CN1390839A - Composition of garcinolic acid compounds, its preparing process and medical composition using it as active component - Google Patents
Composition of garcinolic acid compounds, its preparing process and medical composition using it as active component Download PDFInfo
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Abstract
A composition for garcinolic acid compounds, the process for preparing it, an antineoplastic medical composition containing it, and the application of said composition and medical composition in preparing antineoplastic medicines are disclosed. Said composition features high water solubility and antineoplastic activity, and no influence to hemopoietic system and white cells.
Description
Technical field
The present invention relates to the mixture of novel gambogic acid compounds, its preparation method and be the pharmaceutical composition of active ingredient, and their application in preparation medicine for treating tumor thing with this mixture.
Background technology
There are some researches show that gambogic acid compounds has restraining effect for tumour cell, but the solubleness of gambogic acid compounds in water is minimum, has therefore influenced their pharmaceutical use.
Educational circles was devoted to improve the research of the water solubility of gambogic acid compounds in recent years, thus seek suitable, can with the compound compound that improves its solubleness in water of gambogic acid compounds.
People such as the outstanding Qi Dong of China Medicine University, mixture (the Chinese invention patent application in publication number CN1309125A, open day August 22 calendar year 2001) with arginine and Methionin and gambogic acid compounds has been proposed, think the water solubility that can improve gambogic acid compounds, but fail to announce experimental data and solubleness.
Summary of the invention
Technical problem to be solved by this invention provides that a class is new, that water solubility is high, the mixture of gambogic acid compounds with pharmaceutical use.
Another technical problem to be solved by this invention provides a kind of method for preparing above-mentioned mixture.
The further technical problem to be solved of the present invention provides a kind of antitumor medicine composition.
Another technical problem to be solved by this invention provides the application of above-mentioned mixture in the preparation antitumor drug.
The general formula of the mixture of gambogic acid compounds provided by the invention is:
R=H or R=OH in the formula, B represents the glucosamine compounds.
The gambogic acid compounds of indication of the present invention is total cambogic acid, morellic acid or neogambogic acid, and its preparation method can be with reference to " Jiangxi Medical College's journal " 1980, (2): 1.With Gamboge 100g, pulverize and add acetone 500ml, reflux half an hour, triplicate, united extraction liquid is concentrated into driedly, obtains to contain the mixture that R is H and OH, i.e. total cambogic acid.
Total cambogic acid 10g adds acetone solution, and lysate extracts the Rf value and be 0.49 color spot after chromatographic separation, use the acetone wash-out, is concentrated into driedly, and the compound that obtains R=H is a morellic acid.
Total cambogic acid 10g adds acetone solution, and lysate extracts the Rf value and be 0.23 color spot after chromatographic separation, use the acetone wash-out, is concentrated into driedly, and the compound that obtains R=OH is a neogambogic acid.
The preferred version of the mixture of above-mentioned gambogic acid compounds is: B is glucosamine or meglumine.
In general, basic cpd and gambogic acid compounds are compound, can increase its solubleness in water, but the basic cpd huge amount, compound back effect improved degree is also uneven.The contriver sends out basic cpd existing through a large amount of experiments and gambogic acid compounds can not improve solubleness after compound, such as with benzene methanamine, ethylbenzene amine, 3, the mixture of 5-diaminobenzoic acid, its solubleness is 1: 500g/ml.Mixture provided by the invention has higher water solubility, below is the solubility experiment data statistics contrast table of part experimental subjects:
| Title | Solubleness in water (g/ml) |
| Total cambogic acid | 1/500 |
| Neogambogic acid | 1/500 |
| Morellic acid | 1/500 |
| Morellic acid-arginine mixture | 1/70 |
| Neogambogic acid-Methionin mixture | 1/70 |
| Total cambogic acid-arginine mixture | 1/70 |
| Morellic acid-meglumine mixture | 1/20 |
| Neogambogic acid-glucosamine mixture | 1/20 |
| Total cambogic acid-glucosamine mixture | 1/20 |
| Neogambogic acid-meglumine mixture | 1/20 |
| Morellic acid-glucosamine mixture | 1/20 |
| Total cambogic acid-meglumine mixture | 1/20 |
Obviously, the mixture of gambogic acid compounds and glucosamine compounds solubleness in water is significantly improved than the mixture of gambogic acid compounds and arginine and Methionin.
