CN101040934A - Medicine compound made of haw leaf and rhodiola - Google Patents
Medicine compound made of haw leaf and rhodiola Download PDFInfo
- Publication number
- CN101040934A CN101040934A CN 200610043263 CN200610043263A CN101040934A CN 101040934 A CN101040934 A CN 101040934A CN 200610043263 CN200610043263 CN 200610043263 CN 200610043263 A CN200610043263 A CN 200610043263A CN 101040934 A CN101040934 A CN 101040934A
- Authority
- CN
- China
- Prior art keywords
- radix rhodiolae
- folium crataegi
- group
- extract
- total flavones
- 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.)
- Granted
Links
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a pharmaceutical composition for treating cardiovascular and cerebrovascular diseases and its preparing process, wherein the composition is prepared mainly from the haw thorn leaves and rhodiola root by a weight ratio of 1:0.05-10, or is prepared from haw thorn leaves flavones and rhodiola root extract by a weight ratio of 1:0.05-10. The pharmaceutical composition can be prepared into any clinically or pharmaceutically acceptable dose forms.
Description
[technical field]
The invention belongs to medical technical field, relate to the pharmaceutical composition of a kind of Folium Crataegi that is used for the treatment of cardiovascular and cerebrovascular disease or its extract and Radix Rhodiolae or its extract and contain preparation of this pharmaceutical composition and preparation method thereof.
[background technology]
Cardiovascular and cerebrovascular disease is a kind of common disease of serious threat middle-aged and elderly people health, is called as " first killer " of human health.According to China's Epidemiological study, China rises to 42.6% of calendar year 2001 by 12.07% of nineteen fifty-seven because of cardiovascular and cerebrovascular disease death person accounts for the percentage ratio of total dead population, and the person reaches 2,000,000 to die from the cardiovascular and cerebrovascular disease every year.Therefore, disclose the mechanism that cardiovascular and cerebrovascular disease takes place, develops, carry out effective prevention, treatment and rehabilitation, reduce and disable and mortality rate, be the direction that the personage of the world of medicine is devoted to develop always.
Folium Crataegi is the dried leaves of rosaceous plant Fructus Pyri Pashiae (Crataegus Pinnatifida Bge.var.major N.E.Br) or Fructus Crataegi (CrataegusPinnatifida Bge.), has blood circulation promoting and blood stasis dispelling, the logical heart arteries and veins of a surname, the effect of the easypro network of regulating the flow of vital energy.Folium Crataegi total flavones energy anticoagulant, coronary artery dilator improves blood supply of cardiac muscle, reduces myocardial oxygen consumption, Ischemic Heart is produced significant protective effect, and have blood fat reducing, the effect of blood pressure lowering.Be applicable to coronary heart disease, coronary insufficiency, angina pectoris, hyperlipemia, cerebral arterial insufficiency etc.Studies show that the main effective ingredient of Folium Crataegi is crataegutt, vitexin rhamnoside, hyperin etc.One one 575～576 pages of Chinese Pharmacopoeia versions in 2005 under the Yixintong sheet item, have the standard of Folium Crataegi extract.Standard code, Folium Crataegi extract are pressed dry product and are calculated, and contain total flavones with anhydrous rutin (C
27H
30O
16) meter, must not be less than 80.0%; Contain hyperin (C
21H
20O
12), must not be less than 0.40%.
Radix Rhodiolae is a Crassulaceae Crassulaceae rhodiola Rhodiola L. plant, and the effect that has benefiting QI for activating blood circulation, promotes blood circulation and relieving asthma is used for that blood stasis due to qi deficiency, breast fraud are pained, apoplectic hemiplegia, asthenia asthma.Modern study shows that Radix Rhodiolae is coronary artery dilator effectively, resists myocardial ischemia, and improves cardiac function, also can improve the blood circulation of cerebral tissue, accelerates the recovery of cerebral infarction focus, and to alleviating headache, relieving fatigue, memory reinforcing etc. also have remarkable efficacy.Chemical constitution study shows that the main effective ingredient of Radix Rhodiolae is rhodioside and butyl alcohol.The rhodioside structural formula is as follows:
The rhodioside structural formula
Utilize the interaction of Folium Crataegi and Radix Rhodiolae, composition of prescription is used to prepare the medicine for the treatment of cardiovascular and cerebrovascular disease, yet there are no report.
[summary of the invention]
The invention provides a kind of pharmaceutical composition of new treatment cardiovascular and cerebrovascular disease, it is mainly made by Folium Crataegi and Radix Rhodiolae, and both weight ratios are: 1: 0.05～10, be preferably 1: 0.1～and 5, the best is 1: 0.5.Perhaps can be made by Folium Crataegi total flavones and Radix Rhodiolae extract, the weight proportion of Folium Crataegi total flavones and Radix Rhodiolae extract is 1: 0.05～10, be preferably 1: 0.1～and 5, the best is 1: 0.5.
The ratio of above weight proportion obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
Folium Crataegi and Radix Rhodiolae can with The suitable solvent and method respectively or mixed extraction processing obtain extract, total extract is made arbitrary preparation with mixing acceptable accessories again.Contained main effective ingredient is Folium Crataegi total flavones and rhodioside in the total extract.The total content of the main effective ingredient in the total extract is not less than 30%.
Folium Crataegi total flavones has had the listing of production, can buy listing raw material (the accurate word Z14021005 of traditional Chinese medicines), also can utilize the preparation method of prior art to obtain, for example can utilize the preparation method of Chinese patent application CN03129427.8, CN03133957.3, CN91111834.9, CN03119429.X, CN02116789.3, CN98107298.4 to obtain, also can grope preparation technology voluntarily and obtain.The present invention also provides a kind of preparation method of Folium Crataegi total flavones.
The extraction and preparation technique of Folium Crataegi provided by the invention (is main effective ingredient with Folium Crataegi total flavones) is:
Get Folium Crataegi, add 75% alcohol reflux three times, each 1.5 hours, merge extractive liquid,, filter, decompression filtrate recycling ethanol adds and waits the water gaging dilution, behind 1/2 defat with petroleum ether of measuring after do not have the alcohol flavor, discard petroleum ether liquid, the reuse ethyl acetate extraction, extract reclaim under reduced pressure ethyl acetate and be concentrated into dried, Folium Crataegi crude extract (pro ore).
Folium Crataegi total flavones yield by above-mentioned prepared is 4～6%, and content of total flavone is with anhydrous rutin (C
27H
30O
16) meter, be no less than 60.0%; Hyperin (C
21H
20O
12) content be no less than 0.20%.
