CN101511376A - Cardiovascular preparation - Google Patents
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- CN101511376A CN101511376A CNA2007800334689A CN200780033468A CN101511376A CN 101511376 A CN101511376 A CN 101511376A CN A2007800334689 A CNA2007800334689 A CN A2007800334689A CN 200780033468 A CN200780033468 A CN 200780033468A CN 101511376 A CN101511376 A CN 101511376A
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- 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
- A61K31/66—Phosphorus compounds
- A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- 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
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Abstract
Disclosed is a novel cardiovascular preparation. The cardiovascular preparation comprises a combination of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and taurine.
Description
Technical field
The present invention relates to cardiovascular preparation.More specifically, relate to the prevention of myocardial ischemia and/or the cardiovascular preparation of improvement effect with excellence.
Background technology
Normal heart shrinks and diastole regularly repeatedly, incessantly to the whole body pumping blood.This is to flow into the result that caused excitation contraction coupling rule is correctly carried out by the ionic outflow of Ca in the cell.But,, then cause systolic dysfunction or diastolic function not complete (non-patent literature 1) if known this excitation contraction coupling is unusual.Incomplete these the two kinds of morbid state of systolic dysfunction and diastolic function are confirmed as ischemic heart desease jointly.When the ischemic heart onste, it is important making coronary vasodilator expand, impel blood flow to substantially improve rapidly as far as possible.This is that the dysfunction of cardiac function and coronary vasodilator is with regard to the irreversible cause that becomes more because the myocardial ischemia time prolongs more.Therefore, when ischemic episode, throw medicament with nitroglycerin that promotes coronary vasodilation and so on, but the effect of these medicaments is scarcely abundant or invalid, in this case, implement percutaneous tranluminal coronary angioplasty (PTCA) and coronary vasodilator by-pass operation (tip tremulous pulse or venous are transplanted) etc.
Adenosine 5 '-triphosphoric acid (following brief note be ATP) sometimes is as metabolic materials such as phosphodonor wide participation sugar, fat or protein, and the energy that is produced by the hydrolysis of ATP becomes the motive force of energy requirement reaction in the body.
In containing the medicine of ATP, can confirm the regulatory function in the improvement, heart failure, accommodative asthenopia for each symptom behind the injury of head stabilisation, by digestive tract function descend the chronic gastritis that causes, based on the dizzy usefulness of prunus mume (sieb.) sieb.et zucc. Ni Ershi disease and internal ear obstacle.As the pharmacological action of ATP, can confirm in heart, to make the expansion of coronary vasodilator and peripheral vessel, make coronary flow and cardiac output increase (non-patent literature 2).Report is arranged in addition, its increase ligation the side of Cor Canitis muscle infarction morbid state model coronarius prop up the circulation blood flow, prevent that sb.'s illness took a turn for the worse (non-patent literature 3).And, known ATP and magnesium chloride injection and effective to ischemic myocardium with administration, thereby can be as the curative utilization (non-patent literature 4) of angina pectoris and myocardial infarction.
Taurine (taurine) is that molecular weight is 125.15 the sulfur-containing amino acid with very simple chemical constitution, in being present in the human body until neural and amphiblestroid nearly all internal organs, organizing with high concentration usually.Particularly exist with high concentration in cardiac muscle, skeletal muscle, about 3/4 of taurine is present in the muscle in the body.In addition, the taurine concentration in the skeletal muscle, the height of the ratio fast muscle of slow muscle is not because skeletal muscle and cardiac muscle have the ability of biosynthesis taurine, so its concentration is kept by taking in from the extracellular.
In containing the medicine of taurine, can confirm usefulness to improvement of the liver function in the hyperbilirubinemia and congestive heart failure.As the pharmacological action of taurine, be reported in the cardiac muscle, at low Ca
2+State shows the positive inotropic action down, at high Ca
2+State shows negative inotropic's effect down, thinks that it is according to the Ca in the extracellular fluid
2+Concentration and show biphasic effect, thereby as Ca
2+Actuator plays a role.Report the generation that it promotes ATP in addition, inhibitory enzyme flows out from cardiac muscle, the cytoprotection (non-patent literature 5) when showing ischemia.
