CN102210759B - Application of Chinese medicinal component in preparation of nitric oxide donor medicament - Google Patents

Application of Chinese medicinal component in preparation of nitric oxide donor medicament Download PDF

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CN102210759B
CN102210759B CN201010141230.1A CN201010141230A CN102210759B CN 102210759 B CN102210759 B CN 102210759B CN 201010141230 A CN201010141230 A CN 201010141230A CN 102210759 B CN102210759 B CN 102210759B
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lignum
chinese medicine
water
santali albi
water extraction
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CN102210759A (en
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安军永
李向军
郑立发
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Hebei Yiling Pharmaceutical Research Institute Co Ltd
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Hebei Yiling Pharmaceutical Research Institute Co Ltd
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Abstract

The invention discloses application of a Chinese medicinal component in preparation of a nitric oxide donor medicament. The Chinese medicinal component comprises ginseng, leech, centipede, scorpion, ground beetle, periostracum cicada, red paeony root, borneol and the like, and has the effects of supplementing qi and activating blood, and expelling blood stasis and dredging collateral. The Chinese medicinal component can be effectively converted into nitric oxide in vitro and increase nitric oxide in the blood in vivo, is a nitric oxide donor and can be used for clinical treatment of heart cerebrovascular diseases for protecting vascular endothelium.

Description

The application of a kind of Chinese medicine composition in preparing nitric oxide donors medicine
Technical field
The present invention relates to a kind of new purposes of Chinese medicine composition, particularly, the present invention relates to the application of a kind of Chinese medicine composition in preparing nitric oxide donors medicine, belong to Chinese medicine application.
Background technology
Since illustrate the vasodilative effect of the medicines such as nitroglycerin, sodium nitroprusside be due to the nitric oxide (NO) having discharged as vascular endothelial cell relaxation factor since, the dark people of research of NO is to the various aspects of human body.Quantity research shows greatly, and NO brings into play extremely important physiological function as courier's material or effector molecule in systems such as cardiovascular, nerve, immunity; In body, the formation and development of NO generation deficiency or NO signal conduction abnormalities and various diseases is closely related.Therefore, about the research of NO becomes one of the focus of life sciences and forward position.
NO plays a very important role maintaining aspect antiotasis, blood pressure and hemodynamics.In recent years, people by linking group and known cardiovascular drugs coupling, have researched and developed a series of NO donator type cardiovascular drugses by various NO donors.Release position, burst size and the release time of different NO donors and linking group scalable NO, make NO continuing, controlled mode is discharged in particular organization and/or blood, so not only can improve the cardiac vascular activity of former medicine, can also reduce its untoward reaction.
The formation of Alzheimer (AD) may be relevant with the atrophy gradually of age growth brain microcirculation, blood supply insufficiency.Research shows, cerebral microcirculation disturbance has caused endogenous NO level to decline, and the generation deficiency of NO further causes brain blood flow to decline, and forms vicious cycle.On the other hand, along with the decline of NO generation deficiency and brain blood supply amount, Active Radicals Produced level significantly rises, and some inflammation start to occur simultaneously, progressively cause the particularly formation of vascular dementia of neuronal apoptosis and dementia.In view of the AD cause of disease is complicated, traditional single target spot medical instrument has the medicine of multiple target effect to become a focus of the anti-AD new drug of current research and development.
The research of NO has in recent years obtained significant progress, but also to people, has left many thinkings.NO is one " double-edged sword ".For people build consensus, the NO of low concentration, physiological amount has important function to human body multiple systems, and in body, NO generates deficiency or generates excessive generation and the development that can cause various diseases.That is to say, not NO donor medicine is studied successfully and both can be treated all diseases, this needs the adjusting of many target spots, can maximize favourable factors and minimize unfavourable ones, by exogenous NO donor, bring into play its drug effect [Zhang Yihua, Peng Sixun. nitric oxide donator type new drug research. Acta Pharmaceutica Sinica 2009,44 (11): 1200-1210].
The present invention is the improvement invention of carrying out on the basis of No. 01131203.3 and No. 200410048292.2 patent, at this, quotes in full the content that this two patent document is recorded.Unexposed this Chinese medicine composition of above-mentioned two patents is prepared the application of nitric oxide donors medicine.The present invention has carried out correlational study on its basis, and the application of this Chinese medicine composition in preparing nitric oxide donors medicine is provided.
