CN109620824A - Quassinoids compound is preparing the purposes in anticomplement medicament - Google Patents

Quassinoids compound is preparing the purposes in anticomplement medicament Download PDF

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CN109620824A
CN109620824A CN201910169728.XA CN201910169728A CN109620824A CN 109620824 A CN109620824 A CN 109620824A CN 201910169728 A CN201910169728 A CN 201910169728A CN 109620824 A CN109620824 A CN 109620824A
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quassinoids
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温泉
冯育林
欧阳辉
杨世林
徐旭
陈道峰
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Jiangxi Bencao Tiangong Technology Co Ltd
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Abstract

The present invention relates to field of traditional Chinese medicine pharmacy, and in particular to quassinoids compound is preparing the purposes in anticomplement medicament.The present invention use modern pharmacological research method, have studied Simarubaceae Java brucea (Brucea javanica L.Merr) the anti-complement activity substance in fruit, isolated 2 quassinoids compounds are oriented to from the ethyl acetate extract activity of Java brucea, that is compound 1:Bruceine F and compound 2:20-hydroxylbruceine E-2- β-D-glucopyranoside, it is found through external anticomplement test, the two compounds all have different degrees of inhibiting effect to the classical pathway and alternative pathway of complement system, can be used for preparing anticomplement medicament.

Description

Quassinoids compound is preparing the purposes in anticomplement medicament
Technical field
The present invention relates to field of traditional Chinese medicine pharmacy, and in particular to quassinoids compound is preparing the use in anticomplement medicament On the way.
Background technique
Complement system is one group of activated rear protein with enzymatic activity being present in human serum and tissue fluid, by Liver synthesis more than 30 kinds of soluble proteins and embrane-associated protein constitute, complement by 9 kinds at being grouped as, be respectively designated as C1, C2, C3,…,C9.Complement system has 3 activated pathway, i.e. classical pathway, alternative pathway and mannose binding lectin pathway.Its In, classical pathway of complement is to make complement proper constituent with C1, C4, C2, C3, C5 using antigen antibody complex as main stimulator Enzymatic chain reaction occurs for ~ C9 sequence, and then generates a series of biological effects and cytolysis finally occurs；Bypass way Diameter is different from classical pathway, without activating through C1, C4, C2, but in the presence of Factor B, the D factor and the P factor, directly by C3b Start the chain reaction of complement enzymatic in conjunction with activator and generate a series of biological effects and final generation cytolysis, Its activator is that pathogenic microorganism etc. provides contact surface；Mannose binding lectin pathway be then mannose binding lectin with The mannose residue of bacterium surface combines, and the relevant silk ammonia of mannose binding lectin is then formed in conjunction with serine protease Pepsin, the protease then hydrolyze C4 and C2 and start postorder enzymatic chain reaction, generate a series of biological effects and Final that cytolysis occurs, activator is the albumen and pathogen that inflammatory phase generates.
Complement system is important one of the immune defense system of human body, is also important inflammatory mediator, mediates many inflammation Reaction, in terms of the damaging reaction for being mainly manifested in immunological regulation, antimicrobial defense reaction and mediated immunity pathology.Complement The normal Activate of system, for eliminating external microorganism, removing damage in vivo, the balance of body being maintained to play important work With.However the excessive activation of complement system can also cause a series of autoimmune disease, such as systemic loupus erythematosus, wind Wet arthritis, acute respiratory distress syndrome, gout, leprosy etc..Especially exogenous pathogen microorganism (such as influenza virus H1N1 etc.) invasion, it is easy to promote body complement system excessive activation that complement protein is caused to accumulate in lung, easily causes acute lung Damage, and it is fast-developing as acute respiratory distress syndrome (ARDS), and case fatality rate is up to 45%-50%.Modern pharmacology confirmation, If the drug for inhibiting excess complement activation can be filtered out, there is very positive work to the treatment of excess complement activation related disease With.
Java brucea be Simarubaceae Java brucea (Brucea javanicaL. Merr) dry mature fruit, main product is in me State, coastal tropical and subtropical region, south has significant heat-clearing and damp-drying drug, desinsection removing toxic substances, stop dysentery preventing malaria and other effects.In Java brucea Anticancer active principle based on brucea fruit oil has significantly kinds cancer, such as lung cancer, liver cancer, the carcinoma of the rectum in clinic Inhibitory effect.But so far, there is not yet there is the report of the compound of Complement inhibition effect from wherein separation.
