CN102764280A - Bezoar and musk containing pharmaceutical composition and its application - Google Patents
Bezoar and musk containing pharmaceutical composition and its application Download PDFInfo
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- CN102764280A CN102764280A CN2011101159539A CN201110115953A CN102764280A CN 102764280 A CN102764280 A CN 102764280A CN 2011101159539 A CN2011101159539 A CN 2011101159539A CN 201110115953 A CN201110115953 A CN 201110115953A CN 102764280 A CN102764280 A CN 102764280A
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Abstract
The invention relates to a pharmaceutical composition which is developed on the basis of the modern medicine theory and contains bezoar, musk and natural plant extracts or monomers. The composition has good functions of preventing and treating cerebrovascular diseases. Based on the drug combination of bezoar and musk, a plurality of plant drug combinations are added. The pharmaceutical composition has a more substantial curative effect of treating cerebrovascular diseases (including cerebral thrombus, cerebral ischemia, cerebral infarction, traumatic brain injury and the like) than original medicines.
Description
Technical field
The present invention relates to pharmaceutical composition, is the Calculus Bovis that contains according to the theoretical development of modern pharmacy, Moschus and natural plant extracts or monomeric Pharmaceutical composition and the application aspect prevention and treatment cerebrovascular disease thereof.
Technical background
Calculus Bovis, Moschus are two Chinese medicine animal origin types of drugs, and medicine and pharmacology in modern times have been widely used in the clinical treatment cardiovascular and cerebrovascular disease in using.
The Calculus Bovis traditional Chinese medical science think can be used for analgesic, the detoxifcation, the arresting convulsion.Take orally and control the hyperpyrexia coma, demented, infantile convulsion, diseases such as tic.External is controlled laryngopharynx swelling and pain, aphtha carbuncle, is treated toxication.The discovering it and protect of modern medicine at nervus centralis, the treatment cerebral ischemia, cerebral hemorrhage, there is effect widely the apoplexy aspect.(Liu Xiaoyan etc., In vitro cultured Calculus Bovis treatment acute cerebral infarction clinical observation on the therapeutic effect. Chinese Chinese medicine information magazine, 2010, (5); Han Tiejun. the preparation of Calculus Bovis Annaowan bolus and observation of curative effect Chinese Medicine guide, 2010, (8); Xing Xiaohua etc., Calculus Bovis Fructus Alpiniae Oxyphyllae soup treatment phlegm-fire is held stasis of blood type cerebral arteriosclerosis 50 examples under the arm. the Shaanxi traditional Chinese medical science, 2009, (10); Imperial court's rosy clouds etc., Calculus Bovis relieve dizziness, high fever, infantile convulsions, epilepsy, etc. granule to the influence of acute apoplexy serum NSE research. combination of Chinese and Western medicine cardiovascular and cerebrovascular disease magazine, 2008, (2); Zhao Yanhong etc., the pharmacological action of Calculus Bovis and succedaneum thereof and clinical practice. institute of Military Medical Science Institute periodical, 2007, (2); Liu Chengde etc., the pharmacological action of Calculus Bovis and clinical practice overview. Chinese medicine information, 2006, (6))
Moschus belongs to the Chinese medicine of aromatic and inducing resuscitation, has the effect of blood circulation promoting and blood stasis dispelling.Modern study shows that Moschus has two-way excitement of nervus centralis and inhibitory action, and in addition at antiinflammatory, aspects such as anoxia enduring also show very strong effect.Also reach to extensively at present in the application of treating cardiac and cerebral vascular diseases Moschus.(Luo Hailong, compound Moschus injection cooperate cerebral protective agent treatment acute cerebral infarction 59 routine Chinese experimental pharmacology of Chinese medical formulae magazines, 2011, (7). and class is bright female; Moschus and Borneolum Syntheticum and different proportioning thereof are to the influence of brain frostbite rat blood serum ET, NO. Pharmacology and Clinics of Chinese Materia Medica, 2011, (1). and Song Shuling; Edaravone associating compound Moschus injection treatment hemorrhage of brain stem clinical observation. Chinese tcm emergency, 2011, (2). money is firm; The observation of curative effect of compound Moschus injection auxiliary treatment severe hypertension cerebral hemorrhage. practical cardio-cerebral-pulmo angiopathy magazine, 2011, (1). woods is smooth; Compound Moschus injection treatment viral encephalitis of infant. Guangdong medical science, 2010, (13) .)
