CN104689133A - Pharmaceutical composition for treating myocardial ischemia - Google Patents
Pharmaceutical composition for treating myocardial ischemia Download PDFInfo
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- CN104689133A CN104689133A CN201510147578.4A CN201510147578A CN104689133A CN 104689133 A CN104689133 A CN 104689133A CN 201510147578 A CN201510147578 A CN 201510147578A CN 104689133 A CN104689133 A CN 104689133A
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Abstract
The invention relates to a pharmaceutical composition for treating myocardial ischemia. The pharmaceutical composition comprises salviae miltiorrhizae, flos carthami, herba leonuri, panax notoginseng, radix astragali, hirudo, snakegourd fruits, hawthorn, citrus, red peony roots, manyprickle acanthopanax roots, chinese magnoliavine fruits, stigma maydis, scorpion and ornel. Plasma ET, NO, TXA2 and PGI2 are a set of vaso-active substances which are synthesized and secreted by vascular endothelial cells and have an important function of adjusting the contractile and relaxant function of a coronary artery. The pharmaceutical composition can treat the symptom that the ratio of ET, TXB2, TXB2/6-Keto-PGF1a and IMA are remarkably lowered, and NO and 6-Keto-PGF1a are remarkably increased in myocardial ischemia, and has a good myocardial ischemia treatment effect.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition, particularly relate to a kind of pharmaceutical composition being used for the treatment of myocardial ischemia.
Background technology
After myocardial ischemia occurs, also there is ischemia injury in myocardial cell simultaneously, but the damage of myocardial cell is a dynamic process carried out gradually, even if restoration of blood flow after ischemia 30min, the 26S Proteasome Structure and Function of damaged myocardium cell also can not be recovered completely again, when cardiac muscle cells develops into the damage of irreversibility, also this damage can not be made to alleviate even if recover blood reperfusion, even can accelerate the damage of damaged myocardium cell, even cause cardiomyocyte cell death, therefore the protection strengthening cardiac muscle after myocardial ischemia-reperfusion just to seem particular importance for the protection of ischemic heart function.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of pharmaceutical composition being used for the treatment of myocardial ischemia, to providing a kind of new drug for the treatment of myocardial ischemia definitely clinically, ischemic heart function can be protected.
Pharmaceutical composition of the present invention is: Radix Salviae Miltiorrhizae, Flos Carthami, Herba Leonuri, Radix Notoginseng, the Radix Astragali, Hirudo, Pericarpium Trichosanthis, Fructus Crataegi, Pericarpium Citri Reticulatae, Radix Paeoniae Rubra, Radix Et Caulis Acanthopanacis Senticosi, Fructus Schisandrae Chinensis, Stigma Maydis, Scorpio, Borneolum Syntheticum.
Pharmaceutical composition of the present invention is by weight ratio: Radix Salviae Miltiorrhizae 25 parts, 25 parts, Flos Carthami, Herba Leonuri 20 parts, Radix Notoginseng 20 parts, the Radix Astragali 20 parts, Hirudo 18 parts, Pericarpium Trichosanthis 18 parts, Fructus Crataegi 18 parts, Pericarpium Citri Reticulatae 15 parts, Radix Paeoniae Rubra 15 parts, Radix Et Caulis Acanthopanacis Senticosi 15 parts, Fructus Schisandrae Chinensis 12 parts, Stigma Maydis 10 parts, Scorpio 5 parts, Borneolum Syntheticum 5 parts.
The preparation method of described pharmaceutical composition is: get the mixing of above pharmaceutical composition crude drug, be ground into 10 ~ 20 order coarse granules, add 60% ethanol 6 times (volume), with the continuous 60 DEG C of extractions of microwave assisted extraction methods three times, extract carries out centrifugalize, and clean immersion is concentrated into the thick paste that relative density is 1.20 ~ 1.30, vacuum drying, dried cream powder is broken, adds proper auxiliary materials, makes corresponding dosage form.
Adjuvant in the present invention can be acceptable any excipient or carrier on pharmaceutics.
Radix Salviae Miltiorrhizae: Radix Salviae Miltiorrhizae nourishing blood to tranquillize the mind, blood circulation promoting and blood stasis dispelling.Modern pharmacy research proves, Radix Salviae Miltiorrhizae contains TANSHINONES, salvianolic acid, flavone, the material such as triterpene, sterol, can strengthen myocardial contraction, improve cardiac function, not increase myocardial oxygen consumption.
