CN100408571C - Andrographolide-trimaleate and its salt and their medicine composition - Google Patents
Andrographolide-trimaleate and its salt and their medicine composition Download PDFInfo
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Abstract
The present invention relates to andrographolide-trimaleate half ester of a formula (I) and andrographolide-trimaleate half ester salt of a formula (II) with activity of clearing heat and resisting virus, a preparation process thereof and a medicinal composition containing andrographolide-trimaleate half ester and andrographolide-trimaleate half ester salt. Ps: in the compound of the formula (II), X represents H, Na, K, Ca and NH4; Y represents H, Na, K, Ca and NH4; Z represents H, Na, K, Ca and NH4.
Description
FIELD OF THE INVENTION:
The present invention relates to andrographolidume derivative, the preparation method, and contain their pharmaceutical composition.Specifically, the present invention relates to rographolide trimaleate and rographolide trimaleate Salt And Preparation Method and contain their pharmaceutical composition and in analgesic and clinical application anti-virus aspect.
Background technology:
Herba Andrographis Andrographis Paniculata (Burm.f.) Nees is the clearing heat and detoxicating plant amedica of wide clinical application, has taken in [2000] one ones 220 pages of Chinese Pharmacopoeias; To existing more researchs such as the chemical structure analysis of its introducing culture, effective constituent and derivative preparation, preparation process and pharmacology are clinical, think that its main effective constituent is diterpene ginkgolide more, as [pharmacy circular, 17 4 phases of volume of nineteen eighty-two such as rographolide (Andrographolide), deoxydidehydrorographolide (Dehydroandrographolide); Traditional Chinese Medicine Research Institute, Sichuan Province: the pharmacological action of 13 kinds of Herba Andrographis injections].
Be to improve clinical efficacy, generally extract rographolide after, prepare the injection liquid of various soluble derivatives, as sodium bisulfite affixture, sodium sulfonate affixture and succinic acid half-ester monopotassium salt etc.Wherein sodium bisulfite addition rographolide and andrographolide succinic acid half-ester monopotassium salt (injection potassium dehydroandrographolide succinate) have been taken in the national drug standards.But above-mentioned known medicine solubleness in separating thermal effect and water is all undesirable.
The purpose of invention:
In order to overcome above-mentioned defective, the invention provides following formula (I) and formula (II) compound and preparation method thereof and contain their pharmaceutical composition.Another object of the present invention is formula (I) and formula (II) the compound purposes as preparation antipyretic and antiviral agent.
The content of invention:
The invention provides following formula (I) and formula (II) compound, they can be used as the effective ingredient of antipyretic and antiviral agent.
Annotate: X representative in formula (II) compound: H, Na, K, Ca, NH
4Y representative: H, Na, K, Ca, NH
4Z representative: H, Na, K, Ca, NH
4
The method of above-mentioned preparation formula (I) and formula (II) compound:
The method of preparation formula (I) compound: with the rographolide is raw material, in vacuum tightness is 520～620mmHg, 60～200 ℃, under catalyst action with maleic anhydride generation esterification, refluxed 0.5～10 hour, vacuum is removed in the cooling back, adding water is stirred to till whole curing and the crystallization evacuation, suction filtration, the vacuum-drying of filter cake normal temperature, filter cake adds the sodium bicarbonate aqueous solution dissolving, filters, and filtrate transfers pH to acid, separate out white precipitate, suction filtration, drying obtain rographolide trimaleate (being called for short horse lotus ester).
The method of preparation formula (II) compound: modus ponens (I) compound, add methyl alcohol and make dissolving, with saleratus (sodium bicarbonate, Calcium hydrogen carbonate, the Ammonium bicarbonate food grade) reflux of different amounts 1～2 hour, cold after-filtration, vacuum-drying, De Malian ester list salt, horse lotus ester disalt, the about 3.0g of horse lotus ester three salt respectively.Total recovery is 70～80%.