Also a lot of about the combination of the combination with medication of Calculus Bovis and Moschus clinically, such as the composition that Calculus Bovis and Moschus are just arranged in the cow-bezoar bolus for resurrection, also have preparations such as Moschus Calculus Bovis ball, all be the mutual compatibility of two medicines, in the treatment cerebrovascular, positive effect is arranged.(open luxuriant, Moschus Calculus Bovis pill reason effect experimentation. the Shanxi traditional Chinese medical science, 2003; (3). Liu Yuanxin, cow-bezoar bolus for resurrection is to the influence of spontaneous hypertensive rat acute cerebral hemorrhage associated with hydrocephalus and neurologic impairment. Chinese Chinese medicine magazine, 2011; (3). Han Shouying, the application of cow-bezoar bolus for resurrection in acute cerebral infarction is rescued, Chinese Medicine guide; 2010, (19). early winter prunus mume (sieb.) sieb.et zucc., 'An Gong Niu Huang Wan ' pill for curing hemorrhagic apoplexy history and present situation. Hunan University of Traditional Chinese Medicine's journal; 2009, (8). Luo Qingyun. the acute apoplexy 32 routine observation of curative effect of 'An Gong Niu Huang Wan ' pill for curing. Chinese national folk medicine; 2009, (10) .) these kinds are applied to the treatment of cerebrovascular, have obtained certain achievement.But these compound recipes can not satisfy clinical needs far away.
Existing clinically compound recipe; Mostly be to form according to the dialectical of the traditional Chinese medical science, some big compound recipes are very complicated, often comprised tens of kinds medicine; Be difficult to carry out Study on Modernization, say nothing of its composition is carried out careful research or produced on a large scale.And that the combination of existing simple two kinds of medicines often can not be satisfied is different classes of, the disease of multiple complications.On this basis; We have studied and in the medicine of " Calculus Bovis+Moschus " two kinds of animal origins, have added the natural medicinal plants that cerebrovascular is had positive role, and can in these drug regimens, seek with it has more for numerous diseases that the medicine of positive role newly makes up.
Our compositions is not the combination of the Chinese medicine effective ingredient on the simple meaning, but the combination of the active component of these medicines, these are combined in the compound preparation process possibly possibly be the change of physical property, also possibly be the change on the chemical constitution.Such as changing the dissolved state of medicine, dispersion has perhaps changed the structure of medicine, has formed new chemical compound.In the reactive systems of original medicine, added new active constituents of medicine,, in the combination of medicine, one do not worked, possibly just not have positive effect though be same composition.
The present invention adds medicine such as the Radix Salviae Miltiorrhizae that cerebrovascular disease is had positive role from the basis of " Calculus Bovis+Moschus ", Radix Notoginseng, and Semen Ginkgo etc. are studied various drug regimens.Through combination research, seek safe and effective medicine combination more to them.
Summary of the invention
The object of the invention is the combination that " Calculus Bovis+Moschus+amount of component b " with synergistic function is provided, be mainly used in the treatment with or the prevention of brain angiopathy, comprise ischemic, hemorrhagic brain injury, apoplexy and its sequela.
Medicine in the present invention can be selected medicine directly to pulverize to beat powder to be used as medicine, and extract or other form that also can select to be equivalent to the identical raw medicinal herbs amount of medicine is as will.Therefore drug regimen medicine of the present invention comprises the former powder of medical material, fat-soluble or water solubility extract, and effective ingredient or monomer are perhaps taked other goods form in the existing technology.For example described active component comprises:
A. Moschus: be meant natural or the artificial Moschus, perhaps contain the Moschus extract of muscone, androsterone, perhaps the muscone monomer;
B. Calculus Bovis: natural Calculus Bovis, perhaps contain the artificial Calculus Bovis of cholic acid, deoxycholic acid and chenodeoxycholic acid, bilirubin, taurine, perhaps for containing cholic acid, deoxycholic acid, the Calculus Bovis extract of taurine etc., perhaps taurine monomer.Calculus Bovis material of the present invention is not to be only to be the Calculus Bovis source, cholic acid class wherein, and chenodeoxycholic acid, bilirubinoid, taurine etc. all belong to useful composition.The Calculus Bovis component cpd that it will be understood by those skilled in the art that other source also can be realized the present invention.
