CN1846740A - Medicine composition containing borneol and musk - Google Patents
Medicine composition containing borneol and musk Download PDFInfo
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- CN1846740A CN1846740A CNA2006100579486A CN200610057948A CN1846740A CN 1846740 A CN1846740 A CN 1846740A CN A2006100579486 A CNA2006100579486 A CN A2006100579486A CN 200610057948 A CN200610057948 A CN 200610057948A CN 1846740 A CN1846740 A CN 1846740A
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Abstract
The present invention relates to medicine composition, and is especially medicine composition containing developed based on modern medicine theory and containing natural plant materials or their extract. The medicine contains mainly borneol, musk and Chinese peony. It is used in treating coma, cardiac and cerebral vascular diseases, senile dementia, diabetes and other diseases.
Description
Technical field
The present invention relates to pharmaceutical composition, specifically, is to contain Borneolum Syntheticum and Moschus and natural plant extracts or monomeric Pharmaceutical composition and application thereof according to modern medical theory development.
Background technology
Borneolum Syntheticum is divided into natural Broneolum Syntheticum and synthetic borneol two big classes.Wherein, borneol is mainly dextro Borneolum Syntheticum, is the certified products in the Borneolum Syntheticum, and Blumeae preparatum Tabellae is mainly left-handed Borneolum Syntheticum, and synthetic borneol also contains the epimer isoborneol of a large amount of Borneolum Syntheticum except that containing Borneolum Syntheticum.Moschus also is divided into natural and synthetic two classes, owing to the restriction of rules, that most uses is the artificial Moschus in the medicine at present, and main component is (Liu Yangfeng such as glycoprotein, cholesterol such as muscone, androsterone, Moschus-1, Chinese medicine journal 2003,31 (6): 55-58; He Xiaojing, West China pharmaceutical journal 2005,20 (4): 323-325; Shandong medical industry 2002,21 (1): 26-27; Hour hands traditional Chinese medical science traditional Chinese medicines 2004,15 (4) 4248-249; New Chinese medicine and clinical pharmacology 2000,11 (4): 208-255).
Borneolum Syntheticum, Moschus are all the representative medicine commonly used of aromatic and inducing resuscitation Chinese medicine, and different with Borneolum Syntheticum is that Moschus also has stronger central nervous system's excitement and suppresses pharmacologically actives such as amphicheirality's effect, resisting oxygen lack, cardiac vascular activity, antiinflammatory action.At present, the application (especially cardiovascular and cerebrovascular disease) clinically of Borneolum Syntheticum and/or Moschus is very extensive, and for example compound Salviae Miltiorrhizae class, storax pill for treating coronary heart disease, cow-bezoar bolus for resurrection, HUATUO ZAIZAO WAN, refreshment wait all containing Borneolum Syntheticum and/or Moschus quietly.At this quasi-tradition Cheng Fangzhong, utilized the effect of Borneolum Syntheticum " fragrance is walked to scurry, priming up ", " gesture then of walking alone is weak, assistant make then meritorious " more, increase the therapeutic effect of other drug as " guiding drug ", simultaneously, utilize the effect of Moschus " fragrance is walked to scurry, inducing resuscitation (see through blood brain barrier) " again, produce " returning " effect through going into brain.
For many years, many scholars have done extensive work based on modern medical theory to the aspects such as pharmacodynamics, pharmacokinetics and safety of Borneolum Syntheticum and Moschus, have obtained many new developments.Rely on these progress, scholars are attempting with Borneolum Syntheticum and/or Moschus and the combination of other active component, in the hope of obtaining better curative effect.For example, ZL03110967.5, ZL200310105455.1, (Jilin University's journal (medicine) 2004 such as Zhao Hongmei, 30 (3): 393-395), (2004 26 volumes of Chinese patent medicine supplementary issue: 13-16) such as Lin Jiayi, (1998 17 volumes (9) of Shandong journal of Chinese medicine: 404-405) such as Nie Youzhi, Li Xiangxin (2004 13 19 phases of volume of modern combination of Chinese and Western medicine magazine: 2541-2542), (2002 19 1 phases of volume of Shenyang Pharmaceutical University's journal: 41-42) such as Zhang Li, (2004 21 volumes of Traditional Chinese Medicine University Of Guangzhou's journal, 5 phases: 382-384 such as Yu Shangzhen, (Jilin Chinese medicine 6 phases of calendar year 2001: 34) such as Xue Yafeng, (1999 30 5 phases of volume of Jiangxi Chinese medicine: 9-10) such as Chen Su, and the side's of one-tenth Moschus is rather felt at ease, XINGNAOJING ZHUSHEYE etc., be widely used in the treatment of cardiovascular and cerebrovascular disease, all obtained certain achievement.
Yet above-mentioned compound recipe can not satisfy demand clinically far away.On the one hand, existing compound recipe is normally formed by the principle of " determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs ", and this is for the pathogenesis complexity, with the disease of different classes of complication, existingly contains Borneolum Syntheticum and the Moschus compound preparation is difficult to multi-faceted proving effective.More crucial is, these big compound medicine compositions are too complicated, and the interaction between each composition is not clear, does not meet the trend of modern medicines, the homogeneity that is difficult to ensure the quality of products.
In previous work, we had once carried out careful research to " Borneolum Syntheticum+Radix Paeoniae ", had found useful effect: the combination of Radix Paeoniae and Borneolum Syntheticum can obviously strengthen the inherent pharmacological action of Borneolum Syntheticum, has also reduced the toxicity of Borneolum Syntheticum simultaneously.Making us beat all is, when Borneolum Syntheticum or Radix Paeoniae were made up with other active component (for example Radix Salviae Miltiorrhizae) respectively, the combination of " Borneolum Syntheticum+Radix Salviae Miltiorrhizae " or " Radix Paeoniae+Radix Salviae Miltiorrhizae " did not all have " Borneolum Syntheticum+Radix Paeoniae+Radix Salviae Miltiorrhizae " effect of Combination.This shows, above-mentioned beneficial effect is not only to derive from Borneolum Syntheticum, promptly be not the effect of merely having utilized Borneolum Syntheticum in traditional compound recipe " fragrance is walked to scurry, priming up ", " gesture then of walking alone is weak, assistant make then meritorious ", but derive from " Borneolum Syntheticum+Radix Paeoniae " this basis combination.This discovery, also verified such inference to a certain extent, it is the summation that the material base of compound preparation is not only every kind of effective ingredient, and comprise the interaction of each composition in the compound preparation process, this interaction had both comprised that simple physics changed the chemical change that also comprises complexity, the interaction of various compositions can change the stripping character and the coherent condition of various compositions, even may take place to produce new material behind the chemical reaction.In other words, compound recipe effectiveness is the general performance of compound chemical component mutual relation under the specific effect condition, and some so-called active component leave the compound recipe condition then may not have obvious effect.