Simultaneously, the contriver finds also that through a large amount of experiments the raising of solubleness is not the sufficient condition that improves anti-tumor activity.Such as, experiment shows, be respectively 1 though the mixture solubleness of the mixture of neogambogic acid and triethylamine, total cambogic acid and ethamine is higher: 10g/ml and 1: 20, but its antineoplastic index is not higher than gambogic acid compounds, neogambogic acid and 2, the solubleness of the mixture of the mixture of 3 diaminopropionic acids, total cambogic acid and n-Butyl Amine 99 also improves a lot than gambogic acid compounds and is 1: 70g/ml, but its antineoplastic index is not higher than gambogic acid compounds.
With regard to the preparation cost of medicine, the mixture of total cambogic acid and total cambogic acid class is less than the mixture of morellic acid and gambogic acid, and the mixture of morellic acid and gambogic acid is less than the mixture of neogambogic acid and neogambogic acid class.Not only more in the past obvious raising of mixture solubleness provided by the invention, and its anti-tumor activity also improves significantly with respect to the suitable mixture of cost, and the contriver finds that the anti-tumor activity of mixture of the glucosamine compounds of neogambogic acid has tangible anti-tumor activity advantage in the mixture of gambogic acid compounds.Find also that by experiment mixture provided by the invention to normal hemopoietic system and not obviously influence of white corpuscle, does not have obvious blood vessel irritation in the kill tumor cell.Therefore mixture provided by the invention has higher pharmaceutical use with respect to other mixture.
The preparation method of gambogic acid compounds mixture provided by the invention: gambogic acid compounds and glucosamine compounds are with 1: the ratio of 0.8-2.0 (mol ratio), in water and/or alcoholic solvent, react.Its preferred version be gambogic acid compounds with 1: the ratio of 0.8-1.5 (mol ratio), react in water and/or alcoholic solvent with meglumine or glucosamine.
Antitumor medicine composition provided by the invention: the mixture that contains the above-mentioned general formula of effective therapeutic dose is an active ingredient, and contains one or more pharmaceutically acceptable carriers.It preferably contains the active ingredient of weight ratio 0.1-99.9%, most preferably contains the active ingredient of weight ratio 1-99.9%.
Mixture provided by the invention and pharmaceutical composition can be used for preparing the medicine of treatment liver cancer, intestinal cancer, lung cancer, cancer of the stomach, breast cancer, ovarian cancer, leukemia tumour.
The pharmaceutically acceptable carrier of kind mentioned above is meant thinner, vehicle, weighting agent, tackiness agent, wetting agent, disintegrating agent, absorption enhancer, absorption carrier, lubricant, flavouring agent, sweeting agent etc.
Its formulation of pharmaceutical composition of the present invention comprises: tablet, capsule, granule, oral liquid, injection etc.Its preparation method can be according to the conventional production method preparation of pharmaceutical field.Active ingredient is mixed with one or more carriers, be made into required formulation then.
The amount of application of the mixture of general formula of the present invention can be according to variations such as the type of route of administration, patient's age, body weight, the disease for the treatment of and severity, and its per daily dose can be 0.001-100mg/kg, preferred 0.1-100mg/kg, but one or many is used.
