Summary of the invention
The purpose of this invention is to provide a kind of ginkgo Armillaria mellea oral preparation, this oral formulations has blood fat reducing, blood pressure lowering, prevents angiectatic effect.
In order to achieve the above object, the present invention is by the following technical solutions:
The medicinal raw material that will contain Folium Ginkgo extract and MIHUAN FEN is made oral administration solution, capsule, tablet, syrup, granule and injection; The weight ratio of described Folium Ginkgo extract and MIHUAN FEN is 1~6: 50~200.
When it is oral administration solution, contain the Folium Ginkgo extract of the material of following concentration: 1~6g/L, the MIHUAN FEN of 50~200g/L, the sodium benzoate of 1~6g/L, the cosolvent of 2~7g/L and the sweeting agent of 1~5g/L.
Preferably, the weight ratio of described Folium Ginkgo extract and MIHUAN FEN is 3: 100.
Described Folium Ginkgo extract is the water soluble ginkgo leaf extract that meets Chinese Pharmacopoeia 2005 standards.
Described cosolvent is Polyoxyethylene Sorbitan Monooleate or sodium lauryl sulphate.
Described sweeting agent is stevioside or protein sugar.
The preparation method of this ginkgo Armillaria mellea oral preparation comprises following steps:
(1) extract:
MIHUAN FEN packed into decoct a drug wrapped in the bag, loading amount is 1/5~1/2 of the bag of decocting a drug wrapped, and places the extraction pot extracting in water 3 times, collects extracting solution;
(2) concentrate:
Merge extractive liquid, filters, and filtrate is concentrated into relative density 1.14~1.15, receives cream;
(3) precipitate with ethanol:
Cooled extractum is pumped in the Alcohol-settling tank, accurately add ethanol, the limit edged stirs, and makes medicinal liquid contain the alcohol amount and reaches 60%~80%, and cold preservation is left standstill;
(4) ethanol reclaims: supernatant concentrates to the vacuum concentrator after extracting precipitate with ethanol, reclaims ethanol simultaneously, is concentrated into relative density 1.15~1.17;
(5) dosing:
A. the preparation of Folium Ginkgo extract solution
Cosolvent is diluted to 1~10wt% with pure water, is heated to 70~90 ℃, and load weighted Folium Ginkgo extract is slowly added wherein, and the limit edged stirs, and insulated and stirred is dissolved it fully, makes Folium Ginkgo extract solution;
B. the preparation of sodium benzoate solution
Add purified water in dilute preparing tank, slowly adding sodium benzoate, to make its concentration be 0.2~2wt%, is stirred to dissolving fully, standby;
C. dosing operation
Extractum is added dense preparing tank be diluted to 33~40wt% with pure water, stir, heating was stirred 30 minutes, leave standstill, and filtered while hot, filtrate pumps into thinning tank, adds Folium Ginkgo extract solution, sweeting agent, and the limit edged stirs, and replenishes purified water to 10~12wt%, and is static; After adding sodium benzoate solution, slowly add purified water to 6.67~9.60wt%, be stirred to evenly.
The pharmacological action of ginkgo Armillaria mellea oral preparation of the present invention is as follows:
(1) effectively improve coronary artery circulation, increase blood supply of cardiac muscle: the ginkgetin in the Folium Ginkgo, ginkgetin base parent nucleus, Folium Ginkgo terpene lactones composition have the effect of alleviating coronary artery spasm, elimination arrhythmia, protection myocardial ischemic injury; Increase the myocardial nutritional flow amount, increase myocardium microcirculation, increase STH, LDH, atpase activity, significantly increase DNA, RNA glycogen, promote energy metabolism of myocardial, strengthen myocardial contraction, anti-hypoxia; All there are the coronary vascular resistance of reduction in gastrodine in ginkgetin base in the Folium Ginkgo, Flos Camelliae Japonicae phenol Quercetin, isorhamnetin, Folium Ginkgo terpene lactones and the MIHUAN FEN and gastrodin unit, increase coronary blood flow, improve the effect of myocardial blood circulation.
(2) remarkable cerebral blood flow increasing amount, improve brain function: the ginkgetin parent nucleus in the Folium Ginkgo, Folium Ginkgo terpene lactones composition have and promote the brain cell metabolism, improve the brain cell damage, the regeneration of nerve damage, improve attention and memory; Vanillyl alcohol in the MIHUAN FEN, gastrodin, Vanillin have calmness, analgesia, epilepsy, hypnosis, improve learning and memory, improve cognitive function; Gastrodine in ginkgetin in the Folium Ginkgo, Folium Ginkgo terpene lactones and the MIHUAN FEN and vanilla Suo Jun have the effect that reduces cerebral vascular resistance, cerebral blood flow increasing, improves cerebral blood supply insufficiency.