Summary of the invention
The object of the invention is to provide the application of a kind of Chinese medicine composition in preparing nitric oxide donors medicine, and described Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 3-10 Hirudo 3-11 Eupolyphaga Seu Steleophaga 5-10 Olibanum (system) 1-5 Radix Paeoniae Rubra 3-9 Lignum Dalbergiae Odoriferae 1-5
Lignum Santali Albi 1-5 Scorpio 3-9 Periostracum Cicadae 3-12 Scolopendra 1-3 Borneolum Syntheticum 1-7 Semen Ziziphi Spinosae (stir-fry) 3-10;
Preferably, this Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 6 Hirudo 10 Eupolyphaga Seu Steleophaga 7 Olibanums (system) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 7 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosaes (stir-fry) 5; Or:
Radix Ginseng 10 Hirudo 8 Eupolyphaga Seu Steleophaga 7 Olibanums (system) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 9 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosaes (stir-fry) 5; Or:
Radix Ginseng 6 Hirudo 11 Eupolyphaga Seu Steleophaga 7 Olibanums (system) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 3 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosaes (stir-fry) 5;
More preferably, the active component of above-mentioned Chinese medicine composition is comprised of following ingredients:
A mean diameter is less than Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga, Periostracum Cicadae and the Olibanum (processed) medicated powder of 100 μ m;
B Borneolum Syntheticum medicated powder;
The volatile oil that c is extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi;
D Radix Ginseng is the alcohol-extracted extract after concentrated with the alcohol extract after ethanol extraction;
The water extracted immersing paste being condensed into after water extraction liquid after Lignum Dalbergiae Odoriferae after e extraction composition c and water extraction liquid, Radix Paeoniae Rubra and the Semen Ziziphi Spinosae (parched) of Lignum Santali Albi medicinal residues decoct with water and the water extraction liquid of the medicine residues of Radix Ginseng after extraction ingredient d filter, mix.
The invention also discloses that to contain above-mentioned Chinese medicine composition be capsule, tablet, granule, powder, oral liquid or pill as the pharmaceutical preparation of active component.
The preferred version that the present invention also provides this Chinese medicine composition to prepare the application in nitric oxide donors medicine, i.e. medicine of the present invention application in preparing antitumor drug as nitric oxide donors.
In Chinese medicine composition of the present invention, as the latin name of the crude drug of active component and processing method thereof from < < Chinese medicine voluminous dictionary > > (in July, 1977, front page, Shanghai science tech publishing house) and < < Chinese Pharmacopoeia > > (2005 Nian Ban, Chemical Industry Press).
Chinese medicine composition of the present invention can also be routinely extraction and preparation process, for example, the preparation technology that the green booth < of model < pharmacy of Chinese materia medica > > (Shanghai Science Press 1997 December the 1st edition) records, make the acceptable any conventional dosage form of pharmaceutics, such as capsule, tablet, granule, powder, oral liquid or pill etc.
In application of the present invention, described Chinese medicine composition is a kind of in capsule, tablet, granule, powder, oral liquid or pill preparation, for above-mentioned dosage form can be realized, need when these dosage forms of preparation, add the acceptable adjuvant of pharmacy, such as: filler, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctives, antiseptic, substrate etc.Filler comprises: starch, pregelatinized Starch, lactose, mannitol, chitin, microcrystalline Cellulose, sucrose etc.; Disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc.; Lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.; Suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc.; Binding agent comprises, starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; Sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.; Correctives comprises: sweeting agent and various essence; Antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, acetic acid chloroethene are determined, Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods; Substrate comprises: PEG6000, PEG4000, insect wax etc.
Capsule of the present invention is preferably made by following preparation method: the five kinds of Chinese medicine such as the Hirudo of said ratio, Scorpio, Periostracum Cicadae, Eupolyphaga Seu Steleophaga, Scolopendra cleaned, and oven drying at low temperature, standby; Lignum Santali Albi, Lignum Dalbergiae Odoriferae extract volatile oil, and medicinal residues and aqueous solution are standby; Radix Ginseng extracts secondary with 70% alcohol heating reflux, and 3 hours for the first time, 2 hours for the second time, merge extractive liquid,, reclaimed ethanol extremely without alcohol taste; The medicinal residues of medicine residues of Radix Ginseng and Lignum Santali Albi, Lignum Dalbergiae Odoriferae merge with aqueous solution, add Radix Paeoniae Rubra, Semen Ziziphi Spinosae (stir-fry), decoct with water secondary, 3 hours for the first time, 2 hours for the second time, collecting decoction, filters, and filtrate is concentrated into the clear paste that relative density is 1.20-1.25 (60 ℃), add above-mentioned panaxynol extract, mix, cold drying, is ground into fine powder; The five tastes such as Olibanum (system) and Hirudo are ground into fine powder altogether; Borneolum Syntheticum porphyrize, with above-mentioned fine powder facing-up, mixes respectively, sprays into volatile oil, mixes, and incapsulates, and obtains.
