CN101439077B - Medicament containing dalbergia heartwood for treating blood vessel endothelium dysfunction and preparation method thereof - Google Patents
Medicament containing dalbergia heartwood for treating blood vessel endothelium dysfunction and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a medicine which contains dalbergia wood and cures vessel endothelial dysfunction, and a method for preparing the medicine. Researches prove that the medicine can effectively raise serum NO level and reduce plasma ET level and that the medicine has the function of improving endothelial dysfunction.
Description
Technical field
The present invention relates to medicine of a kind of treatment vascular endothelium dysfunction that contains Lignum Dalbergiae Odoriferae and preparation method thereof, belong to the Chinese herbal and crude drugs preparations technical field.
Background technology
Endothelial function disturbance is atherosclerotic initiating agent and runs through the pathological changes overall process; Hyperhomocysteinemiainjury is the independent hazard factor [Liang Junqing of endothelial function disturbance; Wu Yiling, Zhao Shaohua, etc. the Tongxinluo superfine powder is to the intervention effect of homocysteine hyperamization pipe damage. sick of network basis and clinical research (2); China Science Tech Publishing House, 202～205].
The reduction of endothelium-dependent relaxation stretching reaction or disappearance are goldstandard [Verdejo Paris J.Endothelial function [J] the .Arch Cardiol Mex of internationally recognized evaluation vascular endothelium dysfunction; 2006; 76 (Suppl2): S164-9], NO is the most important vaso-active substance of blood vessel endothelium institute synthesis secretion.NO has blood vessel dilating; The antiplatelet adhesion and aggregation; Effect such as resisting vascular smooth muscle hyperplasia [Moncade S.Nitric Oxide:physiology, pathophysiology and pharmacology [J] .Pharmacol Rev, 1997; 43:109-114], plasma nitric oxide levels can be used as the evaluation criterion of vascular endothelial injury degree.Nitric oxide and endothelin-1 (ET-1) are that blood vessel endothelium is synthetic, excretory 2 kinds of important substance.NO is a kind of micromolecule vaso-active substance; Be important endogenous vascular relaxing factor, in blood vessel endothelium, generate by NO synzyme catalysis L-arginine, and to the rapid disperse of smooth muscle cell of tunica media; Activate guanylate cyclase; Generate cGMP, and activate the cGMP dependence protein, influence Na
+-Ca
2+Exchange makes smooth muscle loosening, vasodilation.In recent years research shows that when existing metabolism indexs such as hypertension and hyperlipidemia unusual as the patient, endothelial function is impaired, the generation of NO and secretion decline [Wu Yiling. network is sick to be learned. Beijing: China Traditional Chinese Medicine Publishing House, 2006.].Endothelin (ET-1) is considered to the most intensive vaso-excitor material known today, in antiotasis relevant with vascular smooth muscle and structure long-term adjusting, works.ET-1 not only itself has the strong blood vessel function that contracts; But also the blood vessel function that contracts of enhancing 5-hydroxy tryptamine (5-HT), norepinephrine; Stimulate the hypertensin conversion enzyme activity of blood vessel endothelium and the release of epinephrine and aldosterone, stimulate mononuclear cell generation cytokine, the dividing a word with a hyphen at the end of a line and hypertrophy of stimulated vascular smooth muscle cell; Thereby promote the process [Zhang Qingde of AS; Wei Zongde. TONGXINLUO JIAONANG is to the influence [J] of serum lipid with coronary heart disease and Endothelin. Chinese cardiovascular magazine, 2006,11 (1): 20-23].ET is the height " toxicity peptide " of heart; Raise one of the sign that is that sb.'s illness took a turn for the worse of its concentration, the amplitude that available clinically ET raises is judged the state of an illness, estimating prognosis [Huang Zongming; Chen Qingzhi; Li Dongye. the damage of patients with coronary heart disease endotheliocyte and mechanism thereof [J]. Xuzhou Medical College's journal, 1999,19 (1): 19-21].Its vasoconstriction that causes, myocardial ischemia, metabolism disorder and cell proliferation are the common paathogenic factors with the blood vessel injury diseases related.
Summary of the invention
The object of the invention provides a kind of medicine of treating vascular endothelium dysfunction and preparation method thereof.