(3) microcirculation improvement, effectively reduce blood ester, blood pressure: the bilobalide in the Folium Ginkgo, Folium Ginkgo extract composition have the effect of antagonism PAF, microcirculation improvement, blood viscosity lowering, blood sugar lowering; Gastrodine in the MIHUAN FEN and gastrodin unit have the platelet of inhibition and focus on; Ginkgetin in the Folium Ginkgo and the gastrodine in the MIHUAN FEN all have the effect of blood pressure lowering, blood fat reducing.
Function of the present invention is annotated and is controlled: QI invigorating, consolidating superficial resistance, hidroschesis.Be used for exterior deficiency, spontaneous perspiration aversion to wind, complexion
In vain, or the empty susceptible ailment said due to cold or exposure person of body.The using method of this oral formulations, normally 3 times on the one, a 10ml.No taboo crowd.
With ginkgo Armillaria mellea oral preparation of the present invention treatment cerebral infarction (wind-phlegm blood stasis disease), Huashan Hospital Affiliated To Fudan Univ calendar year 2001 December carry out clinical verification, 30 examples are organized in treatment.Result of study shows: total effective rate 80.00%.The Longhua Hospital affiliated Shanghai University Of Chinese Traditional Medicine Neurology Department calendar year 2001 JIUYUE to calendar year 2001 December carry out clinical verification, 30 examples are organized in treatment.Result of study shows: treatment group total effective rate is 86.67%.Shuguang Hospital's Neurology Department calendar year 2001 JIUYUE to calendar year 2001 December carry out clinical verification, 30 examples are organized in treatment, matched group 30 examples.Result of study shows: treatment group total effective rate is 83.33%, and the matched group total effective rate is 80.0%, does not have significant difference between two groups of clinical efficacies.Ruijin Hospital Attached to Shanghai Medical Univ No.2 internal medicine calendar year 2001 JIUYUE to calendar year 2001 December carry out clinical verification, 30 examples are organized in treatment.Result of study shows: 26 examples are effective, and treatment group total effective rate is 86.67%.
The present invention has following advantage:
The present invention is by the cooperative effect of Folium Ginkgo extract and MIHUAN FEN, makes described ginkgo Armillaria mellea oral preparation have blood fat reducing, atherosclerosis, blood circulation promoting and blood stasis dispelling, multiple efficacies such as resist myocardial ischemia.
The specific embodiment
Embodiment 1: the preparation and the effect of Semen Ginkgo honey collar extension clothes solution
(1) extract:
MIHUAN FEN packed into decoct a drug wrapped in the bag, loading amount is 1/5~1/2 of the bag of decocting a drug wrapped, and puts in the multi-function extractor extracting in water 3 times, collects extracting solution.
(2) concentrate:
Merge extractive liquid, filters, and filtrate is concentrated into relative density 1.14~1.15, receives cream.
(3) precipitate with ethanol:
Cooled extractum is pumped in the Alcohol-settling tank, accurately add ethanol, the limit edged stirs, and makes medicinal liquid contain the alcohol amount and reaches 75%, and cold preservation is left standstill.
(4) ethanol reclaims: supernatant concentrates to the vacuum concentrator after extracting precipitate with ethanol, reclaims ethanol simultaneously, is concentrated into relative density 1.15~1.17.
(5) dosing:
A. the preparation of Folium Ginkgo extract solution
The cosolvent sodium lauryl sulphate is diluted to 75kg with pure water, is heated to 80 ℃, and load weighted Folium Ginkgo extract is slowly added wherein, and the limit edged stirs, and insulated and stirred is dissolved it fully, makes Folium Ginkgo extract solution.
B. the preparation of sodium benzoate solution
In dilute preparing tank, add purified water 400L, slowly add sodium benzoate 4kg, be stirred to dissolving fully, standby.
C. dosing operation
Extractum 180kg is added dense preparing tank be diluted to 500L with pure water, stir, heating was stirred 30 minutes, leave standstill, filtered while hot, filtrate pumps into thinning tank, adds the solution, the sweeting agent 10kg that contain Folium Ginkgo extract 6kg, the limit edged stirs, and replenishes purified water to 1500L, and is static.Slowly add purified water to 2000L, be stirred to evenly.