But, in above-mentioned whole known technology, all do not have hint or instruction to go up acceptable salt and taurine, to the prevention and/or the improvement effect performance cooperative effect of myocardial ischemia by combination adenosine 5 '-triphosphoric acid or its physiology.
Non-patent literature 1:Folica.Pharmmacol.Jpn rolled up the 87-93 page in 2004 123
Non-patent literature 2: the 25th edition the 69-70 page of Japanese pharmaceuticals collection
Non-patent literature 3:A T P Ji Foundation と Pro bed was rolled up the 137th page in 1964 2
Non-patent literature 4: thousand
The 199-209 page of No. 3, Yi magazine 1985 61 volume
Non-patent literature 5: the 25th edition the 105-106 page of Japanese pharmaceuticals collection
Summary of the invention
Problem of the present invention is to provide a kind of new cardiovascular preparation.
The present inventor furthers investigate in order to solve above-mentioned problem; the result is surprised to find that; by also going up acceptable salt and taurine with adenosine 5 '-triphosphoric acid or its physiology; can confirm the prevention and/or the improvement effect of significant myocardial ischemia; compare during with these medicines of independent use; its combined effect is worked in coordination with, thereby has finished the present invention.
That is, the invention provides a kind of cardiovascular preparation, the combination that it contains adenosine 5 '-triphosphoric acid or its physiology goes up acceptable salt and taurine.
In addition, the invention provides adenosine 5 '-triphosphoric acid or its physiology and go up acceptable salt and taurine use in cardiovascular preparation is made.
In addition, the invention provides a kind of prophylaxis and/or therapy of causing circulatory disease, it is characterized in that, the adenosine 5 '-triphosphoric acid of throwing and effective dose or its physiology go up acceptable salt and taurine.
The effect of invention
Cardiovascular preparation of the present invention, the cooperative effect that goes up acceptable salt and taurine by adenosine 5 '-triphosphoric acid or its physiology has the extremely prevention and/or the improvement effect of the myocardial ischemia of excellence, can compatibly use as cardiovascular preparation.In addition, by the prevention and/or the improvement effect of myocardial ischemia, can be as the agent that prevents and/or treats of ischemic heart desease particularly, and then can compatibly use as the agent that prevents and/or treats of the disease that is selected from angina pectoris and myocardial infarction.In addition, based on myocardial ischemia prevention and/or improvement effect, can eliminate cardiopalmus and/or asthma as the symptom appearance of myocardial ischemia.
Description of drawings
Fig. 1 is illustrated in 30mg/kgATP, 3000mg/kg taurine and and with the figure of the ST segment value in the administration group.
The specific embodiment
Cardiovascular preparation of the present invention is the cardiovascular preparation that contains the combination of adenosine 5 '-triphosphoric acid or last acceptable salt of its physiology and taurine.That is, cardiovascular preparation of the present invention is while or change time to throw the cardiovascular preparation of going up acceptable salt and taurine with adenosine 5 '-triphosphoric acid or its physiology.
Adenosine 5 '-triphosphoric acid or its physiology go up the preparation of unit administering mode of acceptable salt and the combination (medicine box) of preparation that comprises the unit administering mode of taurine provides as comprising for cardiovascular preparation of the present invention, perhaps provide as comprising the medical composition (combination drug) that adenosine 5 '-triphosphoric acid or its physiology go up the unit administering mode of acceptable salt and taurine simultaneously.More preferably provide as the medical composition that comprises last acceptable salt of adenosine 5 '-triphosphoric acid or its physiology and taurine simultaneously.
