CN101103986A - Application of 23-hydroxylbetulinic acid in preparing medicine for treating and preventing liver cancer - Google Patents
Application of 23-hydroxylbetulinic acid in preparing medicine for treating and preventing liver cancer Download PDFInfo
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- CN101103986A CN101103986A CNA2007101307394A CN200710130739A CN101103986A CN 101103986 A CN101103986 A CN 101103986A CN A2007101307394 A CNA2007101307394 A CN A2007101307394A CN 200710130739 A CN200710130739 A CN 200710130739A CN 101103986 A CN101103986 A CN 101103986A
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- acid
- hydroxyl radical
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- hydroxylbetulinic
- radical white
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Abstract
The invention discloses a novel purpose of 23-hydroxylbetulinic acid, namely, an application of 23-hydroxylbetulinic acid in preparation of drug for treating or preventing lever cancer. The drug for treating or preventing lever cancer is a drug compound with 23-hydroxylbetulinic acid as the active ingredient. 23-hydroxylbetulinic acid is safe, non-toxic and strong in pharmacological action and promising with a good prospect in pharmacy; pasqueflower, the Chinese traditional medicine, in the raw material, is rich in resource, low in cost and simple in preparation process.
Description
The application divides an application, and the application number of original application is: 03152904.6, and the applying date is: on 09 02nd, 2003, denomination of invention was: the application of 23-hydroxyl radical white birck acid in preparation treatment or prophylaxis of tumours and AIDS-treating medicine.
Technical field
The present invention relates to the purposes of 23-hydroxyl radical white birck acid in preparation treatment or prevention liver-cancer medicine.
Background technology
Existing bibliographical information, human melanoma cell [NatureMedicine, 1995 are optionally killed in Betula platyphylla Suk. acid; 1 (10): 1645-1651]; The active anticancer of Betula platyphylla Suk. acid and some derivant has passed through with the nude mice (JP 87,301,580) of subcutaneous implantation murine sarcoma 180 cells, growth [Planta Medica, 1988 of its vitro inhibition P338 lymphocytic leukemia cell; 511-513], particularly by suppress ODC Ornithine decarboxylase have an effect (WO 95/04526) etc. proved.Chinese patent (application number is 99813476.0) discloses inhibitory action and the application in treatment clinical cancer thereof of new betulinic acid derivative (to C-2, C-3, C-17, structural modification is carried out in C-20 and/or C-29 position) to tumor cell.Lee etc. (WO 95/04526) disclose Betula platyphylla Suk. acid and dihydro Betula platyphylla Suk. acid acyl derivative has tangible HIV (human immunodeficiency virus)-resistant activity.To C
3-OH, C
17-COOH and C
20-outer methylene has carried out behind the structural modification, finds that Betula platyphylla Suk. acid and dihydro betulinic acid derivative have HIV (human immunodeficiency virus)-resistant activity to actute infection H9 lymphocyte, its EC
50Value is respectively less than 1.7 * 10
-5μ M.
The 23-hydroxyl radical white birck acid is the characteristic chemical constituent of the Chinese medicine Radix Pulsatillae for deriving from the pentacyclic triterpenoid in the Chinese medicine Radix Pulsatillae (Pulsatilla chinensis), document [chemical journal, 1983; 41 (8): 739-745] disclose the structure of this chemical compound in, its structural formula is:
Molecular formula is C
30H
48O
4, the off-white color powder, molecular weight 472 is soluble in organic solvents such as chloroform, ethyl acetate, ethanol.
This research group had once been reported 23-hydroxyl radical white birck acid external and body interior melanoma effect [Chinese clinical tumor and rehabilitation, 2000 in the past; 7 (1): 5-7], and to human leukemia cell K-562 and HL-60, scale cancer HeLa cell [Planta Medica, 2002; 68:183-186; Life Science, 2002; 72:1-9] and to gastric carcinoma cells SGC-7901, Proliferation of Human Ovarian Cell Vo[Southeast China University journal (medical science newspaper), 2001; 20 (3): 141-144] has the obvious suppression effect.But do not appear in the newspapers as yet to the inhibition activity of other tumor cell and HIV (human immunodeficiency virus).
Summary of the invention
The object of the present invention is to provide the new purposes of 23-hydroxyl radical white birck acid, i.e. the application of 23-hydroxyl radical white birck acid in preparation treatment or prevention liver-cancer medicine.