Summary of the invention
The object of the present invention is to provide the compounds with anti-complement activity new in Java brucea, and in particular to quassinoids Compound, including compound 1: bruceine F (Bruceine F) and compound 2:20- hydroxyl bruceine E -2- β-D- pyrans Glucoside (20- hydroxylbruceine E-2- β-D-glucopyranoside).
It is a further object of the present invention to provide above-mentioned quassinoids compounds to prepare the purposes in anticomplement medicament.
Present invention application modern pharmacology screening technique, from the ethyl acetate extract activity of Java brucea guiding isolated 2 Quassinoids compound (compound 1 and compound 2), and confirm two compounds described above to the classical way of complement system Diameter and alternative pathway all have different degrees of inhibiting effect, wherein inhibiting effect of the compound 1 to complement system classical pathway CH50For 0.027 ± 0.003mg/mL, to the inhibiting effect AP of alternative pathway50For 0.063 ± 0.005mg/mL；Compound 2 is right The inhibiting effect CH of complement system classical pathway50For 0.055 ± 0.003mg/mL, to the inhibiting effect AP of alternative pathway50For 0.089±0.005mg/mL.Two quassinoids compounds have following structure general formula:
Wherein, when R=H(protium), compound is compound 1:Bruceine F；
When R=Glucose(glucose), compound is compound 2:20-hydroxylbruceine E-2- β-D- glucopyranoside。
Quassinoids compound of the present invention is prepared by following methods:
Java brucea dry fruit is taken, is successively extracted twice after petroleum ether degreasing with the ethyl alcohol that volume fraction is 90%, is extracted twice Time be 2h, merge resulting alcohol extract twice, be concentrated under reduced pressure into no alcohol taste, then extracted with ethyl acetate, Acetic acid ethyl ester extract is obtained after the concentrated drying of extract liquor；Acetic acid ethyl ester extract is taken to be separated using macroporous absorbent resin Purification, is successively eluted with the ethyl alcohol that volume fraction is respectively 20%, 40%, 80%, obtains 40% ethanol elution stream of chief active position Part Fr.1 and 80% ethanol elution fraction Fr.2；
Fraction Fr.1 ODS column (aperture resin gel rubber column gel column) chromatographic isolation, with methanol-water, (volume ratio of first alcohol and water is respectively 20:1,10:1,0:1) gradient elution, 3 fraction O1-3 are obtained, fraction O3 is using HPLC(High Performance Liquid Chromatography, high performance liquid chromatography) chromatographic isolation, it is washed with the acetonitrile solution that volume fraction is 19% It is de-, obtain compound 1:Bruceine F；
Fraction Fr.2 is through silicagel column (Silica) chromatographic isolation, with methylene chloride-methanol (the volume score of methylene chloride and methanol Wei 100:1,75:1,50:1,25:1,0:1) gradient elution, 5 fraction S1-5 are obtained, fraction S3 is using HPLC chromatogram point From the acetonitrile solution elution for being 48% with volume fraction obtains compound 2:20-hydroxylbruceine E-2- β-D- glucopyranoside。
Compound 1:Bruceine F, white amorphous powder, molecular formula: C20H28O10, molecular weight: HR-MS 427.3452 [M-H]-。
1H-NMR (600 MHz, DMSO) δ H:3.39 (1H, d, H-1), 3.81 (1H, br s, H-2), 5.31 (1H, M, H-3 α), 2.25 (1H, m, H-5), 1.92 (1H, m, H-6a), 1.53 (1H, m, H-6b), 4.86 (1H, dd, J=8.0, 2.0Hz, H-7), 1.91 (1H, m, H-9), 4.37 (1H, t, H-11), 3.70 (1H, d, H-12), 4.45 (1H, d, H-17a), 3.69 (1H, d, H-17b), 1.57 (3H, s, H-18), 1.07 (3H, s, H-19), 3.68-3.94 (2H, d, H-20);
13C-NMR (150MHz, DMSO), δ C:81.5 (C-1), 72.3 (C-2), 125.7 (C-3), 134.1 (C-4), 42.3 (C-5), 27.6 (C-6), 79.2 (C-7), 49.6 (C-8), 44.8 (C-9), 44.2 (C-10), 74.3 (C-11), 75.8 (C- 12), 83.4 (C-13), 82.5 (C-14), 69.2 (C-15), 174.1 (C-16), 69.8 (C-17), 21.2 (C-18), 12.1 (C-19), 62.8 (C-20).