The last acceptable salt of employed adenosine 5 '-triphosphoric acid or its physiology is known material in the cardiovascular preparation of the present invention, and those skilled in the art can obtain easily.The kind that the physiology of adenosine 5 '-triphosphoric acid goes up acceptable salt is not particularly limited, and for example, can enumerate alkali metal salts such as sodium salt, potassium salt; Alkali salt such as magnesium salt, calcium salt.Wherein, from the viewpoint of myocardial ischemia prevention and/or improvement effect, preferred especially adenosine 5 '-triphosphoric acid disodium.The preparation that comprises the last acceptable salt of adenosine 5 '-triphosphoric acid or its physiology goes on the market as the preparation or the injection of oral medication mode, when using the preparation that comprises adenosine 5 '-triphosphoric acid or the last acceptable salt of its physiology separately that medicine of the present invention is provided, can use the preparation of commercially available adenosine 5 '-triphosphoric acid or its salt.For example, commercially available have " ADETPHOS " (Kowa company Ltd) etc.
Employed taurine is known material in the cardiovascular preparation of the present invention, and those skilled in the art can obtain easily.The preparation that comprises taurine when using the preparation that comprises taurine separately that cardiovascular preparation of the present invention is provided, can use commercially available taurine preparation as the preparation listing of oral medication mode." taurine loose " greatly just " " (Taisho Pharmaceutical Co., Ltd) etc. for example, commercially availablely arranged.
Cardiovascular preparation of the present invention can be suitable for prevention and/or improve the incomplete state of cardiac function (heart failure).Be more suitable for prevention and/or improvement effect, use, further be suitable as the disease prevention and/or the therapeutic agent that are selected from angina pectoris and myocardial infarction and use as the agent that prevents and/or treats of ischemic heart desease by myocardial ischemia.In addition, cardiovascular preparation of the present invention also can be used in the purpose of symptoms such as eliminating cardiopalmus and/or asthma.
The portfolio ratio that adenosine 5 ' in the cardiovascular preparation of the present invention-triphosphoric acid or its physiology go up acceptable salt and taurine is not particularly limited, and those skilled in the art can be according to the suitably selections such as test method of concrete expression among the embodiment described later.In the present invention; viewpoint from the cooperative effect of the prevention of myocardial ischemia and/or improvement effect; go up acceptable salt with respect to 1 mass parts adenosine 5 '-triphosphoric acid or its physiology, preferably with the scope of 0.001～10000 mass parts, more preferably with the scope of 0.01～1000 mass parts, especially preferably use taurine with the scope of 0.1～100 mass parts.
As the administering mode of cardiovascular preparation of the present invention, can be any of oral medication or non-oral medication.The preferred oral application method.
In addition, be suitable for the cardiovascular preparation of oral medication, more preferably provide as the solid, shaped, semi-solid or the liquid medical composition that in 1 unit administering mode, comprise last acceptable salt of adenosine 5 '-triphosphoric acid or its physiology and taurine.
As the medicine that is suitable for oral medication or be suitable for the medicine of non-oral medication and when cardiovascular preparation of the present invention was provided, its dosage form was not particularly limited.For example, can be solid, shaped medical compositions such as powder, granule, tablet, chewable tablet, film coated tablet, sugar coated tablet, soft capsule, hard capsule; Aqueous medical composition such as potus; Any of semi-solid medical compositions such as gel.In the present invention, especially preferably make the solid, shaped medical composition.
When cardiovascular preparation of the present invention is provided as the medical composition that comprises last acceptable salt of adenosine 5 '-triphosphoric acid or its physiology and taurine simultaneously; each components matching amount in the medical composition is not particularly limited; on the basis of combinations thereof ratio with due regard to, according to the form decision of medical composition.For example, when providing as the solid, shaped medical composition, the medical composition of each medication unit can cooperate about 10～300mg adenosine, 5 '-triphosphoric acid or its physiology to go up acceptable salt, 10～3000mg taurine.
In cardiovascular preparation of the present invention, can cooperate purpose suitably to cooperate ATP and taurine composition in addition according to it.As such composition, can enumerate vitamin, vitamin D 3-analogies, mineral, caffeine class medicine, aminoacid, crude drug, the medication of liver obstacle etc.
As vitamin, can enumerate thiamine hydrochloride, thiamine nitrate, the nitric acid thiamine disulfide, TATD, thiamine double hexadecyl sulfuric acid, Dicethiamine Hydrochloride, fursultiamine hydrochloride, octotiamine, cycotiamine, vitaberin, bisbentiamine, fursultiamine, prosulthiamine, benfotiamine, Flavin Adenin Dinucleotide Sodium, riboflavin, Riboflavin Sodium Phosphate, hibon, pyridoxine hydrochloride, pyridoxal 5-phosphate, the hydrochloric acid hydroxocobalamin, Hydroxocobalamine Acetate, cobalamin, hydroxocobalamin, mecobalamin, ascorbic acid, calcium ascorbate, sodium ascorbate, nicotinic acid, nicotiamide, pantothenylol, calcium pantothenate, sodium pantothenate, pantethine, biotin, folic acid, retinyl acetate, the retinol cetylate, vitamin A oil, liver oil, strong liver oil, ergocalciferol, cholecalciferol, d-alpha-tocofecol succinic acid ester, dl-alpha-tocofecol succinic acid ester, dl-alpha-tocofecol succinic acid calcium, the d-alpha-tocopherol acetate, dl-alpha-tocofecol succinic acid ester, the d-alpha-tocopherol, dl-alpha-tocopherol etc.
As vitamin D 3-analogies, can enumerate inositol, inositol niacinate, orotic acid, choline orotate, gamma oryzanol, thioctic acid, thioctamide, carnitine hydrochloride, coenzyme, choline bitartrate, rutin etc.
As mineral, can enumerate calcium citrate, calcium glycerophosphate, gluconic acid sodium salt, magnesium carbonate, gluconic acid sodium salt, calcium carbonate, calcium gluconate, winnofil, calcium lactate, calcium phosphate dibasic anhydrous, calcium hydrogen phosphate, ferric ammonium citrate, ferrous fumarate, iron sulfate, sodium sulfate chrondroitin etc.
As caffeine class medicine, can enumerate caffeine, Caffeine Anhydrous, caffeine sodium benzoate, aminophylline, diprophylline, brontyl etc.
As aminoacid, can enumerate L-aspartic acid, L-potassium aspartate, L-NaAsp, L-magnesium aspartate, L-cysteine hydrochloride, L-cysteine, glycine, L-isoleucine, arginine hydrochloride, lysine hydrochloride, L-glutamic acid, L-sodium glutamate, L-threonine, L-valine, L-histidine hydrochloride, L-leucine, DL-methionine, L-phenylalanine, L-tryptophan etc.
As crude drug, can enumerate Colla Corii Asini, gambir, Herba Epimedii extract, Herba Epimedii dry extract, Rhizoma Coptidis, Radix Polygoni Multiflori, Rhizoma Curcumae, god
Radix Glycyrrhizae; Radix Platycodonis; Rhizoma Et Radix Notopterygii; Semen Armeniacae Amarum; Fructus Lycii; Cortex cinnamomi japonici (Ramulus Cinnamomi); Calculus Bovis; Fructus Piperis; succinum; Agkistrodon halys; Cornu rhinocerotis; Radix Bupleuri; Stigma Croci; Rhizoma Dioscoreae; Radix Rehmanniae; Radix Glycyrrhizae Preparata; Radix Paeoniae; Moschus; Lignum Aquilariae Resinatum; Margarita; Venenum Bufonis; animal gallbladder composition (Fel Ursi; Virulizin); Mespilus germinica Linn; Rhizoma Chuanxiong; Rhizoma Atractylodis; Radix Et Rhizoma Rhei; Semen Glycine Germinatum; Fructus Jujubae; Flos Caryophylli; the Lignum Aquilariae Resinatum end; Rhizoma Gastrodiae; Radix Angelicae Sinensis; Radix Ginseng; Radix Ophiopogonis; the Rhizoma Pinelliae; anti-nose; the Rhizoma Atractylodis Macrocephalae; Poria; Radix Saposhnikoviae; Semen Strychni extract; Concha Ostreae; Herba Ephedrae; Fructus Cannabis; Borneolum Syntheticum; リ ヨ Application; Cornu Saigae Tataricae; Cornu Cervi Pantotrichum.
As the medication of liver obstacle, can enumerate ursodeoxycholic acid, dehydrocholic acid, glucuronolactone, glucuronic acid, glucuronic acid amide, glycyrrhizic acid, sodium glycyrrhetate, DIEDI, chlorination methylthio-aminoacids, liver hydrolysate, Ovum Gallus domesticus Flavus lecithin etc.
Cardiovascular preparation of the present invention can adopt the habitual maneuver in this area suitably to modulate.At this moment, as required, can use the normally used preparation additive in this area more than a kind or 2 kinds.As the preparation additive, can enumerate excipient, binding agent, disintegrating agent, lubricant, coloring agent, correctives etc., but be not limited to these.
As excipient, can enumerate lactose, starch based, crystalline cellulose, sucrose, mannitol or light anhydrous silicic acid etc.As binding agent, can enumerate hydroxypropyl emthylcellulose, hydroxypropyl cellulose, gelatin, alphalysed starch, polyvinylpyrrolidone, polyvinyl alcohol or pulullan polysaccharide etc.As disintegrating agent, can enumerate carboxymethyl cellulose, carboxymethylcellulose calcium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, corn starch or low degree of substitution hydroxypropyl cellulose etc.As lubricant, can enumerate magnesium stearate or Talcum etc.As coloring agent, can enumerate tar colorant or iron sesquioxide etc.As correctives, can enumerate Flos Chrysanthemi, aspartame, 1-menthol, d-Borneolum Syntheticum or spice etc.
The dosage of cardiovascular preparation of the present invention is not particularly limited, and can suitably select according to various conditions such as the degree of medical form, applicable symptom or patient ages.Under normal conditions, can according to this dosage, can determine the dosage of taurine by aforementioned proportion with about 10～1000mg/ day, particularly to throw about 30～300mg/ day and adenosine 5 '-triphosphoric acid or its salt to the adult.
The administrated method of cardiovascular preparation of the present invention is not particularly limited, can while or the throwing of change time and adenosine 5 '-triphosphoric acid or last acceptable salt of its physiology and taurine.Go up under the situation of acceptable salt and taurine with adenosine 5 '-triphosphoric acid or its physiology in the throwing of change time; wish formerly to throw and the blood level of effective ingredient do not drop to the concentration of performance effect of the present invention in the following time, throw and other effective ingredient.From the viewpoint of the prevention and/or the improvement effect of myocardial ischemia, the administrated method of cardiovascular preparation of the present invention is preferably thrown simultaneously with adenosine 5 '-triphosphoric acid or its physiology and is gone up acceptable salt and taurine.
Cardiovascular preparation of the present invention has excellent prevention and/or improvement effect to myocardial ischemia, based on the prevention and/or the improvement effect of this myocardial ischemia, can eliminate cardiopalmus that symptom occurred and/or asthma as myocardial ischemia.
Embodiment
Below, the present invention will be described in more detail by embodiment, but the present invention is not subjected to the qualification of following embodiment.
The prevention of test example 1 myocardial ischemia and/or the evaluation test of improvement effect
＜test method 〉
Myocardial ischemia is reflected in the variation of Electrocardiographic ST section and T ripple.Report is arranged, if throw and vassopressin to rat vein, (Life Science 72 (1): 103-112,2002) for S.Satoh, et al then to find to descend persistence ST section owing to myocardial ischemia on electrocardiogram.Calculate the ST segment value according to the test method of in the document, putting down in writing, whether throw and be suppressed, study the prevention and/or the improvement effect of myocardial ischemia because of medicine according to the decline of ST segment value.
Respectively quilt is tested 7 every group male Donryu rats (10 ages in week of drug administration group and control drug administration group, Japan SLC (strain)) oral throwing and quilt test medicine or control drug, after 15 minutes, at pentobarbital (50mg/kg, Nacalai Tesque) under the anesthesia, intravenous is thrown and 0.5IU/mL/kg vassopressin ([Arg
8]-VASOPRESSIN, SIGMA company produces).After 2 days, under pentobarbital (50mg/kg) anesthesia, measure electrocardiogram, calculate the ST segment value.Then, deduct the meansigma methods of control drug administration group (0.5% methylcellulose administration group) ST segment value, the value of gained is estimated as " ST section decline amount of suppression " from each ST segment value of being tested the drug administration group.
In addition, as quilt test medicine, use 30mg/kg adenosine 5 '-triphosphoric acid disodium (CALBIOCHEM produces, below, brief note is done " ATP " in an embodiment.), the combination of 3000mg/kg taurine (mutually pharmaceutical worker's (strain) produce) and 30mg/kg ATP and 3000mg/kg taurine (below; brief note is done " ATP+ taurine " in an embodiment); these medicines are outstanding turbid or be dissolved in 0.5% methylcellulose, for test.In addition, medicine in contrast, use 0.5% methylcellulose (below, brief note is done " MC " in an embodiment.)。
＜result of the test 〉
In table 1 and Fig. 1, represent result of the test.
[table 1]
| By test medicine control drug | Dosage (mg/kg) | ST segment value (delta μ V) MEAN ± S.E. | ST section decline amount of suppression (delta μ V) MEAN ± S.E. |
| 0.5％MC | — | —103.0±6.9 | — |
| ATP | 30 | —93.8±8.9 | 9.2±8.9 |
| Taurine | 3000 | —96.2±9.5 | 6.8±9.5 |
| The ATP+ taurine | 30+3000 | —68.4±5.0* | 34.6±5.0 |
*P＜0.05 vs, 0.5% MC (Tukey Type multiple comparisons)
N＝7
With throw with in the comparison of control drug administration group of 0.5%MC; in individually dosed group of individually dosed group of ATP and taurine, (ST section decline amount of suppression is only 9.2delta μ V, 6.82delta μ V respectively almost can not to confirm the inhibition that the ST section descends.)。But; in cardiovascular preparation administration group of the present invention (ATP+ taurine), can confirm that significant ST section decline suppresses (ST section decline amount of suppression is 34.682delta μ V), in the ST segment value; with throw with in the comparison of matched group of MC, can confirm significant difference.Draw the conclusion of the combination of ATP and taurine thus for myocardial ischemia prevention and/or improvement effect performance cooperative effect.By The above results as can be known, cardiovascular preparation of the present invention have by and the prevention and/or the improvement effect of going up the myocardial ischemia of working in coordination with that acceptable salt and taurine obtain with adenosine 5 '-triphosphoric acid or its physiology.
Production Example 1
After in high-speed stirred comminutor (POWREX:FM-VG-25 type), dropping into 420g Adenosine Triphosphate Disodium, 700g taurine, 35g Venenum Bufonis, 98g Moschus, 21g Calculus Bovis, 175g Radix Ginseng, 42g Cornu Saigae Tataricae end, 52.5g Margarita, 18.9g Borneolum Syntheticum, 56g animal gallbladder, 1447.6g erithritol, 840g crystalline cellulose, 126g cross-linking sodium carboxymethyl cellulose, 126g hydroxypropyl cellulose and mixing; it is mixing to add 700g ethanol, re-uses the broken pelletize of pelletizing machine (field, ridge Seiko: ND-10S type).After using fluidized bed drying machine (FREUND industry: NFLO-5 type) with this pelletize thing drying, use pelletizing machine (field, ridge Seiko: ND-10S type) granulate.Mixer (morning sun industry: after dropping into this granulate thing of 4158g, 42g magnesium stearate and mixing the B2/109 type) in, with tablet machine that diameter 8mm, radius of curvature 14mm drift are installed (
Ironworker institute: HT-AP18SS type) obtains the tablet of 1 200mg.
Production Example 2
After in high-speed stirred comminutor (POWREX:FM-VG-25 type), dropping into 720g Adenosine Triphosphate Disodium, 600g taurine, 30g Calculus Bovis, 60g thiamine hydrochloride, 6g riboflavin, 12g folic acid, 300g DL-methionine, 120g glucuronolactone, 180g inositol, 120g hydrochloric acid L-lysine, 1165.2g D-mannitol, 936g crystalline cellulose, 240g carboxymethyl cellulose, 144g hydroxypropyl cellulose and mixing; it is mixing to add 780g ethanol, re-uses the broken pelletize of pelletizing machine (field, ridge Seiko: ND-10S type).After using fluidized bed drying machine (FREUND industry: NFLO-5 type) with this pelletize thing drying, use pelletizing machine (field, ridge Seiko: ND-10S type) granulate.Mixer (morning sun industry: after dropping into this granulate thing of 4633.2g, 46.8g magnesium stearate and mixing the B2/109 type) in, with tablet machine that diameter 7mm, radius of curvature 10mm drift are installed (
Ironworker institute: HT-AP18SS type) obtains the tablet of 1 130mg.
Production Example 3
After in high-speed stirred comminutor (POWREX:FM-VG-25 type), dropping into 540g Adenosine Triphosphate Disodium, 450g taurine, 18g Calculus Bovis, 18g Moschus, 18g Cornu Cervi Pantotrichum, 25.2g Cornu rhinocerotis, 36g Venenum Bufonis, 27g Fel Ursi, 27g Semen Strychni extract, 13.5g salicylic acid, 18g tocopheryl acetate, 1643.4g D-mannitol, 540g corn starch, 900g crystalline cellulose, 135g cross-linking sodium carboxymethyl cellulose, 135g hydroxypropyl cellulose and mixing; it is mixing to add 800g ethanol, re-uses the broken pelletize of pelletizing machine (field, ridge Seiko: ND-10S type).After using fluidized bed drying machine (FREUND industry: NFLO-5 type) with this pelletize thing drying, use pelletizing machine (field, ridge Seiko: ND-10S type) granulate.In mixer (morning sun industry: after dropping into this granulate thing of 4544.1g, 45.9g magnesium stearate and mixing the B2/109 type), obtain the tablet of 1 170mg with the tablet machine (cigarette ironworker institute: HT-AP18SS type) that diameter 7.5mm, radius of curvature 10mm drift are installed.
Production Example 4
After in high-speed stirred comminutor (POWREX:FM-VG-25 type), dropping into 720g Adenosine Triphosphate Disodium, 300g taurine, 600g carnitine hydrochloride, 15g 1-menthol, the anti-nose of 30g, 39g Flos Caryophylli, 1237.2g D-mannitol, 540g corn starch, 936g crystalline cellulose, 108g cross-linking sodium carboxymethyl cellulose, 108g hydroxypropyl cellulose and mixing; it is mixing to add the 800g ethanol that the dissolving of 24mg cobalamin is obtained, and re-uses the broken pelletize of pelletizing machine (field, ridge Seiko: ND-10S type).After using fluidized bed drying machine (FREUND industry: NFLO-5 type) with this pelletize thing drying, use pelletizing machine (field, ridge Seiko: ND-10S type) granulate.In mixer (morning sun industry: after dropping into this granulate thing of 4633.2g, 46.8g magnesium stearate and mixing the B2/109 type), obtain the tablet of 1 130mg with the tablet machine (cigarette ironworker institute: HT-AP18SS type) that diameter 7mm, radius of curvature 10mm drift are installed.
Production Example 5
After in high-speed stirred comminutor (POWREX:FM-VG-25 type), dropping into 360g Adenosine Triphosphate Disodium, 300g taurine, 180g coenzyme, 120g nicotiamide, 60g riboflavin, 60g d-alpha-tocopherol acetate, 1564.8g D-mannitol, 432g corn starch, 864g crystalline cellulose, 210g carboxymethyl cellulose, 126g hydroxypropyl cellulose and mixing; it is mixing to add 700g ethanol, re-uses the broken pelletize of pelletizing machine (field, ridge Seiko: ND-10S type).After using fluidized bed drying machine (FREUND industry: NFLO-5 type) with this pelletize thing drying, use pelletizing machine (field, ridge Seiko: ND-10S type) granulate.In mixer (morning sun industry: after dropping into this granulate thing of 4276.8g, 43.2g magnesium stearate and mixing the B2/109 type), obtain the tablet of 1 120mg with the tablet machine (cigarette ironworker institute: HT-AP18SS type) that diameter 7mm, radius of curvature 10mm drift are installed.
Claims (18)
1. cardiovascular preparation is characterized in that:
Contain the combination that adenosine 5 '-triphosphoric acid or its physiology go up acceptable salt and taurine.