Medicine of the present invention is to be processed by the crude drug of following ratio:
Per 100 other crude drug gross weights of gram of Radix Ginseng 100-140 weight portion Lignum Dalbergiae Odoriferae 160-240 weight portion Scolopendra 50-80 weight portion add hirudin 140-190ATU anticoagulant specific activity unit.
Be preferably:
Per 100 other crude drug gross weights of gram of Radix Ginseng 120 weight portion Lignum Dalbergiae Odoriferaes 200 weight portion Scolopendras 67 weight portions add hirudin 165ATU anticoagulant specific activity unit.
Or:
Per 100 other crude drug gross weights of gram of Radix Ginseng 100 weight portion Lignum Dalbergiae Odoriferaes 165 weight portion Scolopendras 53 weight portions add hirudin 140ATU anticoagulant specific activity unit.
Or:
Per 100 other crude drug gross weights of gram of Radix Ginseng 140 weight portion Lignum Dalbergiae Odoriferaes 235 weight portion Scolopendras 80 weight portions add hirudin 190ATU anticoagulant specific activity unit.
Or:
Per 100 other crude drug gross weights of gram of Radix Ginseng 125 weight portion Lignum Dalbergiae Odoriferaes 190 weight portion Scolopendras 63 weight portions add hirudin 160ATU anticoagulant specific activity unit.
For ease of clinical practice, medicine of the present invention can be processed capsule, tablet, powder, oral liquid, soft capsule, pill, tincture, syrup, suppository, gel, spray or injection.
Medicine of the present invention can also be processed by said each extracts of bulk drugs.
The active ingredient of medicine of the present invention is processed by following steps:
1) gets prescription amount ginseng crude drug,, add medical material 8-12 the 1st time doubly to measure solvent extraction 1-2 hour, add 6-10 the 2nd time doubly to measure solvent extraction 1-2 hour, add 6-10 and doubly measured solvent extraction 0.5-1 hour for the 3rd time with 60-90% ethanol extraction 1-3 time; Merge said extracted liquid, filter while hot, decompression recycling ethanol, and concentrate, put into stainless steel cask, add pure water and stir, cold preservation 24-36h; Cold preservation liquid is taken out, put to room temperature, plate filter filters, and washs sheet frame with low amounts of water, and filtrating adds the pure water dilution, and is subsequent use; Get the AB-8 type macroporous adsorptive resins of Radix Ginseng concentrated medicament, and use ammonia, 20% ethanol, 80% ethanol elution of pH value 8-9 respectively, collect 80% ethanol elution through handling well; 80% eluent is added pure water, be made into 50% alcoholic solution,, collect eluent through the neutral alumina post, a small amount of 50% washing with alcohol pillar of reuse, it is subsequent use to merge eluent; Taking liquid adds active carbon, and reflux boils 20min, and the sheet frame sucking filtration is collected filtrating while hot, concentrates, and cold preservation is spent the night; The clarification plate filters, and drying under reduced pressure promptly gets Radix Ginseng extract;
2) get the Lignum Dalbergiae Odoriferae of prescription amount, extract volatile oil;
3) get prescription amount Scolopendra coarse powder, the normal saline of doubly measuring with 4-6 extracts 2-3 time in 60 ℃ of warm macerating, each 2-3 hour; The clarification plate filters warm macerating liquid, and filtrating merging concentrates; Add ammonium sulfate, make solution to the 40-60% saturation, placement is spent the night; Deposition is used and clarified the plate filtration, and filtrating adds ammonium sulfate, makes solution to the 80-90% saturation, and is centrifugal after placement is spent the night; The deposition of removing behind the supernatant is used water dissolution, dialysis desalting; Dialysis back solution promptly gets Scolopendra extract with the 1/2-2/3 postlyophilization that the PEG-6000 dehydration is concentrated into original volume;
4) with step 1) Radix Ginseng extract, step 2) gained volatile oil of Lignum Dalbergiae Odoriferae, step 3) gained Scolopendra extract add prescription amount hirudin mixing.
The medicine of the present invention serum NO level level that can raise reduces level of ET in plasma.
Medicine of the present invention can be made by the extraction process of routine [like model Bi Ting " pharmacy of Chinese materia medica " (Shanghai Science Press 1997 December the 1st edition)].