Consider above-mentioned inference, the result of study of relevant " Borneolum Syntheticum+Radix Paeoniae " may represented certain research tendency.Simultaneously, this result of study also is tempting, and it is reminding scholars very likely also to exist similarly other combinations.
The application attempts the combination that contains Borneolum Syntheticum, Moschus and Radix Paeoniae is studied, and in the hope of reducing dosage by adduction between them even synergism, thereby further reduces untoward reaction when guaranteeing (even raising) curative effect.Can be contemplated that there is urgent demand this area to this natural drug safely and effectively (combination).
Summary of the invention
The inventor has carried out deep exploration in this respect, and has obtained many gratifying results.
One object of the present invention is to provide the combination of Borneolum Syntheticum and Moschus and other active component, is used for the treatment of and/or prevents cardio-cerebrovascular diseases.
By a large amount of guiding tests, we tentatively determine to have such potential quality based on the medicine of Borneolum Syntheticum+Moschus+Radix Paeoniae.When attempt from prior art, to seek this bonded according to the time, we find: at Borneolum Syntheticum and/or Moschus can with the Radix Paeoniae use in conjunction, three's mechanism of action is underlying issues such as adduction, collaborative or antagonism, and prior art does not up to now provide scientific basis.Whether can unite with other active component as for the three, prior art does not similarly hint again.
In traditional medicine, extremely extensive to the clinical practice of ranunculaceae plant Radix Paeoniae, for example in " typhoid fever is sunk " pandect 112 sides, count 33 head with the Radix Paeoniae person, account for 1/3rd (Li Zhongnan, Anhui Chinese Medicine College journal 1992,11 (2): 52-53) of total number formulary.The modern plants chemistry is thought, Radix Paeoniae Rubra, Radix Paeoniae Alba chemical constituent basically identical, Radix Paeoniae Alba total glycosides wherein is a main active, has pharmacologically active widely, cardiovascular disease, senile dementia, diabetes, inflammation, tumor, hepatopathy etc. there is certain curative effect (Fourier sea, Anhui medicine 2002,6 (2): 62-63; Ruan Jinlan, Acta Pharmacologica Sinica 2003,19 (9): 695-670).
That has carried out studies show that, the combination of Radix Paeoniae and Borneolum Syntheticum, Moschus can obviously strengthen Borneolum Syntheticum and the inherent pharmacological action of Moschus, such as anti-cerebral ischemia reperfusion injury and protect, anti-inflammatory response effect etc.Surprisingly, three's combination has also reduced the toxicity of Borneolum Syntheticum, and this extensive use for further promotion Borneolum Syntheticum has realistic meaning.
Therefore, one object of the present invention is to provide " Borneolum Syntheticum+Moschus+Radix Paeoniae " with Synergistic and/or Attenuation combination.
In pharmaceutical composition of the present invention, can select flavour of a drug (for example Radix Paeoniae, Moschus, Borneolum Syntheticum) directly to be ground into powder and be used as medicine, extract or other forms that also can be equivalent to above-mentioned natural drug material crude drug amount are used as medicine.Therefore, the active component of pharmaceutical composition of the present invention comprises the former powder of medical material, fat or water solubility extract (or effective site) or effective ingredient or monomer, perhaps adopts existing other goods forms in the prior art.For example, described active component comprises:
A. Borneolum Syntheticum: be meant the processed goods of Borneolum Syntheticum resin or the crystallization that feverfew Herba Blumeae Balsamiferae leaf extracts, or be raw material, through the synthetic highly finished product of chemical method with Camphora, Lignum Pini Nodi wet goods.Comprise borneol (dextro Borneolum Syntheticum), Blumeae preparatum Tabellae (left-handed Borneolum Syntheticum), synthetic borneol (containing Borneolum Syntheticum and isoborneol).
B. Moschus: be meant natural or the artificial Moschus, or contain the Moschus extract of glycoprotein, cholesterol etc. such as muscone, androsterone and/or Moschus-1, or the muscone monomer.
C. Radix Paeoniae: be meant the dry root powder of Radix Paeoniae (Radix Paeoniae Alba, Radix Paeoniae Rubra, river Radix Paeoniae Rubra), contain the extract of Radix Paeoniae Alba total glycosides compounds (being preferably peoniflorin and lactone glucoside of Radix Paeoniae), or the peoniflorin monomer.In addition, studies show that the effective site that contains peoniflorin, lactone glucoside of Radix Paeoniae, Hydroxy peoniflorin, oxypaeoniflorin, benzoylpaeoniflorin, lacdtlorin, paeonol, the former glycosides of paeonol, Cortex Moutan phenolic glycoside, Radix Paeoniae aglycon etc. simultaneously also is useful.The source that it will be appreciated by persons skilled in the art that Radix Paeoniae glycoside of the present invention is not limited to Radix Paeoniae, and the other plant (for example Cortex Moutan) that contains the Radix Paeoniae glycoside also can be realized the present invention, and it extracts and preparation method is a known technology, does not give unnecessary details at this.
In combinations thereof, the content of Borneolum Syntheticum is not less than 1wt%.
Owing to compare with some existing plant amedica, Borneolum Syntheticum and Moschus combination lack the active function of (or being not so good as) blood vessel aspect, so based on above-mentioned achievement, we study " Borneolum Syntheticum+Moschus+Radix Paeoniae " and the probability of other active component combinations.According in the prior art to the understanding of Borneolum Syntheticum, we infer: the medicine in the serum not necessarily all can see through intravital various barriers, and the adding of Borneolum Syntheticum has promoted the penetrating blood brain barrier of other active components, and promptly Borneolum Syntheticum might increase the curative effect of other drug by the mode with " guiding drug ".
Therefore, except that above-mentioned three kinds of active component a, b, c, the present composition can also comprise Herba Erigerontis, can make the present composition have more comprehensive therapeutic effect by Herba Erigerontis.
In the test of carrying out subsequently, found very interesting phenomenon: the combination of " Moschus+Herba Erigerontis " or " Borneolum Syntheticum+Herba Erigerontis ", perhaps " Radix Paeoniae+Herba Erigerontis " all do not have the present invention's " Borneolum Syntheticum+Moschus+Radix Paeoniae+Herba Erigerontis " effect of Combination.This shows that the present invention's beneficial effect is not only to derive from Borneolum Syntheticum, but derives from " Borneolum Syntheticum+Moschus+Radix Paeoniae " this basis combination.
Therefore, another object of the present invention is to provide " Borneolum Syntheticum+Moschus+Radix Paeoniae+Herba Erigerontis " with Synergistic and/or Attenuation combination.
