CN100551921C - The purposes of brasilein - Google Patents
The purposes of brasilein Download PDFInfo
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- CN100551921C CN100551921C CNB2007101220846A CN200710122084A CN100551921C CN 100551921 C CN100551921 C CN 100551921C CN B2007101220846 A CNB2007101220846 A CN B2007101220846A CN 200710122084 A CN200710122084 A CN 200710122084A CN 100551921 C CN100551921 C CN 100551921C
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- brasilein
- blood pressure
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- bush
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- MLWIYODOURBGPI-UHFFFAOYSA-N brazilein Natural products C12=CC=C(O)C=C2OCC2(O)C1=C1C=C(O)C(=O)C=C1C2 MLWIYODOURBGPI-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 230000036772 blood pressure Effects 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 238000000605 extraction Methods 0.000 abstract description 11
- 206010020772 Hypertension Diseases 0.000 abstract description 9
- 241001465754 Metazoa Species 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 2
- 206010008132 Cerebral thrombosis Diseases 0.000 abstract description 2
- 201000001429 Intracranial Thrombosis Diseases 0.000 abstract description 2
- 239000007864 aqueous solution Substances 0.000 abstract description 2
- 208000029078 coronary artery disease Diseases 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 6
- 239000002504 physiological saline solution Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 230000004872 arterial blood pressure Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 230000035487 diastolic blood pressure Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 210000002254 renal artery Anatomy 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 101800004637 Communis Proteins 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- UWHUTZOCTZJUKC-JKSUJKDBSA-N brazilin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C=C1OC2 UWHUTZOCTZJUKC-JKSUJKDBSA-N 0.000 description 2
- UWHUTZOCTZJUKC-CVEARBPZSA-N brazilin Natural products C12=CC(O)=C(O)C=C2C[C@@]2(O)[C@@H]1C1=CC=C(O)C=C1OC2 UWHUTZOCTZJUKC-CVEARBPZSA-N 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 210000003191 femoral vein Anatomy 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- -1 tincture Substances 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 235000015162 Caesalpinia sappan Nutrition 0.000 description 1
- 244000306301 Caesalpinia sappan Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- RLLPVAHGXHCWKJ-UHFFFAOYSA-N permethrin Chemical compound CC1(C)C(C=C(Cl)Cl)C1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 RLLPVAHGXHCWKJ-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The purposes of brasilein relates to a kind of new purposes of the brasilein of separating from the bush heartwood.The present invention adopts alkali aqueous solution to extract, and does not relate to organic solvent, so extraction cost is low, operational safety.Animal experiment proves simultaneously, and prepared brasilein can be used for preparing the caused illness of elevation of blood pressure in the treatment body, as various types of hypertension, atherosclerosis, coronary heart disease, cerebral thrombosis and hematencephalon etc.
Description
Technical field
The present invention relates to the bush is the preparation method of the brasilein that extracts of raw material and the new purposes aspect medical, belongs to technical field of traditional Chinese medicines.
Background technology
Bush is the dry duramen of leguminous plants bush Caesalpinia sappan L..Be distributed in the Guangxi of China, Guangdong, Taiwan, Guizhou, Yunnan, ground such as Sichuan.Can adopt the whole year.Remove crust and sapwood, the material of coring dries.Contain brazilin (brasilin), brasilein compositions such as (brasilein).With the bush is the brasilein (C that raw material extracts
16H
12O
5) structural formula as follows:
Physicochemical characteristic:
Yellow powder (MeOH), mp>300 ℃ (dec.), TLC checks: apparent brilliant white fluorescence under the ultraviolet lamp 365nm.
EI-MSm/z:248(M+),231,214.
IR(KBr)cm-1:3400,1705(C=O),1670,1600,1520,1410,1390,1100。
UV(MeOH)nm:276,352。
1H NMR (DMSO-d
6) δ: 2.5 (2H, with, H-2), 3.2 (2H, with, H-3), 7.3 (1H,, H-7).