The Folium Crataegi total flavones process for refining:
Get above-mentioned Folium Crataegi crude extract, add suitable quantity of water and make dissolving, be added on the polyamide column of having handled well, with the water elution of 2 times of column volumes, discard water lotion earlier, use 70% ethanol elution of 3 times of column volumes then, collect eluent, reclaim ethanol and be concentrated into the concentrated solution of relative density about 1.02～1.08 (60 ℃), spray drying, Folium Crataegi total flavones (for injection or for oral use).
Folium Crataegi total flavones yield by above-mentioned prepared is 2～3%; General flavone content is with anhydrous rutin (C
27H
30O
16) meter, be no less than 80.0%; Contain hyperin (C
21H
20O
12), be no less than 0.40%.
Radix Rhodiolae extract can by the Radix Rhodiolae medical material by precipitate with ethanol, alcohol extraction lead acetate precipitate and separate, alcohol leaching behind the water extract-alcohol precipitation, alcohol leaching after methods such as flocculation behind the microwave breaking cellular wall, alcohol leaching, the absorption of alcohol extraction chitosan prepare, also can utilize Chinese patent application CN200410040268.4, CN03116051.4, CN01128982.1, (Chinese herbal medicine such as Wang Wei, 1999,30 (11): method 824～826) obtains, but is not limited only to said method.The present invention also provides a kind of preparation method of Radix Rhodiolae extract.
The extraction process of a kind of Radix Rhodiolae provided by the invention and process for refining, detailed process is as follows:
Get the Radix Rhodiolae medical material, be ground into coarse powder, with 70% ethanol extraction three times each 1 hour, add 10 times of amounts of alcohol for the first time, second and third time is respectively 8,8 times of amounts.Filter, merge extractive liquid,, recovery ethanol extremely every 5ml contains the 1g raw medicinal herbs, behind 2 times of amount defat with petroleum ether, discards petroleum ether liquid, and the water saturated n-butanol extraction of reuse is evaporated to the thick paste shape, and spray drying promptly gets Radix Rhodiolae extract (pro ore).
The yield of the Radix Rhodiolae crude extract that makes by this technology is 10～20%, and rhodioside content is not less than 3%.
The Radix Rhodiolae process for refining:
The above-mentioned Radix Rhodiolae extract that obtains with after the suitable quantity of water dissolving, is added on the macroporous resin column of handling well in advance, successively water liquid, 10% ethanol, 15% ethanol, 20% ethanol, 30% ethanol elution.Decompression recycling ethanol to relative density is 1.03～1.06 (60 ℃), and spray drying gets Radix Rhodiolae extract (for injection or for oral use).
The Radix Rhodiolae extract yield that makes by this technology is 2～3%, and the content of rhodioside is not less than 10%.
Said composition can add one or more pharmaceutically acceptable carriers, is applied to the patient of this treatment of needs in the mode of oral or parenteral.Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, dispersible tablet, oral liquid, granule, chewable tablet, oral cavity disintegration tablet, drop pill, slow releasing tablet, slow releasing capsule, controlled release tablet, controlled release capsule, make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup etc.; When being used for parenteral, can be made into solution, water or the oil-suspending agent etc. of injection, as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion etc.Preferred form is injection, tablet and capsule.
Medicine of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc.
The present invention in order to increase its dissolubility, can add solubilizing agents such as Tween-80 when making injection.Can add the isoosmotic adjusting agent that is used to regulate osmotic pressure in the transfusion, for example, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, sodium lactate, glucose, xylitol, sorbitol and dextran etc., preferred sodium chloride or glucose.Can add excipient in the powder pin, for example, mannitol, glucose etc.
Pharmaceutical composition of the present invention can coronary artery dilator, increases coronary flow, improves coronary circulation, reduces coronary resistance; Can anticoagulant, blood viscosity lowering improves hemorheology and microcirculation; Reduce cerebral vascular resistance, increase cerebrovascular flow, improve brain microcirculation; Reduce serum cholesterol and triglyceride levels.Be mainly used in coronary heart disease, angina pectoris, cerebral arterial insufficiency, hyperlipemia.
Pharmaceutical composition of the present invention has the following advantages:
(1) the invention provides a kind of new pharmaceutical composition that is used for the treatment of cardiovascular and cerebrovascular disease, satisfied clinical needs.
(2) in the pharmaceutical composition of the present invention, Folium Crataegi energy anticoagulant, coronary artery dilator improves blood supply of cardiac muscle, reduces myocardial oxygen consumption, ischemic heart desease is produced significant protective effect, and have blood fat reducing, the effect of blood pressure lowering; Radix Rhodiolae is coronary artery dilator effectively, resists myocardial ischemia, and improves cardiac function, also can improve the blood circulation of cerebral tissue, accelerates the recovery of cerebral infarction focus, can alleviate headache, relieving fatigue, memory reinforcing.The two pharmacological action is similar, and compatibility is used, and can work in coordination with to play a role.
(3) studies have shown that by pharmacodynamic experiment first: pharmaceutical composition of the present invention, can significantly dwindle rat experiment myocardial inyaretion scope, resist myocardial ischemia; Remarkable antiplatelet aggregation, thrombotic time in the significant prolongation rat carotid artery, antithrombotic; The Medulla Leporis seu Oryctolagi ischemical reperfusion injury there is protective effect, significantly improves the hemodynamics of anesthetized dog, improve the microcirculation of cerebral tissue and heart; Significantly reduce serum cholesterol and the triglyceride levels of experimental hyperlipidemia rat, blood fat reducing.Two medicine compatibilities have synergistic function, and are evident in efficacy, produced beyond thought effect, and this is that those skilled in the art institute is beyond thought.
(4) each proportioning of pharmaceutical composition of the present invention is carried out pharmacodynamic study, drawn the optimal proportion of pharmaceutical composition of the present invention.
(5) drug combination preparation preparation technology of the present invention is simple, and mass discrepancy is little between the different batches medicine, and drug quality is uniform and stable.
(6) confirm drug combination injection good stability of the present invention by stability experiment.
Below routine by experiment beneficial effect of further setting forth medicine of the present invention.The compositions of Folium Crataegi total flavones and Radix Rhodiolae extract is hereinafter to be referred as the SH compositions.Used Folium Crataegi total flavones is taken from embodiment 1 in the experimental example, and Radix Rhodiolae extract is taken from embodiment 2.
Test example 1 SH compositions drug combination pharmacodynamic study-to the influence of rat experiment myocardial inyaretion scope
Animal subject: the Wistar rat, male, body weight 204～228g, 10 every group, is divided into 13 groups at random by 130.
Test sample: Folium Crataegi total flavones injection, self-control, 5ml:50mg;
The Radix Rhodiolae extract injection, self-control, 2ml:25mg;
SH composite injection (the different proportionings of Folium Crataegi total flavones+Radix Rhodiolae extract, proportioning sees Table 1), 10 groups, self-control.