Preparation formula (I) compound reaction equation:
The reaction equation of preparation formula (II) compound:
Annotate: the salt in the reaction equation of preparation formula (II) compound represents carbonate, supercarbonate.
X representative in formula (II) compound: H, Na, K, Ca, NH
4Y representative: H, Na, K, Ca, NH
4Z representative: H, Na, K, Ca, NH
4
The pharmaceutical composition of analgesic and antiviral activity of the present invention, it comprise the formula (I) of treatment significant quantity claim 1 definition or (II) the formula compound as active ingredient and the pharmaceutical carrier of routine/or thinner pharmaceutically.Described treatment significant quantity is that 100mg intravenous drip every day 3rd～4 was a course of treatment.
The present invention also provides formula (I) and formula (II) compound as the purposes for preparing analgesic antiphlogistic and antiviral agent.
Raw material rographolide among the preparation method of the present invention can extract preparation from Herba Andrographis with known method, and maleic anhydride can have been bought on market, and catalyzer wherein can use S-WAT etc.The pharmaceutical carrier of the use in the pharmaceutical composition of the present invention or thinner can be water, pH damping fluid etc.Below describe formula of the present invention (I) and the preparation method of formula (II) compound and the excellent results of The compounds of this invention in detail with specific embodiment.
Description of drawings:
Fig. 1 is rographolide trimaleate mass spectrum (He'nan University)
Fig. 2 is a rographolide trimaleate sodium salt mass spectrum (Jun Keyuan)
Embodiment
Rographolide trimaleate and rographolide trimaleate salt
(be called for short horse lotus ester and Ma Lian ester salt, down together) preparation
The preparation of horse lotus ester: rographolide 2g (0.006mOl), maleic anhydride 2g (0.041mOl), S-WAT 0.2g puts in the reaction flask, mixing is set up reflux and drying tube, begins heating, and adjusting vacuum tightness is 520～620mmHg, 100 ℃, return gold-plating reaction 5 hours, vacuumize after the cooling.Add 40ml water in reaction flask, be stirred well to till the evacuation of whole curing and crystallization.Suction filtration, the vacuum-drying of filter cake normal temperature, filter cake adds the sodium bicarbonate aqueous solution dissolving, filters, and filtrate transfers pH to acid, separates out white precipitate, and suction filtration, drying obtain rographolide trimaleate (being called for short horse lotus ester).
The preparation of horse lotus ester salt: get horse lotus ester, add methyl alcohol and make dissolving, with saleratus (sodium bicarbonate, the Calcium hydrogen carbonate) reflux of different amounts 1～2 hour, cold after-filtration, vacuum-drying, De Malian ester list salt, horse lotus ester disalt, the about 3.0g of horse lotus ester three salt respectively.Total recovery is 70～80%.
Physico-chemical property:
Horse lotus ester: micro-yellow powder, odorless, bitter.Water insoluble, be dissolved in acetone, chloroform or ether.Fusing point: 119～121 ℃.
Horse lotus ester list salt: off-white powder shape or plate crystal, be slightly soluble in water, dissolve in 2% sodium carbonate solution, be insoluble to chloroform or ether.250 ℃ do not melt, but begin to turn to be yellow variable color and decomposition.
Horse lotus ester three salt: micro-yellow powder, odorless, bitter.Soluble in water, slightly be dissolved in Diluted Alcohol, be insoluble to chloroform or ether.250 ℃ do not melt, but begin to turn to be yellow variable color and decomposition.
The effect of invention:
Clinical andrographolide succinic acid half-ester monopotassium salt commonly used claims potassium dehydroandrographolide succinate again at present, year clinical big quantity research surplus in the of 30, prove that it has significantly analgesic, anti-inflammatory, promotion adrenal cortex function and sedative effect, can promote the phagocytic activity of neutrophil leucocyte scavenger cell, improve the content of N,O-Diacetylmuramidase in the serum.Research thinks, the rographolide compound with the early stage capillary permeability of inflammation is increased and ooze out, the oedema restraining effect serves as significantly, prompting rographolide compounds is a kind of non-specific antiphlogiston of novel type.The potassium dehydroandrographolide succinate wide clinical application is in infantile pneumonia, viral upper respiratory tract infection, trachitis, influenza, leptospirosis and acute bacillary dysentery etc., and is wherein remarkable to separate thermal effect.