Embodiment
The following examples can make the professional more fully understand the present invention, but limit this patent never in any form.Embodiment 1: the preparation of total cambogic acid meglumine mixture
Get total cambogic acid 10g (0.0157 mole) in beaker, add an amount of distilled water, stirring slowly adds meglumine 3g (0.0154 mole) to dissolving fully, filters, and the filtrate lyophilize gets 13g left and right sides solid, is total cambogic acid meglumine mixture.Embodiment 2: the preparation of morellic acid glucosamine mixture
Get morellic acid 10g (0.0159 mole) in beaker, add suitable dissolve with ethanol after, slowly add an amount of distilled water again, stir down, slowly add glucosamine 3.1g (0.017 mole), after the dissolving fully, filter, the filtrate lyophilize gets 14g morellic acid glucosamine mixture.Embodiment 3: the preparation of neogambogic acid meglumine mixture
Get neogambogic acid 10g (0.0155 mole) in beaker, add suitable dissolve with ethanol after, stir down, slowly add meglumine 3.1g (0.0159 mole), after the dissolving fully, filter, the filtrate lyophilize, 14g neogambogic acid meglumine mixture.Embodiment 4: the preparation of morellic acid glucosamine mixture powder injection
Morellic acid glucosamine mixture 10g
Dextran 40 g
Morellic acid glucosamine mixture 10g is added an amount of water for injection dissolving, and Dextran 40 g adds an amount of water for injection dissolving, and two solution are mixed, add injection and be diluted with water to 2000ml, with the filtering with microporous membrane of 0.22um, under the aseptic condition, be loaded on respectively in the 10ml cillin bottle, sabot, send in the freeze drying box, after the lyophilize, outlet, roll lid, get final product.Embodiment 5: the preparation of total cambogic acid meglumine composite sheets
Total cambogic acid meglumine mixture 10g
Starch 100g
Starch slurry (8%) is an amount of
Magnesium Stearate 0.4g
Total cambogic acid meglumine mixture is added the starch uniform mixing, add 8% starch slurry and make software, granulate with 14 order nylon mesh, 70-80 ℃ of drying adds Magnesium Stearate, and through the whole grain of 10-12 order iron wire sieve, mixing is with 12mm punch die compressing tablet.Embodiment 6: the preparation of total cambogic acid meglumine composite particles agent
Total cambogic acid meglumine mixture 10g
Soluble starch 80g
Icing Sugar 20g
Essence is an amount of
Total cambogic acid meglumine mixture is water-soluble, add starch 80g, Icing Sugar 20g, it is an amount of to add essence again, and mixing is granulated with the 14-16 mesh sieve, and is dry below 60 ℃, packing.Embodiment 7: the preparation of neogambogic acid meglumine composition capsule agent
Neogambogic acid meglumine mixture 10g
Microcrystalline Cellulose 40g
Lactose 60g
Sodium Hydroxymethyl Stalcs 4g
Starch slurry is an amount of
Magnesium Stearate 1g
Micropowder silica gel 1g
Neogambogic acid meglumine mixture, Microcrystalline Cellulose, lactose, Sodium Hydroxymethyl Stalcs sieves respectively, and mix, add starch slurry and make softwood in right amount, to cross 20 mesh sieves and granulate, wet granular is dry down in 50 ℃, dried particle is crossed the whole grain of 20 mesh sieves, with Magnesium Stearate, micropowder silica gel mixing, can capsule.Embodiment 8; The preparation of morellic acid meglumine mixture oral liquid
Morellic acid meglumine mixture 10g
Asccharin 0.5g
Essence 0.1g
Water for injection 1000ml
After morellic acid meglumine mixture, asccharin, essence is dissolved in water for injection respectively, mixed, be diluted to 1000ml, packing, promptly.
Embodiment 9, inhibition knurl strain test:
Suppress the test of knurl strain selectivity with the neogambogic acid meglumine:
1. take by weighing above-claimed cpd 50mg, be dissolved in water, after the dissolving, be made into the stock solution of 2.5mg/ml fully.
2. get and above-mentionedly stock that to change liquid an amount of, add the cell complete culture solution, mixing is mixed with drug level successively and is respectively: 16ug/ml, 8ug/ml, 4ug/ml, 2ug/ml, 1ug/ml, 0.5ug/ml, the nutrient solution of 0.25ug/ml.
3. cultivate by standard, use microplate reader, 570nm photometry density OD.