The medicine of described treatment or prevention hepatocarcinoma is with the pharmaceutical composition of 23-hydroxyl radical white birck acid as active component.
The 23-hydroxyl radical white birck acid can be used as active component and pharmaceutically acceptable excipient one is used from pharmaceutical compositions, this pharmaceutical composition can adopt the conventional method of this area to be prepared into various dosage forms, as the dosage form of oral administrations such as capsule, pill, tablet, oral liquid, granule, tincture and injection etc. oral beyond form of administration, as injection etc.According to the difference of dosage form, the excipient that this pharmaceutical composition uses is also different, and excipient commonly used comprises diluent, wetting agent, lubricant, filler, antiseptic etc.Wherein diluent is lactose, starch, dextrin, microcrystalline Cellulose, micropowder silica gel etc., and wetting agent is water and 50～85% Different concentrations of alcohol.The preferred dosage form that contains the pharmaceutical composition of 23-hydroxyl radical white birck acid of the present invention is an oral agents, is preferably capsule.Dosage be 20～400mg/ people/time, every day 1～3 time.
The 23-hydroxyl radical white birck acid that the present invention relates to obtains like this: Radix Pulsatillae root coarse powder with 15～95% ethanol percolation or reflux, extract,, is filtered, and filtrate is recycled to does not have the alcohol flavor, and then thin up, filter, filtrate adds hydrochloric acid or sulphuric acid transfers to pH1～3, reflux 10 minutes～2 hours, get precipitate, put cold, sucking filtration or filtration, the washing solids is to medium-sized, oven drying at low temperature gets crude product.Crude product carries out the Soxhlet extraction with organic solvents such as ethyl acetate, reclaims extracting solution to an amount of, places, and gets the powdered 23-hydroxyl radical white birck acid of off-white color.
In order to verify beneficial effect of the present invention, the inventor carries out a series of experiments:
1, animal acute toxicity test
(1) oral administration
Healthy male mice, body weight 18～25 grams are irritated stomach 5.0g/kg with 23-hydroxyl radical white birck acid aqueous solution (suspendible), in a continuous week, do not see dead mouse.
(2) drug administration by injection
Healthy male mice, body weight 18～25 grams carry out lumbar injection with 23-hydroxyl radical white birck acid aqueous solution, in a continuous week, observe the animal dead situation.The LD of 23-hydroxyl radical white birck acid
50Value is 2.13 ± 0.65g/kg.
2, the 23-hydroxyl radical white birck acid is to the inhibitory action of several hepatoma carcinoma cell
With 1,5,10,20,50,100 and 200 * 10
-7The sample of mol/L concentration and positive control drug 5-fluorouracil 200 μ l act in 96 orifice plates that contain tumor cell (3 * 10 respectively
3/ hole), cultivated 3 days, every hole adds 5mg/ml MTT20 μ l and continues to cultivate 4 hours, inhale gently and go supernatant, add 1mmol/LHCI-isopropyl alcohol (1: 10), detect under wavelength 750nm with the nucleic acid-protein detector, learn by statistics and handle, calculate the growth of tumour cell suppression ratio and be listed in table 1.
Table 1.23-hydroxyl radical white birck acid is to the inhibitory action (IC of several liver cancer cell growths
50: 10
-7Mol/L)
| Tumor cell line | The 23-hydroxyl radical white birck acid | 5-fluorouracil * | |
| Hepatoma carcinoma cell | Hep A Bel-7404 SMMC-7721 | 52.2 63.4 22.0 | 7.3 4.5 10.6 |
*Positive control drug
3, the 23-hydroxyl radical white birck acid is to the inhibitory action of mice S-180
Under aseptic condition, get the entity lump of S-180 mice, be cut into fine grained chippings, add normal saline with glass homogenizer and wear into homogenate, give every mouse hypodermic inoculation 2.5 * 10 with shears
6Cell.Be divided into 5 groups, comprise blank group (normal saline), positive drug control group (5-fluorouracil), 0.02g/kg, 0.10g/kg and 0.40g/kg group, every group of 20 mices, in back 24 hours gastric infusions of inoculation, successive administration 10 days is after two weeks, win solid tumor, weigh.Press down tumor in the body and the results are shown in table 2.