Flos Carthami: promoting blood circulation to restore menstrual flow, eliminating stasis to stop pain.Modern pharmacy research proves, Flos Carthami is containing Carthamus yellow and saffloside).Saffloside, through hydrochloric acid hydrolysis, obtains glucose Flos Carthami element, and separately still fatty oil claims safflower oil, is the glyceride type of Palmic acid, stearic acid, arachidic acid, oleic acid, linoleic acid, linolenic acid etc.Flos Carthami has analgesia, calmness, antiinflammatory, fatigue-resisting function.
Herba Leonuri: to restore menstrual flow and invigorate blood circulation, inducing diuresis to remove edema, heat-clearing and toxic substances removing.Modern pharmacy research proves, Herba Leonuri contains active ingredient Herba Leonuri element, can distend the blood vessels and make blood pressure drops, and have the adrenergic effect of antagonism, arteriosclerotic and neuropathic hypertension can be controlled, the frequency of uterus movement can be increased again, for puerperal promotes uterotonic, and cause effectively languisher to long-term metrorrhagia, therefore be widely used in control women's amenorrhea, dysmenorrhea, menoxenia, postpartum hemorrhage too much, lochiorrhea, complete, the frequent fetal movement of uterine contraction in puerperal, uterine prolapse and the inferior disease of red and white leukorrhea.
Radix Notoginseng: hemostasis dissipating blood stasis, subduing swelling and relieving pain.Modern pharmacy research proves, Radix Notoginseng has increase coronary artery blood flow, decreased heart rate, reduces the effect of myocardial oxygen consumption.And the effect that can resist because the blood pressure caused by pituitrin raises, coronary artery shrinks.Radix Notoginseng tuber fluid extract can shorten rabbit blood setting time, has anastalsis.Radix Notoginseng tuber has preventive and therapeutic action to zoopery arthritis.Radix Notoginseng gavage can promote the accumulation of white mice liver glycogen.
The Radix Astragali: Radix Astragali benefiting QI for strengthening the superficies.Modern pharmacy research proves, the Radix Astragali can enhancing human body immunity function, protect the liver, diuresis, defying age, anti-stress, blood pressure lowering and antibacterial.
Hirudo: Hirudo blood circulation promoting and blood stasis dispelling.Modern pharmacy research proves, Hirudo contains can the hirudin of blood coagulation and the analogued histamine material of blood vessel dilating.
Pericarpium Trichosanthis: moistening the lung and resolving phlegm, promoting the circulation of QI the chest stuffiness relieving.Modern pharmacy research proves, the chemical analysis of Pericarpium Trichosanthis is mainly containing 17 seed amino acids such as arginine, leucine, glutamic acid and mineral, on a small quantity volatile oil, saturated fatty alcohol etc.The effect etc. that there is eliminating the phlegm, improve immunity, expand isolated heart coronary artery, increase coronary flow.
Fructus Crataegi: modern pharmacy research proves, Fructus Crataegi has the effects such as blood fat reducing, blood pressure, heart tonifying, arrhythmia, and meanwhile, Fructus Crataegi is also the good medicine of spleen benefiting and stimulating the appetite, relieving dyspepsia, phlegm reduction of blood circulation promoting.The disease such as, hernia, blood stasis full to chest and diaphragm spleen, amenorrhea has good curative effect.Flavone compound vitexin in Fructus Crataegi, be the medicine that a kind of antitumaous effect is stronger, Fructus Crataegi extract all has certain inhibitory action to cancerous cell tumor growth, propagation and infiltration metastasis.
Pericarpium Citri Reticulatae: in regulating qi-flowing for strengthening spleen, tune.Modern pharmacy research proves that volatile oil contained by Pericarpium Citri Reticulatae has gentle stimulation to gastrointestinal tract, can the secretion of facilitating digestion liquid, gets rid of pneumatosis in intestinal tube, also has the effect such as defying age, antioxidation.
Radix Paeoniae Rubra: clearing away heat and cooling blood; Blood circulation promoting and blood stasis dispelling.Modern pharmacy research proves, Radix Paeoniae Rubra can antithrombotic, antiplatelet aggregation, blood fat reducing, arteriosclerosis, scavenging activated oxygen etc.
Radix Et Caulis Acanthopanacis Senticosi: bone and muscle strengthening, arteries and veins of invigorating blood circulation.Modern pharmacy research proves, Radix Et Caulis Acanthopanacis Senticosi has resisting fatigue, improves hypoxia-bearing capability, resisting fatigue, improves the effects such as blood supply in brain amount.
Fructus Schisandrae Chinensis: restrain astringent or styptic treatment for spontaneous sweating, supplementing QI for promoting the production of body fluid, kidney calming.Modern pharmacy research proves, schisandrol extract can reduce the laboratory animal glutamate pyruvate transaminase that caused by carbon tetrachloride, thioethanolamine etc. and raise. and the effect of wuweizisu B (schisandrin B) tool anti-liver injury, also has stable, heart tonifying, enhancing immunity, the effect such as antibacterial.
Stigma Maydis: inducing diuresis to remove edema, expel the heat-evil, suppressing the hyperactive liver function of gallbladder promoting.Modern pharmacy research proves, Stigma Maydis has effect for reducing blood fat to hyperlipemia, thus protection heart and brain, reduce the sickness rate of ischemic cardiovascular.There is the effect such as blood pressure lowering, blood sugar lowering in addition.
Scorpio: the spasmolytic that relieves dizziness, high fever, infantile convulsions, epilepsy, etc., antiinflammatory counteracting toxic substances, removing obstruction in the collateral to relieve pain.Modern pharmacy proves, the primary medicinal component of Scorpio is charybdotoxin, containing more complicated toxic protein and non-toxic albumen in scorpion venom, is the Neurotoxic protein of a kind of similar snake venom.Charybdotoxin brings out cortical potential to Encelialgia, skin scorch pain and nervi trigeminus stronger inhibitory action; But the conduction of exsomatizednerve dry action potential is had no significant effect. the analgesia of prompting scorpion venom may act on the maincenter neuron relevant with the pain sensation.Mouse writhing method experiment shows that the comparatively thick poison of the analgesic activity of charybdotoxin-III is strong 3 times, and comparatively antondin effect is also strong.
Borneolum Syntheticum: modern pharmacy research proves, topical application Borneolum Syntheticum has comparatively microstimulation to sensory nerve, has certain pain relieving and the antisepsis of gentleness.
In order to show that pharmaceutical composition of the present invention has good result to myocardial ischemia, carry out following animal pharmacological test:
1 materials and methods
The clean Wistar male rat (195 ± 16g) of 1.1 material 40, is divided into sham operated rats, normal saline group, compound Salviae Miltiorrhizae group and medicine group of the present invention at random, often organizes 10.Compound Salviae Miltiorrhizae group selects FUFANG DANSHEN PIAN, is produced by Chaohu Zhong Chen pharmaceutcal corporation, Ltd of Shanghai HaiHong Industry group; The embodiment of the present invention 1 medicine; 20% urethane injection; ET, NO, TXB
2, 6-Keto-PGF
1apurchased from Hua Ying institute of biological products, Beijing, IMA test kit is purchased from Bang Ding Tyke, Beijing Bioisystech Co., Ltd, and SN-697 type dual probe γ-enumerator is purchased from day ring instrument one factory of Shanghai nuclear research institute; 7510 type automatic clinical chemistry analyzers are purchased from HIT.
1.2 method compound Salviae Miltiorrhizae groups press 600mg/kg dosed administration, and medicine group of the present invention is by 500mg/kg administration, be made into warm saline the suspension that volume fraction is 50%.Sham operated rats and normal saline group such as all to give at the warm saline of capacity, and 1 time/d, continuous 10d, all takes gastric infusion.1h after last administration, with 20% urethane 5mL/kg abdominal cavity light anaesthesia rat, back of the body position is fixed, and carotid artery intubate connects polygraph, entangles rat head with rubber bulb, connects artificial respirator and practices artificial respiration.Chest unhairing, routine disinfection, 2cm is about along left mid-clavicular line longitudinal incision skin, obviously thorax is pulled open in the place of beating in the apex of the heart, careful exposure heart, cuts off pericardium, light pressure right side thorax, slightly extrude heart, ligation left coronary artery between left auricle root and pulmonary artery cone, sham operated rats only at ligation position threading, not ligation.Recover coronary blood flow 120min after ischemia 45min and terminate experiment, rapid Culling heart blood 3mL, is placed in 100g/L EDTA2Na
2mix in 30 μ L and aprotinin 40 μ L test tube, the centrifugal 20min of 4000r/min at 4 DEG C, after getting blood plasma subpackage, be placed in the standby detection of-70 DEG C of Refrigerator stores.ET, NO, TXB
2, 6-Keto-PGF
1asN-697 type dual probe γ-enumerator that Placenta function adopts day ring instrument one factory of Shanghai nuclear research institute to produce detects; The detection of IMA adopts Hitachi 7510 type automatic clinical chemistry analyzer to detect, and operating process provides description to carry out in strict accordance with test kit.
Statistical procedures: all data acquisition SPSS15.0 software kits carry out statistical procedures measuring index data and use
represent, between group, compare employing variance analysis, compare between two and adopt SNK-q inspection.P < 0.05 is for having significant difference.
2 results
After Experimental Rats of Myocardial Ischemia ischemia pours into again, normal saline group, compound Salviae Miltiorrhizae group and medicine group ET of the present invention, TXB
2, TXB
2/ 6-Keto-PGF
1aratio and IMA are significantly higher than sham operated rats, NO and 6-Keto-PGF
1asignificantly lower than sham operated rats; Compound Salviae Miltiorrhizae group and medicine group of the present invention compare with normal saline group, ET, TXB
2, TXB
2/ 6-Keto-PGF
1aratio and IMA significantly lower than normal saline group, NO and 6-Keto-PGF
1ain being significantly higher than normal saline group.Medicine group of the present invention compared with compound Salviae Miltiorrhizae group, ET, TXB
2, TXB
2/ 6-Keto-PGF
1aratio and IMA significantly reduce, NO and 6-Keto-PGF
1aremarkable rising.Refer to table 1.
Table 1 rat ischemia pours into rear ET, TXB again
2, TXB
2/ 6-Keto-PGF
1aratio and IMA situation of change (n=10,
)
Note: * compared with compound Salviae Miltiorrhizae group, P < 0.05
Blood plasma ET, NO, TXA
2and PGI
2be one group to be synthesized and the vaso-active substance secreted by vascular endothelial cell, have important regulating action to the easypro contracting of coronary vasodilator.ET and NO, TXA
2and PGI
2two to the vasomotion factor of confronting with each other.They come diastole or vasoconstrictive, to safeguard the normal condition of coronary vasodilator by collaborative or antagonism.Usually by measuring TXB
2tXA is reflected with the change of 6-Keto-PGF1a
2and PGI
2situation of change.ET is the contracting vasoactive polypeptides that known effect is so far the strongest, continue at most.
IMA studies more popular detection recently in inspection myocardial ischemia.That first of FDA approval since 1994 is used for evaluating the tentative index of myocardial ischemia.
This pharmacological testing illustrates, medicine of the present invention has good protective effect to Rat Experimental ischemic myocardium.
Specific embodiment
Embodiment 1 Radix Salviae Miltiorrhizae 50g, Flos Carthami 50g, Herba Leonuri 40g, Radix Notoginseng 40g, Radix Astragali 40g, Hirudo 36g, Fructus Trichosanthis 36g, Fructus Crataegi 36g, Pericarpium Citri Reticulatae 30g, Radix Paeoniae Rubra 30g, Radix Et Caulis Acanthopanacis Senticosi 30g, Fructus Schisandrae Chinensis 24g, Stigma Maydis 20g, Scorpio 10g, Borneolum Syntheticum 10g
The preparation method of granule of the present invention: get the mixing of above pharmaceutical composition crude drug, be ground into 10 ~ 20 order coarse granules, add 60% ethanol 6 times (volume), with the continuous 60 DEG C of extractions of microwave assisted extraction methods three times, extract carries out centrifugalize, clean immersion is concentrated into the thick paste that relative density is 1.20 ~ 1.30, vacuum drying, dried cream powder is broken, adds amylum pregelatinisatum 1000g, sodium carboxymethyl cellulose 500g, mixes 80 mesh sieves, adds suitable quantity of water and granulates, 60 DEG C of drying under reduced pressure, granulate, is distributed into 100 bags, obtains final product.
Embodiment 2 Radix Salviae Miltiorrhizae 50g, Flos Carthami 50g, Herba Leonuri 40g, Radix Notoginseng 40g, Radix Astragali 40g, Hirudo 36g, Fructus Trichosanthis 36g, Fructus Crataegi 36g, Pericarpium Citri Reticulatae 30g, Radix Paeoniae Rubra 30g, Radix Et Caulis Acanthopanacis Senticosi 30g, Fructus Schisandrae Chinensis 24g, Stigma Maydis 20g, Scorpio 10g, Borneolum Syntheticum 10g
The preparation method of hard capsule of the present invention: get the mixing of above pharmaceutical composition crude drug, be ground into 10 ~ 20 order coarse granules, add 60% ethanol 6 times (volume), with the continuous 60 DEG C of extractions of microwave assisted extraction methods three times, extract carries out centrifugalize, and clean immersion is concentrated into the thick paste that relative density is 1.20 ~ 1.30, vacuum drying, dried cream powder is broken, incapsulates, and to obtain final product.