Or capsule of the present invention is preferably made by following preparation method:
A) weight ratio of crude drug is: Radix Ginseng 3-10 part, Hirudo 3-11 part, Eupolyphaga Seu Steleophaga 5-10 part, Olibanum (processed) 1-5 part, Radix Paeoniae Rubra 3-9 part, Lignum Dalbergiae Odoriferae 1-5 part, Lignum Santali Albi 1-5 part, Scorpio 3-9 part, Periostracum Cicadae 3-12 part, Scolopendra 1-3 part, Borneolum Syntheticum 1-7 part, Semen Ziziphi Spinosae (parched) 3-10 part;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 100 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae decoct with water again, after water extraction liquid filters, and one-tenth extractum to be concentrated; Radix Ginseng is with after ethanol extraction, then uses water extraction, and alcohol extract reclaims after ethanol, is condensed into alcohol-extracted extract, and water extraction liquid is condensed into the water extracted immersing paste after filtering and mixing with all water extraction liquid;
D) preparation process:
In Fluidbedgranulatingdrier, adding superfine powder flour, then by step c) gained extracts extractum and sprays into granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make capsule.
Or capsule of the present invention is preferably made by following preparation method:
A) weight ratio of crude drug is: Radix Ginseng 3-10 part, Hirudo 3-11 part, Eupolyphaga Seu Steleophaga 5-10 part, Olibanum (system) 1-5 part, Radix Paeoniae Rubra 3-9 part, Lignum Dalbergiae Odoriferae 1-5 part, Lignum Santali Albi 1-5 part, Scorpio 3-9 part, Periostracum Cicadae 3-12 part, Scolopendra 1-3 part, Borneolum Syntheticum 1-7 part, Semen Ziziphi Spinosae (parched) 3-10 part;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 100 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae decoct with water again, after water extraction liquid filters, and one-tenth extractum to be concentrated; Radix Ginseng is with after ethanol extraction, then uses water extraction, and alcohol extract reclaims after ethanol, is condensed into alcohol-extracted extract, and water extraction liquid is condensed into the water extracted immersing paste after filtering and mixing with all water extraction liquid, and extractum Direct spraying is dried to spray powder;
D) preparation process:
By superfine powder flour and step c) be added in Fluidbedgranulatingdrier together with gained spray drying powder, then spray solvent granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make capsule.
The consumption of pharmaceutical composition of the present invention, is converted to the weight of raw medicinal material, is each 0.8-3 gram, and take 2-4 every day, is preferably each 1.11-2.22 gram, takes every day three times.
For illustrating Chinese medicine composition of the present invention as the activity of nitric oxide donors, with the Capsule content making by above-described embodiment 1 method (hereinafter referred to as medicine of the present invention), carried out following pharmacological testing to prove its curative effect, but it can not form any restriction to scope of the present invention.
Experimental example 1: the experimentation of drug release in vitro nitric oxide of the present invention (NO)
1. materials and methods
1.1 medicines and preparation method medicine of the present invention: Shijiazhuang Yiling Pharmaceutical Co., Ltd provides, lot number: 20081205, be chocolate brown powder.Get in the ultra-pure water that 0.05g medicated powder is dissolved in 500 μ l heating, shake up and be placed in the ultrasonic 10min hydrotropy of ultrasonic cleaner, be placed in high speed centrifuge, 12000rpm/min, 5min, separation of supernatant, in 1: 1 ratio, add methanol to mix, recentrifuge (ditto), room temperature is to be checked.
1.2 experimental apparatus: high performance liquid chromatograph (HPLC, Japanese Shimadzu company), model: LC-4A
1.3 chromatographic conditions: leacheate: the mixed solution of 1180mmol/L Na2CO3 and 117mmol/L NaHCO3.Inhibition system solution: 50mmol/L sulphuric acid, ultra-pure water (resistance > 18M Ω); Flow velocity: 0.80ml/min.
