CN1695612A - Compsn. of medication of containing creat lactone of triacetyl and usages - Google Patents
Compsn. of medication of containing creat lactone of triacetyl and usages Download PDFInfo
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- CN1695612A CN1695612A CN 200510017654 CN200510017654A CN1695612A CN 1695612 A CN1695612 A CN 1695612A CN 200510017654 CN200510017654 CN 200510017654 CN 200510017654 A CN200510017654 A CN 200510017654A CN 1695612 A CN1695612 A CN 1695612A
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- andrographolide
- triacetyl
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Abstract
An application of triacetyl andrographolide and its composition in preparing the anti-inflammatory, immunodepressant and antineoplastic medicines is disclosed.
Description
Technical field
The present invention relates to the purposes of triacetyl andrographolide in preparation antiinflammatory, immunosuppressant and antitumor drug.The invention further relates to a kind of pharmaceutical composition that contains the triacetyl andrographolide as active component and pharmaceutically acceptable carrier, and the purposes in preparation antiinflammatory, immunosuppressant and antitumor drug.
Background technology
Herba Andrographis is the dry aerial parts of acanthaceous plant Herba Andrographis Andrographis panniculata (Burm.f.) Nees.Originate in India, there is cultivation on ground such as China East China, Central-South and southwest.Bitter in the mouth, cold in nature, GUIXIN, lung, large intestine, urinary bladder channel.Has heat-clearing and toxic substances removing, the effect of removing heat from blood detumescence.Be used for cold, fever, laryngopharynx swelling and pain, aphtha of the mouth and tongue, pertussis chronic cough, diarrhea dysentery, the puckery pain of pyretic stranguria, carbuncle skin infection, venom.
1896, Boorsma isolates a kind of colourless crystallization thing first from Herba Andrographis, be accredited as diterpene ginkgolide through the Gorter structure in 1911, be named as andrographolide (1), the Chinese andrographolide is held sway over a region fine and soft lactone again, andrographolide, be one of main chemical compositions of Herba Andrographis, at the raw material mass production of antipyretic and anti-inflammatory medicines such as the synthetic Andrographolide of China's conduct, andrographolide.Up to now, the pharmacologically active of relevant triacetyl andrographolide does not report that also the inventor furthers investigate this, and experiment shows that the triacetyl andrographolide has antiinflammatory, immunosuppressant and anti-tumor application in the body.
Summary of the invention
The invention discloses the purposes of triacetyl andrographolide in preparation antiinflammatory, immunosuppressant and antitumor drug.
The invention further relates to a kind of pharmaceutical composition that contains the triacetyl andrographolide as active component and pharmaceutically acceptable carrier, and the purposes in preparation antiinflammatory, immunosuppressant and antitumor drug.
The specific embodiment
1, the preparation of triacetyl andrographolide
Andrographolide (1) 5g (14.3mmol), acetic anhydride 20mL, new fused zinc chloride 2g adds in the 100mL single port flask successively, encloses reflux condensing tube, 80 ℃ of heating of oil bath.Reactant liquor clarification back stopped reaction fills the reactant liquor impouring in the beaker of 80mL frozen water, and vigorous stirring, and sucking filtration washes filter cake with water to pH7.The filter cake alcohol crystal gets white, needle-shaped crystals 4.7g, yield 67.8%.m.p.128℃。IR(cm
-1)：2976，2955，2925，2868，1753，1736，1680，1450，1375，1251，1026，908。MS(ESI)m/z：476.3M
+，477.3(M+1)
+，499.3(M+Na)
+。
1H-NMR (CDCl
3, 6): 7.01 (1H, t, J=5.2,12-H), 5.91 (1H, d, J=6.0,14-H), 4.90,4.53, (each 1H, s, 17-H), 4.60 (1H, dd, J=6.1,11.2,15-H), 4.55 (1H, dd, J=5.0,11.2,15-H), 4.38,4.14 (each 1H, d, J=11.8,19-H), 4.27 (1H, d, J=11.2,3-H), 2.12 (3H, s, 1 * COCH3), 2.05 (3H, s, 2 * COCH3), 1.03 (3H, s, 18-H), 0.76 (3H, s, 20-H).
2, the pharmacology activity research of triacetyl andrographolide
2.1 influence to rat paw edema due to the Ovum Gallus domesticus album
Material:
Animal: the wistar rat, body weight 180～220g is male (Henan Province's medical experiment animal center)
Method:
24 of rats, 180～220g is male, is divided into 3 groups at random, 8 every group.One group of ip normal saline, two groups and three groups of difference ip reagent 300mg/kg, each is organized volumetric injection and is 1mL/100g.Administration is preceding with the right ankle joint flooding boundary of marking pen labelling rat, and the Volume of Displacement method is measured and caused the right sufficient Volume of Displacement of scorching preceding rat for 1 time.After the administration immediately only in the right back sole sc of rat fresh albumen 0.1mL/.1h after the measurement administration, 2h, 4h, the rat foot Volume of Displacement during 6h.Experimental result sees Table 1-1.