Wherein, described Herba Erigerontis is meant: the scutellarin monomer of the lower alcohol extraction thing of the herb powder of Herba Erigerontis (having another name called Herba Erigerontis), the water extract of Herba Erigerontis, Herba Erigerontis (containing scutellarin (being scutellarin), single and or the effective site of dicaffeoylquinic acid etc.), breviscapine (containing scutellarin, breviscapine and other flavones ingredients) or free or sodium-salt form.It will be understood by those skilled in the art that, the source of scutellarin of the present invention is not limited to Herba Erigerontis, the other plant (for example Radix Scutellariae, Herba Scutellariae Barbatae etc.) that contains scutellarin also can be realized the present invention, equally, single and or the source of dicaffeoylquinic acid also be not limited to Herba Erigerontis, such as coffee bean, these extract and preparation method is a known technology, do not give unnecessary details at this.
Advantageously, on the basis of the above-mentioned useful combination of the present invention, other active component that can also add 15-200, preferred 30-120 weight portion in the present composition, for example extract of Radix Salviae Miltiorrhizae (active component salvianolic acid and/or TANSHINONES), Flos Carthami (active component Flos Carthami total flavochromes), Radix Puerariae (active component Radix Puerariae total flavones and/or puerarin), Semen Ginkgo (active component bilobalide and/or ginkgetin), Rhizoma Chuanxiong (active component ligustrazine and/or ferulic acid) or Radix Ginseng (active component Radix Ginseng total saponins).It is pointed out that adopting these plant extract known activity compositions or corresponding monomeric technology is known technology, does not give unnecessary details at this.
In context, the related term " active component " of pharmaceutical composition of the present invention has above-mentioned definition.
In pharmaceutical composition of the present invention, each components contents is:
Component a, 1-15, preferred 2-10, more preferably 5-10 weight portion; With
Components b, 5-65, preferred 10-50, more preferably 15-45 weight portion; With
Amount of component b is counted 5-100, preferred 10-80, more preferably 20-60 weight portion with peoniflorin; With
Component d counts 5-100, preferred 10-80, more preferably 20-60 weight portion with scutellarin.
In addition, in context, " Moschus+Borneolum Syntheticum+Radix Paeoniae 5/1/15 " or " Moschus+Borneolum Syntheticum+Radix Paeoniae+oil lamp 5: 1: 2: 15 ", represent this three, the weight proportion of four kind of active component is 5: 1: 15 and 5: 1: 2: 15.
Following test will confirm: the combination with above-mentioned definition it " Borneolum Syntheticum ", Moschus, " Radix Paeoniae " and Herba Erigerontis according to the present invention describes has beneficial effect of the present invention.In view of the technology that had existed suitable maturation and the effective above-mentioned definition component of preparation/purification in the prior art already, do not make emphasis at this and describe.For example, can adopt modern the extraction and isolation technics, to improve the purity of active substance, remove unwanted impurity, for example: Chinese patent application ZL200410096958 as far as possible, ZL200410041752, ZL011103787, ZL021109737, ZL021332983, ZL031131263, ZL02156681X, ZL011301309, ZL2004100413049, ZL00120986, ZL2003101134541, ZL021179239, ZL02149694, ZL92108623, ZL00113019, ZL02153750X, ZL03117754, ZL03141616, JP2000247890A, GB2317613A, Chinese crude drug 2000 23 (6): 316-6, prolong limit medical college journal nineteen ninety-fives 18 volume (1): 73-78) etc.
Can be at absorption characteristics in the physicochemical property of said components and the body, adopt the standard preparation technology, add pharmaceutic adjuvant and make suitable for oral administration or parenterai administration dosage form, similar techniques is also quite effectively ripe, for example: oral cavity disintegration tablet (ZL2003101133322, ZL200310123852, ZL03102405, ZL200410016510, ZL200410041256), slow controlling agent (ZL011333332, ZL011387106, ZL02116223, ZL200310110709, ZL01117620, ZL02109758, ZL02116795, ZL02129313, ZL02134118, ZL03100021, ZL03133897), cyclodextrin clathrate (ZL01141436, ZL02108778, ZL200310125175,2002 37 volumes (9) of Chinese Pharmaceutical Journal: 673-75), solid dispersion (ZL001194313), injection (ZL001215329, ZL031399428, ZL031573150, ZL2003101241702, ZL021337241, ZL95104038, ZL97101107, ZL02155001, ZL021332983, ZL031279953, ZL03141614, ZL03113037, ZL2003101210259, ZL200410013845), powder pin (ZL200410037717, ZL031323820, ZL021446008, ZL200410002103, ZL03131959.9, ZL200410013937, ZL2003101210259, ZL200410000912), drop pill (ZL200310107292, ZL03136485, ZL01133515, ZL03135325, ZL200310119222), dispersible tablet (ZL03125462, ZL03112974, ZL02153445), little or nanometer formulation (ZL021378630, ZL00119579), phospholipid preparations (ZL001278126, ZL031320627, ZL01139971, ZL03128337,2005 30 4 phases of volume of CHINA JOURNAL OF CHINESE MATERIA MEDICA: 260-263).
Pharmaceutical composition of the present invention; form by the active component of 10-90wt.% and the pharmaceutic adjuvant of 90-10wt.%; can be used for treating stupor, hyperpyrexia, cardiovascular and cerebrovascular disease, senile dementia, brain cell protection, central retinal vein occlusion, hyperlipemia, fatty liver, and be used for the treatment of the recurrence with prevent diabetes and complication thereof, prevention cardiovascular and cerebrovascular disease.Aforementioned pharmaceutical compositions has overcome shortcomings such as the effect that existing medicine exists is single, dosage is big, has represented the natural drug treatment and has prevented the new trend of above-mentioned disease.
The pharmacology pharmacodynamic experimental study
One. the basic research of Moschus, Radix Paeoniae and Borneolum Syntheticum combination
1. collaborative antiinflammatory action
1.1 influence to acute exudative inflammation (dimethylbenzene induced mice ear swelling)
1.1.1 material
Drug regimen of the present invention (Radix Paeoniae Alba extract+Moschus+Borneolum Syntheticum 5: 1: 1) is divided into 10,30, the 50mg/kg group;
Blank group: normal saline;
Positive control drug: the Radix Paeoniae Alba extract that is equivalent to same dosage; 10% Moschus group; Radix Paeoniae Alba extract+Moschus 5: 1,30mg/kg group, aspirin 0.2g/kg group.
1.1.2 method and result
The ICR mice, body weight 19-21g, by body weight all groupings at random, 10 every group, continuous gastric infusion 4 days (0.4ml/20g), the blank group is given the distilled water of equal volume.Behind last administration 1h, 60 μ l dimethylbenzene evenly are applied to every Mus auris dextra two sides, behind the 40min dislocation of mice cervical vertebra is put to death, taking off left and right sides auricle with diameter 8mm scleral perforation device weighs, obtain two ear weight differences, calculate the swelling rate, t check comparable group differences the results are shown in Table 1.