A kind of among the following c1-c6 of said active component c:
C1. Radix Notoginseng refers to contain the ginsenoside, arasaponin, Radix Notoginseng total flavones, the Radix Notoginseng extract of Radix Notoginseng flavone A, Radix Notoginseng flavone B, volatile oil, alkaloid isoreactivity composition, or Radix Notoginseng flavone monomer extremely derivant or these monomeric mixture;
C2. Rhizoma Chuanxiong refers to contain the Rhizoma Chuanxiong extract of ligustrazine, chuanxingol, ferulic acid, volatile oil isoreactivity composition, or ligustrazine monomer and derivant thereof and or ferulic acid monomer and derivant thereof, or these monomeric mixture;
C3. Radix Paeoniae refers to contain Radix Paeoniae (Radix Paeoniae Rubra, the Radix Paeoniae Alba) root powder extracts, contains the chemical compound of Radix Paeoniae Alba total glycosides, perhaps the monomer of peoniflorin, the perhaps monomeric mixture of this type;
C4. Flos Carthami contains the Flos Carthami extract of Flos Carthami total flavochromes, and safflower yellow A, B monomer be derivant extremely, or the monomeric mixture of this type;
C5. Radix Salviae Miltiorrhizae, mainly contain salvia miltiorrhiza tanshinoate with or the Radix Salviae Miltiorrhizae extract of TANSHINONES; Or the Radix Salviae Miltiorrhizae water extract, or the salvia miltiorrhiza tanshinoate monomer with and pharmaceutical salts, or salvianolic acid monomer mixture; Or TANSHINONES monomer and pharmaceutical salts (like sodium sulfonate) thereof, or the TANSHINONES monomer mixture (as, TANSHINONES 1, TANSHINONES 2-A, TANSHINONES 2-B etc.), or the TANSHINONES monomer mixture;
C6. Semen Ginkgo, mainly refer to contain bilobalide with or the Semen Ginkgo extrac of ginkgetin.The Semen Ginkgo water extract, or ginkgolide monomer, bilobalide derivant, chemical modification object, analog (bilobalide-A, bilobalide-B, two obedient lactones, sesquialter lactone etc.) with and pharmaceutical salts, or the monomer mixture of bilobalide and or derivatives thereof; Or ginkgetin (ginkgetin and glycosides thereof, Ginkgo total flavones and glycosides thereof, bisflavone, catechin etc.) monomer, ginkgetin derivant, chemical modification object, analog and pharmaceutical salts thereof and or the monomer mixture of ginkgetin and its derivant; Or ginkgolide monomer and or the monomeric mixture of ginkgetin.
The composition of above-mentioned c1-c2; All very general be applied to clinical cerebrovascular disease; The pharmacological action of its active component also all gets the nod clinically, and same extraction and preparation for these monomers or mixture also all are the technology of using always, very general application.But when going to investigate for the viewpoint of " Calculus Bovis+Moschus+c component " that we proposed; Do not find to have any research about this drug regimen; Have clinically and comprise this three kinds of compositions in prescription or the drug regimen; Or even the composition of all c classes, but do not study the independent research of going textual criticism " Calculus Bovis+Moschus+c active component ".
We select c1-c6 totally six components from " Calculus Bovis+Moschus+c active component ", make up the advantage of investigating this type combination as six different drug, see and whether can play useful effect.
In drug regimen of the present invention, the medicament contg of each component is:
Component a, 5-40, preferred 10-40, more preferably 20-40 weight portion;
Components b, 1-20, preferred 2-15, more preferably 5-10 weight portion;
Amount of component b, 5-100, preferred 10-80, more preferably 20-80 weight portion.
Preparation in view of above-mentioned effective ingredient; Purification with remove technology such as impurity unusual maturation; And existing monomer can carry out chemosynthesis completely (like ginkalide B, TANSHINONES 2-A sodium sulfonate etc.) so these have not just done detailed introduction about technology of preparing.
Can wait to the interior absorption characteristics of physicochemical property activity relationship, body of above-mentioned active component and carry out effective preparation; Can add adjuvant and be prepared in the intestinal of multiple dosage form or form of administration (like tablet, oral cavity disintegration tablet, dispersible tablet, slow controlling agent, injection, powder pin, nanometer formulation etc.) in the non-intestinal, about the also suitable maturation of preparation technique.
Beneficial effect
According to drug regimen of the present invention, form by the active component of 10-90wt.% and the acceptable accessories of 90-10wt.%, on the drug regimen of Calculus Bovis+Moschus, added multiple medicinal plants combination, controlling
Treat in the cerebrovascular disease (comprising cerebral thrombosis, cerebral ischemia, cerebral infarction, traumatic brain injury etc.), have than the significant more curative effect of original medicine.