D. embedding:
Get from the dosing operation and to treat perfusion liquid, with the canned Cover-rolling machine embedding of high-speed liquid.Wait to irritate continuously embedding of liquid, from rare joining beginning to be no more than 1 hour to the sterilization whole process that finishes.At any time check embedding device and seal quality in the embedding process.
E. sterilization:
Advance the vacuum leak hunting steriliser with disinfecting car subject to sterilization is housed, behind subject to sterilization the finishing, the sterilization product carry out vacuum leak hunting, drip washing in cabinet.
F. lamp inspection;
Qualified semi-finished product are selected bottle cap one by one and body pollutes with sterilizing.In the bottle foreign body is arranged, clarity is defective, loading amount is not enough, the breakage of glass bottle, askew lid, mashed lid, trachoma, fall defective works such as limit, loose lid.
The Semen Ginkgo honey collar extension clothes solution of gained, after testing, contain the material of following concentration:
The sodium benzoate of the Folium Ginkgo extract of 3g/L, the MIHUAN FEN of 100g/L, 3g/L, the cosolvent of 5g/L and the sweeting agent of 3g/L.
The pharmacodynamics test of the Semen Ginkgo honey collar extension clothes solution of embodiment 1 gained:
One, effect for reducing fat:
1. to the influence of normal mice serum lipid content:
Get 90 of body weight 18-22g Kunming mouses, male and female half and half, be divided into 6 groups at random, the difference gastric infusion, once a day, continuous 14 days, the normal control group is given the equal-volume normal saline, fasting is 16 hours after the last administration, in the socket of the eye venous blood collection, separation of serum is measured T-CHOL (TC) and triglyceride (TG) content in the serum on BeckHan700 type automatic clinical chemistry analyzer, the result shows that Semen Ginkgo honey collar extension clothes solution does not all have tangible influence (P>0.05) to normal mice serum T-CHOL and triglyceride.
2. to the influence of aged mouse serum lipids content:
Get 60 of the Kunming mouses in 24 months ages of Mus, male and female half and half are divided into 6 groups at random, the difference gastric infusion, once a day, continuous 14 days, the normal control group was given the equal-volume normal saline, fasting is 16 hours after the last administration, in the socket of the eye venous blood collection, separation of serum is measured T-CHOL (TC) and triglyceride (TG) content in the serum on BeckHan700 type automatic clinical chemistry analyzer, the result shows that Semen Ginkgo honey collar extension clothes solution can obviously reduce aged mouse serum total cholesterol and content of triglyceride.
3. egg yolk is caused the influence that the mice blood fat raises:
Get 70 of body weight 18-22g Kunming mouses, male and female half and half, be divided into 7 groups at random, the difference gastric infusion, once a day, continuous 14 days, normal group and egg yolk group are given the equal-volume normal saline, and the last administration is after 1 hour, except that normal group, all the other respectively organize equal lumbar injection 75% egg yolk Emulsion 15ml/kg, fasting is plucked eyeball after 16 hours and is got blood, and separation of serum is measured T-CHOL (TC) and triglyceride (TG) content in the serum on BeckHan700 type automatic clinical chemistry analyzer, the result shows, Semen Ginkgo honey collar extension clothes solution all has the effect of obvious reduction to the content of hyperlipemia in mice serum total cholesterol due to the egg yolk and triglyceride.
4. to the influence of hyperlipidemia rats serum lipids content
Get 60 of male 150~200gSD kind rats, be divided into 6 groups at random.The normal control group is irritated stomach and is given the equal-volume normal saline, and all the other each groups are gastric infusion respectively.The administration while, except that the normal control group, all the other 5 groups equal feed high cholesterol diets (prescriptions: 4% cholesterol, 10% Adeps Sus domestica, 0.2% methylthiouracil and 86-89% normal feedstuff), successive administration 15 days, last administration fasting 16 hours, broken end is got blood, and separation of serum is measured TC, TG, HDL-C, LDL-C etc., the result shows: through the rat of fed with high, its serum lipid metabolism is obviously disorderly, and TC, TG, LDL-C content increase (P<0.05) unusually, and the HDL-C value obviously descends.The antiatherogenic effect of HDL-C gains universal acceptance, and its level and coronary heart disease are negative correlation, is the prevention factor of coronary heart disease.The TC level is the traditional index of appraisal coronary heart disease danger, and it is that atherosclerotic absolute prerequisite takes place that TC increases, and its level and Incidence of CHD and mortality rate have substantial connection.Semen Ginkgo honey collar extension clothes solution can significantly reduce high fat Serum TC, TG, improves HDL-C, LDL-C level, thereby makes AI reduce (P<0.01), illustrates that it has the good atherosclerosis function of preventing and treating, so can prevent and treat coronary heart disease.