4. cell survival rate=(dosing cell OD/ control cells OD)
*100 cell inhibitory rates (I)=100-cell survival rate
With the drug level C of correspondence, cell inhibitory rate I, by formula lg (I/100-)=A+BlgC carries out line and returns, behind the equation, IC50=lg
-1[(A)/B].Following table is an experimental result:
| Clone | IC50 |
| Lung cancer D6 cell | 5.72 |
| Liver cancer SMMC7721 cell | 2.00 |
| Intestinal cancer SW480 cell | 1.87 |
| Cancer of the stomach MNK28 cell | 4.24 |
| Breast cancer Bcap37 cell | 3.71 |
| Ovarian cancer HO-8910PM cell | 4.91 |
| The leukemia K 562 cell | 5.05 |
From last table we as can be seen the neogambogic acid meglumine tumour cell of liver cancer and intestinal cancer is had very strong restraining effect, lung cancer, cancer of the stomach, breast cancer, ovarian cancer, leukemic tumour cell are had suitable restraining effect.Equally, gambogic acid compounds also has identical restraining effect with other mixture of glucosamine compounds to above-mentioned tumour cell
The simultaneous test of the influence of 10 couples of liver cancer SMMC7721 of embodiment cell growth
In the present embodiment the material in the following table has been carried out simultaneous test to the influence of liver cancer SMMC7721 cell growth.Experimental technique is with embodiment 9
| The compound title | IC50(ug/ml) |
| Total cambogic acid | 4.67 |
| Morellic acid | 4.65 |
| Neogambogic acid | 3.12 |
| Morellic acid arginine mixture | 4.15 |
| Neogambogic acid Methionin mixture | 3.26 |
| Total cambogic acid arginine mixture | 4.19 |
| The total cambogic acid glucosamine | 4.14 |
| The total cambogic acid meglumine | 3.98 |
| The morellic acid glucosamine | 3.43 |
| The morellic acid meglumine | 3.21 |
| The neogambogic acid glucosamine | 2.17 |
| The neogambogic acid meglumine | 2.00 |
| Total cambogic acid ethamine | 5.17 |
| Neogambogic acid 2, the 3-diaminopropionic acid | 4.61 |
| The neogambogic acid triethylamine | 4.16 |
Interpretation: mixture provided by the invention has than remarkable advantages the growth that suppresses liver cancer SMMC7721 cell.Total cambogic acid glucose amine mixture improves with respect to the effect of total cambogic acid arginine mixture on this project, morellic acid glucose amine mixture then is significantly improved with respect to neogambogic acid Methionin class mixture with respect to morellic acid arginine class mixture, neogambogic acid glucose amine mixture, and neogambogic acid glucose amine mixture is in very leading status with respect to the effect of mixture on this project of all gambogic acid compounds.
The simultaneous test of the influence of 11 couples of intestinal cancer SW480 of embodiment cell growth
In the present embodiment the material in the following table has been carried out simultaneous test to the influence of intestinal cancer SW480 cell growth.
Experimental technique is with embodiment 9
| The compound title | IC50(ug/ml) |
| Total cambogic acid | 2.95 |
| Morellic acid | 3.11 |
| Neogambogic acid | 2.01 |
| Morellic acid arginine mixture | 3.25 |
| Neogambogic acid Methionin mixture | 2.84 |
| Total cambogic acid arginine mixture | 3.97 |
| The total cambogic acid glucosamine | 2.79 |
| The total cambogic acid meglumine | 2.64 |
| The morellic acid glucosamine | 2.97 |
| The morellic acid meglumine | 3.11 |
| The neogambogic acid glucosamine | 1.45 |
| The neogambogic acid meglumine | 1.87 |
| Total cambogic acid ethamine | 3.12 |
| New rattan acid 2, the 3-diaminopropionic acid | 2.96 |
| The neogambogic acid triethylamine | 3.01 |
Interpretation: mixture provided by the invention has than remarkable advantages the growth that suppresses intestinal cancer SW480 cell, total cambogic acid glucose amine mixture improves with respect to the effect of total cambogic acid arginine mixture on this project, morellic acid glucose amine mixture is with respect to morellic acid arginine class mixture, neogambogic acid glucose amine mixture then is significantly improved with respect to neogambogic acid Methionin class mixture, and neogambogic acid glucose amine mixture is in very leading status with respect to the effect of mixture on this project of all gambogic acid compounds.