13C?NMR(DMSO-d
6)δ:23.7(C-3),32.9(C-2),107.8(C-7),113.1(C-6),115.4(C-4),140.0(C-5),141.4(C-9),144.1(C-8),144.9(C-10),149.1(C-12),160.5(C-11),195.5(C-1)。
The Compendium of Material Medica record: bush has the effect of " broken blood, apocenosis pain relieving ".Cure mainly married woman's vim and vigour pain in the chest and abdomen, subduing inflammation pounce on decrease hemostasis ", " Chinese medicine voluminous dictionary-first volume " record: bush has the effect of " stasis of blood, swelling and pain relieving are broken in promoting circulation of blood ".
In the prior art, organic solvent is adopted in the extraction of brasilein, this method extraction cost height, and processing safety is poor.
Summary of the invention
The purpose of this invention is to provide the new purposes of brasilein aspect medical.
Another object of the present invention provides a kind of preparation method of brasilein, is intended to reduce extraction cost, improves the security of operation.
Technical scheme of the present invention is as follows:
A kind of preparation method of medicament compound brasilein is characterized in that this method comprises the steps:
1) extraction is heated with 5~15 times buck solvent of medicinal material weight by elder generation, obtains extracting solution;
2) extracting solution is at room temperature added acid, making pH value is 2~6, centrifugal or static filtration, and abandoning supernatant, taking precipitate, dry then, get dry thing;
3) dry thing is dissolved with alcohol, carry out chromatographic separation, promptly make brasilein.
In above-mentioned preparation method, it is 0.01~6% that used water liquid caustic soda concentration is extracted in the heating described in the step 1).It is that 30 ℃~100 ℃ described extraction times are 1~3 time that used temperature is extracted in described heating, is 30 minutes to 5 hours at every turn.
The purposes of medicament compound brasilein provided by the present invention mainly is meant the application in the medicine of the disease for preparing the treatment elevation of blood pressure and cause thus.
When clinical application,, use separately or prepare the medicine of operable various different dosage forms clinically with other drug with the preparation process of routine.As powder, pill, capsule, tablet, microcapsule, soft capsule, film, suppository, injection, paste, tincture, powder, electuary, aerosol, various external preparations etc.
Experimental result of the present invention shows that brasilein has the effect that tangible reduction normally reaches hypertensive rat blood pressure.Pharmacological evaluation shows, brasilein has the effect that reduces experimental rat periphery blood pressure, with this compound is activeconstituents, can be used for preparing the caused illness of elevation of blood pressure in the treatment body, as various types of hypertension, atherosclerosis, coronary heart disease, cerebral thrombosis and hematencephalon etc.
Preparation method of the present invention compares with existing preparation method, and this method is simple to operate, owing to adopt potass extraction, do not relate to organic solvent, so extraction cost is low, the processing safety height.
Embodiment
The preparation method of medicament compound brasilein provided by the invention, its concrete processing step is as follows:
1) extraction is heated with 5~15 times buck solvent of medicinal material weight by elder generation, obtains extracting solution.It is 30 ℃~100 ℃ that used temperature is extracted in heating, and extraction time is generally 1~3 time, is 30 minutes to 5 hours at every turn.Used water liquid caustic soda concentration is 0.01~6%.
2) extracting solution is at room temperature added acid, making pH value is 2~6, centrifugal or static filtration, and abandoning supernatant, taking precipitate, dry then, get dry thing;
3) dry thing is dissolved with alcohol, carry out chromatographic separation, promptly make brasilein.
Preparation that the following examples and drug study data make the said brasilein of the present invention and uses thereof is confirmed, should not regard the following example as limitation of the present invention again simultaneously.
Preparation embodiment 1:
Bush heartwood (500 gram) is with 0.01% aqueous sodium hydroxide solution of 5 times of weight, and heating (100 ℃) is extracted 3 times, and each 5 hours, extracting solution is put to the room temperature with in the acid, making pH value is 2, leaves standstill, taking precipitate is abandoned supernatant liquor, drying.Dry product adds dissolve with ethanol, with 200~300 order silica gel mixed samples, separates with silica gel column chromatography, uses sherwood oil: the acetone gradient elution, column chromatography liquid is concentrated, and use the dextrane gel purifying, the final brasilein that gets.