Medicine among the present invention, as the Chinese medicine title of crude drug and processing method thereof from " Chinese medicine voluminous dictionary " (in July, 1977, front page, Shanghai science tech publishing house) and " Chinese pharmacopoeia (version in 2005, Chemical Industry Press).
Chinese medicine composition of the present invention can also be by the preparation process of routine, and for example, the preparation technology of Fan Biting " pharmacy of Chinese materia medica " (Shanghai Science Press 1997 December the 1st edition) record processes the acceptable any conventional dosage form of pharmaceutics.
In the application of the present invention; The preparation formulation of said Chinese medicine composition is capsule, tablet, powder, oral liquid, soft capsule, pill, tincture, syrup, suppository, gel, spray or injection etc.; For above-mentioned dosage form can be realized; Need when these dosage forms of preparation, to add the pharmacy acceptable auxiliary, for example: 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, fixed, the Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods of acetic acid chloroethene; Substrate comprises: PEG6000, PEG4000, insect wax etc.For making above-mentioned dosage form can realize pharmacy of Chinese materia medica, need when these dosage forms of preparation, to add acceptable other adjuvant of pharmacy (adjuvant of each dosage form record among the Fan Biting " pharmacy of Chinese materia medica ", Shanghai Science Press December in 1997 the 1st edition).
For illustrating the activity of Drug therapy vascular endothelium dysfunction of the present invention, use the extract (to call medicine of the present invention in the following text) that makes by embodiment 1 method to carry out following clinical trial.
1 data and method
1.1 animal and grouping: 60 of healthy Wistar male rats, body weight 220～240g purchases the dimension tonneau China Experimental Animal Center in Beijing, rat is divided into following 6 groups at random by body weight, (1) normal control group (normal feed diet).(2) model group.(3) Radix Ginseng group: model group+Ginseng decoction.(4) Hirudo group: model group+Hirudo micropowder decocting liquid.(5) Scolopendra group: model group+Scolopendra decocting liquid.(6) drug group of the present invention: model group+medicine of the present invention.
1.2 medicine
Ginseng decoction: effluent north provides with mountain range Medicine Research Academy, is mixed with 0.12g crude drug/ml, and administration concentration is: 1.2g crude drug/Kg, press 1ml/100g and irritate stomach.6 days weekly.
Hirudo micropowder water decoction: effluent north provides with mountain range Medicine Research Academy, and Hirudo micropowder 300 mesh sieve percent of pass＞95%, decocting 30min filters) decocting becomes 0.1g crude drug/ml, and administration concentration is: 1g crude drug/Kg, press 1ml/100g filling stomach.6 days weekly.
The Scolopendra water decoction: effluent north provides with mountain range Medicine Research Academy, is mixed with 0.067g crude drug/ml, and administration concentration is: 0.67g crude drug/Kg, press 1ml/100g and irritate stomach.6 days weekly.
Medicine of the present invention: effluent north provides with mountain range Medicine Research Academy, is mixed with 0.427g crude drug/ml, and administration concentration is: 4.27g crude drug/Kg; Press 1ml/100g and irritate stomach.6 days weekly.
Above medicine is all processed suspension with 0.5%CMC-Na before use, and 4 ℃ of preservations are subsequent use.The medication group is when irritating the stomach medicine, and normal group and model group are irritated stomach with 0.5%CMC-Na liquid with 1ml/100g by body weight.
1.3 modeling method
Reference literature [Liang Junqing; Wu Yiling; Zhao Shaohua etc. the intervention effect that the Tongxinluo superfine powder damages homocysteine hyperamization pipe. sick basis and clinical research (2), China Science Tech Publishing House, 202～205 learned of network] employing 3% methionine diet (not limitting food); In 4 weeks, set up the endothelial function disturbance rat animal model.Methionine: the 25kg/ bag, purity 99.9%, the academy of agricultural sciences, Hebei province provides.3% homomethionin (Met) feedstuff: make by Hebei province's Experimental Animal Center.
1.4 detection index:
After 1.4.1 NO content adopts nitrate reductase method to be detected on the experiment end, 10% chloral hydrate anesthesia (0.35ml/100g), the carotid artery intubate is got blood; 4 ℃, 3500 rev/mins centrifugal 10 minutes, leave and take serum conventional the separation;-70 ℃ of preservations require to detect in strict accordance with the test kit description.
