | |
| WO1995022324A1 (en) | Treatment of migraine headaches and formulations | |
| CN111840512B (en) | Composition for treating cartilage repair and/or osteoarthritis | |
| CN101564394B (en) | Pharmaceutical composition containing ivabradine and trimetazidine | |
| Kochar et al. | A 52‐week comparison of lisinopril, hydrochlorothiazide, and their combination in hypertension | |
| Poole-Wilson | Timolol maleate (MK 950) in the treatment of essential hypertension | |
| CN1593562A (en) | Ginkgo leaf extract composition | |
| CN1461656A (en) | Medicinal excipient-potassium alginate and its composition | |
| CN1562345A (en) | Drug combination including activator for metabolism of brain and free radical scavenger | |
| CN1281212C (en) | General saponin of stem and leaf of American ginseng in Application of preparing medication for treating mycoarditis | |
| CN1788731A (en) | Compound injection preparation containing ligustrazine and breviscapine and its preparation method | |
| CN109464441B (en) | Application of 3-acetamido coumarin in preparing medicine for treating or preventing hyperuricemia and kidney injury | |
| US10111929B1 (en) | Growth hormone releasing factor analogs and uses | |
| CN102038190A (en) | Application of ampelopsin to preparation of anti-mutagenic health-care foods and medicaments | |
| CN1568973A (en) | Composition of vitamin C and arginine and its application | |
| CN1237975C (en) | Application of general saponin of gen-seng fruit in the preparation process of myocarditis treating medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |