CN1923193A - Application of cumarin kind compound in preparation of antiphlogistic and analgetic medicine - Google Patents
Application of cumarin kind compound in preparation of antiphlogistic and analgetic medicine Download PDFInfo
- Publication number
- CN1923193A CN1923193A CN 200610030920 CN200610030920A CN1923193A CN 1923193 A CN1923193 A CN 1923193A CN 200610030920 CN200610030920 CN 200610030920 CN 200610030920 A CN200610030920 A CN 200610030920A CN 1923193 A CN1923193 A CN 1923193A
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- CN
- China
- Prior art keywords
- hydrogen
- hydroxyl
- phenyl
- coumarin
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000003814 drug Substances 0.000 title claims abstract description 20
- 150000001875 compounds Chemical class 0.000 title claims description 31
- 230000000202 analgesic effect Effects 0.000 title description 5
- PQMOXTJVIYEOQL-UHFFFAOYSA-N Cumarin Natural products CC(C)=CCC1=C(O)C(C(=O)C(C)CC)=C(O)C2=C1OC(=O)C=C2CCC PQMOXTJVIYEOQL-UHFFFAOYSA-N 0.000 title 1
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- 239000002260 anti-inflammatory agent Substances 0.000 title 1
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- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 claims abstract description 9
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
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Abstract
本发明属医药技术领域，具体为一种香豆素类化合物在制备抗炎镇痛药物中的应用。该香豆素类化合物比较典型的有如下10种：7－羟基香豆素、7－羟基－8－甲氧基香豆素、7－甲氧基－8－羟基香豆素、秦皮乙素、3，4－二甲基－7－乙氧基香豆素、瑞香苷、双白瑞香素、Edgeworin、结香苷C和结香苷A。试验表明，该香豆素类化合物具有明显抗炎镇痛作用，因此可以用于制备抗炎镇痛药物。所制备的药物可以是以该香豆素类化合物为活性成分，并含有药学上可以接受的载体的组合物，其中活性成分的重量含量为0.1－99.5％。药物的剂型可以是片剂、粉剂、粒剂、胶囊或注射剂等。The invention belongs to the technical field of medicine, and specifically relates to the application of a coumarin compound in the preparation of anti-inflammatory and analgesic drugs. The typical coumarin compounds are as follows 10 kinds: 7-hydroxycoumarin, 7-hydroxy-8-methoxycoumarin, 7-methoxy-8-hydroxycoumarin, alopecia . Tests show that the coumarin compound has obvious anti-inflammatory and analgesic effects, so it can be used to prepare anti-inflammatory and analgesic drugs. The prepared medicine can be a composition with the coumarin compound as an active ingredient and a pharmaceutically acceptable carrier, wherein the weight content of the active ingredient is 0.1-99.5%. The dosage form of the medicine can be tablet, powder, granule, capsule or injection etc.
Description
Technical field
The invention belongs to medical technical field, be specifically related to the application of coumarin kind compound in the various pain of treatment and relief of symptoms and prevention and the various active chronic inflammation medicines of treatment.
Background technology
Anti-inflammation analgesia medicine is the common drug that a class has antiinflammatory, analgesic, analgesia and anti rheumatism action.Clinical anti-inflammation analgesia medicine commonly used mainly is not a nonsteroidal antiinflammatory drug (NSAIDs) at present.NSAIDs has been widely used in the analgesia of rheumatoid disease and non-atrophic diseases, comprises the abdominal pain and the menstrual pain such as pain, chronic pain, biliary colic and renal colic of acute postoperative.Traditional NSAID (non-steroidal anti-inflammatory drug) gastrointestinal tract, coagulation function and the infringement of ground, renal function aspect occur inevitably because of the increase of dosage, the course of treatment and patient age, has restricted its range of application.Chinese medicine has magical curative effect and is approved by the world aspect promoting health and curing diseases.Therefore the chemical constituent in the research tradition Chinese medicine provides a new approach for the research and development that searching has the little active component of anti-inflammatory and analgesic effect and toxic and side effects.
Just have being that the coumarin kind compound of representative has the bibliographical information of anti-inflammatory and analgesic effect with the daphnetin as far back as the 1980s, but do further investigation and developmental research.In recent years the research of coumarin kind compound is further goed deep into, but up to the present, still found no the Coumarins composition and make the bibliographical information of anti-inflammation analgesia medicine with it.The inventor confirms that through great deal of experimental coumarin kind compound has anti-inflammatory and analgesic effect, can treat various pain and relief of symptoms and prevention and the various active chronic inflammations of treatment, and make medicament, has finished the present invention.
Summary of the invention
The objective of the invention is to propose the medical usage of a kind of coumarin kind compound aspect the preparation anti-inflammation analgesis medicament.
The present invention also further provides one group to be active component with this compounds, is used for the treatment of the pharmaceutical composition of various pain and relief of symptoms and prevention and the various active chronic inflammations of treatment.
The coumarin kind compound that is used to prepare anti-inflammation analgesis medicament that the present invention proposes has a kind of of following general structure:
R in the formula
1Be hydrogen, alkoxyl, alkylamino, phenyl or carboxyl; R
2Be hydrogen, C
1-6Alkyl, a 1-5 unitary sugar chain or C
1～6Acyl group; R
3Be hydrogen, hydroxyl, alkoxyl, alkylamino, phenyl or carboxyl; R
4, R
5Be hydrogen, hydroxyl, phenyl or isopentene group.
R in the formula
1Be hydrogen, C
1-6Alkyl, a 1-5 unitary sugar chain or C
1～6Acyl group; R
2Be hydrogen, hydroxyl, alkoxyl, alkylamino, phenyl or carboxyl; R
3Be hydrogen, hydroxyl, phenyl or isopentene group; R
4Be hydrogen, hydroxyl, phenyl or isopentene group.
R in the formula
1, R
3Be hydrogen, C
1-6Alkyl, 1-5 unitary sugar chain, C
1～6Acyl group; R
2, R
4Be hydrogen, hydroxyl, alkoxyl, alkylamino, phenyl, carboxyl.
R in the formula
1, R
3Be hydrogen, C
1-6Alkyl, a 1-5 unitary sugar chain or C
1～6Acyl group; R
2, R
4Be hydrogen, hydroxyl, alkoxyl, alkylamino, phenyl or carboxyl.R
5, R
6Be hydrogen, hydroxyl, phenyl or isopentene group.
These four kinds of coumarin kind compounds mainly are distributed in botanic many kind of plant, can prepare and get by extraction separation from plant, also can obtain with the chemosynthesis mode.
Physiologically active:
The present invention has carried out the evaluation experimental (seeing Table 1) of anti-inflammatory and antalgic activity to typical following 10 coumarin kind compounds wherein.
(1) mouse writhing method
1. laboratory animal
Swiss kind mice, male, body weight 20-24g.
2. experimental model and method of testing
The mice random packet is divided blank group (NS group), positive controls (aspirin group), administration group, 10 every group.Every animal equal gastric infusion every day once, each 0.5ml, altogether administration 5d (positive controls since the 3rd day to aspirin liquid 0.5ml, all the other times are all to NS 0.5ml).The 5th day mouse stomach administration 1h pneumoretroperitoneum only injected 0.8% acetum 0.2ml/, and that observes mice in the 20min thereafter turns round the body number of times.Abdominal part and hind leg extend because of stimulation and once are defined as writhing response one time.
3 statistical analysiss:
Suppress percentage rate=(the blank group is on average turned round body number of times-administration group and on average turned round the body number of times)/blank group and on average turn round body number of times * 100%;
All experimental result is all represented with mean ± standard error.Respectively organize data and the blank significant difference of organizing with student t-check, P＜0.05, expression difference has the significance meaning.
4 result of the tests:
Table 1: the coumarin kind compound Dichlorodiphenyl Acetate causes the influence of mice pain
Compare with the blank group,
*P＜0.05,
*P＜0.01,
* *P＜0.001
The result shows, the pain that positive control drug hydrocortisone, 10 Coumarins composition Dichlorodiphenyl Acetates cause mice has significant inhibitory effect, and the action effect of 7-hydroxyl-8-methoxy coumarin, daphnoretin and Edgeworthia chrysantha Lindl. glycosides A is the strongest.
(2) mice hot plate method
1. laboratory animal
Swiss kind mice, female, body weight 20-24g.
2. experimental model and method of testing
Mice is placed on the hot plate of preheating 10min in (55 ± 0.5) ℃ water-bath 1/time.Mice is from being placed on the hot plate to the pain threshold of sufficient metapedes required time (second) as this Mus occurring licking, allly licks the sufficient time and gives it up less than 5s or greater than 30s or leaper.Get the qualified mice random packet of screening, divide blank group (NS group), positive controls (aspirin group), administration group, 10 every group.Survey pain threshold of each group, with the meansigma methods of 2 pain thresholds as its normal pain threshold.Administration subsequently, every equal gastric infusion of animal once, each 0.5ml.After the administration 20,40,60min surveys the mice pain threshold.
3 statistical analysiss:
All experimental result is all represented with mean ± standard error.Respectively organize data and the blank significant difference of organizing with student t-check, P＜0.05, expression difference has the significance meaning.
4 result of the tests:
Table 2 coumarin kind compound is to the influence of thermostimulation pain
| Group | Dosage (mg/kg) | n | Pain threshold before the administration (x ± s) | Pain threshold after the administration (x ± s) | ||
| 20min | 40min | 60min | ||||
| Blank | - | 10 | 16.2±2.1 | 16.0±5.2 | 14.2±4.3 | 13.2±4.3 |
| Aspirin | 300 | 10 | 17.2±4.0 | 34.1±6.0 ** | 39.8±4.7 ** | 47.0±5.6 ** |
| Umbelliferone | 10 20 40 | 10 10 10 | 17.2±4.5 16.3±3.4 17.0±4.4 | 21.0±14.3 29.4±17.1 ** 34.3±18.2 ** | 20.3±9.2 22.0±6.1 * 22.1±9.1 * | 18.2±6.3 22.1±9.0 * 22.3±8.3 * |
| 7-hydroxyl-8-methoxy coumarin | 10 20 40 | 10 10 10 | 16.2±1.3 17.1±2.7 16.4±5.2 | 20.4±4.4 22.7±6.5 * 26.4±6.5 * | 25.4±4.4 * 27.4±5.1 ** 30.6±4.7 ** | 25.1±3.3 * 27.8±4.1 ** 33.5±4.8 ** |
| 7-methoxyl group-8-Hydroxycoumarin | 10 20 40 | 10 10 10 | 17.1±3.8 17.0±4.6 16.8±5.1 | 18.6±3.1 22.0±8.6 * 22.5±7.2 * | 18.8±5.1 23..8±5.6 * 23.0±6.5 * | 19.3±3.2 23.5±6.4 * 23.2±6.2 * |
| Aesculetin | 10 20 40 | 10 10 10 | 16.7±2.5 16.9±3.1 16.9±1.9 | 17.7±3.1 22.1±5.2 * 22.4±2.9 * | 17.9±4.3 23.5±4.5 * 23.6±3.4 * | 18.0±2.6 23.6±3.2 * 23.6±2.0 * |
| 3.4-dimethyl-7-ethoxy coumarin | 10 20 40 | 10 10 10 | 17.0±3.1 17.1±2.9 16.8±4.7 | 17.9±2.3 21.8±4.2 21.6±2.7 | 18.6±3.1 22.0±6.1 22.2±5.6 * | 18.9±2.8 22.0±4.5 22.1±2.9 * |
| Daphnin | 10 20 40 | 10 10 10 | 16.9±3.3 16.6±2.5 17.0±5.1 | 20.5±6.11 21.6±9.0 24.2±7.0 * | 21.1±7.2 24.8±4.2 * 23.1±4.4 * | 22.9±5..3 * 25.4±4.2 * 25.6±3.2 * |
| Daphnoretin | 10 20 40 | 10 10 10 | 16.5±3.6 16.6±4.5 16.9±4.3 | 21.4±2.1 24.1±1.9 * 25.3±2.1 * | 23.9±9.1 * 25.3±6.3 * 27.1±6.0 ** | 23.8±6.8 * 23.2±6.1 * 27.9±7.1 ** |
| Edgeworin | 10 20 40 | 10 10 10 | 16.8±4.2 17.2±4.8 17.0±3.1 | 21.2±4.4 21.6±9.2 22.8±3.1 * | 21.4±5.1 23.7±5.2 * 24.8±4.3 * | 22.1±4.7 26.9±3.3 * 25.2±3.1 * |
| Edgeworthia chrysantha Lindl. glycosides C | 10 20 40 | 10 10 10 | 16.6±4.7 17.1±3.7 17.1±4.2 | 22.3±3.8 21.9±7.1 21.5±7.3 | 22.9±5.4 21.7±6.2 26.7±6.0 ** | 21.44±5.0 29.8±6.2 ** 27.6±7.2 ** |
| Edgeworthia chrysantha Lindl. glycosides A | 10 20 40 | 10 10 10 | 17.0±2.9 16.5±4.8 16.7±5.0 | 25.1±3.1 * 24.3±9.0 * 25.3±7.0 * | 22.9±1.1 27.1±6.2 ** 27.6±5.6 ** | 29.2±4.1 ** 27.7±7.2 ** 30.3±6.3 ** |
Compare with the blank group,
*P＜0.05,
*P＜0.01,
* *P＜0.001
The result shows that positive control drug aspirin, 10 Coumarins compositions cause that to thermostimulation right pain has significant inhibitory effect, and the action effect of umbelliferone, 7-hydroxyl-8-methoxy coumarin and Edgeworthia chrysantha Lindl. glycosides A is the strongest.
(3) mice ear model
1 laboratory animal
Swiss kind mice, male, body weight 20-24g.
2. experimental model and method of testing
Get 260 of mices, be divided into 26 groups at random, press the dosage gastric infusion 3d shown in the table 3,1h after the last administration, dimethylbenzene with 0.05ml causes inflammation with mice left side ear, the card punch that with diameter is 7mm is the overlapping punching of ears, and the disk of laying is gone up weighing at torsion balance (sensitivity be ten thousand/), represents its swelling degree with the weight difference of Mus ear two disks.
3 statistical analysiss:
All experimental result is all represented with mean ± standard error.Respectively organize data and the blank significant difference of organizing with student t-check, P＜0.05, expression difference has the significance meaning.
4 result of the tests:
Table 3. coumarin kind compound is to the influence of mice ear test
| Group | Dosage (mg/kg) | n | Ear swelling (mg) | Suppression ratio (%) |
| Blank | - | 10 | 19.58±2.31 | - |
| Hydrocortisone | 20 | 10 | 10.17±2.15 * | 48.1 |
| Umbelliferone | 10 20 40 | 10 10 10 | 16.42±5.32 12.22±1.09 * 12.38±3.76 * | 16.1 37.6 36.8 |
| 7-hydroxyl-8-methoxy coumarin | 10 20 40 | 10 10 10 | 13.49±1.96 12.04±4.50 * 9.81±3.13 ** | 31.1 38.5 49.9 |
| 7-methoxyl group-8-Hydroxycoumarin | 10 20 40 | 10 10 10 | 14.98±2.67 12.35±4.31 * 12.03±6.22 * | 23.5 36.9 38.6 |
| Aesculetin | 10 | 10 | 14.56±1.96 | 25.6 |
| 20 | 10 | 11.59±3.04 * | 40.8 | |
| 40 | 10 | 11.07±3.25 * | 43.5 | |
| 3,4-dimethyl-7-ethoxy coumarin | 10 | 10 | 14.23±3.45 | 27.3 |
| 20 | 10 | 13.05±3.11 | 33.3 | |
| 40 | 10 | 12.39±4.48 * | 36.7 | |
| Daphnin | 10 20 40 | 10 10 10 | 12.13±3.05 * 10.07±2.14 ** 9.91±1.29 ** | 38.0 48.6 49.4 |
| Daphnoretin | 10 20 40 | 10 10 10 | 13.78±1.14 12.08±3.15 * 10.17±3.02 ** | 29.6 38.3 48.1 |
| Edgeworin | 10 20 40 | 10 10 10 | 14.51±4.07 13.04±5.01 10.25±2.21 ** | 25.9 33.4 47.7 |
| Edgeworthia chrysantha Lindl. glycosides C | 10 20 40 | 10 10 10 | 15.31±4.06 13.49±1.00 12.01±2.05 * | 21.8 31.1 38.7 |
| 10 | 10 | 16.15±5.10 | 17.5 |
| Edgeworthia chrysantha Lindl. glycosides A | 20 40 | 10 10 | 15.38±2.97 12.25±4.53 * | 21.5 37.4 |
Compare with the blank group,
*P＜0.05,
*P＜0.01
The result shows that positive control drug hydrocortisone, 10 Coumarins compositions have significant inhibitory effect to the inflammation that the mice ear model causes, wherein the action effect of 7-hydroxyl-8-methoxy coumarin, daphnin and daphnoretin is stronger.
(4) rat carrageenan foot swelling model
1 laboratory animal
The SD rat, male and female dual-purpose, body weight 180-220g.
2. experimental model and method of testing
Get 260 of rats, be divided into 26 groups at random, press the dosage gastric infusion 4d shown in the table 4, before the last administration, measure and cause scorching preceding volume; 30min after the last administration, the sufficient subcutaneous injection 1% carrageenin 0.1ml that wastes time causes inflammation in rat right hind leg.Respectively at cause scorching back 2,4,6h measures the following volume of right ankle joint.
3 statistical analysiss:
All experimental result is all represented with mean ± standard error.Respectively organize data and the blank significant difference of organizing with student t-check, P＜0.05, expression difference has the significance meaning.
4 result of the tests:
Table 4. coumarin kind compound is to the influence of rat carrageenan foot swelling test
| Group | Dosage (mg/kg) | N | Paw swelling (ml) | ||
| 2h | 4h | 6h | |||
| Blank | - | 10 | 1.31±0.85 | 1.15±0.72 | 0.97±0.61 |
| Aspirin | 300 | 10 | 0.35±1.15 ** | 0.31±1.07 ** | 0.26±1.19 ** |
| Umbelliferone | 10 20 40 | 10 10 10 | 1.43±0.32 1.17±0.62 0.87±0.45 * | 1.03±0.12 0.95±0.26 0.67±0.42 ** | 0.92±0.42 0.84±0.36 0.53±0.64 * |
| 7-hydroxyl-8-methoxy coumarin | 10 20 40 | 10 10 10 | 1.06±0.12 * 1.02±0.09 * 0.50±0.21 ** | 0.91±0.21 0.73±0.65 * 0.28±0.56 ** | 0.80±0.20 0.58±0.44 * 0.22±0.26 ** |
| 7-methoxyl group-8-Hydroxycoumarin | 10 20 40 | 10 10 10 | 1.34±0.12 1.10±0.10 0.80±0.18 ** | 1.23±0.31 1.08±0.64 0.89±0.64 * | 1.14±0.21 1.01±0.34 0.83±0.58 * |
| Aesculetin | 10 | 10 | 1.45±0.28 | 1.13±0.29 | 1.01±0.17 |
| 20 | 10 | 1.18±0.145 | 1.02±0.48 | 0.97±0.34 | |
| 40 | 10 | 0.89±0.13 | 0.76±0.17 * | 0.77±0.47 * | |
| 10 | 10 | 1.36±0.22 | 1.21±0.21 | 1.10±0.16 | |
| 20 | 10 | 1.04±0.42 | 0.78±0.63 | 0.68±0.61 | |
| Coumarin | 40 | 10 | 0.80±0.36 * | 0.61±0.27 * | 0.52±0.41 * |
| Daphnin | 10 20 40 | 10 10 10 | 1.01±0.15 * 0.94±0.19 * 0.42±0.07 ** | 0.79±0.61 * 0.35±0.36 ** 0.21±0.08 *** | 0.79±0.19 0.31±0.26 ** 0.12±0.32 *** |
| Daphnoretin | 10 20 40 | 10 10 10 | 1.04±0.18 * 1.00±0.21 * 0.53±0.21 ** | 1.10±0.41 0.74±0.22 * 0.37±0.14 ** | 1.07±0.13 0.55±0.25 * 0.56±0.23 * |
| Edgeworin | 10 20 40 | 10 10 10 | 1.24±0.31 1.18±0.29 1.09±0.11 * | 1.31±0.27 1.05±0.23 0.83±0.34 * | 1.22±0.43 0.96±0.33 0.54±0.19 * |
| Edgeworthia chrysantha Lindl. glycosides C | 10 20 40 | 10 10 10 | 1.32±0.17 1.16±0.21 1.02±0.35 * | 1.24±0.12 1.06±0.50 * 0.75±0.61 * | 1.17±0.25 0.98±0.26 0.56±0.24 * |
| Edgeworthia chrysantha Lindl. glycosides A | 10 20 40 | 10 10 10 | 1.27±0.09 1.13±0.13 1.03±0.14 * | 1.22±0.16 1.09±0.61 0.86±0.56 * | 1.10±0.27 0.79±0.34 0.58±0.16 * |
Compare with the blank group,
*P＜0.05,
*P＜0.01
The result shows that positive control drug dexamethasone, 10 coumarin kind compounds have significant inhibitory effect to the caused inflammation of rat carrageenan foot swelling model, 7-hydroxyl-8-methoxy coumarin, daphnin and daphnoretin action effect stronger.
Pharmaceutical composition of the present invention contains in the above-mentioned coumarin kind compound for the treatment of effective dose one or more for active component, and contains one or more pharmaceutically acceptable carriers.Wherein, the weight content of active component is 0.1-99.5%.
Chemical compound of the present invention and pharmaceutical composition can be used for treating various pain and relief of symptoms and prevention and the various active chronic inflammations of treatment, are used for the analgesia of rheumatoid disease and non-rheumatism.
Pharmaceutically acceptable carrier mentioned above is meant the pharmaceutical carrier of pharmaceutical field routine, for example: diluent, excipient such as water etc., filler such as starch, sucrose etc.; Binding agent such as cellulose derivative, alginate, gelatin and polyvinylpyrrolidone; Wetting agent such as glycerol; Disintegrating agent such as agar, calcium carbonate and sodium bicarbonate; Absorption enhancer such as quaternary ammonium compound; Surfactant such as hexadecanol; Absorption carrier such as Kaolin and soap clay; Lubricant such as Pulvis Talci, calcium stearate and magnesium and Polyethylene Glycol etc.Can also in compositions, add other adjuvant such as flavouring agent, sweeting agent etc. in addition.
The compounds of this invention can compositions form by oral, snuffing is gone into, the mode of rectum or parenteral is applied to the patient who needs this treatment.Be used for when oral, can be made into conventional solid preparation such as tablet, powder, granule, capsule etc., make liquid preparation such as water or oil-suspending agent or other liquid preparation such as syrup, elixir etc.; When being used for parenteral, can be made into solution, water or the oiliness suspending agent etc. of injection.Preferred form is tablet, coated tablet, capsule, suppository, nasal spray and injection.
The various dosage forms of pharmaceutical composition of the present invention can be according to the conventional production method preparation of pharmaceutical field.Active component is mixed with one or more carriers, be made into required dosage form then.
The specific embodiment
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment 1: preparation umbelliferone and daphnoretin
The root bark of 7Kg hair winter daphne (Daphne odora Thunb.var.atrocaulis Rehd.) medical material, pulverize the back with 75% alcohol reflux 3 times, merge extractive liquid,, decompression recycling ethanol to volume is 10L, filter, filtrate is successively with chloroform, ethyl acetate and n-butanol extraction, collect each extraction part and be condensed into extractum, ethyl acetate extraction part extractum 200g wherein, to carry out silica gel column chromatography after the dissolve with methanol filtration, carry out gradient elution with chloroform-methanol, check the eluting flow point with thin layer chromatography, flow point with identical single speckle merges, concentrate, get flow point 1,2,3,4,5,6,7,8,9, wherein flow point 2 is through further silica gel column chromatography separation and purification, obtain white powder, structure is accredited as umbelliferone; Wherein flow point 5 obtains pale yellow powder through further silica gel column chromatography and sephadex chromatography separation and purification, and structure is accredited as daphnoretin.
The structural formula of umbelliferone is as follows:
The structural formula of daphnoretin is as follows:
Embodiment 2: preparation 7-hydroxyl-8-methoxy coumarin and 7-methoxyl group-8-Hydroxycoumarin
The root bark and the peel of stem of 10Kg Daphne Giraldii Nitsche (Daphne giraldii Nitsche.) medical material are pulverized the back with 95% ethanol percolate extraction, obtain extracting solution 50L, and successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction, extract is condensed into extractum after concentrating.The chemical constituent of utilizing means such as silica gel column chromatography, polyamide chromatograph, Sephadex LH-20 and preparation HPLC that system is carried out at each extraction position is separated and is identified.The result obtains 15 chemical compounds in the ethyl acetate extract separation, identifies that through structure wherein 1 white powder is 7-hydroxyl-8-methoxy coumarin; The chloroform extract separation obtains 12 chemical compounds, identifies that through structure wherein 1 white powder is 7-methoxyl group-8-Hydroxycoumarin.
The structural formula of 7-hydroxyl-8-methoxy coumarin is as follows:
The structural formula of 7-methoxyl group-8-Hydroxycoumarin is as follows:
Embodiment 3: preparation Edgeworin and Edgeworthia chrysantha Lindl. glycosides C
5Kg Edgeworthia chrysantha Lindl. (Edgeworthia chrysantha Lindl.) medical material rhizome is pulverized the back with 75% soak with ethanol 24hr, collect soak, be concentrated into and do not have the alcohol flavor, add suitable quantity of water and be diluted to fluid extract, extract with petroleum ether, chloroform, ethyl acetate and n-butyl alcohol successively, collect and respectively extract the position, be condensed into extractum.The extractum at each position is carried out the chemical composition analysis of system, chloroform extract separation as a result obtains 12 chemical compounds, identify through structure, wherein 1 pale yellow powder is the plain Edgeworin of Edgeworthia chrysantha Lindl., ethyl acetate extract is got 6 chemical compounds, identify that through structure wherein 1 white powder is edgeworosideC.
The structure of Edgeworin is as follows:
The structure of Edgeworthia chrysantha Lindl. glycosides C is as follows:
Embodiment 4: the preparation daphnin
The root bark and the peel of stem of the sweet winter daphne in 10Kg Shan (Daphne tangutica Maxim.) medical material are pulverized the back with 75% ethanol percolate extraction, obtain extracting solution 50L, and successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction, extract is condensed into extractum after concentrating.The chemical constituent of utilizing means such as silica gel column chromatography, polyamide chromatograph, Sephadex LH-20 and preparation HPLC that system is carried out at each extraction position is separated and is identified.The result obtains 15 chemical compounds in the ethyl acetate extract separation, identifies that through structure wherein 1 white powder is a daphnin.
The structural formula of daphnin is as follows:
Embodiment 5: preparation 3,4-dimethyl-7-ethoxy coumarin and Edgeworthia chrysantha Lindl. glycosides A
7.5kg the peel of stem of VC.Aureomariginatn (Daphne odora Thunb.var.marginata) medical material, pulverize the back with 70% ethanol percolate extraction, extracting solution is evaporated to does not have the alcohol flavor, adds suitable quantity of water and is diluted to fluid extract, extracts with petroleum ether, chloroform, ethyl acetate, n-butyl alcohol successively.Chloroform extract is carried out the chemical composition analysis of system, and chloroform extract separates and obtains 12 chemical compounds as a result, through structure, wherein identifies that one is 3,4-dimethyl-7-ethoxy coumarin for 1.Concentrated acetic acid ethyl acetate extract makes into extractum.With the dissolve with methanol after-filtration, silicagel column carries out system's separation on the filtrate, is divided into from obtaining 16 chemical compounds, identifies that through structure one of them is Edgeworthia chrysantha Lindl. glycosides A.
3, the structure of 4-dimethyl-7-ethoxy coumarin is as follows:
The structure of Edgeworthia chrysantha Lindl. glycosides A is as follows:
Embodiment 6: the preparation aesculetin
Get the stem skin 10kg that fraxinus rhynchophylla Hance is produced in Liaoning, powder is worn in chopping, with the continuous heating extraction 10～12h of ethanol 40L, and the extracting solution concentrating under reduced pressure, the warm dissolving of the about 4L of residue water is with equal-volume chloroform washing 2 times.Water layer boils off chloroform wherein, reuse ethyl acetate extraction 2 times.Acetic acid ethyl acetate extract is condensed into extractum, and extractum is gone up silicagel column after with dissolve with methanol and carried out chromatography, with the chloroform-methanol gradient elution, check the eluting flow point with thin layer chromatography, the flow point with identical single speckle merges, and concentrates, obtain 5 chemical compounds, identify that through structure one of them is an aesculetin.
The structural formula of aesculetin is as follows:
Embodiment 7: the acetylate of preparation Edgeworthia chrysantha Lindl. element
Get the Edgeworthia chrysantha Lindl. element of gained among the embodiment 3, add the heating of acetic anhydride and sodium acetate, generate acetylizad Edgeworthia chrysantha Lindl. element, course of reaction is as follows:
Embodiment 8: the preparation of preparation coumarin kind compound
Tablet: active component 20mg
Lactose 177mg
Corn starch 50mg
Magnesium stearate 3mg
Preparation method: active component, lactose and starch are mixed, and water is evenly moistening, the mixture after moistening is sieved and drying, after sieve, adds magnesium stearate, then with the mixture tabletting, and every heavy 250mg, active component content is 20mg.
Embodiment 9: the analgesic activities research of daphnoretin drop pill
Getting daphnetin 5g, get fine powder after micronizing is crossed 200 mesh sieves, be added in the fused 15g polyethylene glycol 6000 substrate, stir evenly, is coolant with dimethylbenzene silicone oil, the dropping preparation method pill, and drying promptly gets the daphnoretin drop pill.This drop pill is used to alleviate the diseases such as pain that sciatica, rheumatic arthritis cause and has good effect.
Embodiment 10: the anti-inflammatory activity research of daphnoretin drop pill
Getting daphnetin 5g, get fine powder after micronizing is crossed 200 mesh sieves, be added in the mixed-matrix of fused 10g Macrogol 4000 and 5g polyethylene glycol 6000, stir evenly, is coolant with dimethylbenzene silicone oil, the dropping preparation method pill, and drying promptly gets the daphnoretin drop pill.This drop pill is used for the treatment of prevention and treats various inflammation such as pharyngolaryngitis, gastroenteritis etc., has good effect.