Test method: rat is divided into 13 groups at random: the normal saline matched group; Model group; The Folium Crataegi total flavones group; The Radix Rhodiolae extract group; SH composite injection group: Folium Crataegi total flavones+Radix Rhodiolae extract (1: 0.05,1: 0.1,1: 0.2,1: 0.5,1: 0.75,1: 1,1: 2,1: 5,1: 7.5,1: 10).Each medicine all is diluted to desired concn with normal saline, the tail vein injection administration.
The rat experiment myocardial infarction model: it is fixing that animal pentobarbital intraperitoneal injection of anesthesia (45mg/kg) is faced upward the position.Tracheal intubation is made the longitudinal incision of 2cm in breastbone left side, nearly breastbone side is cut off the 3rd, the 4th costicartilage, open the thoracic cavity after, connect artificial respirator (ventilation 2ml/100g, 50 times/min).Cut off pericardium, expose heart, left anterior descending coronary artery root threading is in order to ligation, and record standard II lead electrocardiogram was stablized 10 minutes, and the ligation left anterior descending coronary artery is closed the thoracic cavity.With syringe sucking-off animal throat secretions, make animal recover autonomous respiration.Behind the ligation coronary artery 15min, intravenously administrable.Behind the ligation coronary artery 4 hours, win heart, 5 of the following crosscuts of ligature, carry out chlorination nitro blue tetrazolium (N-BT) dyeing, calculating myocardium infarcted region area accounts for the percentage ratio of ventricle and heart area, and carries out statistical procedures (t check).The results are shown in Table 1.
Table 1 SH compositions is to the influence of rat experiment myocardial inyaretion scope (x ± s)
| Group | Dosage (mg/kg) | Infarcted region/ventricle (%) | Infarcted region/heart (%) |
| Physiological saline control group haw thorn leaf total flavone group gadol extract group SH composition (1: 0.05) group SH composition (1: 0.1) group SH composition (1: 0.2) group SH composition 1: 0.5) group SH composition (1: 0.75) group SH composition (1: 1) group SH composition (1: 2) group SH composition (1: 5) group SH composition (1: 7.5) group SH composition (1: 10) group | 10 10 10 10 10 10 10 10 10 10 10 10 10 | 35.21±7.26 23.09±6.54 * 27.12±5.92 * 19.82±5.49 **#△ 17.36±5.97 **#△ 13.76±4.57 **##△△ 11.72±4.23 **##△△ 13.07±4.68 **##△△ 13.64±4.78 **##△△ 14.35±3.26 **##△△ 15.68±5.24 **#△ 16.49±5.64 *#△ 18.27±5.13 **#△ | 18.84±5.23 19.67±5.60 * 22.13±4.97 * 16.37±5.54 **#△ 13.24±4.96 **#△ 11.57±4.81 **##△△ 8.76±3.27 **##△△ 9.79±3.44 **##△△ 10.09±3.87 **##△△ 10.78±3.96 **##△△ 12.67±5.15 **#△ 14.59±4.52 **#△ 15.97±4.91 **#△ |
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01; Compare with the Folium Crataegi total flavones group,
#P＜0.05,
##P＜0.01; Compare with the Radix Rhodiolae extract group,
△P＜0.05,
△ △P＜0.01
Conclusion: compare with the normal saline group, each administration group all have tangible function of resisting myocardial ischemia (
*P＜0.05 or
*P＜0.01).With single with the Folium Crataegi total flavones group with singly compare with the Radix Rhodiolae extract group, each proportioning group of SH compositions all can dwindle rat experiment myocardial inyaretion scope (
#P＜0.05 He
△P＜0.05), wherein SH compositions (1: 0.2,1: 0.5,1: 0.75,1: 1,1: 2) group curative effect more remarkable (
#P＜0.01 He
△P＜0.01), point out two medicine compatibilities that synergistic function is arranged; Wherein with SH compositions (1: 0.5) group, curative effect is the most remarkable.
The antiplatelet aggregative activity of test example 2 SH compositionss
Experimental animal: the Wistar rat, male, body weight 201～225g, 10 every group, is divided into 8 groups at random by 80.
Test sample: Folium Crataegi total flavones injection, self-control, 5ml:50mg;
The Radix Rhodiolae extract injection, self-control, 2ml:25mg;
SH composite injection (different proportionings, proportioning sees Table 2), 5 groups, self-control.
Test method: rat is divided into 8 groups at random, every group 10, be respectively normal saline matched group, Radix Rhodiolae extract injection group, Folium Crataegi total flavones injection group, the different proportioning groups (1: 0.2,1: 0.5,1: 0.75,1: 1,1: 2) of SH composite injection.Each treated animal intraperitoneal injection, once a day, successive administration 7 days, after the last administration 1 hour, from abdominal aortic blood, anticoagulant adopted 3.28% sodium citrate after the Animal Anesthesia, with blood with 1: 9 mixed.With anticoagulated whole blood 1500r.min under 20 ℃ of conditions
-1Centrifugal 5min obtains platelet rich plasma (PPR).After leaving and taking quantitative PPR, will remain PPR once more with 3000r.min
-1Centrifugal 10min obtains own control platelet poor plasma (PPP).Regulate PPR concentration with PPP, make each PPR concentration identical.In 37 ℃ constant temperature hole after the preheating, (final concentration is 3 μ mol.L to add ADP with PPR
-1) cause and write down maximum agglutination rate by platelet aggregation.The results are shown in Table 2.
Table 2 SH compositions antiplatelet aggregative activity (X ± SD)
| Group | Dosage (mg/kg) | Mus number (only) | Maximum agglutination rate |
| Physiological saline control group haw thorn leaf total flavone group gadol extract group SH composition (1: 0.2) group SH composition (1: 0.5) group SH composition (1: 0.75) group SH composition (1: 1) group SH composition (1: 2) group | - 10 10 10 10 10 10 10 | 10 10 10 10 10 10 10 10 | 91.56±19.27 71.59±17.64 * 77.29±18.04 * 52.38±16.35 **#△ 37.56±15.64 **##△△ 45.68±16.78 **#△ 42.14±17.02 **#△ 48.67±15.39 **#△ |
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01; Compare with the Folium Crataegi total flavones group,
#P＜0.05,
##P＜0.01; Compare with the Radix Rhodiolae extract group,
△P＜0.05,
△ △P＜0.01
Conclusion: with the normal saline matched group relatively, Radix Rhodiolae extract injection, Folium Crataegi total flavones injection and SH composite injection all can make the thrombus formation time of experimental rat prolong (
*P＜0.05 or
*P＜0.01), shows that Folium Crataegi total flavones injection, Radix Rhodiolae extract injection and SH composite injection all have anti thrombotic action.With single with the Folium Crataegi total flavones group with singly compare with the Radix Rhodiolae extract group, each proportioning group of SH compositions all can make the thrombus formation time of experimental rat prolong (
#P＜0.05 He
△P＜0.05), point out two medicine compatibilities that synergistic function is arranged; Wherein with SH composite injection (Folium Crataegi total flavones+Radix Rhodiolae extract 1: 0.5) group, curative effect is the most remarkable.