1.4.2 blood plasma ET Determination on content: adopt the method for exempting from of putting.After experiment finished, carotid artery was got blood 2ml injection and is contained 10% EDTA-Na
2In the aseptic anticoagulant test tube of 30 μ l and aprotinin 40 μ l, mixing, 4 ℃, 3000r/min, centrifugal 10min, separated plasma ,-70 ℃ of preservations require to detect in strict accordance with the test kit description.
1.5 aortic tissue light microscopic and electron microscopic observation
1.5.1 om observation is respectively organized after experiment finishes, 10% chloral hydrate intraperitoneal injection of anesthesia, the careful separation and the intercepting thoracic aorta; Fix with 4% paraformaldehyde solution; Dehydration, FFPE, section; Row HE dyeing, the general form change of laboratory animal thoracic aorta is respectively organized in observation under optical microscope.
1.5.2 transmission electron microscope observing is respectively organized after experiment finishes; 10% chloral hydrate intraperitoneal injection of anesthesia; The careful separation and a bit of tremulous pulse of intercepting; Immerse in the Electronic Speculum liquid rapidly, accomplish 1mm * 1mm * 1mm size piece of tissue, put 4 ℃ of preservations (effluent north preclinical medicine institute of medical university Electron Microscopy Room assists to accomplish) in the Electronic Speculum liquid.
1.6 statistical method:
All data are represented with mean ± standard deviation
.Adopt the SPSS-11.5 statistical package; A plurality of sample averages are relatively used one factor analysis of variance (One-Way ANOVA); Relatively use least significant difference (least significant difference in twos between a plurality of sample averages; LSD), if heterogeneity of variance then adopts Satterthwaite-t ' check row to compare in twos, with the standard of P＜0.05 as the judgement significance of difference.
2 results:
2.1 the variation of endothelial function
The model group rat obviously increases than normal group ET, and NO obviously descends, and has significant difference (P＜0.01); Each treatment group can obviously reduce the ET level (P＜0.05 or P＜0.01) of rat model; Each treatment group can increase the NO level (P＜0.05 or P＜0.01) of rat model; Drug group of the present invention has obvious effect (P＜0.05 or P＜0.01) than Radix Ginseng group, Hirudo group, Scolopendra group respectively.No significant difference (P＞0.05) between three groups of the Radix Ginsengs, Hirudo, Scolopendra.See table 1.
Between each group of table 1 Endothelin (ET), NO change relatively (
, n=10)
| Group | ET(pg/ml) | NO(umol/L) |
| Normal model group Radix Ginseng group Hirudo group Scolopendra group drug group of the present invention | 140.32±9.81171.23±10.56 **162.54±8.78 #159.38±9.45 #154.91±8.67 ##142.58±10.27 ##△△& | 44.36±5.4324.81±7.32 **35.89±4.75 ##32.76±8.52 #34.73±6.74 #42.35±9.64 ##△△&& |
Compare with normal group
*P＜0.01; Compare with model group
#P＜0.05,
##P＜0.01; Compare with the Radix Ginseng group
△P＜0.05, P＜0.01; Compare with the Hirudo group
P＜0.05,
P＜0.01; Compare with the Scolopendra group
&P＜0.05,
& &P＜0.01:
2.2 aorta pathology inspection
Normal group aorta vessel form is normal, the endotheliocyte structural integrity, and middle film elastic fibers is normal.The adventitia form is normal basically.Model group endotheliocytic swelling, skewness, density increase, and inner membrance has the volume lymphocyte to attach has cell infiltration, interior elastic plate that fracture is arranged in wall, the inner membrance; The smooth muscle cell edema.Each medication group can be improved the aorta general structure of rat model, and is more obvious with drug group of the present invention especially.See Fig. 1.
Organize the Ultrastructural variation of endotheliocyte 2.3 respectively organize rat aorta
The most of ridge of model group endotheliocyte mitochondrion merges with few part film or disappears, and almost can not see rough endoplasmic reticulum and gulps down the drink vesicle.Radix Ginseng group, Hirudo group, Scolopendra group, drug group endotheliocyte Change of Ultrastructure of the present invention alleviate than model group, and drug group effect of the present invention is organized more obvious than Radix Ginseng group, Hirudo group, Scolopendra.See Fig. 2.