Table 1-1 triacetyl andrographolide is to the influence of rat paw edema due to the Ovum Gallus domesticus album
( X±S，n＝8)
| Group | Basis volume mL | Different time (h) Volume of Displacement (mL) | |||
| ?????????1 | ?????????2 | ?????????4 | ????????6 | ||
| NS andrographolide triacetyl andrographolide | ???1.29±0.08 ???1.29±0.12 ? ???1.44±0.12 | ???1.06±0.24 ???0.76±0.19 *? ???0.63±0.12 ** | ????0.75±0.08 ????0.64±0.10 *? ????0.45±0.10 ** | ????0.71±0.19 ????0.45±0.11 ? ????0.30±0.09 ** | ???0.69±0.18 ???0.33±0.11 ? ???0.18±0.13 |
Annotate: compare * P＜0.05, * * P＜0.01 with the NS group
Experimental result shows: the rat paw edema due to the internal energy highly significant inhibition of the triacetyl andrographolide administration 4h Ovum Gallus domesticus album, its antiinflammatory action obviously is better than andrographolide.
2.2 immunity
2.2.1 carbon granule is cleaned up
Material:
Instrument: enzyme connection detector Multiskan Ascent (Thermo Labsystems)
Animal: kunming mice, 18～22g is male (Henan Province's medical experiment animal center)
Reagent: india ink (Beijing honest and sincere meticulous preparation factory)
Method:
Get 30 of kunming mices, 18～22g is male.Be divided into 3 groups at random, 10 every group, the 1st group of negative contrast (solvent control) group, 2～3 groups is the reagent group.Each organizes ig administration every day 1 time, and drug level 5mg/mL, dosage are 100mg/kg, administration volume 0.2mL/10g, omnidistance administration 8d.Finish the back and respectively organize mice iv india ink 0.1mL/10g next day, and in injection back 1min, 10min socket of the eye venous blood collection, 20 μ L take a blood sample at every turn.Institute's blood sampling added to fill 2mL 0.1% NaHCO
3Test tube in, fill 2mL 0.1% NaHCO to wait capacity mice normal blood 0.2mL to add to
3Test tube in as blank.Jolting mixes the back and surveys absorbance in the 620nm place with microplate reader, and is calculated as follows carbon granule and cleans up index.The result is shown in table 1-2.
Carbon granule is cleaned up index K=(logA
1-logA
2)/(t
2-t
1)
Wherein, A
1: the 1min absorbance of surveying of taking a blood sample
A
2: the 10min absorbance of surveying of taking a blood sample
t
2: 10min
t
1: 1min
Table 1-2 triacetyl andrographolide carbon granule clean up experimental result (X ± S, n=10)
| Group | Carbon granule is cleaned up index |
| Negative control andrographolide triacetyl andrographolide | ?????0.0405±0.0079 ?????0.0279±0.0078 **?????0.0120±0.0062 ** |
Annotate: compare * P＜0.05, * * P＜0.01 with matched group
Experimental result shows: the triacetyl andrographolide has the immunosuppressive action of highly significant, and its effect is better than andrographolide.
2.2.2 tardy paraphilia reaction
Material:
Animal: kunming mice, 18～22g is male (Henan Province's medical experiment animal center)
Reagent: 2,4-dinitrochlorobenzene (DNCB)
Method:
Get 30 of kunming mices, 18～22g is male.Be divided into 3 groups at random, 10 every group, the 1st group of negative contrast (solvent control) group, 2～3 groups is the reagent group.(1.5cm * 1.5cm), the DNCB acetone drop back of the body with 7% excites, and dosage is 50 μ L/ to get the mouse back cropping.Next day after the sensitization, the ig administration, drug level is 5mg/mL, dosage is 1mg/10g.Behind the successive administration 8d, the DNCB acetone solution of reuse 7% is attacked mice left side ear, in contrast.Put to death mice after exciting 16h, lay auricle, divide another name left and right auricle weight with the 9mm card punch.Be calculated as follows the swelling degree.The results are shown in Table 1-3.
Swelling degree=auris dextra sheet weight-left auricle is heavy
The tardy paraphilia reaction experiment of table 1-3 triacetyl andrographolide result (X ± S, n=10)
| Group (by structure number) | Swelling degree/mg |
| Negative control andrographolide triacetyl andrographolide | ?????14.14±6.86 ?????24.26±10.54 *?????23.20±10.98 * |
Annotate: compare * P＜0.05, * * P＜0.01 with matched group
Experimental result shows: the triacetyl andrographolide can significantly suppress tardy paraphilia reaction, and its effect is suitable with andrographolide.