The influence of table 1 xylol induced mice ear swelling (X ± SD, n=10)
| Group | Dosage (mg/kg) | Swelling rate (%) |
| The blank group aspirin peony extract Moschus peony extract+Moschus present composition (height) present composition (in) present composition (low) | - 0.2 30 5.0 30 50 30 10 | 145.26±38.38 63.88±31.77 ** 91.96±32.16 ** 96.81±27.22 * 69.27±26.51 **# 63.31±30.03 **△# 67.97±25.11 **# 87.99±24.06 * |
Annotate: swelling rate=[(auris dextra heavy-left ear is heavy)/left ear is heavy] * 100%;
Compare with the blank group:
*P＜0.05,
*P＜0.01;
Compare △ P＜0.05, △ △ P＜0.01 with the Radix Paeoniae group; Compare #P＜0.05 with the Moschus group.
1.2 xylol causes the influence of mouse skin capillary permeability
1.2.1 material
Pharmaceutical composition of the present invention (Radix Paeoniae Alba extract+Moschus+Borneolum Syntheticum 10: 1: 3) is divided into 10,30, the 50mg/kg group;
Positive control drug: the Radix Paeoniae Alba extract that is equivalent to same dose; 10% Moschus group; Radix Paeoniae Alba extract+Moschus 10: 1, the 30mg/kg group; Aspirin 0.2g/kg group.
1.2.2 method and result
Make the animal inflammatory model with reference to " herbal pharmacology research methodology ", the results are shown in following table 2:
The influence of table 2 xylol induced mice capillary of skin permeability (X ± SD, n=10)
| Group | The OD value |
| The Normal group aspirin peony extract Moschus Chinese herbaceous peony+Moschus present composition (low) present composition (in) present composition (height) | 0.067±0.022 0.035±0.023 ** 0.039±0.018 ** 0.040±0.017 ** 0.025±0.015 **△# 0.037±0.021 ** 0.023±0.014 **△# 0.020±0.013 **△△## |
Compare with matched group: * P＜0.05, * * P＜0.01; Compare with Radix Paeoniae Alba extract: △ P＜0.05, △ △ P＜0.01;
Compare with Moschus: #P＜0.05, ##P＜0.01.
The result shows: present composition xylol induced mice ear swelling and xylol induced mice capillary of skin permeability have the obvious suppression effect, has the effect that the early stage capillary permeability of inflammation-inhibiting increases, compare with matched group and to have significant difference, compare with the one pack system extract group of Isodose, also has significant difference (P＜0.05), senior middle school's dosage group and blank group be P＜0.05-0.01 relatively, other antiinflammatory experiments have also been done simultaneously, the result shows, the present composition has also shown significant effect in rat foot due to suppressing Ovum Gallus domesticus album is wasted time swelling, and effect obviously is better than Radix Paeoniae Alba extract and Moschus group, the prompting Moschus, Borneolum Syntheticum and Radix Paeoniae are single with having on the basis of antiinflammatory action separately at it, a certain proportion of compatibility share the antiinflammatory action that more can promote Radix Paeoniae/Borneolum Syntheticum/Moschus single medicinal material, plays collaborative antiphlogistic effect; Compositions of the present invention (Radix Paeoniae+Moschus+Borneolum Syntheticum) antiinflammatory action effect is better than the combination of Radix Paeoniae+Moschus, but does not have significant difference.
2 improve the active constituents of medicine absorption in vivo
2.1 material
Pharmaceutical composition of the present invention: peoniflorin+muscone+Borneolum Syntheticum 1: 1: 1;
Blank group: normal saline;
Positive control drug: the peoniflorin and muscone and the Borneolum Syntheticum that are equivalent to the one pack system of same dosage.
2.2 method and result
Rat is divided into single with peoniflorin, muscone group, Borneolum Syntheticum group, pharmaceutical composition group of the present invention, (respectively with oral and intravenous injection dual mode administration) different time points after the administration, use gas chromatography determination blood drug level, experiment shows, muscone can be absorbed soon, thereby improve its blood drug level, oral administration can see through blood brain barrier at 5-6 minute and enter the central nervous system, and intravenously administrable can see through blood brain barrier about 2 minutes; Same method (gas chromatography), the blood drug level of mensuration peoniflorin has proved that also muscone and Borneolum Syntheticum can promote medicine (peoniflorin) to absorb; Simultaneously the three is repeated above-mentioned experiment in the proportion of 1-5: 1-5: 1-5, the result has confirmed that all muscone and peoniflorin and Borneolum Syntheticum share the effect that improves drug absorption.
Two. the pharmacological action for the treatment of cardiac and cerebral vascular diseases
1. global brain ischemia is poured into again the influence of rat cerebral tissue's amino acid neurotransmitter
1.1 material
Pharmaceutical composition of the present invention (peoniflorin+Moschus+Borneolum Syntheticum 1: 2: 3,40mg/kg irritates stomach);
Positive control drug: peoniflorin 10mg/kg, muscone+Borneolum Syntheticum suspension 12mg/kg;
1.2 method
The every day of administration at twice before the modeling for three days on end, undergos surgery after 30 minutes in administration in the morning in the 4th day.According to the standard method modeling, separate bilateral common carotid arteries, pour into 6h again, sacrificed by decapitation, get brain and place rapidly and get the right side brain on the ice pan and be divided into A, B, C, D five equilibrium, get C, D brain sheet is weighed, and adds methanol homogenate according to 1ml/50mg from antinion to occipital lobe, centrifugal collection supernatant, boil off methanol, add 80% ethanol again, ultrasonic Treatment, centrifugal, collect supernatant and be used to detect the cerebral tissue amino acid neurotransmitter.
Most of neurotransmitter is an amino acids among the central nervous system, comprise γ-An Jidingsuan (GABA), glutamic acid (Glu), aspartic acid (Asp) and glycine (Gly), under the physiological conditions, Glu, Asp have extremely strong excitation to neuron, GABA, Gly neuron enforcement effect are important inhibitory aminoacid.
Analytical method: reversed-phase HPLC, peak area external standard method, statistical analysis then.
1.3 result
See the following form 3.
Table 3 is respectively organized global brain ischemia and is poured into the content of rat cerebral tissue's amino acid neurotransmitter (μ mol/g) again
| Glu | Asp | GABA | Gly | |
| Sham operated rats | 3.77±0.91 | 3.67±1.01 | 10.69±3.40 | 2.61±0.58 |
| The model group peoniflorin muscone+Borneolum Syntheticum present composition | 5.59±0.93 ** 5.22±1.13 ** 5.18±1.06 ** 4.21±0.89 *△△# | 5.79±0.96 ** 4.19±0.97 △△ 4.20±0.56 △△ 4.01±0.67 △△ | 10.95±4.00 15.65±3.12 *△ 16.71±3.44 *△ 19.85±3.01 *△△# | 3.41±0.62 * 4.11±0.59 **△ 4.12±0.66 **△ 4.21±0.59 **△△ |
Compare with sham-operation,
*P＜0.05
*P＜0.01; Compare with model group,
△P＜0.05,
△ △P＜0.01; Compare #P＜0.05 with Moschus+Borneolum Syntheticum group.