3 conclusions:
This experimental result shows that during endothelial function disturbance, NO is synthetic to be reduced; ET obviously increases, and pathological examination visible vessels endotheliocyte is badly damaged, the collateral dredging Drug therapy serum NO level level that can obviously raise; Obviously reduce level of ET in plasma, shown that the collateral dredging medicine has the effect that improves endothelial function disturbance, and medicine of the present invention is more obvious than single medicinal material Radix Ginseng, Hirudo, Scolopendra effect; Aortic tissue light microscopic and electron microscopic examination have also confirmed this point, have shown the systemic effect of compound medicine.
Description of drawings:
Fig. 1: each is organized rat aorta and organizes HE dyeing (400 *)
Fig. 2: each is organized rat aorta and organizes endotheliocyte Change of Ultrastructure (20000 *)
The specific embodiment
Used hirudin is available from GuangXi KeKang hirudin Co., Ltd in implementing below the present invention to be listed as, and other Chinese crude drugs are available from Anguo medical material market.But it does not constitute any restriction to scope of the present invention.
Embodiment 1: the preparation of drug extract of the present invention
Radix Ginseng 120 gram Lignum Dalbergiae Odoriferaes 200 gram Scolopendras 67 gram hirudin 640ATU
Method for making:
1) gets prescription amount ginseng crude drug,, add 8 times of amounts of medical material solvent extraction 2 hours the 1st time, add 10 times of amounts solvent extraction 2 hours the 2nd time with 75% ethanol extraction 2 times; Merge said extracted liquid, filter while hot, decompression recycling ethanol, and concentrate, put into stainless steel cask, add pure water and stir, cold preservation 36h; Cold preservation liquid is taken out, put to room temperature, plate filter filters, and washs sheet frame with low amounts of water, and filtrating adds the pure water dilution, and is subsequent use; Get the AB-8 type macroporous adsorptive resins of Radix Ginseng concentrated medicament, and use ammonia, 20% ethanol, 80% ethanol elution of pH value 8.5 respectively, collect 80% ethanol elution through handling well; 80% eluent is added pure water, be made into 50% alcoholic solution,, collect eluent through the neutral alumina post, a small amount of 50% washing with alcohol pillar of reuse, it is subsequent use to merge eluent; Taking liquid adds active carbon, and reflux boils 20min, and the sheet frame sucking filtration is collected filtrating while hot, concentrates, and cold preservation is spent the night; The clarification plate filters, and drying under reduced pressure promptly gets Radix Ginseng extract;
2) get the Lignum Dalbergiae Odoriferae of prescription amount, extract volatile oil;
3) get prescription amount Scolopendra coarse powder, extract 2 times each 2 hours with the normal saline of 6 times of amounts in 60 ℃ of warm macerating; The clarification plate filters warm macerating liquid, and filtrating merging concentrates; Add ammonium sulfate, make solution to 50% saturation, placement is spent the night; Deposition is used and clarified the plate filtration, and filtrating adds ammonium sulfate, makes solution to 70% saturation, and is centrifugal after placement is spent the night; The deposition of removing behind the supernatant is used water dissolution, dialysis desalting; Dialysis back solution promptly gets Scolopendra extract with 3/5 postlyophilization that the PEG-6000 dehydration is concentrated into original volume;
4) with step 1) Radix Ginseng extract, step 2) gained volatile oil of Lignum Dalbergiae Odoriferae, step 3) gained Scolopendra extract add prescription amount hirudin mixing.