Specific embodiment
The therapeutical effect of 1. pairs of cerebral ischemia of embodiment
A, material
Pharmaceutical composition A of the present invention (Calculus Bovis+Moschus+sodium tanshinone IIA sulfate 3: 2: 5,5,10,20mg/kg injection)
Pharmaceutical composition B of the present invention (Calculus Bovis+Moschus+bilobalide 3: 1: 6,5,10,20mg/kg injection)
Blank group: normal saline
Positive controls: bovine bezoar injection liquid, muscone injection, bilobalide injection 5mg/kg, sodium tanshinone IIA sulfate injection 5mg/kg
B, method
96 of cleaning level male SD rats, body weight 250-300g, adopt internal carotid artery line bolt legal system to be equipped with intraluminal middle cerebral artery occlusion in rats obturation (MCAO) model: the isolated from rat internal carotid artery, to make a call to one with silk thread at the external carotid artery root and release, folder closes common carotid artery and internal carotid artery.Fishing line (long 40mm, diameter 0.26mm) through external carotid artery trunk otch, is slowly gone into the cranium direction to internal carotid artery and advanced, reach in the anterior cerebral artery, all blood of having blocked MCA supply the source to cause MCAO to cause focal cerebral ischemia-re-perfusion model.Behind the sham operated rats rat anesthesia, only expose the inside and outside aortic bifurcation of neck, not inaccessible MCA.Animal is divided into 12 groups, be respectively sham operated rats, ischemia model matched group, positive controls, receive reagent high (20mg/kg), in (10mg/kg), low dose group (5mg/kg), 8 every group.Each group is respectively at the multiple back 3h drug administration by injection of irritating, and every 24h is administered once, successive administration 3 times, and 24h detects each item index after the last administration.
Respectively at 24h after the last administration function of nervous system's defective of animal is carried out rank scores, standard is following:
0 minute: do not observe nervous symptoms;
1 minute: carry tail when unsettled, the operation offside forelimb of animal showed as wrist elbow flexing, the shoulder inward turning, and the elbow abduction is close to thoracic wall;
2 minutes: animal is placed on the smooth flat, and pushing hands art side was takeed on to side shifting the time, and resistance reduces;
3 minutes: side ring is changeed or turn-take to operation during the animal walking freely;
4 minutes; Collapse from physical exhaustion, limbs do not have spontaneous activity;
After These parameters was measured, the sacrificed by decapitation rat was taken out full brain and weighs, the preparation brain sections, and pale district (infarct) and non-pale district (normal area) are separated with the ophthalmology tweezer in the back, and it is following to calculate infraction percentage ratio:
Infraction percentage ratio (%)=pale district weight/(pale district weight+non-pale district weight) * 100%
C, result
Experimental result is seen table 1:
The influence of focal cerebral ischemia rat nerves behavior due to table 1 pharmaceutical composition is irritated MCAO again, cerebral infarction rate (
n=8)
* p＜0.05, * * p＜0.01 vs. model control group
After MCAO ischemia 2h pours into 3h again, begin gastric infusion, every 24h is administered once, successive administration 3 times; Compare with model control group, drug regimen A 20mg/kg, 10mg/kg dose groups can obviously be improved animal nerve and learn scoring, reduce the cerebral infarction rate; Significant difference (p＜0.01, p＜0.05), and the effect of high dose group will obviously surpass sodium tanshinone IIA sulfate; Calculus Bovis, Moschus uses separately; Drug regimen B 20mg/kg, 10mg/kg dose groups can obviously be improved animal nerve and learn scoring, reduce the cerebral infarction rate, significant difference (p＜0.01, p＜0.05), and the effect of high dose group will obviously surpass bilobalide, Calculus Bovis, and Moschus uses separately.
The anoxybiotic effect of 2. pairs of anti-cerebral ischemias of mice of embodiment
A, material
Pharmaceutical composition A of the present invention (Calculus Bovis+Moschus+arasaponin 3: 2: 5,10,20,40mg/kg irritates stomach)
Pharmaceutical composition B of the present invention (Calculus Bovis+Moschus+ligustrazine 2: 1: 7,10,20,40mg/kg irritates stomach)
Blank group: normal saline
Positive controls: Calculus Bovis, Moschus, arasaponin 20mg/kg, ligustrazine 20mg/kg
B, method
Acute cerebral ischemia property anoxia experiment is divided into 11 groups at random with 110 mices, be respectively ischemia model matched group, positive controls, receive reagent high (40mg/kg), in (20mg/kg), low dose group (10mg/kg), 10 every group.Each organizes mice continuous irrigation stomach 10d, 1h after last is irritated stomach, and each organizes mouse peritoneal injection NaNO2 solution (mass concentration 25%) 250mg/kg.Record begins to dead time, record mice time-to-live from the injection sodium nitrite.