Preparation embodiment 2:
Bush heartwood (500 gram) is with 2% aqueous sodium hydroxide solution of 10 times of weight, and heating (80 ℃) is extracted 2 times, and each 3 hours, extracting solution is put to the room temperature with the acid neutralization, making pH value is 5, leaves standstill, and abandons supernatant liquor, gets precipitation, will precipitate drying.Dry product adds dissolve with ethanol, mixes sample with 60~80 order polymeric amide, and with the polyamide column chromatography separation, water and ethanol elution are collected ethanol eluate and concentrated respectively, use the dextrane gel purifying, the final brasilein that gets.
The preparation embodiment 3: the extraction of brasilein with separate preparation
Bush heartwood (500 gram) is with 6% potassium hydroxide aqueous solution of 15 times of weight, and heating (30 ℃) is extracted 2 times, and each 1 hour, extracting solution put to the room temperature neutralize with acid that to make pH value be 6, leave standstill, abandon supernatant liquor, get precipitation, drying.Dry product adds dissolve with methanol, and with oppositely (ODS) column chromatography separation, difference water and methanol-eluted fractions, the collection meoh eluate also concentrates, and uses the dextrane gel purifying, the final brasilein that gets.
Effect experiment example 1: to the influence of normal rat periphery blood pressure
Observe the influence of brasilein of the present invention to normal rat periphery blood pressure.The used brasilein of the present invention, lot number: 070131.Brasilein is dissolved with DMSO, be mixed with desired concn with physiological saline.Testing used animal is male Wistar rat, and Institute of Experimental Animals, Chinese Academy of Medical Sciences provides, and body weight is 250-320g.Laboratory room temperature 25-28 ℃, relative humidity 40%~60%, the ventilator ventilation, lamp 12h/ day, raise in cages, 5 in every cage, per three days cleaning cage houses are once.
Get normal rat, 10% urethane abdominal injection, with its anesthesia, fixing.Separate arteria carotis communis, insert plastic catheter, be connected in pressure transducer and four and lead physiograph.Open computer, monitored 15 minutes, the record normal arterial pressure.Femoral vein gives brasilein.Respectively at observation in 5,10,15,30,45,60,75,90 minutes and recording blood pressure value after the administration.Calculate systolic pressure, diastolic pressure and mean arterial pressure.
The gained data are through the EXCEL software processes.The SPSS10.0 software processes, variance analysis, t check between group.
This test brasilein dosage is respectively 1.25,2.5,5mg/kg.
This test is prepared with solubility promoter physiological saline with brasilein, its solubility promoter concentration 0.5%DMSO, 4% hydroxypropyl-beta-cyclodextrin.This tests used blank is equal-volume solubility promoter physiological saline (0.5%DMSO, 4% hydroxypropyl-beta-cyclodextrin).
The variation of normal rat blood pressure before table 1 administration (x ± s)
Compare P>0.05 with control group.n=6
The variation of 45 minutes normal rat blood pressures after table 2 administration (x ± s)
Compare * P<0.05, * * P<0.01 with control group.n=6
This experimental result shows that brasilein has the reduction effect to normal rat blood pressure.Its subliminal dose is 2.5mg/kg.Be characterized in dropping to the master many behind medicine 30-45 minute of the blood pressure drops time after the administration with diastolic pressure.The prompting brasilein has certain hypotensive activity, because of the caused cardiovascular and cerebrovascular diseases of hyperpiesia positive meaning is arranged all for control.
Effect experiment example 2: to the influence of acute hypertension rat periphery blood pressure
Observe the influence of brasilein of the present invention to acute hypertension rat periphery blood pressure.The used brasilein of the present invention, lot number: 070131.Brasilein is dissolved with DMSO, be mixed with desired concn with physiological saline.Testing used animal is male Wistar rat, and Institute of Experimental Animals, Chinese Academy of Medical Sciences provides, and body weight is 250-320g.Laboratory room temperature 25-28 ℃, relative humidity 40%~60%, the ventilator ventilation, lamp 12h/ day, raise in cages, 5 in every cage, per three days cleaning cage houses are once.