1.4 conclusion
Pharmaceutical composition of the present invention, peoniflorin injection and muscone+Borneolum Syntheticum injection rat cerebral tissue's ischemia 45 minutes, pours into (Glu, Asp obviously raise) after 6 hours again, and to the Asp decrease to some degree, present composition group is the most obvious; And peoniflorin injection and muscone+Borneolum Syntheticum injection is not obvious to the Glu reduction, and pharmaceutical composition of the present invention can reduce Glu, compares with contrast medicine group to have significant difference; The rising of GABA and Gly also is that present composition group is the most obvious; compare with peoniflorin and muscone+Borneolum Syntheticum group; has significant difference between group; may be peoniflorin and the beneficial effect that jointly bring different with the mechanism of action of Moschus extract (muscone) and Borneolum Syntheticum; the combination that the present composition is described is by reducing the Asp in the ischemic region cerebral tissue; improved the toxicity of the content of GABA and Gly with the antagonism excitatory amino acid; thereby the damage of the follow-up unit of going crazy of protection cerebral ischemia; though these are one of medical mechanisms of drugs of causing resuscitation by administering aromatic drugs (muscone and Borneolum Syntheticum); but muscone of the present invention; share of Borneolum Syntheticum and peoniflorin; improve drug effect undoubtedly, brought into play collaborative effect.
2. to preventing postangioplasty restenosis
Postangioplasty restenosis (RS), belong to the syndrome of blood stasis category, its sickness rate height, the abnormality proliferation of vascular smooth muscle cell (VSMCs), be the Chinese medicine pathological characters of RS, therefore suppress the important means that the VSMCs abnormality proliferation becomes worldwide cardiovascular research prevention RS.
2.1 material
Pharmaceutical composition of the present invention (peoniflorin+Moschus+Borneolum Syntheticum 3: 5: 4,4,8mg/kg injection);
Blank group: normal saline;
Positive control drug: peoniflorin injection, each 8mg/kg of muscone injection;
2.2 method
Vascular smooth muscle cell is separated, cultivates, is identified reference literature (Piper HM edits, Cell CultureTechinques in Heart and Vessel Research.Springer-Verlag:Germany.1990:280).
Cultivate attached cell, change DMEM (containing penicillin 100U/ml, streptomycin 100 μ g/ml) continuation cultivation again into and make the cell growth synchronously, add medicine at last at random, each concentration is diluted to 10 μ l/ holes with DMEM.
3H-TdR mixes experiment: replace the DMEM of every hole 1ml, add luCi's
3H-TdR measures the CPM value in each hole.
Cell survival rate=attached cell/total cell number (attached cell+not attached cell)
2.3 result
This experiment cell counting analysis, each organize the influence of medicine on cell proliferation with to smooth muscle cell
3H-TdR mixes basically identical, and records not obviously influence of cell survival rate, all more than 90%.Pharmaceutical composition of the present invention, peoniflorin injection and muscone injection are all inhibited to the abnormality proliferation of vascular smooth muscle cell (VSMCs), but pharmaceutical composition of the present invention is the strongest, compare with peoniflorin and muscone, having significant difference between group, may be peoniflorin and the beneficial effect that jointly bring different with the mechanism of action of Moschus extract (muscone) and Borneolum Syntheticum.
Three. the short effect of waking up
1. material
Mice: Kunming kind, body weight 18-22g, male and female half and half.
Reagent: oil lamp+Radix Paeoniae injection (self-control); Oil lamp injection (the biological paddy in Yunnan pharmaceutical factory); Muscone injection (self-control); Caffeine and sodium benzoate injection raw material (Shanghai the 14 pharmaceutical factory); The present composition 1 (Radix Paeoniae+Moschus+Borneolum Syntheticum, weight ratio 2: 1: 1) group; The present composition 2 (Radix Paeoniae+Moschus+caffeoylquinic acids+Borneolum Syntheticum 2/1/3/1).
2. method and result
The mice random packet, difference tail vein injection sodium chloride injection, caffeine and sodium benzoate normal saline solution, oil lamp+reagents such as Radix Paeoniae injection, once a day, successive administration 2 days, 15min after the last administration, lumbar injection pentobarbital sodium normal saline solution (3mg/ml) 0.3ml/20g, record mice righting reflex loss is to the time of recovering, calculate each class mean and standard deviation, carry out the t check, the results are shown in Table 4.
The short effect of waking up of table 4 pair mice (X ± SD, n=10)
| Group | Dosage | The length of one's sleep (minute) |
| The physiological saline group muskone group fleabane flower group oil lamp+Chinese herbaceous peony group caffeine sodium benzoate group present composition 1 present composition 2 | - 40ml/kg 40ml/kg 40ml/kg 2mg/kg 40mg/kg 40mg/kg | 29.9±6.3 20.1±4.8 *△# 25.1±6.6 24.5±6.1 11.5±4.3 **△△## 15.8±4.9 **△# 18.0±5.0 **△# |
Compare with the blank group:
*P＜0.05,
*P＜0.01; Compare with the oil lamp group: △ P＜0.05, △ △ P＜0.01;
Compare with oil lamp+Radix Paeoniae: #P＜0.05, ##P＜0.01.
3. conclusion
Compare with matched group, the present composition, contrast medicine caffeine and sodium benzoate group all show short effect of waking up.Compare with oil lamp+Radix Paeoniae, this compositions presents significant difference, shows share of Radix Paeoniae Moschus and Borneolum Syntheticum, has greatly strengthened the pharmacologically active of the short aspect of waking up of medicine.
Four. the pharmacological action of diabetes aspect
1. material
Pharmaceutical composition of the present invention: Radix Paeoniae+Moschus+Borneolum Syntheticum+Herba Erigerontis group (weight ratio 2: 1: 0.2: 1)
Normal control group: normal saline;
Diabetic groups: normal saline;
Positive control drug: peoniflorin group; Radix Paeoniae+Moschus (weight ratio 2: 1) group, 80mg/kg irritates stomach; JIANGZHILING PIAN;
2. method and result
The foundation of diabetes experimental model: secondary SD rat is according to 150mg/kg body weight tail vein injection alloxan liquid, under the effect of alloxan liquid, the beta Cell of islet of rat sustains damage, cause insulin generation obstacle, tail vein blood is surveyed fasting glucose after 3 days, and blood glucose value is a diabetes rat greater than 11.0mmol/L's.
Once a day, in continuous 4 weeks, afterwards, tail vein blood is surveyed fasting glucose (FBG) and serum I ns.