1.4 nitrite ion (NO 2-) and nitrate ion (NO 3-) assay: get drug extract of the present invention after 25 μ l separation and be placed in HPLC and detect NO 2 -with NO 3 -express, by graphics area, convert its content.Repeat 6 experiments, set up ultra-pure water blank group simultaneously.
1.5 statistical analysiss: adopt PEMS 3.1 statistical softwares to carry out t check, result with mean ± standard deviation (
Figure GSA00000071559600061
) form represents, P < 0.05 has statistical significance for difference.
2. result:
From table 1, with the comparison of blank group, medicine group NO of the present invention 2-content obviously increases (0.98 ± 0.01vs0.11 ± 0.02, P < 0.01), and NO3-level is obviously rising (1.24 ± 0.02vs0.12 ± 0.02, P < 0.01) also.
Table 1 is respectively organized nitrite ion (NO 2 -) and nitrate ion (NO 3 -) assay
Figure GSA00000071559600062
Table 1 (continuing) is respectively organized nitrite ion (NO 2 -) and nitrate ion (NO 3 -) assay
Figure GSA00000071559600063
3. conclusion: vascular endothelial cell can produce endothelium derivation relaxing factor and endothelium derivation contraction factor under physiological conditions, regulate vasomotion, the NO that vascular endothelial cell produces has strong blood vessel dilating effect, and suppress hematoblastic adhesion and gathering, be important informational molecule and effector molecule in body, NO is the active gas messenger molecule of a kind of character, its poor stability, half-life is very short, is oxidized to soon stable metabolite nitrate anion (NO 3 -) and nitrite anions (NO 2 -), therefore often infer the level of NO with expressions of both.NO in medicine group extracting solution of the present invention in this experiment 3-with NO 2-high expressed, show that this medicine can release in vitro NO, be a kind of exogenous NO donor, this provides foundation for illustrating its performance blood vessel endothelium and cardiovascular protection effect.
Experimental example 2: be converted into nitric oxide production research in medicine body of the present invention
1. materials and methods:
1.1 animal male mice in kunming, body weight 18-20g, is purchased from Beijing Vital River Experimental Animals Technology Co., Ltd., licence numbering: SCXK (capital) 2009-0001.
1.2 tested medicine medicine of the present invention: Shijiazhuang Yiling Pharmaceutical Co., Ltd provides, lot number: 20090207, be chocolate brown powder.With distilled water diluting, preparation before experiment.Cyclophosphamide (CTX), Hualian Pharmaceutical Co., Shanghai provides, lot number: 970101, specification: 200mg/ bottle.
Key step and the method for 1.3 tests: get well-grown S180 ascites, with after normal saline dilution in 1: 4, every mice axil subcutaneous vaccination 0.2ml, 50 mice random packet, if normal saline blank group, medicine of the present invention is established high, medium and low three dosage groups, is respectively 0.625,2.5,10g/kg.Rise next day and give different medicines, gavage is 7 days continuously.The 10th day mouse anesthesia by the conventional separation of serum of carotid artery intubate collecting blood sample 3ml after, nitrate reductase method Indirect Determination is measured the content of nitric oxide (NO).
1.4 statistical procedures: adopt SPSS 13.0 statistical softwares to carry out data analysis, meet normality and distribute and the neat data of variance, with mean ± standard deviation (
Figure GSA00000071559600071
) form represents, a plurality of sample averages are relatively used one factor analysis of variance (One-Way ANOVA), and P < 0.05 has statistical significance for difference.
2. result
2.1 impacts of medicine of the present invention on mice plasma NO content
The results are shown in Table 2.With the comparison of blank group, medicine group mice plasma NO level of the present invention is significantly rising (P < 0.01) all.
In table 2. medicine body of the present invention, transform nitric oxide production effect
Figure GSA00000071559600081
Note: with blank group comparison: * * P < 0.01.
3. conclusion
Early 1990s, [the NATHAN CF such as Nathan, HIBRS JB, Jr.Role of nitricoxide synthesis in macrophage antimicrohial activity.Curr Open Immunol, 1991,3 (1): 65-70.] research finds that NO plays an important role in immune system.NO is combined with oxygen-derived free radicals, generates a series of active nitrogens, as N 2o 3,, NO 2and ONOO -(peroxinitrites root) thus etc. component performance pharmacological action [WINK DA, VODOVOTZ Y, LAVAL J, et al.Themultifaceted roles of nitric oxide in cancer.Carcinogenesis, 1998,19 (5): 711-721.].