Rographolide trimaleate and rographolide trimaleate salt pharmacodynamic study show that it separates thermal effect and be higher than potassium dehydroandrographolide succinate far away.
The stability test of horse lotus ester
1, instrument and reagent
Instrument UV-265FW type spectrophotometer (day island proper Tianjin)
Reagent Meta-dinitrobenzene (Shanghai reagent one factory), ethanol (Beijing Chemical Plant)
2, constant temperature accelerated test method
Sample is placed four thermostat containers of 97 ℃, 87 ℃, 77 ℃ and 67 ℃ respectively, and content is measured in sampling as follows at regular intervals.
3, measuring method
3.1 the preparation of reference substance (rographolide trimaleate monopotassium salt, purity are 99%) solution:
It is an amount of that minute is got the reference substance of putting 4 ℃ of dark places preservations per sample, is dissolved into the solution of 1mg/ml with Diluted Alcohol.
3.2 the preparation of sample (rographolide trimaleate monopotassium salt, purity are 99%) solution: be taken at the about 0.1g of sample of heating certain hour under the certain temperature, the accurate title, decide, and puts in the 100ml volumetric flask, is diluted to scale with Diluted Alcohol, shakes up.
3.3 determination step
Precision is measured sample solution and each 5ml of reference substance solution respectively, puts in the 10ml volumetric flask, adds 0.5% Meta-dinitrobenzene ethanol liquid 2ml and 0.2mol NaOH solution 1ml, uses the Diluted Alcohol constant volume.Placing 3 minutes, and put in the 1cm cuvette, measure optical density at the 485nm place, is 100% calculation sample content with reference substance solution content.The result is as follows:
97℃
87℃
77℃
67℃
Can be by above data in the hope of, K
25=5.328 * 10
-6, t
0.9=2.3 years.So it is 2 years that validity period can be fixed tentatively.
The pharmacodynamic study of horse lotus ester monopotassium salt
Purpose: investigate the effective dose and the pharmacological action of horse lotus ester monopotassium salt, for clinical application provides foundation.Method: egg white causes rat paw edema, rat granuloma is swollen and the anti-inflammatory action of mice caused by dimethylbenzene xylene peritonitis model observation horse lotus ester monopotassium salt; Dry yeast causes rat fever, dinitrophenol(DNP) causes rat fever and intracellular toxin causes the refrigeration function that rabbit fever models is observed horse lotus ester monopotassium salt; The test tube culture method is observed the anti-microbial effect of horse lotus ester monopotassium salt.The result: horse lotus ester monopotassium salt dose-effect relationship is obvious: 300mg/kg and 150mg/kg all have good refrigeration function to rat fever and the fever in rabbits due to the intracellular toxin due to dry yeast and the dinitrophenol(DNP), and 75mg/kg is all not obvious to three kinds of heating functioins; 400mg/kg and 200mg/kg to the rat paw edema due to the egg white, rat granuloma is swollen and dimethylbenzene due to the mouse peritoneum inflammation good anti-inflammatory action is all arranged, 100mg/kg is all not obvious to three kinds of inflammatory effect.
Horse lotus ester monopotassium salt large intestine bar and the MIC of dysentery bacterium be that 2mg/ml is the 1mg/ml conclusion to gold-coloured staphylococci and pneumococcal MIC: horse lotus ester monopotassium salt has better antipyretic and anti-inflammatory action, but its anti-microbial effect a little less than.