2. cardiovascular preparation as claimed in claim 1 is characterized in that:
It is the agent that prevents and/or treats of ischemic heart desease.
3. cardiovascular preparation as claimed in claim 1 is characterized in that:
It is selected from angina pectoris and myocardial infarction disease prevent and/or treat agent.
4. as each described cardiovascular preparation in the claim 1～3, it is characterized in that:
It is for eliminating the medicine of cardiopalmus and/or asthma.
5. as each described cardiovascular preparation in the claim 1～4, it is characterized in that:
It is the prevention that can be used in myocardial ischemia/or medicine of improving.
6. as each described cardiovascular preparation in the claim 1～5, it is characterized in that:
It is an oral medication.
7. adenosine 5 '-triphosphoric acid or its physiology go up acceptable salt and the use of taurine in cardiovascular preparation is made.
8. use as claimed in claim 7 is characterized in that:
Cardiovascular preparation is the agent that prevents and/or treats of ischemic heart desease.
9. use as claimed in claim 7 is characterized in that:
Cardiovascular preparation be selected from angina pectoris and myocardial infarction disease prevent and/or treat agent.
10. as each described use in the claim 7～9, it is characterized in that:
Cardiovascular preparation is a medicine of eliminating cardiopalmus and/or asthma.
11., it is characterized in that as each described use in the claim 7～10:
Cardiovascular preparation is the medicine that can be used in the prevention and/or the improvement of myocardial ischemia.
12., it is characterized in that as each described use in the claim 7～11:
Cardiovascular preparation is an oral medication.
13. the prophylaxis of a causing circulatory disease and/or therapy is characterized in that:
The adenosine 5 '-triphosphoric acid of throwing and effective dose or its physiology go up acceptable salt and taurine.
14. prophylaxis as claimed in claim 13 and/or therapy is characterized in that:
The causing circulatory disease is an ischemic heart desease.
15. prophylaxis as claimed in claim 13 and/or therapy is characterized in that:
The causing circulatory disease is the disease that is selected from angina pectoris and myocardial infarction.
16. as each described prophylaxis and/or therapy in the claim 13～15, it is characterized in that: it is for eliminating the prophylaxis and/or the therapy of cardiopalmus and/or asthma.
17. as each described prophylaxis and/or therapy in the claim 13～15, it is characterized in that: it is prophylaxis and/or the therapy that can be used in the prevention and/or the improvement of myocardial ischemia.
18. as each described prophylaxis and/or therapy in the claim 13～15, it is characterized in that: administering mode is an oral medication.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006263674 | 2006-09-28 | ||
| JP263674/2006 | 2006-09-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101511376A true CN101511376A (en) | 2009-08-19 |
Family
ID=39229862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800334689A Pending CN101511376A (en) | 2006-09-28 | 2007-09-27 | Cardiovascular preparation |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPWO2008038417A1 (en) |
| KR (1) | KR20090057220A (en) |
| CN (1) | CN101511376A (en) |
| TW (1) | TW200816989A (en) |
| WO (1) | WO2008038417A1 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8200252L (en) * | 1982-01-18 | 1983-07-19 | Pharmacia Ab | PHARMACEUTICAL COMPOSITION |
| US5582839A (en) * | 1995-04-18 | 1996-12-10 | Nutrition 21 | Magnesium taurate and other mineral taurates |
-
2007
- 2007-09-27 KR KR1020097003656A patent/KR20090057220A/en not_active Application Discontinuation
- 2007-09-27 WO PCT/JP2007/001045 patent/WO2008038417A1/en active Application Filing
- 2007-09-27 JP JP2008536282A patent/JPWO2008038417A1/en not_active Ceased
- 2007-09-27 CN CNA2007800334689A patent/CN101511376A/en active Pending
- 2007-09-28 TW TW096136470A patent/TW200816989A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW200816989A (en) | 2008-04-16 |
| JPWO2008038417A1 (en) | 2010-01-28 |
| WO2008038417A1 (en) | 2008-04-03 |
| KR20090057220A (en) | 2009-06-04 |
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