The FBG of table 5 pair diabetes rat and serum I ns influence n=15
| Medicine | Dosage | FBG(mmol/L) | Ins(mIU/L) |
| Normal control group diabetic groups peoniflorin JIANGZHILING PIAN Radix Paeoniae+Moschus pharmaceutical composition of the present invention | - - 80mg/kg 80mg/kg 80mg/kg 80mg/kg | 4.96±0.40 ** 16.5±3.1 11.4±3.0* 8.9±3.5 ** 7.9±2.0 **△△ 7.8±2.1 **△△ | 23.6±3.2 ** 17.5±2.3 18.9±2.7 17.6±2.6 17.8±2.1 17.6±2.0 |
Compare with diabetic groups:
*P＜0.05
*P＜0.01; Compare with peoniflorin: △ P＜0.05, △ △ P＜0.01.
Above-mentioned experiment shows that the effect of the present composition (Radix Paeoniae+Moschus+Borneolum Syntheticum compositions) is obvious.The present composition has obviously reduced the blood glucose of alloxan diabetes, and it is not obvious to serum I ns level affects, this shows that Radix Paeoniae, Moschus drug combination have produced stronger hypoglycemic activity to alloxan diabetes rats, and hypoglycemic activity is not realized by improving insulin level.
Five. to the antioxidation of hyperlipidemia rat
1. material
Pharmaceutical composition of the present invention: Radix Paeoniae+Moschus+Borneolum Syntheticum 8: 1: 2,50mg/kg irritates stomach;
Normal control group: normal saline;
Hyperlipidemia group: normal saline;
Positive control drug: peoniflorin (50mg/kg); VE (50mg/kg); 10% Borneolum Syntheticum.
2. method and result
Set up high blood lipid model, compare with normal group: the LPO of hyperlipidemia model serum and liver obviously raises, and obviously reduces and SOD is active.
Medicine is irritated stomach, handles animal, according to the operation of test kit description, surveys LPO and SOD, the results are shown in Table 6:
Influence (nmol/L) n=10 of table 6 pair hyperlipemia rat serum and liver LPO and SOD
| Group | Serum LPO | SOD in serum | Liver L PO | Liver SOD |
| Hyperlipidemia group VE group peoniflorin Borneolum Syntheticum compositions group | 8.99±2.00 6.54±1.23 ** 7.89±1.17 8.57±1.29 6.20±1.10 **△△ | 400.9±56.7 440.1±28.9 451.6±40.1 * 427.1±30.3 463.9±27.7 *△ | 6.91±1.18 5.61±1.13 * 5.89±1.37 6.31±1.36 5.17±1.16 ** | 7.59±1.19 8.87±1.27 * 8.73±1.18 * 7.70±1.29 9.44±1.13 ** |
Compare with the hyperlipidemia group:
*P＜0.05,
*P＜0.01; Compare with Radix Paeoniae: △ P＜0.05, △ △ P＜0.01.
Conclusion
Experiment shows, the antioxidant activity of the present composition significantly is better than Radix Paeoniae, the Borneolum Syntheticum used separately.
The above results also proves: being combined in of Radix Paeoniae+Moschus+Borneolum Syntheticum promoted antioxidant activity to a certain extent more, but contains Radix Paeoniae and Moschus simultaneously, is compositions obtains outstanding effect aspect antioxidation essential condition.
Moschus is through experimental results show that ability and the effect with enhancing maincenter anoxia enduring, and it is verified, the ability of the enhancing maincenter anoxia enduring of Moschus is to the direct effect of cental system but not remote-effects, therefore claim its causing resuscitation with aromatic drugs on the traditional Chinese medical science, not only control apoplectic coma but also control infantile convulsion with Moschus, but do not prove that it has tangible antioxidation, the application experimental results show that itself and Radix Paeoniae and Borneolum Syntheticum share, antioxidant activity significantly is better than single Radix Paeoniae of using, the composition explanation is aspect the hyperlipidemia antioxidation, and there is the enhancing synergism in the three.
5 usefulness of the present composition are not then found toxic and side effects, the adverse side effect that does not bring.
In addition; also from aspects such as neuroprotective cell, minimizing cerebral tissue malonaldehyde (MDA) and NO generations; investigated the antioxidation of the present composition; the result proves that the present composition has the obvious suppression effect to cerebral tissue MDA; reduced the NO that raises in the cerebral tissue, neurocyte has also been shown protective effect.
Six. the brain cell protective effect
1 material
Laboratory animal: healthy Wistar rat;
Medicine: present composition A: Borneolum Syntheticum+peoniflorin+Moschus 1: 2: 1; Compositions B: Borneolum Syntheticum+peoniflorin+Moschus+scutellarin 1/2/1/5; Each 30mg/kg;
Positive control drug: peoniflorin+scutellarin injection, 30mg/kg; Borneolum Syntheticum+scutellarin injection, 30mg/kg; The Edaravone Injection injection, 10mg/kg; The muscone injection, 10mg/kg;
2 methods
Rat is divided into 6 groups at random, 12 every group.The normal control group: by left external jugular vein intubate, quiet notes 1% heparin (2ml/kg) is given 0.9% sodium chloride liquid 3ml/kg respectively at reaching 1.5h at once through left external jugular vein intubate, gets brain detection or fixing behind the 3h.Model group: set up the cerebral ischemia re-pouring animal model with reference to Kaizumis bolt collimation method.The equal ischemia 1.5h of experimental animal model gets brain detection or fixing, takes out the bolt line then and pours into 1.5h again, gets brain detection or fixing.Specimen: rat broken end is got brain, peel off cerebral tissue, get and get brain cortex and tail shell nuclear light, electron microscope specimen between two coronal sections of optic chiasma and interpeduncular fossa respectively.
The mensuration of cerebral edema and brain calcium content: get right front brain 50-100mg, dry, be dry weight to constant weight.
Brain water content is measured: use formula: (weight in wet base-dry weight)/weight in wet base, calculate brain water content.
3 results
1. rat cerebral tissue's infarct is observed:
Under the light microscopic: model group neuron soft edge, cell space is painted to deepen, and karyon is little, the kytoplasm boundary is unclear.The cell peripheral clear zone broadens and there were significant differences (P＜0.01) for the normal control group.Two groups of the present compositions and Edaravone group neuronal structure are still clear, and karyon and kytoplasm boundary still can be distinguished, and cell peripheral clear zone broad dwindles there was no significant difference though compare with model group.Positive control drug group neuronal structure except Edaravone Injection owes clear, and karyon and kytoplasm boundary can be distinguished, and cell peripheral clear zone broad is compared with model group and not seen obviously and dwindle.