Horse lotus ester tripotassium salt and horse lotus ester monopotassium salt results of pharmacodynamic test basically identical.
Key is raised: the therapeutic action of horse lotus ester monopotassium salt pharmacodynamics
Horse lotus ester monopotassium salt is the kind new medicine that Beijing medical professionals's biological study is developed, and through the pharmacodynamics screening good analgesic and anti-inflammatory action is arranged, and this paper studies the pharmacodynamics of horse lotus ester monopotassium salt by the provisions for new drugs approval requirement, now is reported as follows:
1 material
1.1 medicine horse lotus ester monopotassium salt, effluent Nanjing University learns medicine lot number is provided: 20010701, and purity: the phosphate buffered saline buffer of 92.83% usefulness pH6.8 is made into 4% solution with medicine, is high dosage; High dosage is diluted to 2% and is middle dosage: high dosage is diluted to 1% and is low dosage, all fresh at every turn preparation.
Potassium dehydroandrographolide succinate powder pin, sino-america joint-venture Heilungkiang pharmaceutical Co. Ltd, lot number: 010504
1.2 the golden grape coccus of bacterial strain, intestinal bacteria, streptococcus pneumoniae, dysentery bacterium, Medical House provides by the Kaifeng.
1.3 the animal mouse, body weight 22～25g, ♂: the Wistar rat, body weight 150～200g, ♀ ♂ dual-purpose: rabbit, 2.5～3.0kg, ♀ ♂ dual-purpose provides by Henan Province's medical experiment animal center, conformity certification number: 4109.
1.4 reagent Angel dry yeast, Angel, Hubei dry yeast limited-liability company, lot number: 20010621; Intracellular toxin 10EU/ props up, Chinese biological goods institute product; Dimethylbenzene, chemical four factories that break a seal, lot number: 20001013; 2,2, 4-dinitrophenol, Lanxi City chemical reagent factory, lot number: 20000802; Nutrient agar medium, the difficult to understand special star biotechnology in Beijing branch office product.
1.5 instrument 751-type uv-spectrophotometric instrument, Shanghai medicine equipment two factories.
1.6 testing circumstance, temperature: 23 ± 3 ℃, humidity: 55 ± 10%,
Natural lighting 7:00～19:00 freely drinks water, quantitatively feeding.
2. experimental technique
2.1 refrigeration function
2.1.1 dry yeast is caused the influence of rat fever
Test preceding 2 day every day and survey rat temperature 1 time, select body temperature and change in 37C～38. ℃, and self body temperature changes 60 of rats that are lower than 0.3 ℃, 150～180g, ♀ ♂ half and half is divided into 5 groups at random, 12 every group.One group of ip physiological saline, two groups of ip potasium dehydroandrographolisuccinate succinate injection 150mg/kg, three, distinguish ip horse lotus ester monopotassium salt injection liquid 300mg/kg, 150mg/kg, 75mg/kg for four, five groups, each is organized volumetric injection and is 1ml/100g, before the administration 2.5h take temperature once, as 0 o'clock basal body temperature, the fresh dry yeast suspension 1ml/100g of SC20% immediately behind the thermometric, the body temperature when 2.5h the back, is measured 3h, 4h behind the injection dry yeast, 7h, 9h, 11h to each group relative medicine.(seeing Table 1)
2.1.2 interior intracellular toxin is caused the influence of fever in rabbits
Test preceding 2 day every day and survey rabbit body temperature 1 time, select body temperature, and self body temperature changes less than 40 of 0.3 ℃ rabbit at 38.0～39.5 ℃, 2.5～3.0kg, ♀ ♂ half and half is divided into 5 groups at random, and 8 every group, male and female half and half.One group in rabbit left side auricular vein injecting normal saline, two groups in rabbit left side auricular vein injection potassium dehydroandrographolide succinate 150mg/kg, three, four, five groups respectively at rabbit left side auricular vein injection horse lotus ester monopotassium salt injection liquid 300mg/kg, 150mg/kg, 75mg/kg, and each is organized volumetric injection and is 6ml/kg.Measuring a body temperature and make 0 o'clock basal body temperature before administration, is 1ml/kg in rabbit right auricular vein injection intracellular toxin 200ng/kg capacity immediately after the administration, the body temperature when measuring 1h, 2h after the administration, 3h, 4h, 6h.(seeing Table 2)