Table 2.23-hydroxyl radical white birck acid is to the inhibitory action of mice S-180
| Group | Dosage regimen (g/kg * number of times) | Animal weight (g) before the administration | Animal weight after the administration (g) | Heavy (the g) ± SD of tumor | Tumour inhibiting rate (%) |
| Blank group 5-fluorouracil 23-hydroxyl radical white birck acid | 0.1ml/10g×5 0.025×5 0.02×5 0.10×5 0.40×5 | 20.6 20.4 20.6 20.5 20.5 | 27.6 26.6 27.2 27.0 26.9 | 3.04±0.84 1.18±0.44 **2.22±0.54 *1.52±0.52 **0.84±0.18 ** | 61.4 27.4 50.3 83.3 |
Compare with the blank group:
*P＜0.05;
*P＜0.01
From above result, can draw and the invention has the advantages that:
(1), the present invention excavated new medical application to known compound 23-hydroxyl radical white birck acid, opened up a new application.
(2), 23-hydroxyl radical white birck acid safety non-toxic of the present invention, pharmacological action is strong, is indicating good prospect in medicine.
(3), raw material of substance Chinese medicine Radix Pulsatillae aboundresources of the present invention, inexpensive, preparation technology is simple.
Various details embodiment all is confined to this but content of the present invention is intact.
The specific embodiment
Embodiment 1: take by weighing the dry coarse powder 1.0kg of Radix Pulsatillae root, with 15% ethanol percolation of 3000ml, merge ethanol percolation liquid, reclaim under reduced pressure is filtered to there not being the alcohol flavor, filtrate transfers to pH2 with hydrochloric acid, heats 30 minutes, gets precipitate, puts cold, filter, washing, drying gets crude product.Crude product refluxes with the ethyl acetate Soxhlet, and backflow is concentrated in right amount, places, and sucking filtration gets 23-hydroxyl radical white birck acid 38.2g.
Embodiment 2: take by weighing the dry coarse powder 1.0kg of Radix Pulsatillae root, with 60% ethanol percolation of 3000ml, merge ethanol percolation liquid, reclaim under reduced pressure is filtered to there not being the alcohol flavor, filtrate transfers to pH2 with hydrochloric acid, heats 30 minutes, gets precipitate, puts cold, filter, washing, drying gets crude product.Crude product refluxes with the ethyl acetate Soxhlet, and backflow is concentrated in right amount, places, and sucking filtration gets 23-hydroxyl radical white birck acid 51.0g.
Embodiment 3: take by weighing the dry coarse powder 1.0kg of Radix Pulsatillae root, with 95% ethanol percolation of 3000ml, merge extractive liquid,, reclaim under reduced pressure is filtered to there not being the alcohol flavor, and filtrate transfers to pH2 with hydrochloric acid, heat 30 minutes, precipitate, put coldly, filter, washing, drying gets crude product.Crude product refluxes with the ethyl acetate Soxhlet, and backflow is concentrated in right amount, places, and sucking filtration gets 23-hydroxyl radical white birck acid 45.6g.
Embodiment 4: get 23-hydroxyl radical white birck acid 20mg of the present invention and micropowder silica gel 280mg, fully mix homogeneously sieves, and adds an amount of magnesium stearate, and mixing with non-slurry pelletizing mechanism grain, sieves, and sieve is got the granule between the 40-80 order, incapsulates every dress 0.3g.
Embodiment 5: prepare capsule according to embodiment 4 described methods, different 400mg 23-hydroxyl radical white birck acid of the present invention, 100mg micropowder silica gel and an amount of magnesium stearate of being to use, every capsules dress 0.5g.
Embodiment 6: prepare the tablet of 23-hydroxyl radical white birck acid by those skilled in the art of the present technique's known method, wherein said tablet is made the 23-hydroxyl radical white birck acid that contains 20 ~ 200mg by actual needs.Get 23-hydroxyl radical white birck acid 150g of the present invention, micropowder silica gel 420g, Lactis Anhydrous 380g, silicon oxide 30g, mix after 30 minutes, rescreen magnesium stearate, continue mixing, use 12/32 inch standard concave punching press in blocks at last into 200g.
Claims (6)
1.23-the application of hydroxyl radical white birck acid in preparation treatment or prevention liver-cancer medicine.
2. application according to claim 1 is characterized in that: the medicine of described treatment or prevention hepatocarcinoma is with the pharmaceutical composition of 23-hydroxyl radical white birck acid as active component.
3. application according to claim 2, it is characterized in that: described 23-hydroxyl radical white birck acid is used from pharmaceutical compositions as active component and pharmaceutically acceptable excipient one, and this pharmaceutical composition adopts the conventional method of this area to be prepared into the dosage form or the oral form of administration in addition of oral administration.