2.3 antitumor
Material:
Animal: kunming mice, 18～22g is male (Henan Province's medical experiment animal center)
Method:
Get 30 of kunming mices, 18～22g is male.Get the well-grown HepA mouse ascites of inoculation 8d,, only be inoculated under the right side of mice axillary fossa with 0.2mL/ with NS dilution in 1: 5.Postvaccinal mice is divided into 3 groups by body weight, 10 every group.If the 1st group is the normal control group, lumbar injection NS; 2～3 groups is the reagent group, lumbar injection andrographolide or triacetyl andrographolide 300mg/kg, and volumetric injection is 0.2mL/10g, once a day, continuous 10d.Drug withdrawal next day puts to death, and peels off tumor, weighs, tumor is heavy, is calculated as follows the tumour inhibiting rate of reagent.The results are shown in Table 1-4.
Tumour inhibiting rate=(normal control group tumor weight-administration group tumor is heavy)/normal control group tumor heavy * 100%
Table 1-4 triacetyl andrographolide anti-tumor in vivo experimental result (n=10)
| Group | Tumour inhibiting rate (%) |
| Andrographolide triacetyl andrographolide | ?????64.4 **?????70.8 ** |
Annotate: compare * P＜0.05, * * P＜0.01 with matched group
The anti-tumor in vivo experimental result shows: the triacetyl andrographolide has the anti-tumor activity of highly significant, and also higher than the anti-tumor activity of andrographolide.
Above experimental result proves: the triacetyl andrographolide has significant antiinflammatory, immunosuppressant and antitumor activity.
Claims (5)
1, the triacetyl andrographolide is in the purposes of preparation antiinflammatory, immunosuppressant and antitumor drug.
2, a kind of pharmaceutical composition is characterized in that: contain the triacetyl andrographolide as active component and pharmaceutically acceptable carrier.
3, the purposes of the pharmaceutical composition of claim 2 in the preparation anti-inflammatory drug.
4, the purposes of the pharmaceutical composition of claim 2 in the preparation immunosuppressive drug.
5, the purposes of the pharmaceutical composition of claim 2 in the preparation antitumor drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100176546A CN100367955C (en) | 2005-06-06 | 2005-06-06 | Compsn. of medication of containing creat lactone of triacetyl and usages |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100176546A CN100367955C (en) | 2005-06-06 | 2005-06-06 | Compsn. of medication of containing creat lactone of triacetyl and usages |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007101484990A Division CN101129354B (en) | 2005-06-06 | 2005-06-06 | Pharmaceutical composition containing triacetyl andrographolidume and medical use of the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1695612A true CN1695612A (en) | 2005-11-16 |
| CN100367955C CN100367955C (en) | 2008-02-13 |
Family
ID=35348601
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100176546A Expired - Fee Related CN100367955C (en) | 2005-06-06 | 2005-06-06 | Compsn. of medication of containing creat lactone of triacetyl and usages |
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|---|---|
| CN (1) | CN100367955C (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101371832B (en) * | 2007-08-20 | 2012-05-09 | 烟台靶点药物研究有限公司 | Medical use of triacetyl andrographolide as proinflammatory cytokine inhibitor |
| CN101284003B (en) * | 2007-04-13 | 2012-09-05 | 烟台靶点药物研究有限公司 | Medicinal composition containing andrographolide derivatives and preparation method thereof and application |
| CN102702147A (en) * | 2012-06-18 | 2012-10-03 | 辽宁利锋科技开发有限公司 | Andrographolide analogue and application of andrographolide analogue to treatment |
| CN103224492A (en) * | 2013-04-15 | 2013-07-31 | 南京工业大学 | 14-aryl-ether andrographolide derivative and preparation method and application thereof |
| CN116850178A (en) * | 2023-09-04 | 2023-10-10 | 中国中医科学院广安门医院 | Application of andrographolide modified compound F2 or derivative thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6388124A (en) * | 1986-09-30 | 1988-04-19 | Toyo Jozo Co Ltd | Antitumor agent |
-
2005
- 2005-06-06 CN CNB2005100176546A patent/CN100367955C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284003B (en) * | 2007-04-13 | 2012-09-05 | 烟台靶点药物研究有限公司 | Medicinal composition containing andrographolide derivatives and preparation method thereof and application |
| CN101371832B (en) * | 2007-08-20 | 2012-05-09 | 烟台靶点药物研究有限公司 | Medical use of triacetyl andrographolide as proinflammatory cytokine inhibitor |
| CN102702147A (en) * | 2012-06-18 | 2012-10-03 | 辽宁利锋科技开发有限公司 | Andrographolide analogue and application of andrographolide analogue to treatment |
| CN102702147B (en) * | 2012-06-18 | 2016-06-08 | 辽宁利锋科技开发有限公司 | The application of andrographolide analog and treatment thereof |
| CN103224492A (en) * | 2013-04-15 | 2013-07-31 | 南京工业大学 | 14-aryl-ether andrographolide derivative and preparation method and application thereof |
| CN103224492B (en) * | 2013-04-15 | 2016-01-13 | 南京工业大学 | 14-aryl-ether andrographolide derivative and its preparation method and application |
| CN116850178A (en) * | 2023-09-04 | 2023-10-10 | 中国中医科学院广安门医院 | Application of andrographolide modified compound F2 or derivative thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100367955C (en) | 2008-02-13 |
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Granted publication date: 20080213 Termination date: 20170606 |