The restraining effect that embodiment 12 neogambogic acid meglumine mixtures are transplanted the Heps solid tumor to mouse transplanted sarcoma S180, mouse
Medicine preparation: quantitatively take by weighing the neogambogic acid meglumine, add 0.9%NaCl solution and be made into desired concn.
Route of administration: ip
The administration cycle: in inoculation back 24h successive administration 9 days, once a day, after the drug withdrawal first
It puts to death dissection.
Dosage is provided with: establish five groups altogether
The A group: neogambogic acid meglumine group (8,4,2mg/kg)
B group: neogambogic acid Methionin (8mg/kg)
C group: blank group (physiological saline 0.4ml/20g)
Mouse type: Kunming mouse body weight 18-22g
Administration volume: 0.4ml/20g
Experimental technique: get 50 of above-mentioned specification mouse, press the inoculation of transplanted tumor organon, inoculate back 24 hours and claim mouse heavy, and be divided into 5 groups at random, every group 10, male and female half and half, physiological saline and neogambogic acid Methionin are respectively the yin, yang control group, and neogambogic acid meglumine group is established high, medium and low three dosage groups.After drug withdrawal, weighed in first day, put to death and also to separate the knurl piece, claim that knurl is heavy and carry out statistical procedures (t check) table 1 neogambogic acid meglumine ip the restraining effect of mouse transplanting S180 (x ± SD)
Table 2 neogambogic acid meglumine ip transplants the Heps solid tumor to mouse restraining effect (x ± SD) is compared in P＜0.01 with the physiological saline control group
| Group | Mouse number (only) | Dosage mg/kg | Body weight (g) | Knurl heavy (g) | Tumour inhibiting rate (%) | |
| Before the administration | After the administration | |||||
| C group A group B group | ?10 ?10 ?10 ?10 ?10 | ?8 ?4 ?2 ?8 | ?19.6±1.42 ?19.5±1.32 ?19.5±1.27 ?19.6±1.49 ?19.6±1.30 | 25.2 ± 1.57 23.9 ± 1.21 24.9 ± 1.34 25.1 ± 1.25 23.1 scholars 1.31 | 2.41±0.21 0.38±0.16·· 0.89±0.29·· 1.64±0.37·· 0.58±0.18·· | ?84.2 ?63.1 ?32.1 ?75.9 |
| Group | Mouse number (only) | Dosage mg/kg | Body weight (g) | Knurl heavy (g) | Tumour inhibiting rate (%) | |
| Before the administration | After the administration | |||||
| C group A group | ?10 ?10 ?10 ?10 | ?8 ?4 ?2 | ?19.4±1.01 ?19.4±1.30 ?19.5±1.27 ?19.5±1.18 | ?26.4±1.56 ?24.7±1.30 ?25.8±1.21 ?26.3±1.27 | ?2.46±0.26 ?0.53±0.11·· ?1.08±0.16·· ?1.63±0.35·· | ?78.5 ?56.1 ?33.7 |
| The B group | 10 | ?8 | ?19.6±1.10 | ?23.9±1.32 | ?0.81±0.22·· | 67.1 |
P＜0.01 is compared with the physiological saline control group
Experimental result: the result shows with the physiological saline control group and compares, the neogambogic acid meglumine has the growth effect that suppresses mouse S180, transplantability Heps solid tumor very significantly, and weight of mice do not had obvious influence, and the tumor-inhibiting action of neogambogic acid meglumine is better than neogambogic acid Methionin.
Embodiment 13 morellic acid glucosamines are to the prolongation effect of mice transplanted tumor life
Medicine preparation: quantitatively take by weighing the morellic acid glucosamine, add 0.9%NaCl solution and be made into desired concn.
Route of administration: ip
The administration cycle: in the 24h administration of inoculation back, once a day, administration is 10 days altogether, observes altogether after the administration 60 days.