This result of study shows that medicine of the present invention is to the effect of being significantly increased of mice body NO level, and this is obviously that medicine of the present invention is converted into NO in vivo.
In sum, no matter in vivo still in vitro, medicine of the present invention all can synthesize and discharge nitric oxide, therefore can be used as nitric oxide donors application, but not nitric oxide donors just can be treated the disease relevant with nitric oxide, if confirm its effect, also need a large amount of pharmacology or clinical experiment to confirm.
The specific embodiment
Embodiment 1: the preparation of capsule
A) crude drug formula is:
Radix Ginseng 39.6g Hirudo 72.6g Eupolyphaga Seu Steleophaga 46.2g Olibanum (system) 13.2g
Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 19.8g
Periostracum Cicadae 46.2g Scolopendra 6.6g Borneolum Syntheticum 33g Semen Ziziphi Spinosae (stir-fry) 33g;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 30-40 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae add suitable quantity of water and decoct secondary again, and each 3 hours, merge water extraction liquid, after filtration, one-tenth extractum to be concentrated; Appropriate 70% ethanol extraction secondary for Radix Ginseng, each 3 hours, merge extractive liquid,, reclaim ethanol extremely without alcohol taste, use again water extraction, it is 0.9~1.1 (60 ℃) alcohol-extracted extract that alcohol extract is condensed into relative density, and water extraction liquid is concentrated into the clear paste that relative density is 0.9~1.1 (60 ℃) after filtering and mixing with above-mentioned all water extraction liquid, standby;
D) preparation process:
In Fluidbedgranulatingdrier, adding superfine powder flour, then by step c) gained extracts extractum and sprays into granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make 1000 capsules.
The consumption of medicine of the present invention, for each 2-4 grain, takes three times every day.
Embodiment 2: the preparation of tablet
A) crude drug formula is:
Radix Ginseng 66g Hirudo 52.8g Eupolyphaga Seu Steleophaga 46.2g Olibanum (system) 13.2g
Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 59.4g
Periostracum Cicadae 46.2g Scolopendra 6.6g Borneolum Syntheticum 33g Semen Ziziphi Spinosae (stir-fry) 33g
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 70-90 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae add suitable quantity of water and decoct secondary again, and each 3 hours, merge water extraction liquid, after filtration, one-tenth extractum to be concentrated; Appropriate 70% ethanol extraction secondary for Radix Ginseng, each 3 hours, merge extractive liquid,, reclaim ethanol extremely without alcohol taste, use again water extraction, alcohol extract is condensed into relative density and is determined as 1.0~1.05 alcohol-extracted extracts at 60 ℃, and water extraction liquid is concentrated into 60 ℃ after filtering and mixing with above-mentioned all water extraction liquid and measures the clear paste that relative density is 1.0~1.1, standby;
D) preparation process:
In Fluidbedgranulatingdrier, adding superfine powder flour, then by step c) gained extracts extractum and sprays into granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, preparation process is pressed into 1000 routinely.
The consumption of medicine of the present invention, for each 2-4 sheet, takes three times every day.
Embodiment 3: the preparation of pill
A) crude drug formula is:
Radix Ginseng 39.6g Hirudo 66g Eupolyphaga Seu Steleophaga 46.2g Olibanum (system) 13.2g
Radix Paeoniae Rubra 33g Lignum Dalbergiae Odoriferae 13.2g Lignum Santali Albi 13.2g Scorpio 46.2g
Periostracum Cicadae 46.2g Scolopendra 6.6g Borneolum Syntheticum 33g Semen Ziziphi Spinosae (stir-fry) 33g
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter 10-20 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae add suitable quantity of water and decoct secondary again, and each 3 hours, merge water extraction liquid, after filtration, one-tenth extractum to be concentrated; Appropriate 70% ethanol extraction secondary for Radix Ginseng, each 3 hours, merge extractive liquid,, reclaim ethanol extremely without alcohol taste, use again water extraction, it is 0.9~1.0 alcohol-extracted extract that alcohol extract is condensed into 60 ℃ of mensuration relative densities, and water extraction liquid is concentrated into 60 ℃ after filtering and mixing with above-mentioned all water extraction liquid and measures the clear paste that relative densities are 1.0~1.1, standby;
D) preparation process:
Preparation process, makes 1000 pills routinely.
The consumption of medicine of the present invention, for each 2-4 grain, takes three times every day.