Compound 2:20-hydroxylbruceine E-2- β-D-glucopyranoside, colorless needles, molecular formula: C26H38O15, molecular weight: HR-MS 591.2252 [M+H]+.
1H-NMR (600 MHz,DMSO) δH: 3.64 (1H, d, H-1), 3.92 (1H, br s, H-2), 5.56 (1H, M, H-3 α), 2.29 (1H, m, H-5), 1.94 (1H, m, H-6a), 1.50 (1H, m, H-6b), 4.86 (1H, dd, J=8.0, 2.0Hz, H-7), 2.02 (1H, m, H-9), 4.42 (1H, t, H-11), 3.70 (1H, d, H-12), 4.46 (1H, d, H-17a), 3.69 (1H, d, H-17b), 1.56 (3H, s, H-18), 1.11 (3H, s, H-19), 3.71-3.94 (2H, d, H-20), 4.33 (1H, d, J=8.0 Hz, Glu-1);
13C-NMR (150MHz, DMSO), δ C:79.6 (C-1), 84.3 (C-2), 123.9 (C-3), 135.3 (C-4), 42.1 (C-5), 27.4 (C-6), 79.2 (C-7), 49.6 (C-8), 44.4 (C-9), 43.8 (C-10), 74.4 (C-11), 75.8 (C- 12), 83.5 (C-13), 82.6 (C-14), 69.3 (C-15), 174.1 (C-16), 69.9 (C-17), 21.2 (C-18), 12.1 (C-19), 62.8 (C-20).105.8 (Glu-1), 74.6 (Glu-2), 77.2 (Glu-3), 70.4 (Glu-4), 76.9 (Glu- 5), 61.5 (Glu-6).
Compared with prior art, the beneficial effects of the present invention are:
Present invention application modern pharmacology screening technique is oriented to isolated 2 quassias from the ethyl acetate extract activity of Java brucea Chlorins compound, i.e. compound 1:Bruceine F and compound 2:20-hydroxylbruceine E-2- β-D- Glucopyranoside has found through external anticomplement test, classical pathway and bypass way of the two compounds to complement system Diameter all has different degrees of inhibiting effect, wherein inhibiting effect CH of the compound 1 to complement system classical pathway50It is 0.027 ± 0.003mg/mL, to the inhibiting effect AP of alternative pathway50For 0.063 ± 0.005mg/mL；Compound 2 is to complement system classics The inhibiting effect CH of approach50For 0.055 ± 0.003mg/mL, to the inhibiting effect AP of alternative pathway50For 0.089 ± 0.005mg/mL can be used for preparing anticomplement medicament.
Detailed description of the invention:
Fig. 1 is quassinoids compound Bruceine F and 20-hydroxylbruceine E-2- β-D- in Java brucea The extraction separation process figure of glucopyranoside.
Specific embodiment
Specific embodiments of the present invention will be further explained below.It should be noted that for these implementations The explanation of mode is used to help understand the present invention, but and does not constitute a limitation of the invention.In addition, invention described below Technical characteristic involved in each embodiment can be combined with each other as long as they do not conflict with each other.
Embodiment 1. has the activity guiding separation preparation of the quassinoids compound of anti-complement activity:
According to the flow chart in Fig. 1, the separation of activity guiding has the quassinoids compound of anti-complement activity, tool from Java brucea Body method is as follows:
10kg Java brucea dry fruit is taken, is successively extracted twice, twice after petroleum ether degreasing with the ethyl alcohol that volume fraction is 90% The time of extraction is 2h, merges resulting alcohol extract twice, is concentrated under reduced pressure into no alcohol taste, obtains 15L concentrate, then use Ethyl acetate extracts concentrate, obtains 350g acetic acid ethyl ester extract after the concentrated drying of extract liquor；Take ethyl acetate Extract using macroporous absorbent resin HP-20 carry out separation and purification, with volume fraction be respectively 20%, 40%, 80% ethyl alcohol successively Elution, obtains 40% ethanol elution fraction Fr.1(182g of chief active position) and 80% ethanol elution fraction Fr.2(114g)；
Fraction Fr.1 ODS pillar layer separation, with methanol-water (volume ratio of first alcohol and water is respectively 20:1,10:1,0:1) ladder Degree elution, obtains 3 fraction O1-3, wherein the methanol-water that the methanol-water of 20:1 affords fraction O1,10:1 affords The methanol-water of fraction O2,0:1 affords fraction O3, and fraction O3 is separated using HPLC chromatogram, is 19% with volume fraction Acetonitrile solution elution, obtains 102.1mg compound 1:Bruceine F；
Fraction Fr.2 through Silica chromatographic isolation, with methylene chloride-methanol (volume ratio of methylene chloride and methanol is respectively 100: 1,75:1,50:1,25:1,0:1) gradient elution, obtain 5 fraction S1-5, wherein the methylene chloride-methanol of 100:1 elutes To fraction S1,75:1 methylene chloride-methanol afford fraction S2,50:1 methylene chloride-methanol afford fraction S3, The methylene chloride-methanol that the methylene chloride-methanol of 25:1 affords fraction S4,0:1 affords fraction S5, and fraction S3 is passed through again HPLC chromatogram separation is crossed, is eluted with the acetonitrile solution that volume fraction is 48%, obtains 325.7mg compound 2:20- hydroxylbruceine E-2-β-D-glucopyranoside。