Dosage is provided with: establish five groups altogether
A group: morellic acid glucosamine group
B group: morellic acid Methionin
C group: blank group (physiological saline 0.4ml/20g)
Mouse type: Kunming mouse body weight 18-22g
Administration volume: 0.4ml/20g
Experimental technique: get 50 of above-mentioned specification mouse, press the inoculation of transplanted tumor organon, after the inoculation, be divided into 5 groups at random, 10 every group, male and female half and half, physiological saline and morellic acid Methionin are respectively the yin, yang control group, and morellic acid glucosamine group is established high, medium and low three dosage groups.After the administration, observe tumor-bearing mice survival fate (survival more than 60 days mouse by 60 days) and survival rate (by survival more than 60 days and asymptomatic mouse), and carry out statistical procedures (t check)
Table 1 morellic acid glucosamine ip prolongs vital action to EAC ascitic type mice-transplanted tumor
| Group | Mouse number (only) | Dosage mg/kg | The survival fate (x ± SD) | Increase in life span (%) | Survival rate (%) |
| ?C ?A ?B | ?10 ?10 ?10 ?10 ?10 | ?1.50 ?0.75 ?0.50 ?1.50 | 10.1±1.97 33.6±16.80·· 22.5±9.52·· 17.0±4.51·· 28.6±14.17·· | ?232.6 ?122.7 ?68.3 ?183.2 | ?20 ?0 ?0 ?10 |
P＜0.01 is compared table 2 morellic acid glucosamine ip Heps ascitic type mouse transplanted sarcoma is prolonged vital action with the physiological saline control group
| Group | Mouse number (only) | Dosage mg/kg | The survival fate (x ± SD) | Increase in life span (%) | Survival rate (%) |
| ?C ?A ?B | ?10 ?10 ?10 ?10 ?10 | ?1.50 ?0.75 ?0.50 ?1.50 | 10.3±2.2 36.9±16.90·· 23.8±6.29·· 19.4±3.27·· 31.0±11.19·· | ?258.3 ?131.1 ?88.3 ?201.0 | ?30 ?0 ?0 ?10 |
Experimental result is compared with the physiological saline control group in P＜0.01: the result shows, compare with the physiological saline control group, the morellic acid glucosamine has the EAC of prolongation ascitic type mouse, Heps ascitic type mouse survival fate effect (P＜0.01), and increase in life span and the survival rate of EAC ascitic type mouse, Heps ascitic type mouse all is better than morellic acid Methionin.
Embodiment 14 neogambogic acid meglumines are to the influence of leukocyte count in the mouse blood
Experimental technique: get the 18-22g mouse, press the transplanted tumor organon, inoculation S180, inoculation is afterwards weighed and be divided into 5 groups at random next day, every group 10, male and female half and half, ip administration, 9d altogether, weigh and get blood by the eye socket vein in after drug withdrawal first day, the microscopy total white blood cells, anatomical isolation knurl piece is simultaneously weighed and is carried out statistical procedures.
The A group: neogambogic acid meglumine group (8,4,2mg/kg)
B group: neogambogic acid Methionin (8mg/kg)
C group: blank group (physiological saline 0.4ml/20g)
P＜0.01 is compared with the physiological saline control group
| Group | Mouse number (only) | Dosage mg/kg | Body weight (g) | WBC ?No./mm 3 | Knurl heavy (g) | Tumour inhibiting rate (%) | |
| Before the administration | After the administration | ||||||
| C group A group B group | ?10 ?10 ?10 ?10 ?10 | ?8 ?4 ?2 ?8 | ?19.6±1.42 ?19.5±1.32 ?19.5±1.27 ?19.6±1.49 ?19.6±1.30 | ?25.2±1.57 ?23.9±1.21 ?24.9±1.34 ?25.1±1.25 ?23.1±1.31 | ?10383±2636 ?12188±4863 ?9943±3190 ?11942±3508 ?10169±3241 | 2.41±0.21 0.38±0.16·· 0.89±0.29·· 1.64±0.37·· 0.58±0.18·· | ?84.2 ?63.1 ?32.1 ?75.9 |
Experimental result: the result shows with the physiological saline control group and compares that the neogambogic acid meglumine has the growth effect that suppresses mouse S180 very significantly, and its effect is better than neogambogic acid Methionin, and white corpuscle in the mouse peripheral blood is not had obvious influence.The white corpuscle of high dose group also increases to some extent.