Embodiment 3 Radix Salviae Miltiorrhizae 50g, Flos Carthami 50g, Herba Leonuri 40g, Radix Notoginseng 40g, Radix Astragali 40g, Hirudo 36g, Fructus Trichosanthis 36g, Fructus Crataegi 36g, Pericarpium Citri Reticulatae 30g, Radix Paeoniae Rubra 30g, Radix Et Caulis Acanthopanacis Senticosi 30g, Fructus Schisandrae Chinensis 24g, Stigma Maydis 20g, Scorpio 10g, Borneolum Syntheticum 10g
The preparation method of Tablets: get the mixing of above pharmaceutical composition crude drug, be ground into 10 ~ 20 order coarse granules, add 60% ethanol 6 times (volume), with the continuous 60 DEG C of extractions of microwave assisted extraction methods three times, extract carries out centrifugalize, and clean immersion is concentrated into the thick paste that relative density is 1.20 ~ 1.30, vacuum drying, dried cream powder is broken, add starch, Pulvis Talci and Magnesium Stearate proper quantity, granulate, tabletted, coating, to obtain final product.
Claims (4)
1. treat a pharmaceutical composition for myocardial ischemia, the raw material that its feature is making this pharmaceutical composition active component is: Radix Salviae Miltiorrhizae, Flos Carthami, Herba Leonuri, Radix Notoginseng, the Radix Astragali, Hirudo, Pericarpium Trichosanthis, Fructus Crataegi, Pericarpium Citri Reticulatae, Radix Paeoniae Rubra, Radix Et Caulis Acanthopanacis Senticosi, Fructus Schisandrae Chinensis, Stigma Maydis, Scorpio, Borneolum Syntheticum.
2. pharmaceutical composition as claimed in claim 1, it is characterized in that according to parts by weight, the raw material making this pharmaceutical composition active component is: Radix Salviae Miltiorrhizae 25 parts, 25 parts, Flos Carthami, Herba Leonuri 20 parts, Radix Notoginseng 20 parts, the Radix Astragali 20 parts, Hirudo 18 parts, Pericarpium Trichosanthis 18 parts, Fructus Crataegi 18 parts, Pericarpium Citri Reticulatae 15 parts, Radix Paeoniae Rubra 15 parts, Radix Et Caulis Acanthopanacis Senticosi 15 parts, Fructus Schisandrae Chinensis 12 parts, Stigma Maydis 10 parts, Scorpio 5 parts, Borneolum Syntheticum 5 parts.
3. pharmaceutical composition as claimed in claim 1 or 2, it is characterized in that method for making is as follows: get the mixing of aforementioned pharmaceutical compositions crude drug, be ground into 10 ~ 20 order coarse granules, add 60% ethanol 6 times (volume), with the continuous 60 DEG C of extractions of microwave assisted extraction methods three times, extract carries out centrifugalize, clean immersion is concentrated into the thick paste that relative density is 1.20 ~ 1.30, vacuum drying, and dried cream powder is broken, add proper auxiliary materials, make corresponding dosage form.
4. pharmaceutical composition as claimed in claim 3, it is characterized in that method for making is as follows: get Radix Salviae Miltiorrhizae 50g, Flos Carthami 50g, Herba Leonuri 40g, Radix Notoginseng 40g, Radix Astragali 40g, Hirudo 36g, Pericarpium Trichosanthis 36g, Fructus Crataegi 36g, Pericarpium Citri Reticulatae 30g, Radix Paeoniae Rubra 30g, Radix Et Caulis Acanthopanacis Senticosi 30g, Fructus Schisandrae Chinensis 24g, Stigma Maydis 20g, Scorpio 10g, Borneolum Syntheticum 10g, be ground into 10 ~ 20 order coarse granules, add 60% ethanol 6 times (volume), with the continuous 60 DEG C of extractions of microwave assisted extraction methods three times, extract carries out centrifugalize, clean immersion is concentrated into the thick paste that relative density is 1.20 ~ 1.30, vacuum drying, dried cream powder is broken, add amylum pregelatinisatum 1000g, sodium carboxymethyl cellulose 500g, mixed 80 mesh sieves, add suitable quantity of water to granulate, 60 DEG C of drying under reduced pressure, granulate, be distributed into 100 bags.
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| CN105079555A (en) * | 2015-09-08 | 2015-11-25 | 刘玉财 | Medicine composition for treating myocardial ischemia |
| CN106344606A (en) * | 2016-11-01 | 2017-01-25 | 侯建生 | Medical applications and administration route for ozonized oil |
| CN113975331A (en) * | 2021-10-28 | 2022-01-28 | 湖南润农生态茶油有限公司 | Antithrombotic tea oil, preparation method and application |
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Application publication date: 20150610 |