The test of the external anticomplement classical pathway of embodiment 2.:
(1) experimental principle: it is molten that complement can be such that the sheep red blood cell (SRBC) (SRBC) of hemolysin (anti-sheep red blood cell (SRBC) antibody) sensitization occurs Blood, when the sheep red blood cell (SRBC) constant concentration of sensitization, degree of hemolysis and complement content and active proportional.Therefore, will It after fresh serum to be checked does different dilutions, is reacted with sensitized erythrocyte, measures degree of hemolysis, minimum serum when with 50% haemolysis Amount determines terminal, can predict the total hemolytic activity of complement.
50% hemolytic test is to acquire the minimum serum that can make 50% sensitization sheep red blood cell that haemolysis occur, and is then calculated every Complement content in milliliter serum.Using complement amount as abscissa, Percent hemolysis can be obtained one clearly as ordinate Serpentine curve.Around 50% haemolysis, line segment approximation straight line.Therefore when complement dosage slightly changes, so that it may to haemolysis journey Very big influence occurs for degree.So using 50% haemolysis more more sensitive than 100% haemolysis as terminal.
50% hemolytic test determines complement content in serum to be indicated with following formula: complement content (unit) in every milliliter of serum= (1/ amount of serum) × extension rate.
(2) specific experimentation are as follows: take complement (guinea pig serum) 0.1ml, barbitol buffer solution (BBS) is added and is configured to Volume ratio be 1:10 solution, then again with BBS two-fold dilution at the other 1:20,1:40 of volume score, 1:80,1:160,1:320, The complement solution of 1:640 and 1:1280.The complement of each concentration of 0.2ml is taken, and hemolysin is taken (to need before use dilute with buffered saline Release, the volume ratio of hemolysin and buffered saline is 1:1000) and volume fraction be 2% sheep erythrocyte suspension (2%SRBC) it is each 0.1ml is dissolved in 0.2ml BBS, be uniformly mixed, be put into low-temperature and high-speed centrifuge after 37oC water-bath 30min, 5000rpm, 10min is centrifuged under the conditions of 4oC.It takes every pipe supernatant 0.2ml in 96 orifice plates respectively, measures its absorbance in 405nm.Experiment is simultaneously Full haemolysis group (0.1ml 2%SRBC is dissolved in 0.5ml tri-distilled water) is set, using the absorbance of tri-distilled water haemolysis pipe as full haemolysis mark Standard calculates hemolysis rate.Using the dilution of complement as X-axis, percentage of hemolysis is Y-axis mapping.Selection reaches similar hemolysis rate most Low complement concentration is as critical complement concentration needed for ensuring the normal haemolysis of system energy.
200ul BBS is added, test sample (compound 1 and compound 2) is configured to 8 concentration gradient (1.25mg/ respectively ml、0.625mg/ml、0.3125mg/ml、0.15625mg/ml、0.078125mg/ml、0.039063mg/ml、 0.019531mg/ml, 0.009766mg/ml), the test sample of the complement and each concentration gradient that take critical concentration mixes, and respectively It is put into low-temperature and high-speed centrifuge after 100ul hemolysin and 2% SRBC, 37oC water-bath 30min is added, 5000rpm, 4oC condition Every pipe supernatant 0.2ml is taken to measure absorbance under 96 orifice plates, 405nm respectively after lower centrifugation 10min.It tests while test sample is set Three repetitions are arranged in control group (being free of complement), positive control (heparin), complement group and full haemolysis group, each experimental group.It will be for Test product absorbance value calculates hemolysis rate after deducting corresponding test sample control group absorbance value.It is molten using the concentration of test sample as X-axis Blood inhibiting rate is mapped as Y-axis, the Cmin (CH of test sample needed for calculating 50% inhibition haemolysis50).Test result is shown in Table 1.