Under the Electronic Speculum: the distortion of model group neuron, the light and shade neuron is not easily distinguishable, karyon distortion, surperficial indentation, in the nuclear heterochromatin increase, nuclear membrane and perinuclear space is smudgy, the caryoplasm boundary is unclear, network structure disappears, organelle minimizing or distortion, structure are unclear.Mitochondrion is the swelling of balloon sample, plasma structure is unclear or disappearance is ruptured, cell peripheral has a large amount of edematous fluid to be the low electron density clear zone.The all nuclear membranes of two groups of present composition groups and Edaravone group neuronal kernel are clear, the interior heterochromatin of nuclear increases slightly, the perinuclear space is narrower, the kytoplasm inner cell organ is obvious but mitochondrion all has the change of edema sample, cell peripheral that a small amount of edematous fluid is arranged.Positive control drug group neuronal kernel except Edaravone Injection week nuclear membrane owe in clear, the nuclear heterochromatin slightly showed increased, the perinuclear space is narrower, the kytoplasm inner cell organ is not obvious, mitochondrion has the edema sample to change.Model group astrocyte edema, kytoplasm electron density reduce, organelle reduces, the local cells membrane structure is unclear.The edema performance of two groups of present composition groups and Edaravone group astrocyte is light than model group, and organelle is compared obviously more with model group.Positive control drug group astrocyte except Edaravone Injection is then similar substantially to model group.
2. the experimental result of cerebral tissue calcium, malonaldehyde, superoxide dismutase, brain moisture: model group cerebral tissue mda content, calcium content, brain moisture all obviously raise (P＜0.01) than normal matched group, and the SOD activity then is starkly lower than normal control group (P＜0.01); Two groups of rising and increased SOD activity (P＜0.01) that all can suppress perfusion back cerebral tissue mda content of the present composition, improve brain water content (P＜0.01), effect and Edaravone are suitable, obviously are better than the Chinese medicine positive control drug group except that Edaravone Injection.
4 conclusions
The present composition can significantly suppress the rising and the SOD activity improving of the MDA of cerebral ischemia re-pouring rat cerebral tissue content, improves brain water content, and confirms that from ultrastructure membranous structure is still had certain protective role.The present composition is removed oxygen-derived free radicals, thereby brain cell is shielded mainly by SOD activity improving, and its effect is suitable with Edaravone, obviously is better than other matched groups (peoniflorin+scutellarin injection; Borneolum Syntheticum+scutellarin injection; The muscone injection).
The clinical observation of cardiovascular and cerebrovascular disease aspect
1 medicine
The present invention's combination: muscone, 15mg/ days; Borneolum Syntheticum, 10mg/ days; With Radix Paeoniae Alba extract, 60mg/ days, merge oral.
Contrast: muscone 15mg/ days, Radix Paeoniae Alba extract (containing peoniflorin) 60mg/ days, Borneolum Syntheticum, 10mg/ days, oral.
2 methods and result
Adopt the method for randomized controlled to investigate its curative effect and untoward reaction, observe coronary heart disease patient 200 examples altogether, wherein 100 examples (oral combination of the present invention), curative effect cure-remarkable-effectiveness rate 47.15%, total effective rate 93.17% are organized in treatment; Matched group 100 examples, cure-remarkable-effectiveness rate 27.96%, 70.21%, two group of coronary heart disease curative effect of total effective rate is learned processing by statistics, and there is significant difference P＜0.01, and the treatment group is better than matched group.The treatment group is not seen tangible untoward reaction.
Adopt the method for randomized controlled to investigate its curative effect and untoward reaction, observe acute ischemic patient 160 examples altogether, wherein 80 examples are organized in treatment, curative effect cure-remarkable-effectiveness rate 36.13%, total effective rate 85.65%; Matched group 80 examples, cure-remarkable-effectiveness rate 26.87%, total effective rate 73.17%.Two groups of coronary heart disease curative effects are learned processing by statistics, and there is significant difference P＜0.05, and the treatment group is better than matched group.The treatment group is not seen tangible untoward reaction.
Example of formulations
Embodiment 1 tablet
Get Radix Paeoniae Rubra, be ground into coarse powder, add the 80-90% alcohol reflux three times, merge extractive liquid,, use n-butanol extraction three times behind the concentrating under reduced pressure, each 600ml merges n-butanol extracting liquid, be evaporated to no n-butyl alcohol flavor, add water 400ml, heating for dissolving filters, the filtrate spray drying, it is standby to get extract I;
Natural Broneolum Syntheticum 0.5g is ground into fine powder, with 6g extract I and 3g Moschus mixing, adds adjuvant (gross weight 5%) low-substituted hydroxypropyl cellulose, magnesium stearate, starch, microcrystalline Cellulose, granulates and tablet forming technique prepares according to standard.
Embodiment 2 tablets
Get Herba Erigerontis and be ground into coarse powder, add 75% alcohol reflux three times, first and second time each 2 hours, 1 hour for the third time, merge extractive liquid,, concentrating under reduced pressure, with n-butanol extraction three times, each 300ml merges n-butanol extracting liquid, be evaporated to no n-butyl alcohol flavor, add the water heating for dissolving, add dilute sodium hydroxide again and regulate pH value to 7, filter, the filtrate spray drying, it is standby to get extract II;
Natural Broneolum Syntheticum 2g is ground into fine powder, with 10g extract I, 20g extract II and 15g Moschus mixing, adds low-substituted hydroxypropyl cellulose, magnesium stearate, starch, microcrystalline Cellulose, prepares 1000 according to standard granulation and tablet forming technique.
Embodiment 3 soft capsules
Get the CO of peoniflorin 2g, Borneolum Syntheticum cyclodextrin clathrate 25g (containing Borneolum Syntheticum 2.5g), Moschus
2Supercritical extract 4g, with the glycerol mixing, 1000 of pills promptly get soft capsule.
Embodiment 4 drop pill
Get Radix Paeoniae Rubra, use water extraction after being ground into coarse powder, with macroporous adsorptive resins on the water extract, water, 70% ethanol elution are collected ethanol elution, concentrate back elimination precipitate, the filtrate spray drying, extract II I is standby;
Get natural Broneolum Syntheticum 3.5g and be ground into fine powder,, get IV with 15g extract II I, 20g breviscapine, Moschus water vapour extract 20g mixing;
It is evenly mixed to get xylitol and Furcellaran, adds the IV of method for preparing, fully mixes, the mixture heated fusion stirs and is incubated, and splashes under about 60 ℃ in 0 ℃ the methyl-silicone oil, make 10000 drop pill, the most and most liquid coolant of wiping with the drop pill drop, back packing to be dried.
Embodiment 5 oral cavity disintegration tablets
Get cyclodextrin clathrate 20g (containing Borneolum Syntheticum 2g, Moschus 2g), aspartame, Fructus Citri Limoniae essence and the magnesium stearate of Radix Paeoniae Alba extract 10g, Herba Erigerontis extract (scutellarin content is not less than 60%) 50g, Borneolum Syntheticum and Moschus water vapour extract, mixed 100 mesh sieves.Add cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose, cross 100 mesh sieves behind the mix homogeneously, tabletting is made 1000 altogether.