Test example 3 SH compositionss are to thrombotic influence in the rat carotid artery
Experimental animal: the Wistar rat, the male and female dual-purpose, body weight 207～227g, 10 every group, is divided into 6 groups at random by 60.
Test sample: Folium Crataegi total flavones injection, self-control, 5ml:50mg;
The Radix Rhodiolae extract injection, self-control, 2ml:25mg;
SH composite injection (5ml contains Folium Crataegi total flavones 50mg, Radix Rhodiolae extract 25mg), self-control, preparation method is with reference to embodiment 3.
Test method: rat is divided into 6 groups at random, 6 every group, is respectively normal saline matched group, Radix Rhodiolae extract group, Folium Crataegi total flavones group, the basic, normal, high dosage group of SH compositions.The tail vein injection administration.The blank group gives the isometric(al) normal saline, and administration begins test after 20 minutes.Animal is with 2.5% pentobarbital sodium (25mg/kg) intraperitoneal injection of anesthesia, the rat dorsal position is fixed, separate right carotid, adopt electrical injuries carotid artery intima method, form instrument with the experimental thrombus in vivo of BT87-3 and measure different group animal carotid artery thrombus formation time.Electrode is seated on the carotid artery it carried out electricity irritation (2mA 7min), with induction electrode continuous measurement arterial distal surface temperature, observes the tremulous pulse temperature bust time.The record electricity irritation began to the time of aorta temperature bust, and this time is decided to be carotid artery thrombus formation time (surpassing 3000 seconds persons in 3000 seconds).Experimental result sees Table 3.
Table 3 SH compositions is to thrombotic influence in the rat carotid artery
| Group | Dosage (mg/kg) | Number of animals | Thrombus formation time (second) |
| Dosage group SH composition low dose group in the physiological saline control group haw thorn leaf total flavone group gadol extract group SH composition high dose group SH composition | - 30 30 30 20 10 | 10 10 10 10 10 10 | 943.26±417.56 1432.56±362.15 * 1296.84±326.48 * 2045.12±486.37 **##△△ 1869.25±402.56 **##△△ 1597.44±319.64 *#△ |
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01; Compare with the Folium Crataegi total flavones group,
#P＜0.05,
##P＜0.01; Compare with the Radix Rhodiolae extract group,
△P＜0.05,
△ △P＜0.01
Conclusion: Folium Crataegi total flavones, Radix Rhodiolae extract and SH compositions all can make thrombotic time lengthening in the rat carotid artery (
*P＜0.05 or
*P＜0.01).Compare with the Radix Rhodiolae extract group with Folium Crataegi total flavones group and list with single, thrombus formation time in the equal energy of each dosage group of the SH compositions significant prolongation rat carotid artery (
#P＜0.05,
##P＜0.01 He
△P＜0.05,
△ △P＜0.01), wherein with the middle and high dosage group of SH compositions, curative effect significantly (
#P＜0.01 He
△P＜0.01).
Test example 4 SH compositionss are to the protective effect of Medulla Leporis seu Oryctolagi ischemical reperfusion injury
Experimental animal: rabbit, 78, body weight 2.2～2.7kg is divided into 13 groups at random, 6 every group.
Test sample: Folium Crataegi total flavones injection, self-control, 5ml:50mg;
The Radix Rhodiolae extract injection, self-control, 2ml:25mg;
SH composite injection (5ml contains Folium Crataegi total flavones 50mg, Radix Rhodiolae extract 25mg), self-control, preparation method is with reference to embodiment 3.
Test method: rabbit is divided at random: ischemia-reperfusion group (I/R group), SH combination treatment group, Folium Crataegi total flavones treatment group, Radix Rhodiolae extract treatment group and Sham-operated control group (SOC group).(1) ischemia-reperfusion group (I/R group): 18, urethane lipoprotein solution 1g/kg body weight auricular vein anesthesia with 25%, the cervical region median incision separates trachea and inserts tracheal casing pipe, expose bilateral carotid, close 20min with bulldog clamp both sides folder, cause cerebral ischemia, pine folder pours into 1h, 6h and 12h respectively again, each 6 of three time points.Behind pine folder 10min, auricular vein is injected normal saline 5ml/kg body weight respectively.(2) SH combination treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected SH composite injection 10mg/kg respectively.(3) Folium Crataegi total flavones treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected Folium Crataegi total flavones injection 10mg/kg respectively.(4) Radix Rhodiolae extract treatment group: 18, operation method is organized with I/R, each 6 of three time points, and behind pine folder 10min, auricular vein is injected Radix Rhodiolae extract injection 10mg/kg respectively.(5) Sham-operated control group (SOC group): 6, animal only row anesthesia and tremulous pulse exclusion and not pressing from both sides closes, and puts to death behind the 1h.Above-mentioned each group promptly breaks end after testing and finishing, and strips out brain in ice bath, separates on the ice pan and cuts bilateral hippocampus tissue, is placed in 4 ℃ of refrigerators with the tinfoil parcel to store, and is standby.Use the pH acidometer and detect hippocampal tissue PLA
2Activity; Adopt the weight in wet base method of doing, TTC staining mensuration cortex brain water content, infarct size; Light microscopic is observed the cerebral tissue pathological change down.
Result of the test: (1) is to hippocampal tissue PLA
2After active influence: I/R group is poured into 1h, 6h and 12h again, hippocampal tissue PLA
2Activity obviously increases (P＜0.01) than SOC, and prolongs PLA with infusion time
2The activity trend that tapers off, but comparing difference not significantly (P＞0.05) between each time point; SH combination treatment group (1h, 6h, 12h) PLA
2Active obviously reduction relatively has significant difference (P＜0.01, P＜0.001) with SOC group and each corresponding time point of I/R, and with irritating time lengthening, PLA again
2Activity is recovered to normal level gradually; Radix Rhodiolae extract treatment group and Folium Crataegi total flavones treatment group (1h, 6h, 12h) PLA
2The active reduction relatively has notable difference (P＜0.05, P＜0.01) with SOC group and each corresponding time point of I/R, and the effect of Radix Rhodiolae extract is lower than Folium Crataegi total flavones.
(2) to the influence of cortical tissue's water content (%) and infarct size (%): I/R organizes each time point brain water content and all increases; Each time point brain water content of SH combination treatment group is compared obviously with the I/R group and is alleviated (P＜0.001), and brain infarction area is compared obviously with the I/R group and dwindled (P＜0.01); Radix Rhodiolae extract treatment group with Folium Crataegi total flavones treatment organize each time point brain water content and I/R group and compare all and alleviate (P＜0.01), brain infarction area is compared all with the I/R group and is dwindled (P＜0.05, P＜0.01).