Embodiment 2: the preparation of medicament capsule of the present invention
Radix Ginseng 140 gram Lignum Dalbergiae Odoriferaes 235 gram Scolopendras 80 gram hirudin 864.5ATU
Method for making:
1) gets prescription amount ginseng crude drug,, add 8 times of amounts of medical material solvent extraction 2 hours the 1st time, add 6 times of amounts solvent extraction 2 hours the 2nd time, add 6 times of amounts solvent extraction 0.5 hour the 3rd time with 60% ethanol extraction 3 times; Merge said extracted liquid, filter while hot, decompression recycling ethanol, and concentrate, put into stainless steel cask, add pure water and stir, cold preservation 24h; Cold preservation liquid is taken out, put to room temperature, plate filter filters, and washs sheet frame with low amounts of water, and filtrating adds the pure water dilution, and is subsequent use; Get the AB-8 type macroporous adsorptive resins of Radix Ginseng concentrated medicament, and use ammonia, 20% ethanol, 80% ethanol elution of pH value 8.7 respectively, collect 80% ethanol elution through handling well; 80% eluent is added pure water, be made into 50% alcoholic solution,, collect eluent through the neutral alumina post, a small amount of 50% washing with alcohol pillar of reuse, it is subsequent use to merge eluent; Taking liquid adds active carbon, and reflux boils 20min, and the sheet frame sucking filtration is collected filtrating while hot, concentrates, and cold preservation is spent the night; The clarification plate filters, and drying under reduced pressure promptly gets Radix Ginseng extract;
2) get the Lignum Dalbergiae Odoriferae of prescription amount, extract volatile oil;
3) get prescription amount Scolopendra coarse powder, extract 2 times each 2 hours with the normal saline of 6 times of amounts in 60 ℃ of warm macerating; The clarification plate filters warm macerating liquid, and filtrating merging concentrates; Add ammonium sulfate, make solution to 55% saturation, placement is spent the night; Deposition is used and clarified the plate filtration, and filtrating adds ammonium sulfate, makes solution to 85% saturation, and is centrifugal after placement is spent the night; The deposition of removing behind the supernatant is used water dissolution, dialysis desalting; Dialysis back solution promptly gets Scolopendra extract with 1/2 postlyophilization that the PEG-6000 dehydration is concentrated into original volume;
4) with step 1) Radix Ginseng extract, step 2) gained volatile oil of Lignum Dalbergiae Odoriferae, step 3) gained Scolopendra extract add prescription amount hirudin mixing.
5) process capsule by conventional formulation technology.
Embodiment 3: the preparation of medicinal tablet of the present invention
Radix Ginseng 100 gram Lignum Dalbergiae Odoriferaes 165 gram Scolopendras 53 gram hirudin 445.2ATU
Method for making:
1) gets prescription amount ginseng crude drug,, add 12 times of amounts of medical material solvent extraction 1 hour the 1st time, add 6 times of amounts solvent extraction 1 hour the 2nd time with 90% ethanol extraction 2 times; Merge said extracted liquid, filter while hot, decompression recycling ethanol, and concentrate, put into stainless steel cask, add pure water and stir, cold preservation 24h; Cold preservation liquid is taken out, put to room temperature, plate filter filters, and washs sheet frame with low amounts of water, and filtrating adds the pure water dilution, and is subsequent use; Get the AB-8 type macroporous adsorptive resins of Radix Ginseng concentrated medicament, and use ammonia, 20% ethanol, 80% ethanol elution of pH value 8.5 respectively, collect 80% ethanol elution through handling well; 80% eluent is added pure water, be made into 50% alcoholic solution,, collect eluent through the neutral alumina post, a small amount of 50% washing with alcohol pillar of reuse, it is subsequent use to merge eluent; Taking liquid adds active carbon, and reflux boils 20min, and the sheet frame sucking filtration is collected filtrating while hot, concentrates, and cold preservation is spent the night; The clarification plate filters, and drying under reduced pressure promptly gets Radix Ginseng extract;
2) get the Lignum Dalbergiae Odoriferae of prescription amount, extract volatile oil;
3) get prescription amount Scolopendra coarse powder, extract 2 times each 3 hours with the normal saline of 5 times of amounts in 60 ℃ of warm macerating; The clarification plate filters warm macerating liquid, and filtrating merging concentrates; Add ammonium sulfate, make solution to 55% saturation, placement is spent the night; Deposition is used and clarified the plate filtration, and filtrating adds ammonium sulfate, makes solution to 87% saturation, and is centrifugal after placement is spent the night; The deposition of removing behind the supernatant is used water dissolution, dialysis desalting; Dialysis back solution promptly gets Scolopendra extract with 3/5 postlyophilization that the PEG-6000 dehydration is concentrated into original volume;
4) with step 1) Radix Ginseng extract, step 2) gained volatile oil of Lignum Dalbergiae Odoriferae, step 3) gained Scolopendra extract add prescription amount hirudin mixing.
5) process tablet by conventional formulation technology.