4. application according to claim 3 is characterized in that: described excipient comprises diluent, wetting agent, lubricant, filler and antiseptic.
5. application according to claim 4 is characterized in that: described diluent is lactose, starch, dextrin, microcrystalline Cellulose or micropowder silica gel, and wetting agent is that water or volumetric concentration are 50～85% ethanol.
6. application according to claim 3 is characterized in that: this pharmaceutical composition is made capsule or tablet.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031529046A CN100551375C (en) | 2003-09-02 | 2003-09-02 | The application of 23-hydroxyl radical white birck acid in preparation treatment or prevention of brain neuroglia tumor medicine |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031529046A Division CN100551375C (en) | 2003-09-02 | 2003-09-02 | The application of 23-hydroxyl radical white birck acid in preparation treatment or prevention of brain neuroglia tumor medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101103986A true CN101103986A (en) | 2008-01-16 |
Family
ID=34240717
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101307411A Pending CN101103988A (en) | 2003-09-02 | 2003-09-02 | Application of 23-hydroxylbetulinic acid in preparing medicine for treating and preventing lung cancer |
| CNB031529046A Expired - Fee Related CN100551375C (en) | 2003-09-02 | 2003-09-02 | The application of 23-hydroxyl radical white birck acid in preparation treatment or prevention of brain neuroglia tumor medicine |
| CNA200710130738XA Pending CN101172110A (en) | 2003-09-02 | 2003-09-02 | Application of 23-hydroxyl radical white birck acid in preparing medicament for treating or preventing intestinal canal tumour |
| CNA2007101307394A Pending CN101103986A (en) | 2003-09-02 | 2003-09-02 | Application of 23-hydroxylbetulinic acid in preparing medicine for treating and preventing liver cancer |
| CNA2007101307407A Pending CN101103987A (en) | 2003-09-02 | 2003-09-02 | Application of 23-hydroxylbetulinic acid in preparing medicine for treating and preventing AIDS |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101307411A Pending CN101103988A (en) | 2003-09-02 | 2003-09-02 | Application of 23-hydroxylbetulinic acid in preparing medicine for treating and preventing lung cancer |
| CNB031529046A Expired - Fee Related CN100551375C (en) | 2003-09-02 | 2003-09-02 | The application of 23-hydroxyl radical white birck acid in preparation treatment or prevention of brain neuroglia tumor medicine |
| CNA200710130738XA Pending CN101172110A (en) | 2003-09-02 | 2003-09-02 | Application of 23-hydroxyl radical white birck acid in preparing medicament for treating or preventing intestinal canal tumour |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101307407A Pending CN101103987A (en) | 2003-09-02 | 2003-09-02 | Application of 23-hydroxylbetulinic acid in preparing medicine for treating and preventing AIDS |
Country Status (1)
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|---|---|
| CN (5) | CN101103988A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101230082B (en) * | 2006-05-12 | 2010-12-01 | 中国药科大学 | 23-hydroxy betulinic acid derivative, preparation method, preparation and use thereof |
| CN101704872B (en) * | 2009-11-23 | 2012-06-27 | 张南 | 23-hydroxybetulinic acid derivatives as well as preparation methods and application thereof |
| CN112121054A (en) * | 2020-09-23 | 2020-12-25 | 遵义医科大学 | Application of 23-hydroxy betulinic acid in preparing medicine for treating ulcerative colitis |
| CN113173965A (en) * | 2021-04-14 | 2021-07-27 | 籍建亚 | Anti-tumor betulinic acid derivative and preparation method thereof |
-
2003
- 2003-09-02 CN CNA2007101307411A patent/CN101103988A/en active Pending
- 2003-09-02 CN CNB031529046A patent/CN100551375C/en not_active Expired - Fee Related
- 2003-09-02 CN CNA200710130738XA patent/CN101172110A/en active Pending
- 2003-09-02 CN CNA2007101307394A patent/CN101103986A/en active Pending
- 2003-09-02 CN CNA2007101307407A patent/CN101103987A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN101103987A (en) | 2008-01-16 |
| CN1491651A (en) | 2004-04-28 |
| CN101103988A (en) | 2008-01-16 |
| CN100551375C (en) | 2009-10-21 |
| CN101172110A (en) | 2008-05-07 |
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