(3) brain tissue pathology change: SOC organizes no infarction kitchen range, and the neuronal structure form is normal, continuously the matter edema; The I/R group has the infarction kitchen range, the neuron swelling of infarction kitchen range week, and cell outline is unclear, and interstitial edema is obvious; SH combination treatment group, Radix Rhodiolae extract treatment group, Folium Crataegi total flavones treatment group infarction kitchen range area all dwindle, and the neuron swelling of infarction kitchen range week is not obvious, and interstitial edema obviously alleviates; The effect of SH combination treatment group is more obvious.
Conclusion: above-mentioned result of the test shows that SH compositions, Folium Crataegi total flavones, Radix Rhodiolae extract all can be by reducing PLA
2Activity is improved cerebral circulation, alleviates cerebral ischemia reperfusion injury, and the performance cerebral protection.The SH compositions all is higher than the effect of Folium Crataegi total flavones and the independent medication of Radix Rhodiolae extract in every index, point out two medical instruments that synergistic function is arranged.
Test example 5 SH compositionss are to the hemodynamic influence of anesthetized open-chest dog
Experimental animal: hybrid dog, 20, body weight 11.2～13.5kg.
Test sample: Folium Crataegi total flavones injection, self-control, 5ml:50mg;
The Radix Rhodiolae extract injection, self-control, 2ml:25mg;
SH composite injection (5ml contains Folium Crataegi total flavones 50mg, Radix Rhodiolae extract 25mg), self-control, preparation method is with reference to embodiment 3.
Test method: dog is divided into 4 groups at random, 5 every group, is respectively normal saline matched group, Folium Crataegi total flavones group, Radix Rhodiolae extract group, SH compositions group.Dog is taked under the right arm reclining malleation artificial respiration after anaesthetizing with pentobarbital sodium (30mg/kg) intravenous injection, opens breast between 4～5 sides of body of a left side, opens pericardium in distance vagus nerve 2cm place, and parietal layer is made outstanding bed it is sutured in thoracic wall, and heart is fully exposed.Separate aorta, aortic root be inserted in the electromagnetic flowmeter probe (10～12mm), measure cardiac output (CO); At the left anterior descending coronary artery root, separate visceral pericardium, isolate about 1cm coronary artery, be inserted in the electromagnetic flowmeter probe (2～3mm), measurement coronary flow (CBF); This two probe is connected on the LMTC-621 type electromagnetic flowmeter, separates a bilateral common carotid artery, intubate connects pressure transducer, record arteriotony (AP) and mean arterial pressure (MAP); With internal diameter is that the cardiac catheter of 1.5mm is inserted left ventricle from the apex of the heart, amplify left indoor pressure (LVP) by YZ-1 type pressure transducer through carrier wave, the LVP electric signal amplifies 10 times through direct current amplifier, write down left chamber EDP (LVEDP), with the LVP electric signal again through BMI type differentiator derivative recording left indoor pressure rate of change (dP/dt
Max), it is subcutaneous to insert the animal subject extremity with pin type electrode, and record mark II lead electrocardiogram (EGG-II) is to measure heart rate (HR).These parameters changes equal synchronous recording and leads instrument in RM-6300 physiology more.
Separate femoral artery and take out arterial blood, through External Carotid Artery for Intubation to the coronary sinus vein venous blood samples, according to CY-2 oxygen analyser operation instructions, add the anhydrous sodium sulfite crystallization with freshly prepared anaerobic solution (0.01M) borax soln and be mixed with 2% sodium sulfite solution zeroing, use with the distilled water of air balance temperature constant and make sensitivity adjusting.Treat to measure oxygen content with oxygen analyser behind the instrument stabilizer.Calculating myocardium oxygen consumption after the off-test.
After operation finishes, observe above-mentioned every index, after stable with the index of record value before as administration, vein respectively behind administration normal saline, Folium Crataegi total flavones injection, Radix Rhodiolae extract injection and the SH composite injection in 1,3,5,10,20,30min, gather above-mentioned every index, and with every index rate of change (%) of each time point after the administration, the t-test that does significance pairing data between group with every index rate of change (%) of each corresponding time point of matched group handles.
Result of the test and conclusion: SH compositions, Folium Crataegi total flavones, Radix Rhodiolae extract are to being tried dog heart rate (HR), mean arterial pressure (MBP), left indoor pressure (LVP) and ventricular muscles contractility (dp/dt
Max), myocardial oxygen consumption all has the reduction effect.Especially SH compositions, the reduction amplitude is all obviously greater than Folium Crataegi total flavones group and Radix Rhodiolae extract group, and myocardial oxygen consumption is in beginning reduction about 2 minutes after the administration, and maximum is 26.2%, reach action time more than 30 minutes, curative effect P＜0.01 of highly significant is relatively arranged with matched group.
Test example 6 SH compositionss are to the influence of rat experiment hyperlipidemia
Experimental animal: Wistar rat, male and female half and half, body weight 208～230g.
Test sample: Folium Crataegi total flavones injection, self-control, 5ml:50mg;
The Radix Rhodiolae extract injection, self-control, 2ml:25mg;
SH composite injection (5ml contains Folium Crataegi total flavones 50mg, Radix Rhodiolae extract 25mg), self-control, preparation method is with reference to embodiment 3.
Test method: rat, behind cholesterol and the triglyceride levels, build hyperlipidemia model before the survey medicine.Except that the blank group gives the normal diet, all the other each groups all give high lipid food (prescription is normal diet 86.8%, cholesterol 3%, Adeps Sus domestica 10%, propylthiouracil 0.2%), feed was surveyed serum cholesterol and triglyceride levels after 10 days continuously, determined that hyperlipidemia model builds up.Continue to raise high lipid food after model builds up, wherein distinguish gastric infusion SH compositions, Folium Crataegi total flavones and Radix Rhodiolae extracts for three groups, every day, gastric infusion was 1 time, and successive administration was got blood again and surveyed cholesterol and triglyceride levels after 20 days.Result of the test sees Table 4 and table 5.
Table 4 SH compositions is to the influence of diet hyperlipemia rat serum cholesterol
| Group | Dosage (mg/kg) | Mus number (only) | Before the test | After the modelling | After the administration 20 days |
| Dosage group SH composition low dose group hyperlipidemia model group in the blank group haw thorn leaf total flavone group gadol extract group SH composition high dose group SH composition | - 30 30 30 20 10 - | 10 10 10 10 10 10 10 | 1.82±0.15 1.84±0.17 1.81±0.26 1.85±0.17 1.83±0.21 1.86±0.29 1.82±0.14 | 1.86±0.16 7.89±1.44 7.76±1.59 7.81±1.37 7.83±1.69 7.92±1.58 7.80±1.45 | 1.90±0.19 *** 5.42±1.52 ** 6.72±1.47 * 4.27±1.23 **#△△ 4.59±1.56 **#△△ 4.92±1.62 **#△△ 7.99±1.74 ** |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001; Compare with the Folium Crataegi total flavones group,
#P＜0.05; Compare with the Radix Rhodiolae extract group,
△ △P＜0.01.