It is tested and is found by anticomplement classical pathway, compound 1 and compound 2 all have the classical pathway of complement system Apparent inhibiting effect, Cmin (CH needed for compound 1 inhibits haemolysis to complement system classical pathway 50%50) it is 0.027 ± 0.003mg/mL, Cmin (CH needed for compound 2 inhibits haemolysis to complement system classical pathway 50%50) be 0.055 ± 0.003mg/mL。
The test of the external anticomplement alternative pathway of embodiment 3.:
(1) experimental principle: rabbit erythrocyte can activate people's alternative pathway of complement without sensitization, and rabbit erythrocyte is caused to dissolve.It is reacting Be added in system the double amino tetraacethyls (ethyleneglycol-bis-aminotetracetate, EGTA) of ethylene glycol can and blood Ca2+ chelating is starched, EGTA and Mg2+ binding ability are very weak, therefore classical pathway is closed.It, can according to the degree of hemolysis of rabbit erythrocyte Measure the complement activity of alternative pathway of complement.
(2) specific experimentation are as follows: take 0.2 ml of complement (human serum), AP dilution (barbitol buffer solution, pH is added =7.4, Mg2+ containing 5mM, 8mM EGTA) it is configured to the solution of 1:1, two-fold dilution is at 1:2,1:4,1:8,1:16,1:32,1:64 With the solution of 1:128.Taking each concentration complement 0.15ml, AP dilution 0.15ml and volume fraction is 0.5% rabbit erythrocyte suspension (0.5%RE) 0.20ml is mixed, and 30 min of 37oC water-bath is placed in low-temperature and high-speed centrifuge, under the conditions of 5000 rpm, 4oC It is centrifuged 10min.It takes every pipe supernatant 0.2ml in 96 orifice plates respectively, measures absorbance in 405nm.It tests while full haemolysis is set Group (0.20ml 0.5%RE is dissolved in 0.3ml tri-distilled water) is calculated molten using the absorbance of tri-distilled water haemolysis pipe as full haemolysis standard Blood rate.Using the dilution of complement as X-axis, percentage of hemolysis is Y-axis mapping.The minimum complement that selection reaches similar high hemolysis rate is dense Degree is as critical complement concentration needed for ensuring the normal haemolysis of system energy.
200ul AP dilution is added, test sample (compound 1 and compound 2) is configured to 8 concentration gradients respectively (1.25mg/ml, 0.625mg/ml, 0.3125mg/ml, 0.15625mg/ml, 0.078125mg/ml, 0.039063mg/ml, 0.019531mg/ml, 0.009766mg/ml), the test sample of the complement and each concentration gradient that take critical concentration mixes, in 37oC After pre- 10 min of water-bath, 0.2ml 0.5%RE is added.Every pipe 37oC water-bath 30min is placed in low-temperature and high-speed centrifuge, After being centrifuged 10min under the conditions of 5000rpm, 4oC, takes every pipe supernatant 0.2ml in 96 orifice plates respectively, its extinction is measured under 405nm Degree.It tests while test sample control group (without complement), positive control (heparin), complement group and full haemolysis group, Mei Geshi is set Test group three repetitions of setting.Hemolysis rate is calculated after test sample absorbance value is deducted corresponding test sample control group absorbance value.With Test sample concentration is mapped as X-axis, haemolysis inhibiting rate as Y-axis, the Cmin of test sample needed for calculating 50% inhibition haemolysis (AP50).Test result is shown in Table 1.
It is tested and is found by anticomplement alternative pathway, compound 1 and compound 2 all have the alternative pathway of complement system Apparent inhibiting effect, Cmin (AP needed for compound 1 inhibits haemolysis to complement system alternative pathway 50%50) it is 0.063 ±0.005mg/mL；Cmin (AP needed for compound 2 inhibits haemolysis to complement system alternative pathway 50%50) be 0.089 ± 0.005mg/mL。
1. compound of table to the inhibiting effect of complement system classical pathway and alternative pathway (Mean ± SD,n=3)
CH50 (mg/ml) AP50 (mg/ml)
Compound 1 0.027± 0.003 0.063± 0.005
Compound 2 0.055 ± 0.003 0.089 ± 0.005
Positive control (heparin) 0.035± 0.003 0.057 ± 0.004
Note: CH50It is Cmin needed for inhibiting haemolysis to classical pathway 50%；AP50It is to alternative pathway 50%
Cmin needed for inhibiting haemolysis.