2.1.3 paradinitrobenzene phenol causes the influence of rat fever
Test preceding 2 day every day and survey rat temperature 1 time, select body temperature and change, and change 50 of rats that are lower than 0.3 ℃ from health at 37 ℃～38.5 ℃, 150～180g, ♀ ♂ is divided into 5 groups at random, 10 every group.One group of ip physiological saline, two groups of ip potasium dehydroandrographolisuccinate succinate injection 150mg/kg distinguish ip horse lotus ester monopotassium salt injection liquid 300mg/kg, 150mg/kg, 75mg/kg for three, four, five groups, and each is organized volumetric injection and is 1ml/100g.Before the administration take temperature once, as 0 o'clock basal body temperature, after the administration immediately SC 0.15% newly join dinitrophenol(DNP) 1ml/100g, the body temperature when measuring 1h, 2h behind the drug administration by injection, 3h, 4h.(seeing Table 3)
2.2 anti-inflammatory action
2.2.1 egg white is caused the influence of rat paw edema
60 of rats, 180～220g, ♀ ♂ half and half is divided into 5 groups at random, 12 every group.One group of ip physiological saline, two groups of ip potassium dehydroandrographolide succinate 200mg/kg, three, four, five groups of difference ip horse lotus ester monopotassium salt 400mg/kg, 200mg/kg, 100mg/kg, each is organized volumetric injection and is 1ml/100g.Before the administration with the right ankle joint flooding boundary of marking pen mark rat, the Volume of Displacement method measure cause for 1 time scorching before the right sufficient Volume of Displacement of rat, after the administration immediately only in the right back sole SC of rat fresh albumen 0.1ml/.Rat foot Volume of Displacement when measuring 1h, 2h after the administration, 3h, 5h.(seeing Table 4)
2.2.2 p-Xylol causes the influence of mouse peritoneum inflammation
75 of mouse are divided into 5 groups at random, 15 every group.Cut off the about 3 * 3cm of mouse web portion center belly wool with scissors before the experiment
2One group of subcutaneous injection physiological saline, two groups of subcutaneous injection potassium dehydroandrographolide succinate 200mg/kg distinguish subcutaneous injection horse lotus ester monopotassium salt 400mg/kg, 200mg/kg, 100mg/kg for three, four, five groups, and each is organized volumetric injection and is 0.1ml/10g.40min after the administration gives mouse tail intravenous injection 1% she Wen blue 0.1ml/10g, after the injection immediately only in the melted paraxylene 0.1ml/ of belly unhairing place, put to death mouse behind the 20min, peel off skin of abdomen, dyeing place is cut, dye level is carried out integration, shred dyeing skin then, put into test tube, add 5ml (acetone: NS=7: 3) liquid, immersion 48h (middle jolting 10 times), centrifugal, get supernatant liquor and sentence blank (acetone: NS=7: 3) liquid zeroing photometry density in 751 spectrophotometer 610nm.(seeing Table 5)
2.2.3 to the swollen influence of rat granuloma