C, result
Result of the test is seen table 2:
Table 2 pharmaceutical composition is to the influence (
n=10) of mouse brain ischemic anoxia
* p＜0.05, * * p＜0.01 vs. model control group
Visible by last table; After gastric infusion 10d; The time-to-live of mice behind the observation injection sodium nitrite; Find all can prolong the time-to-live of mice significantly, significant difference (p＜0.01, p＜0.05) is arranged on the statistics with model control group comparative drug combination A and pharmaceutical composition B senior middle school dose groups.And effect obviously will surpass Radix Notoginseng, ligustrazine, and Calculus Bovis, Moschus uses separately.It is thus clear that drug regimen is having positive effect aspect the anti-mouse brain anoxia, drug regimen A and B can play the effect of Synergistic.
Embodiment 3. anti-electrocoagulations are induced the thrombosis effect
A. material
Pharmaceutical composition A of the present invention (Calculus Bovis+Moschus+Carthamus yellow 3: 1: 6,5,10,20mg/kg injection)
Pharmaceutical composition B of the present invention (Calculus Bovis+Moschus+bilobalide 5: 2: 3,5,10,20mg/kg injection)
Blank: normal saline
Positive control: Calculus Bovis, Moschus, Carthamus yellow 10mg/kg, bilobalide 10mg/kg
B. method
Rat tail vein injectable drug combination A, the continuous 3d of B once a day, inject 1h for the last time after, rats by intraperitoneal injection 12% chloral hydrate 350mg/kg anesthesia, dorsal position is fixed.Cervical region median line otch, free left carotid, proximal part is placed the stimulating electrode that the experimental thrombus in vivo of BT87-3 type forms analyzer, distal end laying temperature probe.After the stimulating electrode turn-on current, owing to causing blood vessel injury, heating effect of current forms thrombosis, and the current intensity of stimulation is 2mA, continued stimulus 5min; Distal end temperature decrease when thrombosis, temperature probe can be measured its temperature shock, be the blood vessel bolt close the time this moment, from begin to stimulate to required time of temperature decrease as artery thrombosis time (s)
Measurement index: the mensuration of TFT
Record is from beginning to stimulate interval to arterial distal temperature bust as the artery thrombosis time.
C. result
The TFT (* p＜0.05, * * p＜0.01) visible by table 3, that injectable drug combination A, B can prolong rats, visible drug regimen can play antithrombotic effect; Wherein the effect of drug regimen B obviously will exceed bilobalide separately as the effect of positive drug.And the effect of drug regimen A is with the use Carthamus yellow is suitable separately.Being illustrated in antithrombotic formation aspect drug regimen B has the effect above the single medicine, explains that Calculus Bovis+Moschus+bilobalide can play the effect of Synergistic in this combination.
The external protective effect of embodiment 4. drug regimens to the inductive neural cell injury of anoxia reoxygenation
A. material
Pharmaceutical composition A of the present invention (Calculus Bovis+Moschus+Carthamus yellow 2: 3: 5)
Table 3 pharmaceutical composition is induced the thrombotic influence of rat carotid artery (
n=10) to electrocoagulation
* p＜0.05, * * p＜0.01 vs. model control group
Pharmaceutical composition B of the present invention (Calculus Bovis+Moschus+bilobalide 2: 2: 6)
Pharmaceutical composition C of the present invention (Calculus Bovis+Moschus+ligustrazine 2: 2: 6)
Pharmaceutical composition D of the present invention (Calculus Bovis+Moschus+arasaponin 2: 2: 6)
Blank: normal saline
Positive control: Calculus Bovis+Moschus, bilobalide
B. method
Former primary cultures of rat cerebral cortex neurocyte is divided into 4 groups (every group 6 holes) at random with the rat cerebral cortex neurocyte of cultivating 10d.Normal group: do not add processing; Model group: change culture fluid, place 37 ℃, 5% CO2 nitrogen anoxia jar to lack sugar/anoxia and cultivate 4h, put back to reoxygenation 14h in 37 ℃, 5% CO2 incubator again with sugar-free Earles; Drug regimen: changing with drug compositions A, B, C, D final concentration is the sugar-free Earles culture fluid of 1g/L, places 37 ℃, 5% CO2 nitrogen anoxia jar to lack sugar/anoxia and cultivates 4h, puts back to reoxygenation 14h in 37 ℃, 5% CO2 incubator then; Matched group: changing to contain Calculus Bovis+Moschus, bilobalide, ligustrazine, arasaponin final concentration is the sugar-free Earles culture fluid of 0.5g/L; Place 37 ℃, 5% CO2 nitrogen anoxia jar to lack sugar/anoxia and cultivate 4h, put back to reoxygenation 14h in 37 ℃, 5% CO2 incubator then.