The test of embodiment 15 neogambogic acid meglumine blood vessel irritations
Experimental technique: get 2 of body weight 2.2-2.4kg healthy rabbits, rabbit is placed fixer, rabbit left side auricular vein instillation neogambogic acid meglumine injection 8mg/kg amounts to 6ml, auris dextra instillation chloride injection is dared liquid 6ml/kg, drip velocity is 20 droplets/minute, every morning instils once, a continuous week.Observe left and right sides auricular vein reaction, observe the injection site blood vessel every day and have or not rubescent, oedema, have or not oozing of blood on every side, touch blood vessel and have or not the hardening phenomenon, left and right sides ear is more now examined.After time administration 12 hours,, take off left and right sides ear, cut sections for microscopic examination with sacrifice of animal.
Experimental result: after two rabbit administrations, every day, left and right ear was all normal, and is not rubescent, no oedema, and histopathological examination is Non Apparent Abnormality also.The blood vessel irritation test of neogambogic acid meglumine shows that this medicine does not have obvious local irritant effect to the rabbit auricular vein.
Claims (10)
1. the mixture that has the gambogic acid compounds of following general formula
R=H or R=OH in the formula, B represents the glucosamine compounds.
2. the mixture of gambogic acid compounds as claimed in claim 1 is characterized in that B is a meglumine.
3. the mixture of gambogic acid compounds as claimed in claim 1 is characterized in that B is a glucosamine.
4. the preparation method of the mixture of the gambogic acid compounds of claim 1 is characterized in that gambogic acid compounds and glucosamine compounds are with 1: the ratio of 0.8-2.0 (mol ratio), in water and/or alcoholic solvent, react.
5. the preparation method of the mixture of gambogic acid compounds as claimed in claim 4, it is characterized in that its preferred version be gambogic acid compounds with 1: the ratio of 0.8-1.5 (mol ratio), react in water and/or alcoholic solvent with meglumine or glucosamine.
6. the pharmaceutical composition that is used for the treatment of tumour is characterized in that wherein containing the mixture and the pharmaceutically acceptable carrier of the claim 1 of effective therapeutic dose.
7. the pharmaceutical composition that is used for the treatment of tumour as claimed in claim 6 is characterized in that the R=H of described mixture.
8. the pharmaceutical composition that is used for the treatment of tumour as claimed in claim 6 is characterized in that the R=OH of described mixture.
9. the pharmaceutical composition that is used for the treatment of tumour as claimed in claim 6 is characterized in that described mixture is the mixture of arbitrary proportion of the mixture of the mixture of R=H and R=OH.
10. any mixture among the claim 1-3 is preparing the application for the treatment of in liver cancer, intestinal cancer, lung cancer, cancer of the stomach, breast cancer, ovarian cancer, the leukemia tumour medicine.
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| CN100413868C (en) * | 2004-05-21 | 2008-08-27 | 台湾森本生物科技开发股份有限公司 | Compounds separated from gamboges with activities of inhibiting tumour/cancer cell growth and pharmaceutical compositions containing same |
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| CN102276621B (en) * | 2010-06-11 | 2015-01-07 | 台湾森本生物科技开发股份有限公司 | Compound separated from gamboge resin and derivative thereof and pharmaceutical composition comprising compound and derivative |
| TWI432191B (en) | 2010-06-11 | 2014-04-01 | Taiwan Sunpan Biotechnology Dev Co Ltd | Compounds isolated from gamboge resin , and pharmaceutical compositions comprising the same |
| CN103421021B (en) * | 2010-06-11 | 2016-08-10 | 台湾森本生物科技开发股份有限公司 | Separated compound and its derivative from Gamboge, and the pharmaceutical composition that includes these compounds and derivative |
-
2002
- 2002-06-17 CN CN 02124510 patent/CN1245407C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100413868C (en) * | 2004-05-21 | 2008-08-27 | 台湾森本生物科技开发股份有限公司 | Compounds separated from gamboges with activities of inhibiting tumour/cancer cell growth and pharmaceutical compositions containing same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1245407C (en) | 2006-03-15 |
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