50 of rats, 200～220g, ♀ ♂ is divided into 5 groups at random, 10 every group.One group of ip physiological saline, two groups of ip potasium dehydroandrographolisuccinate succinate injection 150mg/kg, three, four, five groups of difference ip horse lotus ester monopotassium salt injection liquid 300mg/kg.150mg/kg, 75mg/kg, each is organized volumetric injection and is 1ml/100g.Test is initial, the vetanarcol 1ml/100g anesthetized rat of ip0.25%, cut off the epigastrium hair, sterilization, cut skin along ventrimeson, the cotton balls that 2 50mg are heavy (autoclaving, each cotton balls adds penicillin, each 0.1ml of Streptomycin sulphate of 1%) is in advance implanted the oxter, both sides, sew up the incision, sterilization treats that rat begins administration, every day 1 time after clear-headed, continuous 7d, rat is put to death in the dislocation of 8d cervical vertebra, peels off the cotton balls granulation tissue, puts 60 ℃ of oven for drying to constant weight, analytical balance is weighed, and deducts the raw cotton ball weight and is granulation tissue weight.(seeing Table 6)
2.3. antibacterial tests
Extracorporeal bacteria inhibitor test (agar test tube doubling dilution)
Ditalimfos phthalate buffer with pH6.8 is made into 2% injection liquid with horse lotus ester monopotassium salt, make starting point concentration after the filtering with microporous membrane degerming, reduce by half with the ditalimfos phthalate buffer again and be diluted to 1/2,1/4,1/8,1/16,1/32 concentration, with injection physiological saline potassium dehydroandrographolide succinate powder pin is made into 2% injection liquid, make starting point concentration after the filtration sterilization, reduce by half with physiological saline again and be diluted to 1/2,1/4,1/8,1/16,1/32 concentration, divide and draw 1ml in addition in sterile test tube, add the 9ml nutrient agar medium, shake up, cultivating 24h in 37 ℃ of incubators behind the inoculated bacteria and observe, is minimum MIC (parallel 3 pipes of each test tube) (seeing Table 7) with the asepsis growth test tube
3. test-results
3.1 horse lotus ester monopotassium salt 300mg/kg and 150mg/kg all have good refrigeration function to the rat fever due to the dry yeast, rat fever and the fever in rabbits due to the intracellular toxin due to the dinitrophenol(DNP), 75mg/kg is all not obvious to three kinds of heating functioins.(see Table 1, table 2, table 3)
3.2 horse lotus ester monopotassium salt 400mg/kg and 200mg/kg to the rat paw edema due to the egg white, rat granuloma is swollen and dimethylbenzene due to the mouse peritoneum inflammation good anti-inflammatory action is all arranged, 100mg/kg is all not obvious to three kinds of inflammatory effect.(see Table 4, table 5, table 6)
3.3 the MIC of horse lotus ester monopotassium salt intestinal bacteria and dysentery bacterium is 2mg/ml, is 1mg/ml to gold-coloured staphylococci and pneumococcal MIC.(seeing Table 7)
4. conclusion
4.1 horse lotus ester monopotassium salt has better antipyretic and anti-inflammatory action.
4.2 horse lotus ester monopotassium salt anti-microbial effect a little less than.
4.3. horse lotus ester tripotassium salt and horse lotus ester monopotassium salt pharmacodynamics basically identical (testing data slightly).
Person: Du Gangjun is responsible in test
Test design person: divergent Li Ming in the Du Gang military discipline
Test operation person: divergent Li Ming in the Du Gang military discipline
The long Song Guorui of red Zou of vast stretch of wooded country
Date of test: October calendar year 2001～2002 year April
Starting material preservation place: Beijing medical professionals's biological study institute
Contact person: old brave phone: (0378) 5956970
Reference:
1, Qi Chen's herbal pharmacology research methodology People's Health Publisher (the 2nd edition) 1993.
2, the pretty new drug of tall uncle Yuan of Wang Zhi clinical before safety evaluation with put into practice military medicine Science Press 1997.
3, Zhang Li jasmine Li Guodong Lee opens up the pharmacodynamic study Pharmacology and Clinics of Chinese Materia Medica 200016 (2): 29 of golden blue or green oral liquid.
4, the antipyretic-antalgic anti-inflammatory action herbal medicine 1980 (6): 436 of the yellow generation English match of sieve scheme opinion clock literary composition certain herbaceous plants with big flowers.