C. result
Table 4 pharmaceutical composition is induced the influence (
n=6) of former generation neuronal apoptosis to the anoxia reoxygenation
*＜0.05, * * p＜0.01 vs. model control group
By the visible drug regimen A of table 4, B, D can effectively protect because the anoxia reoxygenation cause former generation neurocyte apoptosis (* p＜0.05; * p＜0.01); Wherein, show effectively neuroprotective cell of this drug regimen with the best results of Calculus Bovis+Moschus+bilobalide group.
The inductive platelet aggregation effect of embodiment 5. anti-ADP
A. material
Pharmaceutical composition A of the present invention (Calculus Bovis+Moschus+peoniflorin 3: 1: 6)
Pharmaceutical composition B of the present invention (Calculus Bovis+Moschus+ligustrazine 2: 2: 6)
Blank: normal saline
Positive control: Calculus Bovis+Moschus, ligustrazine, peoniflorin
B. method
Blank rat is used procaine local anesthesia; The blood-letting of carotid artery intubate, the anticoagulant in 1: 9 of 3.8% sodium citrate is with the centrifugal 10min of 800r/min; Get platelet rich plasma (PRP); Remainder is got platelet poor plasma (PPP) with the centrifugal 10min of 3000r/min, and the aggregation inducing agent is with ADP (final concentration 30 μ mol/L) and TXA2 (final concentration 10 μ mol/L).Add the medicine PPP30ul that contains variable concentrations among the blank P of Rats RP of every pipe 270 μ l, add normal saline 30ul among the matched group PRP, incubation 3min adds ADP then and induces gathering, detects the platelet maximum agglutination rate with LG-PABER-1 type platelet aggregation instrument.
Calculate platelet aggregation inhibition rate by following formula:
C. result
The inductive platelet aggregation effect of the external anti-ADP of table 5 drug regimen (
n=10)
* p＜0.05, * * p＜0.01 vs. model control group
Visible by table 5; This pharmaceutical composition A, B can the inductive platelet aggregation of effective anti-ADP (* p＜0.05*; * p＜0.01) and the effect of compositions aspect antiplatelet of medicine to surpass the medicine of matched group, explain that this drug regimen also has unique effect aspect antiplatelet.
The preparation of embodiment 6. preparation prescriptions
Get natural Calculus Bovis 6g and be ground into fine powder and 2g Moschus, also have the ginkalide B of 10g, add low-substituted hydroxypropyl cellulose, magnesium stearate, starch, microcrystalline Cellulose, prepare 1000 according to standard granulation and tablet forming technique.
The preparation of embodiment 7. preparation prescriptions
Get peoniflorin 5g, natural Calculus Bovis 10g, the CO2 supercritical extract 3g of Moschus with the glycerol mixing, becomes 1000 of soft capsules according to the prepared of the preparation soft capsule of standard.
The preparation of embodiment 8. preparation prescriptions
Material: natural Calculus Bovis 8g is ground into fine powder, the CO2 supercritical extract 5g of Moschus, Radix Salviae Miltiorrhizae extract 20g, adjuvant PEG6000.
Get PEG6000, put in the micro beaker, in water-bath, be heated to fusing, add natural Calculus Bovis 8g again and be ground into fine powder; The CO2 supercritical extract 5g of Moschus, Radix Salviae Miltiorrhizae extract 20g stirs, and moves into rapidly in the dropper of 80 ℃ of insulations; Open the dropper switch, drop splashes into becoming ball in the ice-cooled liquid paraffin naturally, drips and finishes; Placed 0.5 hour, filtering coolant, drop pill place in the absorbent paper; The liquid paraffin on absorption drop pill surface (available in case of necessity ethanol or ether washing) is wiped only, dries naturally promptly to get in 10 minutes.1000 of preparation drop pill.