Table 5 SH compositions is to the influence of diet hyperlipemia rat serum triglycerides
| Group | Dosage (mg/kg) | Mus number (only) | Before the test | After the modelling | After the administration 20 days |
| Dosage group SH composition low dose group hyperlipidemia model group in the blank group haw thorn leaf total flavone group gadol extract group SH composition high dose group SH composition | - 30 30 30 20 10 - | 10 10 10 10 10 10 10 | 0.69±0.15 0.64±0.15 0.65±0.19 0.67±0.21 0.64±0.20 0.66±0.13 0.65±0.17 | 0.69±0.14 0.95±0.23 0.92±0.34 1.03±0.29 1.01±0.24 0.99±0.21 1.02±0.27 | 0.68±0.16 ** 0.98±0.18 * 1.05±0.29 * 0.69±0.15 **#△△ 0.78±0.17 **#△△ 0.85±0.19 **△ 1.19±0.24 |
Annotate: compare with model group,
*P＜0.05,
*P＜0.01; Compare with the Folium Crataegi total flavones group,
#P＜0.05; Compare with the Radix Rhodiolae extract group,
△P＜0.05 He
△ △P＜0.01.
Conclusion: the result shows, SH compositions, Folium Crataegi total flavones, Radix Rhodiolae extract all can significantly reduce the serum cholesterol of diet hyperlipemia rat and triglyceride (
*P＜0.05 He
*P＜0.01) level.Compare with the Folium Crataegi total flavones group with single, each dosage group of SH compositions all can significantly reduce serum cholesterol (
#P＜0.05) level, in the SH compositions high dose group significantly reduce serum triglycerides (
#P＜0.05) level; Compare with the Radix Rhodiolae extract group with single, each dosage group of SH compositions all can significantly reduce serum cholesterol (
△ △P＜0.01) and serum triglycerides (
△P＜0.05 He
△ △P＜0.01) level, prompting Folium Crataegi and Radix Rhodiolae drug combination have synergistic function.Wherein remarkable with SH compositions high dose group curative effect.
Test routine 7:SH composite injection stability test
Test sample: SH composite injection (5ml contains Folium Crataegi total flavones 50mg, Radix Rhodiolae extract 25mg), the SH composite injection that adopts embodiment 3 to make.
Investigation project: character, pH value, clarity
Long-term stable experiment method and result: this product is put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 6 months, 12 months, every index has no significant change, experimental result show the SH composite injection long-term place basicly stable.
[specific embodiment]
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can be replaced with acceptable accessories in following examples, perhaps reduces, increases.Folium Crataegi total flavones used among the embodiment 3～9 is all taken from embodiment 1, and used Radix Rhodiolae extract is all taken from embodiment 2.
The preparation of embodiment 1 Folium Crataegi total flavones
Get Folium Crataegi, add 75% alcohol reflux three times, each 1.5 hours, merge extractive liquid,, filter, decompression filtrate recycling ethanol adds and waits the water gaging dilution, behind 1/2 defat with petroleum ether of measuring after do not have the alcohol flavor, discard petroleum ether liquid, the reuse ethyl acetate extraction, extract reclaim under reduced pressure ethyl acetate and be concentrated into dried, Folium Crataegi total flavones (for oral formulations with).Get above-mentioned Folium Crataegi total flavones, add suitable quantity of water and make dissolving, be added on the polyamide column of having handled well, with the water elution of 2 times of column volumes, discard water lotion earlier, use 70% ethanol elution of 3 times of column volumes then, collect eluent, reclaim ethanol and be concentrated into the concentrated solution of relative density about 1.02～1.08 (60 ℃), spray drying, Folium Crataegi total flavones (for oral or injection).
Differentiate
Get this product 50mg, add ethanol 5ml, shake up, supersound process 5 minutes filters, and gets filtrate as need testing solution.Other gets control substance of Rutin, hyperin reference substance, adds ethanol respectively and makes the solution that every 1ml contains 0.2mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB), draw each 1 μ l of above-mentioned three kinds of solution, putting respectively on same polyamide film, is developing solvent with ethanol-acetone-water (7: 5: 6), launches, take out, dry, spray dries up with the aluminum chloride test solution, place after 1 hour, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with reference substance chromatograph relevant position on, show the fluorescence of same color.
Assay
The preparation precision of reference substance solution takes by weighing at the control substance of Rutin 25mg of 120 ℃ of drying under reduced pressure to constant weight, put in the 50ml measuring bottle, it is an amount of to add ethanol, supersound process (power 300W, frequency 50kHz) makes dissolving, put coldly, add ethanol dilution to scale, shake up, promptly get (containing no rutin 0.2mg among every 1ml).
The preparation precision of standard curve is measured reference substance solution 1ml, 2ml, 3ml, 4ml, 5ml, 6ml, put respectively in the 25ml measuring bottle, respectively add water to 6ml, add 5% aluminum nitrate solution 1ml, make mixing, placed 6 minutes, and added 10% aluminum nitrate solution 1ml, shake up, placed 6 minutes, hydro-oxidation sodium test solution 10ml adds water to scale again, shakes up, placed 15 minutes, with the reagent corresponding is blank, according to ultraviolet visible spectrophotometry (appendix VA), measures absorbance at the wavelength place of 500nm, with the absorbance is that vertical coordinate, concentration are abscissa, the drawing standard curve.
Algoscopy is got this product 0.15g, and accurate the title decides, and puts in the tool plug conical flask, accurate Diluted Alcohol 25ml, the close plug of adding, shake up, supersound process 5 minutes was placed more than 3 hours, filtered, and precision is measured subsequent filtrate 2ml, put in the 25ml measuring bottle, be diluted with water to scale, shake up, as need testing solution.Precision is measured need testing solution 2ml, and to the 25ml measuring bottle, the method under the preparation of sighting target directrix curve is from " adding water to 6ml ", measure absorbance, precision is measured need testing solution 2ml simultaneously, puts in the 25ml volumetric flask in accordance with the law, add water to scale, shake up, as blank solution.Read the amount of rutin the need testing solution from standard curve, calculate, promptly.
The hyperin assay is according to high performance liquid chromatography (appendix VID)
Chromatographic condition and system suitability are filler with the octadecyl silane; With methanol-acetonitrile-oxolane-0.5% acetum (1: 1: 19.4: 78.6) be mobile phase; The detection wavelength is 363nm.Theoretical cam curve is calculated by the hyperin peak should be not less than 3000.