Get normal rat, with 10% urethane intraperitoneal injection of anesthesia, the ventricumbent position is fixed on the operating table, separates arteria carotis communis, inserts plastic catheter, is connected in pressure transducer and four and leads physiograph.Open computer, monitored 15 minutes, the record normal arterial pressure.Open the abdominal cavity then, separate left renal artery, close left renal artery with the bulldog clamp folder, in the time of 15 minutes, femoral vein gives brasilein, unclamps bulldog clamp in 15 minutes after the administration, makes left renal artery logical again, at this moment recording blood pressure.Respectively at unclamping behind the bulldog clamp 5,10,15,30, observed and the recording blood pressure value in 45,60 minutes.Systolic pressure, diastolic pressure and mean arterial pressure when calculating is unclamped behind the artery 15 minutes.
The gained data are through the EXCEL software processes.The SPSS10.0 software processes, variance analysis, t check between group.
This test brasilein dosage is respectively 1.25,2.5,5mg/kg.
This test is prepared with solubility promoter physiological saline with brasilein, its solubility promoter concentration 0.5%DMSO, 4% hydroxypropyl-beta-cyclodextrin.This tests used blank is equal-volume solubility promoter physiological saline (0.5%DMSO, 4% hydroxypropyl-beta-cyclodextrin).
Table 3 brasilein is to the influence of hypertensive rat blood pressure (irritating again 15 minutes) (x ± s)
Compare * * P<0.01, * P<0.05 with control group.n=6
This experimental result shows that brasilein has the reduction effect to normal and hypertensive rat blood pressure.Its subliminal dose is 2.5mg/kg.The prompting brasilein has certain hypotensive activity, because of the caused cardiovascular and cerebrovascular diseases of hyperpiesia positive meaning is arranged all for control.
Claims (1)
1. the application of brasilein in the medicine of the disease for preparing the treatment elevation of blood pressure and cause by elevation of blood pressure.
Priority Applications (1)
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CNB2007101220846A CN100551921C (en) | 2007-09-21 | 2007-09-21 | The purposes of brasilein |
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CNB2007101220846A CN100551921C (en) | 2007-09-21 | 2007-09-21 | The purposes of brasilein |
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CN101984959A (en) * | 2010-11-09 | 2011-03-16 | 清华大学 | Freeze-dried powder injection for injecting brazilein and preparation method thereof |
CN102329294A (en) * | 2011-07-26 | 2012-01-25 | 苏州宝泽堂医药科技有限公司 | Method for extracting brasilein |
JP2013116857A (en) * | 2011-12-01 | 2013-06-13 | Kao Corp | Angiotensin ii activity inhibitor |
CN105726529A (en) * | 2016-02-18 | 2016-07-06 | 云南民族大学 | Water-soluble drug dracaena fragrans compound and preparing method thereof |
AU2018267059B2 (en) * | 2017-05-10 | 2021-08-12 | Ventana Medical Systems, Inc. | Stabilized two-part hematoxylin solution utilizing pH adjustment |
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2007
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Non-Patent Citations (6)
Title |
---|
Brazilin protects cultured rat hepatocytes from BrCCl3-inducedtoxicity. Chang-kiu Moon, et al.Drug and chemical toxicology,Vol.15 No.1. 1992 |
Brazilin protects cultured rat hepatocytes from BrCCl3-inducedtoxicity. Chang-kiu Moon, et al.Drug and chemical toxicology,Vol.15 No.1. 1992 * |
正交法优选中药材苏木水提取工艺. 郭荣辉等.四川大学学报(工程科学版),第36卷第3期. 2004 |
正交法优选中药材苏木水提取工艺. 郭荣辉等.四川大学学报(工程科学版),第36卷第3期. 2004 * |
苏木精提取工艺研究. 郭宝星.四川中医,第21卷第4期. 2003 |
苏木精提取工艺研究. 郭宝星.四川中医,第21卷第4期. 2003 * |
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