Embodiment 4: the preparation of medicine oral liquid of the present invention
Radix Ginseng 100 gram Lignum Dalbergiae Odoriferaes 165 gram Scolopendras 53 gram hirudin 445.2ATU
Method for making:
1) gets prescription amount ginseng crude drug,, add 8 times of amounts of medical material solvent extraction 1 hour the 1st time, add 10 times of amounts solvent extraction 2 hours the 2nd time with 65% ethanol extraction 2 times; Merge said extracted liquid, filter while hot, decompression recycling ethanol, and concentrate, put into stainless steel cask, add pure water and stir, cold preservation 30h; Cold preservation liquid is taken out, put to room temperature, plate filter filters, and washs sheet frame with low amounts of water, and filtrating adds the pure water dilution, and is subsequent use; Get the AB-8 type macroporous adsorptive resins of Radix Ginseng concentrated medicament, and use ammonia, 20% ethanol, 80% ethanol elution of pH value 8.5 respectively, collect 80% ethanol elution through handling well; 80% eluent is added pure water, be made into 50% alcoholic solution,, collect eluent through the neutral alumina post, a small amount of 50% washing with alcohol pillar of reuse, it is subsequent use to merge eluent; Taking liquid adds active carbon, and reflux boils 20min, and the sheet frame sucking filtration is collected filtrating while hot, concentrates, and cold preservation is spent the night; The clarification plate filters, and drying under reduced pressure promptly gets Radix Ginseng extract;
2) get the Lignum Dalbergiae Odoriferae of prescription amount, extract volatile oil;
3) get prescription amount Scolopendra coarse powder, the normal saline of doubly measuring with 4-6 extracts 2 times each 3 hours in 60 ℃ of warm macerating; The clarification plate filters warm macerating liquid, and filtrating merging concentrates; Add ammonium sulfate, make solution to 55% saturation, placement is spent the night; Deposition is used and clarified the plate filtration, and filtrating adds ammonium sulfate, makes solution to 85% saturation, and is centrifugal after placement is spent the night; The deposition of removing behind the supernatant is used water dissolution, dialysis desalting; Dialysis back solution promptly gets Scolopendra extract with 2/3 postlyophilization that the PEG-6000 dehydration is concentrated into original volume;
4) with step 1) Radix Ginseng extract, step 2) gained volatile oil of Lignum Dalbergiae Odoriferae, step 3) gained Scolopendra extract add prescription amount hirudin mixing.
5) process oral liquid by conventional formulation technology.
Embodiment 5: the preparation of medicament gelling agent of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process gel by conventional method.
Embodiment 6: the preparation of drug injection of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process injection by conventional method.
Embodiment 7: the preparation of medicinal tincture of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process tincture by conventional method.
Embodiment 8: the preparation of bolus of drug of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process pill by conventional method.
Embodiment 9: the preparation of medical syrup agent of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process syrup by conventional method.
Embodiment 10: the preparation of drug powder of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process powder by conventional method.
Embodiment 11: the preparation of drug suppository of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process suppository by conventional method.
Embodiment 12: the preparation of medicament spraying agent of the present invention
Prescription and method for making according to embodiment 1 make activity extract, process spray by conventional method.
Claims (9)
1. medicine that contains the treatment vascular endothelium dysfunction of Lignum Dalbergiae Odoriferae is characterized in that being being processed by the crude drug of following ratio:
Per 100 other crude drug gross weights of gram of Radix Ginseng 100-140 weight portion Lignum Dalbergiae Odoriferae 160-240 weight portion Scolopendra 50-80 weight portion add hirudin 140-190ATU anticoagulant specific activity unit.
2. medicine according to claim 1, the ratio of its crude drug is:
Per 100 other crude drug gross weights of gram of Radix Ginseng 120 weight portion Lignum Dalbergiae Odoriferaes 200 weight portion Scolopendras 67 weight portions add hirudin 165ATU anticoagulant specific activity unit.
3. medicine according to claim 1, the ratio of its crude drug is:
Per 100 other crude drug gross weights of gram of Radix Ginseng 100 weight portion Lignum Dalbergiae Odoriferaes 165 weight portion Scolopendras 53 weight portions add hirudin 140ATU anticoagulant specific activity unit.
4. medicine according to claim 1, the ratio of its crude drug is:
Per 100 other crude drug gross weights of gram of Radix Ginseng 140 weight portion Lignum Dalbergiae Odoriferaes 235 weight portion Scolopendras 80 weight portions add hirudin 190ATU anticoagulant specific activity unit.