It is an amount of that the hyperin reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds Diluted Alcohol and makes the solution that every 1ml contains 25 μ g, promptly.
This product 0.15g is got in the preparation of need testing solution, and accurate the title decided porphyrize, get about 0.5g, the accurate title, decide, and puts in the 50ml measuring bottle, add Diluted Alcohol 40ml, supersound process (power 300W, frequency 50kHz) 30 minutes, put cold, be diluted to scale with Diluted Alcohol, shake up, centrifugal (per minute 12000 change) 10 minutes or filter with microporous filter membrane (0.45 μ m), get supernatant or subsequent filtrate, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Refining respectively three batches of Folium Crataegi total flavoness, yield and total flavones and hyperin assay the results are shown in following table.
Table 6 Folium Crataegi total flavones yield and assay result
| Batch | General flavone content (%) | Hyperin content (%) | Yield (%) |
| 123 is average | 85.24 84.39 87.26 85.63 | 0.59 0.48 0.55 0.54 | 2.52 2.14 2.90 2.52 |
By the result as can be seen, the Folium Crataegi total flavones yield by this prepared is 2～3%, and content of total flavone is not less than 80%, and the content of hyperin is not less than 0.4%.
The preparation of embodiment 2 Radix Rhodiolae extracts
Get the Radix Rhodiolae medical material, be ground into coarse powder,, add 10 times of amounts of alcohol for the first time, be respectively 8,8 times of amounts the two or three time with 70% ethanol extraction three times each 1 hour.Filter, merge extractive liquid,, recovery ethanol extremely every 5ml contains the 1g raw medicinal herbs, behind 2 times of amount defat with petroleum ether, discards petroleum ether liquid, and the water saturated n-butanol extraction of reuse is evaporated to the thick paste shape, and spray drying promptly gets the Radix Rhodiolae crude extract.
The Radix Rhodiolae crude extract with after the suitable quantity of water dissolving, is added on the macroporous resin column of handling well in advance, successively water liquid, 10% ethanol, 15% ethanol, 20% ethanol, 30% ethanol elution.Decompression recycling ethanol to relative density is 1.03～1.06 (60 ℃), and spray drying gets the Radix Rhodiolae essence extract.
Differentiate
Get this product 0.1g, add methanol 10ml, supersound process 30min shakes up, and filters, and filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Radix Rhodiolae medical material 1g, shines medical material solution in pairs with legal system.Draw above-mentioned two kinds of each 5ul of solution, put respectively on same silica gel g thin-layer plate, (6: 3: 1: lower floor's solution 1) was developing solvent, launched, and took out, and dried, and put in the iodine vapor smoked with chloroform-methanol-acetone-water.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The assay of rhodioside
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; With methanol-water (15: 85) is mobile phase, and the detection wavelength is 275nm.Number of theoretical plate calculates by the rhodioside peak should be not less than 1500.
The preparation precision of reference substance solution takes by weighing the rhodioside reference substance, adds methanol and makes the solution that every 1ml contains 0.5mg, promptly.
The preparation precision of need testing solution takes by weighing this product 0.1g, grinds well, and puts in the tool plug conical flask, accurate methanol 10ml, the close plug of adding, shake up, claim decide weight, supersound process 30 minutes is put coldly, and weight decided in title again, supply with methanol and to subtract weight loss, shake up, filter, get subsequent filtrate, promptly.
Accurate respectively reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects chromatograph of liquid, measures, promptly.
According to three batches of Radix Rhodiolae extracts that above-mentioned process for refining makes, rhodioside content and yield see Table 7.
The assay result and the yield of table 7 Radix Rhodiolae extract
| Batch | Rhodioside content (%) | Yield (%) |
| 1 2 3 | 13.56 15.78 18.24 15.86 | 2.88 2.41 2.21 2.50 |
By the result as can be seen, the Radix Rhodiolae extract yield by this prepared is 2～3%, and the content of rhodioside is not less than 10%.
The preparation of embodiment 3 SH compositions aqueous injection
Prescription:
Folium Crataegi total flavones 50.2g (being equivalent to Folium Crataegi 2kg)
Radix Rhodiolae extract 25.0g (being equivalent to Radix Rhodiolae 1kg)
Water for injection adds to 5000ml
Prepare 1000 altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) get the water for injection of dosing amount 80%, add the Folium Crataegi total flavones and the Radix Rhodiolae extract of recipe quantity, the heated and stirred dissolving fully.
3) benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) with the solution sealing by fusing in glass ampule.
9) 100 ℃ of flowing steam sterilizations are 30 minutes.
10) while hot sample being put into 0.01% methylene blue solution hunts leak.
11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 4 SH composition powder injections
Prescription:
Folium Crataegi total flavones 50.2g (being equivalent to Folium Crataegi 2kg)
Radix Rhodiolae extract 25.0g (being equivalent to Radix Rhodiolae 1kg)
Mannitol 400g
Sterile water for injection adds to 3000ml
Prepare 1000 altogether
Preparation technology:
1) vessel of at first dosing being used and antibiotic glass bottle, plug etc. carry out aseptic process.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) get the sterile water for injection of dosing amount 80%, Folium Crataegi total flavones and Radix Rhodiolae extract are added the heated and stirred dissolving fully.Add the dissolving of mannitol heated and stirred more fully, add sterile water for injection to full dose.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.22um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.In-40 ℃ of pre-freezes 4 hours, in-40 ℃～0 ℃ low-temperature vacuum drying 30 hours, heat up then, in 30 ℃ of insulation vacuum dryings 2.5 hours.
9) lyophilizing finishes, and lid is rolled in tamponade.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 5 SH compositions sodium chloride transfusion
Prescription:
Folium Crataegi total flavones 50.2g (being equivalent to Folium Crataegi 2kg)
Radix Rhodiolae extract 25.0g (being equivalent to Radix Rhodiolae 1kg)
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Preparation technology:
1) handles the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) water for injection of getting dosing amount 20% adds the heated and stirred dissolving fully with Folium Crataegi total flavones and Radix Rhodiolae extract.Sodium chloride is complete with the water for injection dissolving of dosing amount 40%.
3) merge two solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6 SH compositions glucose infusion liquids
Prescription:
Folium Crataegi total flavones 50.2g (being equivalent to Folium Crataegi 2kg)
Radix Rhodiolae extract 25.0g (being equivalent to Radix Rhodiolae 1kg)
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Preparation technology:
1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse.
2) water for injection of getting dosing amount 20% adds the heated and stirred dissolving fully with Folium Crataegi total flavones and Radix Rhodiolae extract.Glucose is complete with the water for injection dissolving of dosing amount 40%.
3) merge two solution, benefit adds to the full amount of water for injection.