Claims (7)

1. the application of Chinese medicine composition in preparing nitric oxide donors medicine, is characterized in that, this Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 3-10 Hirudo 3-11 Eupolyphaga Seu Steleophaga 5-10 Olibanum (processed) 1-5 Radix Paeoniae Rubra 3-9 Lignum Dalbergiae Odoriferae 1-5
Lignum Santali Albi 1-5 Scorpio 3-9 Periostracum Cicadae 3-12 Scolopendra 1-3 Borneolum Syntheticum 1-7 Semen Ziziphi Spinosae (parched) 3-10.
2. application as claimed in claim 1, is characterized in that, this Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 6 Hirudo 10 Eupolyphaga Seu Steleophaga 7 Olibanum (processed) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 7 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosae (parched)s 5.
3. application as claimed in claim 1, is characterized in that, this Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 10 Hirudo 8 Eupolyphaga Seu Steleophaga 7 Olibanum (processed) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 9 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosae (parched)s 5.
4. application as claimed in claim 1, is characterized in that, this Chinese medicine composition is made by the crude drug of following weight portion:
Radix Ginseng 6 Hirudo 11 Eupolyphaga Seu Steleophaga 7 Olibanum (processed) 2 Radix Paeoniae Rubra 5 Lignum Dalbergiae Odoriferaes 2
Lignum Santali Albi 2 Scorpio 3 Periostracum Cicadae 7 Scolopendra 1 Borneolum Syntheticum 5 Semen Ziziphi Spinosae (parched)s 5.
5. the application as described in any one in claim 1-4, is characterized in that, the active component of described Chinese medicine composition is comprised of following ingredients:
A mean diameter is less than Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga, Periostracum Cicadae and the Olibanum (processed) medicated powder of 100 μ m;
B Borneolum Syntheticum medicated powder;
The volatile oil that c is extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi;
D Radix Ginseng is the alcohol-extracted extract after concentrated with the alcohol extract after ethanol extraction;
The water extracted immersing paste being condensed into after water extraction liquid after Lignum Dalbergiae Odoriferae after e extraction composition c and water extraction liquid, Radix Paeoniae Rubra and the Semen Ziziphi Spinosae (parched) of Lignum Santali Albi medicinal residues decoct with water and the water extraction liquid of the medicine residues of Radix Ginseng after extraction ingredient d filter, mix.
6. the application as described in any one in claim 1-4, is characterized in that, this Chinese medicine composition is capsule, tablet, granule, powder, oral liquid or pill as the pharmaceutical preparation of active component.
7. application as claimed in claim 6, is characterized in that described capsule is to be prepared from through following steps:
A) weighting raw materials in proportion, cleaning, drying;
B) pulverizing medicinal materials technique:
Scorpio, Hirudo, Scolopendra, Eupolyphaga Seu Steleophaga and five kinds of worm medicines of Periostracum Cicadae after cleaning, washing processing and clean Olibanum (processed) after the process of preparing Chinese medicine by prescription batching, are pulverized by pulverizer, more than medicated powder fineness reaches 80 orders; Medicated powder after coarse powder carries out micronizing through various superfine communication techniques, makes medicated powder mean diameter be less than 100 μ m; Wait the medical material of pulverizing, after cleaning, drying sterilizing, prepare burden;
C) extract concentrated and drying process:
After the first extracting in water volatile oil of Lignum Dalbergiae Odoriferae and Lignum Santali Albi, use water extraction, Radix Paeoniae Rubra and Semen Ziziphi Spinosae (parched) decoct with water again, after water extraction liquid filters, and one-tenth extractum to be concentrated; Radix Ginseng is with after ethanol extraction, then uses water extraction, and alcohol extract reclaims after ethanol, is condensed into alcohol-extracted extract, and water extraction liquid is condensed into the water extracted immersing paste after filtering and mixing with all water extraction liquid;
D) preparation process:
In Fluidbedgranulatingdrier, adding superfine powder flour, then by step c) gained extracts extractum and sprays into granulation; The granule of making, through granulate, is added to Borneolum Syntheticum fine powder, spray into the volatile oil being extracted by Lignum Dalbergiae Odoriferae and Lignum Santali Albi, after mixing, by capsule filler filling, make capsule.
CN201010141230.1A 2010-04-08 2010-04-08 Application of Chinese medicinal component in preparation of nitric oxide donor medicament Active CN102210759B (en)

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