5. medicine according to claim 1, the ratio of its crude drug is:
Per 100 other crude drug gross weights of gram of Radix Ginseng 125 weight portion Lignum Dalbergiae Odoriferaes 190 weight portion Scolopendras 63 weight portions add hirudin 160ATU anticoagulant specific activity unit.
6. according to the arbitrary described medicine of claim 1-5, it is characterized in that this medicine is capsule, tablet, powder, oral liquid, pill, tincture, syrup, suppository, gel, spray or injection.
7. medicine as claimed in claim 6 is characterized in that the active ingredient of this medicine is processed by following steps:
1) gets prescription amount ginseng crude drug,, add medical material 8-12 the 1st time doubly to measure solvent extraction 1-2 hour, add 6-10 the 2nd time doubly to measure solvent extraction 1-2 hour, add 6-10 and doubly measured solvent extraction 0.5-1 hour for the 3rd time with 60-90% ethanol extraction 1-3 time; Merge said extracted liquid, filter while hot, decompression recycling ethanol, and concentrate, put into stainless steel cask, add pure water and stir, cold preservation 24-36h; Cold preservation liquid is taken out, put to room temperature, plate filter filters, and washs sheet frame with low amounts of water, and filtrating adds the pure water dilution, and is subsequent use; Get the AB-8 type macroporous adsorptive resins of Radix Ginseng concentrated medicament, and use ammonia, 20% ethanol, 80% ethanol elution of pH value 8-9 respectively, collect 80% ethanol elution through handling well; 80% eluent is added pure water, be made into 50% alcoholic solution,, collect eluent through the neutral alumina post, a small amount of 50% washing with alcohol pillar of reuse, it is subsequent use to merge eluent; Taking liquid adds active carbon, and reflux boils 20min, and the sheet frame sucking filtration is collected filtrating while hot, concentrates, and cold preservation is spent the night; The clarification plate filters, and drying under reduced pressure promptly gets Radix Ginseng extract;
2) get the Lignum Dalbergiae Odoriferae of prescription amount, extract volatile oil;
3) get prescription amount Scolopendra coarse powder, the normal saline of doubly measuring with 4-6 extracts 2-3 time in 60 ℃ of warm macerating, each 2-3 hour; The clarification plate filters warm macerating liquid, and filtrating merging concentrates; Add ammonium sulfate, make solution to the 40-60% saturation, placement is spent the night; Deposition is used and clarified the plate filtration, and filtrating adds ammonium sulfate, makes solution to the 80-90% saturation, and is centrifugal after placement is spent the night; The deposition of removing behind the supernatant is used water dissolution, dialysis desalting; Dialysis back solution promptly gets Scolopendra extract with the 1/2-2/3 postlyophilization that the PEG-6000 dehydration is concentrated into original volume;
4) with step 1) income earner conopsea extraction, step 2) gained volatile oil of Lignum Dalbergiae Odoriferae, step 3) gained Scolopendra extract add prescription amount hirudin mixing.
8. medicine as claimed in claim 6 is characterized in that this medicine processes capsule, tablet, powder, oral liquid, pill, tincture, syrup, suppository, gel, spray or injection by the active component that makes according to claim 7 according to conventional method.
9. the pharmaceutical applications of medicine as claimed in claim 6 is characterized in that said medicine in preparation rising serum NO level level, reduces the application in the level of ET in plasma medicine.
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| CN2007101880579A CN101439077B (en) | 2007-11-23 | 2007-11-23 | Medicament containing dalbergia heartwood for treating blood vessel endothelium dysfunction and preparation method thereof |
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| CN2007101880579A CN101439077B (en) | 2007-11-23 | 2007-11-23 | Medicament containing dalbergia heartwood for treating blood vessel endothelium dysfunction and preparation method thereof |
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| CN102038940A (en) * | 2009-10-09 | 2011-05-04 | 伍丽娟 | Hirudin combination medicament for treating cardiovascular and cerebrovascular diseases |
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| CN1485061A (en) * | 2002-09-23 | 2004-03-31 | 天津天士力制药股份有限公司 | Gingko leaf drop pill |
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| CN1485061A (en) * | 2002-09-23 | 2004-03-31 | 天津天士力制药股份有限公司 | Gingko leaf drop pill |
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