4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes.
5) through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution.
6) through the microporous filter membrane fine straining of 0.45um.
7) clarity of inspection solution, the semi-finished product chemical examination.
8) fill is in the infusion bottle of 100ml.
9) 115 ℃ of pressure sterilizings are 30 minutes.
10) lamp inspection, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 7 SH composition tablets
Prescription:
Folium Crataegi total flavones 50.2g (being equivalent to Folium Crataegi 2kg)
Radix Rhodiolae extract 25.0g (being equivalent to Radix Rhodiolae 1kg)
Starch 120.0g
Pregelatinized Starch 80g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 2.0g
Micropowder silica gel 5.0g
Carboxymethylstach sodium 8.0g
Prepare 1000 altogether
Preparation technology:
1) it is standby Folium Crataegi total flavones and Radix Rhodiolae extract to be pulverized 100 mesh sieves.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Folium Crataegi total flavones, Radix Rhodiolae extract, starch, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 60 ℃ condition.
7) dry good granule adds magnesium stearate, carboxymethylstach sodium and micropowder silica gel, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) the sheet weight sheet of determining according to chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 8 SH composition capsules
Prescription:
Folium Crataegi total flavones 50.2g (being equivalent to Folium Crataegi 2kg)
Radix Rhodiolae extract 25.0g (being equivalent to Radix Rhodiolae 1kg)
Starch 30g
Pregelatinized Starch 80g
Microcrystalline Cellulose 20g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 1g
Prepare 1000 altogether
Preparation technology:
1) it is standby Folium Crataegi total flavones and Radix Rhodiolae extract to be pulverized 80 mesh sieves.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) hypromellose 2% the aqueous solution made soluble in water is standby.
4) with Folium Crataegi total flavones, Radix Rhodiolae extract, starch, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is dried under 55 ℃ condition.
7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) loading amount of determining according to chemical examination incapsulates.
10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 9 SH composition granules
Prescription:
Folium Crataegi total flavones 50.2g (being equivalent to Folium Crataegi 2kg)
Radix Rhodiolae extract 25.0g (being equivalent to Radix Rhodiolae 1kg)
Steviosin 20g
Icing Sugar 3000g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Preparation technology:
1) it is standby sucrose to be pulverized 100 mesh sieves.It is standby that Folium Crataegi total flavones and Radix Rhodiolae extract were pulverized 100 mesh sieves.
2) take by weighing raw material and adjuvant according to recipe quantity.
3) the method mix homogeneously that Folium Crataegi total flavones, Radix Rhodiolae extract and steviosin, Icing Sugar are progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material,
4) cross 20 mesh sieve system granules.
5) granule is dried under 60 ℃ condition.
6) dried granule is crossed 18 mesh sieve granulate.
7) inspection of semifinished product
8) determine loading amount, packing.
9) finished product is examined entirely, the packing warehouse-in.
Claims (10)
1. pharmaceutical composition is characterized in that this pharmaceutical composition mainly made by Folium Crataegi and Radix Rhodiolae, and both weight ratios are: 1: 0.05～10.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the weight ratio of described Folium Crataegi and Radix Rhodiolae is: 1: 0.1～5.
3. pharmaceutical composition as claimed in claim 2 is characterized in that the weight ratio of described Folium Crataegi and Radix Rhodiolae is: 1: 0.5.
4. as the described arbitrary preparation of drug combination method of claim 1～3, it is characterized in that, Folium Crataegi wherein and Radix Rhodiolae can singly be carried or mix to obtain through refining and obtain extract fully with The suitable solvent and method, and total extract is made arbitrary preparation with mixing acceptable accessories again.
5. preparation of drug combination method as claimed in claim 4 is characterized in that, main effective ingredient contained in the total extract is: Folium Crataegi total flavones and rhodioside, the total content of the main effective ingredient in the total extract is not less than 30%.
6. pharmaceutical composition as claimed in claim 1 is characterized in that, this pharmaceutical composition can also be made by Folium Crataegi total flavones and Radix Rhodiolae extract, and both weight proportions are: 1: 0.05～10.
7. pharmaceutical composition as claimed in claim 6 is characterized in that, the weight ratio of described Folium Crataegi total flavones and Radix Rhodiolae extract is: 1: 0.1～5.
8. pharmaceutical composition as claimed in claim 7 is characterized in that the weight ratio of described Folium Crataegi total flavones and Radix Rhodiolae extract is: 1: 0.5.
9. as the described arbitrary pharmaceutical composition of claim 6～8, it is characterized in that in the described Folium Crataegi total flavones, content of total flavone is with anhydrous rutin (C
27H
30O
16) meter be no less than 60.0%, hyperin (C
21H
20O
12) content be no less than 0.20%; The content of rhodioside is not less than 3% in the described Radix Rhodiolae extract.
10. as claim 1～3,6～8 described arbitrary pharmaceutical compositions, it is characterized in that this pharmaceutical composition can make clinically any or pharmaceutically acceptable dosage form with mixing acceptable accessories.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100432636A CN100563682C (en) | 2006-03-24 | 2006-03-24 | A kind of pharmaceutical composition of making by Folium Crataegi and Radix Rhodiolae and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100432636A CN100563682C (en) | 2006-03-24 | 2006-03-24 | A kind of pharmaceutical composition of making by Folium Crataegi and Radix Rhodiolae and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101040934A true CN101040934A (en) | 2007-09-26 |
| CN100563682C CN100563682C (en) | 2009-12-02 |
Family
ID=38806863
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100432636A Expired - Fee Related CN100563682C (en) | 2006-03-24 | 2006-03-24 | A kind of pharmaceutical composition of making by Folium Crataegi and Radix Rhodiolae and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100563682C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103816205A (en) * | 2012-11-16 | 2014-05-28 | 邢秋苓 | Rhodiola extract and application thereof |
| CN103816206A (en) * | 2012-11-16 | 2014-05-28 | 邢秋苓 | Rhodiola rosea extract capable of promoting formation of osteoblast bones |
| CN104510902A (en) * | 2013-10-08 | 2015-04-15 | 肖延斌 | Compound traditional Chinese medicine preparation for treating cardiovascular and cerebrovascular diseases |
-
2006
- 2006-03-24 CN CNB2006100432636A patent/CN100563682C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103816205A (en) * | 2012-11-16 | 2014-05-28 | 邢秋苓 | Rhodiola extract and application thereof |
| CN103816206A (en) * | 2012-11-16 | 2014-05-28 | 邢秋苓 | Rhodiola rosea extract capable of promoting formation of osteoblast bones |
| CN104510902A (en) * | 2013-10-08 | 2015-04-15 | 肖延斌 | Compound traditional Chinese medicine preparation for treating cardiovascular and cerebrovascular diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100563682C (en) | 2009-12-02 |
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