Two, study of anti-atherogenic effect
1. to the influence of rabbit hyperlipemia and arteriosclerosis:
Get 40 new zealand rabbits, body weight 2 ± 0.2kg, sub-cage rearing are raised Adeps Sus domestica 10g/kg, methylthiouracil 5mg/kg, cholesterol 0.2g/kg every day, admix feedstuff and take in voluntarily by it.Experiment divides 5 groups, 8 every group.The administration group is given Semen Ginkgo honey collar extension clothes solution in addition except that above-mentioned feedstuff, admix in the above-mentioned feedstuff, takes in voluntarily.Matched group is raised the feedstuff of afore mentioned rules, continuous 12 weeks.The result shows that Semen Ginkgo honey collar extension clothes solution can obviously reduce the formation of atherosclerosis plate, thereby has the function of better treatment coronary heart disease.
Three, blood circulation promoting and blood stasis dispelling effect
1. select 60 of the purebred rat of body weight 240 ± 10g, normal group is irritated stomach equal-volume normal saline, continuous 10 days every day; " blood stasis " model group is irritated stomach equal-volume normal saline every day, continuous 10 days, in the 10th day subcutaneous injection 0.1% epinephrine 0.08ml/100g body weight, totally 2 times, two minor ticks 4 hours. injecting back 2 hours for the second time, rat was invaded frozen water 4 minutes, stop eating then, get blood in morning next day broken end, anticoagulant heparin (40 μ/ml), carrying out hemorheology detects. and the administration group is irritated stomach 5 respectively, the Semen Ginkgo honey collar extension clothes solution of 15 and 30 times and 15 times people's consumption per days, continuous 10 days, all the other methods are with " blood stasis " model group. and the result shows, whole blood viscosity of " blood stasis " model group and plasma viscosity be apparently higher than normal group, shows the success of this test " blood stasis " model modeling. and the Semen Ginkgo honey collar extension of irritating 15 times of stomach administration of human consumption per days and 30 times is obeyed solution Folium Pruni oral administration solution, all can obviously reduce the whole blood viscosity and the plasma viscosity (P<0.05) of rat acute " blood stasis " model group, it is sticking to improve blood, dense, the state of coagulating helps the formation of anti-tampon.
2. the influence that the rabbit experimental thrombosis is formed
Get 40 of the healthy Japan large ear rabbits of 2.0-2.5kg, be divided into 5 groups at random.Gastric infusion, once a day, continuous 10 days, normal group was given isopyknic normal saline.Anaesthetize with 3% pentobarbital sodium auricular vein injection 1ml/kg immediately after the last administration.Through 1.5mm, the polyethylene tube of long 22cm is full of heparin-saline 50 μ/ml in the pipe in getting, 4 long trumpeter's art silk threads of a built-in 5cm.One section with polyethylene tube is inserted right common carotid artery, and the other end inserts left common carotid artery.After administration 60 minutes, open blood flow took out silk thread and weighs after 15 minutes, and gross weight deducts line and heavily is wet weight of thrombus.The result shows that Semen Ginkgo honey collar extension clothes solution has highly significant inhibitory action (P<0.01) to thrombosis.
3. to the influence of rabbit platelet adhesion function
Imitative Wright method (circumgyration).Get 40 of the healthy Japan large ear rabbits of body weight 2.0-2.5kg, be divided into 5 groups at random.Gastric infusion, once a day, continuous 10 days, normal group was given isopyknic normal saline.After the last administration 60 minutes, with 3% pentobarbital sodium lumbar injection 1ml/kg anesthesia, open cervical region, with mixing in the 5ml silication test tube, getting blood 1ml adding capacity from test tube is in the long-neck Ball-shaped bottle of 8ml.Place on formation of XSR-RII type external thrombus and the platelet adhesion double-purpose instrument rotating disk, 37 ℃ of constant temperature with 3.7r/min rotation 15 minutes, are measured rotation front and back platelet count respectively, count 2 times meansigma methods, platelet Counting and platelet adhesion rate.The result shows, the Semen Ginkgo honey collar extension clothes solution of 15 times and 30 times can obviously suppress rabbit platelet adhesion function (P<0.05).
