CN101125846A - Preparation method for medicament compound brasilein and use thereof - Google Patents
Preparation method for medicament compound brasilein and use thereof Download PDFInfo
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- CN101125846A CN101125846A CNA2007101220846A CN200710122084A CN101125846A CN 101125846 A CN101125846 A CN 101125846A CN A2007101220846 A CNA2007101220846 A CN A2007101220846A CN 200710122084 A CN200710122084 A CN 200710122084A CN 101125846 A CN101125846 A CN 101125846A
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- brasilein
- preparation
- medicament compound
- blood pressure
- extraction
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Abstract
A medicine compound Brazilian haematein prime and a preparation method and function thereof relate to the preparation method of a medicine compound that is separated from lignum sappan heartwood. Aqueous alkaline solution extraction is adopted in the method, and no organic solvent is involved, therefore, the extraction cost is low and the operation is safe. Experiments with animals also prove that the produced Brazilian haematein prime is suitable for medicine preparation or curing diseases that are caused by blood pressure elevation in human body, such as various high blood pressures, arterial sclerosis of porridge type, coronary heart disease, cerebral thrombosis and cerebral hemorrhage, 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 preparation method of a kind of medicament compound brasilein, be intended to reduce extraction cost, improve the security of operation.
Another object of the present invention provides the new purposes of medicament compound brasilein aspect medical.
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)
| Grouping | Drug dose (mg/Kg) | Systolic pressure (mmHg) | Diastolic pressure (mmHg) | Mean arterial pressure (mmHg) |
| Control group brasilein brasilein brasilein | 1.25 2.5 5.0 | 124.0±7.45 123.83±9.33 126.5±10.63 125.17±11.05 | 92.17±6.21 91.5±6.28 93.5±5.28 92.33±3.93 | 108.08±3.94 107.67±4.86 110.0±4.32 108.75±5.52 |
Compare P＞0.05 with control group.n＝6
The variation of 45 minutes normal rat blood pressures after table 2 administration (x ± s)
| Grouping | Drug dose (mg/Kg) | Systolic pressure (mmHg) | Diastolic pressure (mmHg) | Mean arterial pressure (mmHg) |
| Control group brasilein brasilein brasilein | 1.25 2.5 5.0 | 125.67±10.01 102.83±6.85** 110.17±11.05* 1107.17±12.54 | 89.67±9.16 69.83±4.17** 76.83±8.33* 79.5±6.25* | 107.67±8.19 86.33±4.27** 93.5±7.48* 98.33±5.36 |
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)
| Grouping | Drug dose (mg/Kg) | Systolic pressure (mmHg) | Diastolic pressure (mmHg) | Mean arterial pressure (mmHg) |
| The control group brasilein | 1.25 | 136.67±10.13 106.17±10.48** | 93.5±5.61 71.83±8.79** | 116.58±5.83 89.0±7.04** |
| The brasilein brasilein | 2.5 5.0 | 117.33±10.23* 129.67±6.71 | 82.0±9.65* 84.5±6.53* | 99.67±8.84* 107.08±5.16* |
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 (6)
1. the preparation method of a medicament compound brasilein is characterized in that this method comprises the steps:
1) extraction is heated with 5～15 times alkali aqueous solution 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.
2. according to the preparation method of the described medicament compound brasilein of claim 1, it is characterized in that: the concentration that used alkali aqueous solution is extracted in the heating described in the step 1) is 0.01～6%.
3. according to the preparation method of the described medicament compound brasilein of claim 1, it is characterized in that: it is 30 ℃～100 ℃ that used temperature is extracted in the heating described in the step 1).
4. according to the preparation method of the described medicament compound brasilein of claim 1, it is characterized in that: the extraction time described in the step 1) is 1～3 time, is 30 minutes to 5 hours at every turn.
5. according to the preparation method of the described medicament compound brasilein of claim 1, it is characterized in that: described alcohol adopts ethanol or methyl alcohol.
6. the application of medicament compound 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)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007101220846A CN100551921C (en) | 2007-09-21 | 2007-09-21 | The purposes of brasilein |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007101220846A CN100551921C (en) | 2007-09-21 | 2007-09-21 | The purposes of brasilein |
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| Publication Number | Publication Date |
|---|---|
| CN101125846A true CN101125846A (en) | 2008-02-20 |
| CN100551921C CN100551921C (en) | 2009-10-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007101220846A Expired - Fee Related CN100551921C (en) | 2007-09-21 | 2007-09-21 | The purposes of brasilein |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110621974A (en) * | 2017-05-10 | 2019-12-27 | 文塔纳医疗系统公司 | Stabilized two-part hematoxylin solution with pH adjustment |
-
2007
- 2007-09-21 CN CNB2007101220846A patent/CN100551921C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110621974A (en) * | 2017-05-10 | 2019-12-27 | 文塔纳医疗系统公司 | Stabilized two-part hematoxylin solution with pH adjustment |
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| Publication number | Publication date |
|---|---|
| CN100551921C (en) | 2009-10-21 |
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Granted publication date: 20091021 Termination date: 20100921 |