The preparation of embodiment 9. preparation prescriptions
Get natural Calculus Bovis 20g, Moschus CO2 supercritical extract 5g (be prepared into cyclodextrin clathrate and get 20g), Carthamus yellow 20g and aspartame, Fructus Citri Limoniae essence, magnesium stearate were mixed 100 mesh sieves.Add cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, cross 100 mesh sieves behind the mixing, tabletting makes 1000.
The preparation of embodiment 10. preparation prescriptions
Get natural Calculus Bovis 30g; Moschus CO2 supercritical extract 8g (be prepared into cyclodextrin clathrate and get 25g); Arasaponin extract 40g uniform mixing adds lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, magnesium stearate, polyethylene pyrroles, mixes 100 mesh sieves.Tabletting makes 1000.
The preparation of embodiment 11. freezing-dried powder injections
The concrete prescription as follows:
Manufacture method:
(1) get the CO2 supercritical extract 15g of natural Calculus Bovis and the CO2 supercritical extract 2g of Moschus, add polyoxyethylene sorbitan monoleate, uniform mixing adds HP-again, and ultrasonic agitation enclose 3 hours obtains clathrate.
(2) ligustrazine 20g adds water for injection 900ml, the stirring and adjusting pH value
(3) above-mentioned (1) gained clathrate is added in (2), add mannitol then, add water for injection to 1L.
(4) activated carbon adsorption, carbon removal is filtered, through 0.22 μ m water system membrane filtration
(5) canned ,-20 ℃ down freezing, drying under reduced pressure obtains finished product.
The preparation of embodiment 12. injectable emulsions
Get the water extract 8g of natural Calculus Bovis, the CO2 supercritical extract 10g of Moschus adds propylene glycol, glycerol, makes clarification, is heated to 60 ℃ and keep constant, obtains water.Get bilobalide, emulsifying agent phospholipid, add adequate amount of ethanol and make it dissolving, add Oleum Glycines, VE, be heated with stirring to 60 ℃, obtain oil phase.
Under constant temperature stirs, water is added drop-wise in the oil phase slowly, dropwise the back and add homothermic distilled water standardize solution, continue to stir 15min and obtain colostrum.Cross homogenize behind the 0.8 μ m filter membrane, cross 0.22 μ m filter membrane, promptly get.
Claims (4)
1. a drug regimen comprises the active component of 10-90wt.% and the acceptable accessories composition of 90-10wt.%, and described active component is:
A. Calculus Bovis, natural Calculus Bovis or contain the artificial Calculus Bovis of cholic acid, deoxycholic acid and chenodeoxycholic acid, bilirubin, taurine, the 10-50 weight portion;
B. Moschus, the muscone monomer perhaps contains the Moschus extract of muscone, androsterone, 5-20 weight portion;
C. from following c1-c6 kind, choose the 10-80 weight portion:
C1. Radix Notoginseng refers to contain the ginsenoside, arasaponin, Radix Notoginseng total flavones, the Radix Notoginseng extract of Radix Notoginseng flavone A, Radix Notoginseng flavone B, volatile oil, alkaloid isoreactivity composition, or Radix Notoginseng flavone monomer extremely derivant or these monomeric mixture;
C2. Rhizoma Chuanxiong refers to contain the Rhizoma Chuanxiong extract of ligustrazine, chuanxingol, ferulic acid, volatile oil isoreactivity composition, or ligustrazine monomer and derivant thereof and or ferulic acid monomer and derivant thereof, or these monomeric mixture;
C3. Radix Paeoniae refers to contain the Radix Paeoniae Alba extract of Radix Paeoniae Alba total glycosides, peoniflorin, lactone glucoside of Radix Paeoniae, and perhaps peoniflorin is monomeric;
C4. Flos Carthami contains the Flos Carthami extract of Flos Carthami total flavochromes, and safflower yellow A, B monomer be derivant extremely, or the monomeric mixture of this type;
C5. Radix Salviae Miltiorrhizae, mainly contain salvia miltiorrhiza tanshinoate with or the Radix Salviae Miltiorrhizae extract of TANSHINONES; Or the Radix Salviae Miltiorrhizae water extract, or the salvia miltiorrhiza tanshinoate monomer with and pharmaceutical salts, or salvianolic acid monomer mixture; Or TANSHINONES monomer and pharmaceutical salts thereof, or the TANSHINONES monomer mixture, or TANSHINONES and salvia miltiorrhiza tanshinoate monomer mixture;
C6. Semen Ginkgo, mainly refer to contain bilobalide with or the Semen Ginkgo extrac of ginkgetin.The Semen Ginkgo water extract, or ginkgolide monomer, bilobalide derivant, chemical modification object, analog with and pharmaceutical salts, or the monomer mixture of bilobalide and or derivatives thereof; Or ginkgetin monomer, ginkgetin derivant, chemical modification object, analog and pharmaceutical salts thereof and or the monomer mixture of ginkgetin and its derivant; Or ginkgolide monomer and or the monomeric mixture of ginkgetin.