Subordinate list: 1～7
Table 1. horse lotus ester monopotassium salt is to the impact (n=12) of rat fever due to the dry ferment
Compare * P＜0.05**p＜0.01 with the physiological saline group
The impact (n=8) of fever in rabbits due to the table 2. horse lotus ester monopotassium salt induced by endotoxin
Compare * P＜0.05, * * P＜0.01 with the physiological saline group
The impact (n=10) of rat fever due to the table 3. horse lotus ester monopotassium salt paradinitrobenzene phenol
The physiological saline group is * P＜0.05 relatively, * * P＜0.01
Table 4. horse lotus ester monopotassium salt is to the impact (n=12) of rat paw edema due to the egg white
Compare * P＜0.05**P＜0.01 with the physiological saline group
The impact (n=15) of table 5. horse lotus ester monopotassium salt paraxylene induced mice peritonitis
Compare * P＜0.05**P＜0.01 with the physiological saline group
Table 6. horse lotus ester monopotassium salt is to the swollen impact (n=10) of rat granuloma
With the physiological saline group relatively * P＜0.05**P＜0.01,
The impact that table 7. horse lotus ester monopotassium salt is grown up to bacterium
-no bacterial growth ,+bacterial growth had or not
Claims (4)
1. rographolide trimaleate list salt, disalt or three salt of the expression of the rographolide trimaleate of formula (I) expression and formula (II):
In its Chinese style (II) compound, X, Y, Z representative: H or Na, K, Ca.
2. prepare formula (I) compound of claim 1 and the method for formula (II) compound:
The method of preparation formula (I) compound: with the rographolide is raw material, in vacuum tightness is 520～620mmHg, and 60～200 ℃ and catalyst action refluxed 0.5～10 hour down and maleic anhydride generation esterification, vacuum is removed in the cooling back, add water and be stirred to till whole curing and the crystallization evacuation, suction filtration, filter cake add the sodium bicarbonate aqueous solution dissolving, filter, filtrate transfers pH to acid, separates out white precipitate, and suction filtration, drying obtain formula (I) rographolide trimaleate;
The method of preparation formula (II) compound: the saleratus of formula (I) compound and different concns or sodium bicarbonate, calcium bicarbonate solution reaction production (II) rographolide trimaleate salt,
Preparation formula (I) compound reaction equation:
The reaction equation of preparation formula (II) compound:
Wherein, the salt in the reaction equation of preparation formula (II) compound is represented supercarbonate;
X, Y, Z representative in formula (II) compound: H, Na, K, Ca.
3. the pharmaceutical composition of analgesic and antiviral activity, it comprises that the formula (I) of treatment significant quantity claim 1 definition or formula (II) compound are as active ingredient and the pharmaceutical carrier of routine/or thinner pharmaceutically.
4. the formula (I) of claim 1 definition or formula (II) compound are as the purposes of analgesic antiphlogistic of preparation and antiviral agent.
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| CNA031053459A CN1478774A (en) | 2003-02-25 | 2003-02-25 | Andrographolide trimaleate mono potassium salt and androgra pholide dimaleate tripotassium salt and their medicinal composition |
| CN03105345.9 | 2003-02-25 | ||
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001043704A1 (en) * | 1999-12-14 | 2001-06-21 | Avon Products, Inc. | A skin care composition that mediates cell to cell communication |
| WO2001057026A1 (en) * | 2000-02-03 | 2001-08-09 | Dr. Reddy's Laboratories Limited | Compounds having antitumor activity: process for their preparation and pharmaceutical compositions containing them |
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| WO2001043704A1 (en) * | 1999-12-14 | 2001-06-21 | Avon Products, Inc. | A skin care composition that mediates cell to cell communication |
| WO2001057026A1 (en) * | 2000-02-03 | 2001-08-09 | Dr. Reddy's Laboratories Limited | Compounds having antitumor activity: process for their preparation and pharmaceutical compositions containing them |
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