Above the embodiments of the present invention are described in detail, but the present invention is not limited to described embodiments.It is right For those skilled in the art, in the case where not departing from the principle of the invention and spirit, these embodiments are carried out more Kind change, modification, replacement and modification, still fall in protection scope of the present invention.

Claims (8)

1. quassinoids compound is preparing the purposes in anticomplement medicament, it is characterised in that: the quassinoids compound has Following general structure:
As R=H, which is compound 1；
As R=Glucose, which is compound 2.
2. quassinoids compound is preparing the purposes in anticomplement medicament according to claim 1, it is characterised in that: described Quassinoids compound pass through following methods prepare:
Java brucea dry fruit is taken, is successively extracted twice, is merged twice with the ethyl alcohol that volume fraction is 90% after petroleum ether degreasing Resulting alcohol extract is concentrated under reduced pressure into no alcohol taste, is then extracted with ethyl acetate, obtains after the concentrated drying of extract liquor Acetic acid ethyl ester extract；It takes acetic acid ethyl ester extract to carry out separation and purification using macroporous absorbent resin, is respectively with volume fraction 20%, 40%, 80% ethyl alcohol successively elutes, and obtains 40% ethanol elution fraction Fr.1 of chief active position and 80% ethanol elution stream Part Fr.2；
Fraction Fr.1 ODS pillar layer separation obtains 3 fraction O1-3 with methanol-water gradient elution, fraction O3 using HPLC chromatogram separation is eluted with the acetonitrile solution that volume fraction is 19%, obtains compound 1；
Fraction Fr.2 is separated through silica gel column chromatography, with methylene chloride-methanol gradient elution, obtains 5 fraction S1-5, fraction S3 is again It is separated by HPLC chromatogram, is eluted with the acetonitrile solution that volume fraction is 48%, obtain compound 2.
3. quassinoids compound is preparing the purposes in anticomplement medicament according to claim 2, it is characterised in that: twice The time that the ethyl alcohol extracts is 2h.
4. quassinoids compound is preparing the purposes in anticomplement medicament according to claim 2, it is characterised in that: described The concentration of methanol-water gradient elution to be respectively as follows: the volume ratio of first alcohol and water be respectively 20:1,10:1,0:1.
5. quassinoids compound is preparing the purposes in anticomplement medicament according to claim 2, it is characterised in that: described Methylene chloride-methanol gradient elution concentration be respectively as follows: methylene chloride and methanol volume ratio be respectively 100:1,75:1, 50:1、25:1、0:1。
6. quassinoids compound is preparing the purposes in anticomplement medicament according to claim 1, it is characterised in that: described Quassinoids compound have inhibiting effect to the classical pathway and alternative pathway of complement system.
7. quassinoids compound is preparing the purposes in anticomplement medicament according to claim 6, it is characterised in that: described Compound 1 and compound 2 have inhibiting effect to the classical pathway and alternative pathway of complement system.
8. quassinoids compound is preparing the purposes in anticomplement medicament according to claim 7, it is characterised in that: described Inhibiting effect CH of the compound 1 to complement system classical pathway50For 0.027 ± 0.003mg/mL, the inhibition of alternative pathway is made Use AP50For 0.063 ± 0.005mg/mL；Inhibiting effect CH of the compound 2 to complement system classical pathway50For 0.055 ± 0.003mg/mL, to the inhibiting effect AP of alternative pathway50For 0.089 ± 0.005mg/mL.
CN201910169728.XA 2019-03-07 2019-03-07 Quassinoids compound is preparing the purposes in anticomplement medicament Pending CN109620824A (en)

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CN113398155A (en) * 2021-06-23 2021-09-17 广州白云山明兴制药有限公司 Preparation method of brucea javanica dreg effective part containing quassia lactone component

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Publication number Priority date Publication date Assignee Title
CN113278026A (en) * 2021-05-29 2021-08-20 南京中医药大学 Novel quassin compound with anti-tumor activity and preparation method and application thereof
CN113398155A (en) * 2021-06-23 2021-09-17 广州白云山明兴制药有限公司 Preparation method of brucea javanica dreg effective part containing quassia lactone component

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Application publication date: 20190416