2. pharmaceutical composition as claimed in claim 1, said active component is:
Calculus Bovis, the Calculus Bovis that contains cholic acid, deoxycholic acid and chenodeoxycholic acid, bilirubin, taurine is carried
A. get thing, the 10-50 weight portion;
B. Moschus has the Moschus extract of muscone, androsterone, 5-20 weight portion;
C.10-80 weight portion is selected from the active component of following c1-c6:
C1. contain arasaponin, ginsenoside and or the Radix Notoginseng extract of Radix Notoginseng flavone;
C2. the Rhizoma Chuanxiong extract that contains ligustrazine, ferulic acid;
C3. contain peoniflorin with or the Radix Paeoniae Alba extract of peony lactone;
C4. the Flos Carthami extract that contains Carthamus yellow;
C5. contain salvia miltiorrhiza tanshinoate with or the Radix Salviae Miltiorrhizae extract of TANSHINONES;
C6. bilobalide with or the Semen Ginkgo extrac of ginkgetin.
3. like the pharmaceutical composition of one of claim 1-3, wherein said active component is:
A. taurine, the 10-50 weight portion;
B. muscone, the 5-20 weight portion;
C. be selected from following c1-c6, the 10-80 weight portion:
C1. the Radix Notoginseng water extract that contains arasaponin;
C2. ligustrazine monomer and derivant thereof;
C3. the Radix Paeoniae water extract that contains peoniflorin;
C4. safflower yellow A, B monomer, and both mixture;
C5. salvia miltiorrhiza tanshinoate with or the TANSHINONES monomer, and or derivatives thereof, or these monomeric mixture;
C6. ginkgolide monomer.
The treatment with or the prevention of brain angiopathy, comprise ischemic, hemorrhagic brain injury, apoplexy and its sequela.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101159539A CN102764280A (en) | 2011-05-06 | 2011-05-06 | Bezoar and musk containing pharmaceutical composition and its application |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101159539A CN102764280A (en) | 2011-05-06 | 2011-05-06 | Bezoar and musk containing pharmaceutical composition and its application |
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| Publication Number | Publication Date |
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| CN102764280A true CN102764280A (en) | 2012-11-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2011101159539A Pending CN102764280A (en) | 2011-05-06 | 2011-05-06 | Bezoar and musk containing pharmaceutical composition and its application |
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| CN109985047A (en) * | 2017-12-29 | 2019-07-09 | 广州市赛普特医药科技股份有限公司 | Application of -3 beta, 5,6 beta-triol of 5 α-androstane in preparation treatment hemorrhagic apoplexy drug |
| CN112717104A (en) * | 2021-02-23 | 2021-04-30 | 王江涛 | Ointment for treating apoplexy and preparation method thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017004282A1 (en) * | 2015-06-29 | 2017-01-05 | Takasago Internation Corporation (Usa) | Musk compositions and methods of use thereof |
| WO2017004281A1 (en) * | 2015-06-29 | 2017-01-05 | Takasago International Corporation (Usa) | Musk composition and methods of use thereof |
| CN107864620A (en) * | 2015-06-29 | 2018-03-30 | 高砂香料工业株式会社 | Moschus composition and its application method |
| US10988706B2 (en) | 2015-06-29 | 2021-04-27 | Takasago International Corporation | Musk compositions and methods of use thereof |
| US11820961B2 (en) | 2015-06-29 | 2023-11-21 | Takasago International Corporation | Musk compositions and methods of use thereof |
| CN109985047A (en) * | 2017-12-29 | 2019-07-09 | 广州市赛普特医药科技股份有限公司 | Application of -3 beta, 5,6 beta-triol of 5 α-androstane in preparation treatment hemorrhagic apoplexy drug |
| CN112717104A (en) * | 2021-02-23 | 2021-04-30 | 王江涛 | Ointment for treating apoplexy and preparation method thereof |
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Application publication date: 20121107 |