Four, function of resisting myocardial ischemia
1. to myocardial ischemia mice LDH due to the isoproterenol and the active influence that raises of CK
Get 60 healthy Kunming mouses, male and female half and half, body weight 20 ± 2g is divided into 6 groups at random, and gastric infusion is 7 days continuously, and normal group is given isopyknic normal saline.After administration 4-6 days, normal control group intraperitoneal injection of saline 10ml/kg, all the other group lumbar injection isoproterenol 4mg/kg, in last administration isoproterenol after 24 hours, from the socket of the eye venous blood collection, separation of serum is measured LDL (lactic acid dehydrogenase) and CPK (creatine phosphokinase) activity in the serum on BeckMan700 type automatic clinical chemistry analyzer.The result shows that 30 multiple dose Semen Ginkgoes honey collar extension clothes solution has obvious reduction effect (P<0.05) to LDH in the myocardial ischemia mice serum due to the isoproterenol, does not have obvious influence (P>0.05) to CPK.
Conclusion:
Semen Ginkgo honey collar extension clothes solution has effect for reducing fat preferably, can reduce aged mouse serum total cholesterol and content of triglyceride, antagonism egg yolk induced mice blood fat (TC, TG) raises, can significantly reduce high fat Serum TC, TG, improve HDL-C, LDL-C level, thereby " activate arteries and veins hardenability value " (AI) reduced, illustrate that it has the good atherosclerosis function of preventing and treating.It can also resist rabbit hyperlipidemia mass formed by blood stasis and atherosclerosis due to the high lipid food, shows as remarkable reduction rabbit anteserum TC, TG, and the HDL-C that significantly raises reduces AI, reduces aorta and crown artery plaque and forms, thereby have the good coronary heart disease function of preventing and treating.
Blood circulation promoting and blood stasis dispelling test shows that this product can obviously reduce the whole blood viscosity and the plasma viscosity of rat acute " blood stasis " model, improves sticking, dense, the state with fixed attention of blood; Can reduce the rabbit experimental thrombosis and form, and obviously suppress the rabbit platelet adhesion function, have the better activity silt function of dispelling.Myocardial ischemia mice LDH due to the isoproterenol is raise, and 30 multiple dose Semen Ginkgoes honey collar extension clothes solution has certain reduction effect.
Embodiment 2
Semen Ginkgo honey ring preparation of granules flow process:
(1) extract:
MIHUAN FEN packed into decoct a drug wrapped in the bag, loading amount is 1/5~1/2 of the bag of decocting a drug wrapped, and puts in the multi-function extractor extracting in water 3 times, collects extracting solution.
(2) concentrate:
Merge extractive liquid, filters, and filtrate is concentrated into relative density 1.14~1.15, receives cream.
(3) precipitate with ethanol:
Cooled extractum is pumped in the Alcohol-settling tank, accurately add ethanol, the limit edged stirs, and makes medicinal liquid contain the alcohol amount and reaches 60%~80%, and cold preservation is left standstill.
(4) ethanol reclaims: supernatant concentrates to the vacuum concentrator after extracting precipitate with ethanol, reclaims ethanol simultaneously, is concentrated into relative density 1.0~1.5.
(5) granulate:
With Folium Ginkgo extract, MIHUAN FEN extractum and appropriate amount of auxiliary materials mixing, make granule, drying is made 1000g, promptly.
Embodiment 3
Semen Ginkgo honey ring capsule preparation flow:
(1) extract:
MIHUAN FEN packed into decoct a drug wrapped in the bag, loading amount is 1/5~1/2 of the bag of decocting a drug wrapped, and puts in the multi-function extractor extracting in water 3 times, collects extracting solution.
(2) concentrate:
Merge extractive liquid, filters, and filtrate is concentrated into relative density 1.14~1.15, receives cream.
(3) precipitate with ethanol:
Cooled extractum is pumped in the Alcohol-settling tank, accurately add ethanol, the limit edged stirs, and makes medicinal liquid contain the alcohol amount and reaches 60%~80%, and cold preservation is left standstill.
(4) ethanol reclaims: supernatant concentrates to the vacuum concentrator after extracting precipitate with ethanol, reclaims ethanol simultaneously, is concentrated into relative density 1.0~1.5.
(5) granulate:
With Folium Ginkgo extract, MIHUAN FEN extractum and appropriate amount of auxiliary materials mixing, make granule, drying, encapsulated, make 1000, promptly.
More than ginkgo Armillaria mellea oral preparation provided by the present invention and preparation method thereof is described in detail, used specific case herein principle of the present invention and embodiment are set forth, the explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof; Simultaneously, for one of ordinary skill in the art, according to thought of the present invention, the part that all can change in specific embodiments and applications, in sum, this description should not be construed as limitation of the present invention.