Embodiment 11: the capsular analgesic activities research of Edgeworthia chrysantha Lindl. glycosides A
Get Edgeworthia chrysantha Lindl. glycosides A 30g, cross 100 mesh sieves; Get Cera Flava 4.2g, add Radix Oenotherae erythrosepalae oil 125g, fusion mixing under 80 ℃ of water-baths is cooled to room temperature (25 ℃).Add butylated hydroxyarisol, citric acid, fully mixing.Add Edgeworthia chrysantha Lindl. glycosides A, lecithin 5g adds Radix Oenotherae erythrosepalae oil to 250g, and fully mixing as capsule heart liquid, is pressed into 1000 soft capsules, is used for the treatment of acute postoperative pain, chronic pain, has good result.
Embodiment 12: the capsular anti-inflammatory activity research of Edgeworthia chrysantha Lindl. glycosides A
Get Edgeworthia chrysantha Lindl. glycosides A 30g, cross 100 mesh sieves; Get Cera Flava 4.2g, add a moon soybean oil 125g, fusion mixing under 80 ℃ of water-baths is cooled to room temperature (25 ℃).Add butylated hydroxyarisol, citric acid, fully mixing.Add Edgeworthia chrysantha Lindl. glycosides A, lecithin 5g, to 250g, fully mixing as capsule heart liquid, is pressed into 1000 soft capsules, is used for the treatment of upper respiratory tract infection, tonsillitis, has good result with soybean oil.
Embodiment 13: the analgesic activities research of coumarin kind compound tablet
The tablet for the treatment of excess syndrome example 7 is used for the treatment of snake bite and insect sting, and traumatic injury has good result.
Embodiment 14: the anti-inflammatory activity research of coumarin kind compound tablet
The tablet for the treatment of excess syndrome example 7 is used for the treatment of chronic enteritis, has good result.
Claims (6)
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829132A (en) * | 2010-05-18 | 2010-09-15 | 云南大学 | Application of 7-O-beta-D-acetylation sugar-coumarin compounds in treating chronic neuropathic pains |
| CN102688231A (en) * | 2012-05-27 | 2012-09-26 | 吉林圣亚医药科技有限公司 | Drug combination |
| CN110025614A (en) * | 2019-05-27 | 2019-07-19 | 牡丹江医学院 | A kind of oral care composition and its purposes in treatment chronic oral inflammation |
| CN111303104A (en) * | 2020-03-23 | 2020-06-19 | 广西壮族自治区中医药研究院 | Preparation method and application of 7-hydroxy-8-methoxycoumarin standard substance |
| CN111747921A (en) * | 2020-07-16 | 2020-10-09 | 中国药科大学 | Preparation method of daphnetin derivatives and medical use thereof |
| CN113940944A (en) * | 2021-12-07 | 2022-01-18 | 东阳市人民医院 | A Chinese medicinal composition for treating chronic pharyngitis |
-
2006
- 2006-09-07 CN CN 200610030920 patent/CN1923193A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829132A (en) * | 2010-05-18 | 2010-09-15 | 云南大学 | Application of 7-O-beta-D-acetylation sugar-coumarin compounds in treating chronic neuropathic pains |
| CN102688231A (en) * | 2012-05-27 | 2012-09-26 | 吉林圣亚医药科技有限公司 | Drug combination |
| CN110025614A (en) * | 2019-05-27 | 2019-07-19 | 牡丹江医学院 | A kind of oral care composition and its purposes in treatment chronic oral inflammation |
| CN110025614B (en) * | 2019-05-27 | 2020-05-12 | 牡丹江医学院 | Oral care composition and application thereof in treating chronic stomatitis |
| CN111303104A (en) * | 2020-03-23 | 2020-06-19 | 广西壮族自治区中医药研究院 | Preparation method and application of 7-hydroxy-8-methoxycoumarin standard substance |
| CN111303104B (en) * | 2020-03-23 | 2023-10-10 | 广西壮族自治区中医药研究院 | Preparation method and application of 7-hydroxy-8-methoxy coumarin standard substance |
| CN111747921A (en) * | 2020-07-16 | 2020-10-09 | 中国药科大学 | Preparation method of daphnetin derivatives and medical use thereof |
| CN113940944A (en) * | 2021-12-07 | 2022-01-18 | 东阳市人民医院 | A Chinese medicinal composition for treating chronic pharyngitis |
| CN113940944B (en) * | 2021-12-07 | 2023-10-17 | 东阳市人民医院 | A Chinese medicinal preparation for treating chronic pharyngitis |
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