Embodiment 6 slow releasing tablets
Get the cyclodextrin clathrate 30g (containing Borneolum Syntheticum 3g, Moschus 5g) of peoniflorin 18g, Herba Erigerontis extract (total coffee acid ester content is not less than 50%) 100g, Borneolum Syntheticum and Moschus water vapour extract, uniform mixing, add lactose, microcrystalline Cellulose, hydroxypropyl methyl base cellulose, polyethylene pyrroles, hard magnesium, prepare 1000 according to standard granulation and tablet forming technique.
Embodiment 7 lyophilized injections
Get scutellarin 25g, an amount of organic base, add the injection water approximately to 900ml, stir and make dissolving, behind the adjusting pH value, add peoniflorin 15g to dissolving, mix homogeneously filters, and it is standby to get V;
Get artificial Moschus's supercritical carbon dioxide extraction thing VI (containing macrocyclic ketone of Moschus more than 30%) 12g, Borneolum Syntheticum 4g, add polyoxyethylene sorbitan monoleate, uniform mixing adds HP-again, and the ultrasonic agitation enclose got HP-beta-CD inclusion VI after 2 hours.
Get V3g, VI, add lyophilizing figuration mannitol, add to the full amount of water for injection, add active carbon, absorption, decarbonization filtering; Gained filtrate is continued with 0.22 μ m filtering with microporous membrane, packing, lyophilization.
Embodiment 8 injectable emulsions
Get the about 6g of water vapour extract of Moschus, add 1,2-propylene glycol, glycerol, heating makes clarification, other gets peoniflorin 10g and adds, and continues to be heated with stirring to 60 ℃ and keep constant, water.Get Borneolum Syntheticum 12g, emulsifying agent phospholipid, add an amount of dehydrated alcohol and make dissolving, add refining Oleum Glycines, VE, cholic acid then, be heated with stirring to 60 ℃ and keep constant, oil phase.Constant temperature stirs down water slowly is added drop-wise in the oil phase, adds the distilled water standardize solution of equality of temperature after dropwising, and continues stir about 15min and gets colostrum.After crossing 0.80 μ m filter membrane, 0.22 μ m filter membrane is crossed in homogenize, then fill, inflated with nitrogen, seal, sterilize.
Claims (7)
1. a pharmaceutical composition is made up of the active component of 10-90wt.% and the pharmaceutic adjuvant of 90-10wt.%, and described active component is:
A. Borneolum Syntheticum, the 1-15 weight portion; With
B. Moschus, or contain the Moschus extract of muscone, androsterone, Moschus-1, or the muscone monomer, the 5-65 weight portion; With
C. Radix Paeoniae dry root powder, or contain the Radix Paeoniae Alba extract of peoniflorin, lactone glucoside of Radix Paeoniae, Hydroxy peoniflorin, oxypaeoniflorin, benzoylpaeoniflorin, lacdtlorin, or the peoniflorin monomer, the 5-100 weight portion.
2. pharmaceutical composition as claimed in claim 1, wherein component a is the 2-10 weight portion, components b is that 10-50 weight portion and amount of component b are the 10-80 weight portion.
3. a pharmaceutical composition is made up of the active component of 10-90wt.% and the pharmaceutic adjuvant of 90-10wt.%, and described active component is:
A. Borneolum Syntheticum, the 1-15 weight portion; With
B. Moschus, or contain the Moschus extract of muscone, androsterone and Moschus-1, or the muscone monomer, the 5-65 weight portion; With
C. Radix Paeoniae dry root powder, or contain the Radix Paeoniae Alba extract of peoniflorin, lactone glucoside of Radix Paeoniae, Hydroxy peoniflorin, oxypaeoniflorin, benzoylpaeoniflorin, lacdtlorin, or the peoniflorin monomer, the 5-100 weight portion; With
The alcohol extract of d. Herba Erigerontis herb powder, or Herba Erigerontis, or breviscapine, or the scutellarin monomer of free or sodium-salt form, the 5-100 weight portion.
4. pharmaceutical composition as claimed in claim 3, described active component is:
A. Borneolum Syntheticum, the 2-10 weight portion; With
B. the Moschus extract that contains muscone, androsterone, Moschus-1, the 10-50 weight portion; With
C. the Radix Paeoniae Alba extract that contains peoniflorin, lactone glucoside of Radix Paeoniae, the 10-80 weight portion; With
D. contain scutellarin, list and or the Herba Erigerontis alcohol extract of dicaffeoylquinic acid, the 10-80 weight portion.
5. pharmaceutical composition as claimed in claim 3, wherein component a is the 5-10 weight portion, and components b is the 15-45 weight portion, and amount of component b is that 20-60 weight portion and component d are the 20-60 weight portion.
6. as the pharmaceutical composition of one of claim 3-5, wherein said active component is:
A. Borneolum Syntheticum; With
B. muscone monomer; With
C. peoniflorin monomer; With
D. single and or dicaffeoylquinic acid.
7. as the pharmaceutical composition of one of claim 3-5, wherein said active component is:
A. Borneolum Syntheticum; With
B. muscone monomer; With
C. peoniflorin monomer; With
D. breviscapine or scutellarin monomer or its sodium salt.
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| EP2255804A1 (en) * | 2008-03-04 | 2010-12-01 | Jiangsu Simcere Pharmaceutical R&D Co., Ltd. | A pharmaceutical composition and the application thereof in the preparation of medicine for the treatment of cerebrovascular diseases |
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| CN1173707C (en) * | 2001-04-23 | 2004-11-03 | 深圳市生物谷科技有限公司 | Medicinal composition containing baicalin and caffoeoylchinic acid |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2255804A1 (en) * | 2008-03-04 | 2010-12-01 | Jiangsu Simcere Pharmaceutical R&D Co., Ltd. | A pharmaceutical composition and the application thereof in the preparation of medicine for the treatment of cerebrovascular diseases |
| EP2255804A4 (en) * | 2008-03-04 | 2011-08-03 | Jiangsu Simcere Pharmaceutical R & D Co Ltd | A pharmaceutical composition and the application thereof in the preparation of medicine for the treatment of cerebrovascular diseases |
| AU2009221546B2 (en) * | 2008-03-04 | 2012-07-05 | Jiangsu Simcere Pharmaceutical Co., Ltd | A pharmaceutical composition and the application thereof in the preparation of medicine for the treatment of cerebrovascular diseases |
| US8658684B2 (en) | 2008-03-04 | 2014-02-25 | Jiangsu Simcere Pharmaceutical R & D Co., Ltd. | Pharmaceutical composition and its use in the preparation of a medicament for the treatment of cerebrovascular diseases |
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