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| 500mg |
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Lappaconite Hydrobromide is a naturally occuring alkaloid extracted from Aconitum sinomontanum Nakai and has anti-inflammatory effects. Its absorption percentage in rat stomachs after administration was 9.67%.The absorption percentages at duodenum,jejunum,ileum and colon were 19.61%,11.83%,12.95% and 9.51%, respectively.When the concentration was raised from 10 mg/L to 40 mg/L, the uptake of lappaconite hydrobromide was linearly increased,whereas the absorption rate constant kept at the same level.
| Targets |
Voltage-gated sodium channels (VGSCs, e.g., Nav1.5) [2]
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| ln Vitro |
In vitro activity: Lappaconite Hydrobromide is a kind of alkaloid extracted from Aconitum sinomontanum Nakai and has anti-inflammatory effects. Its absorption percentage in rat stomachs after administration was 9.67%.The absorption percentages at duodenum,jejunum,ileum and colon were 19.61%,11.83%,12.95% and 9.51%, respectively.When the concentration was raised from 10 mg/L to 40 mg/L, the uptake of lappaconite hydrobromide was linearly increased,whereas the absorption rate constant kept at the same level.
In pH 7.4 PBS, Lappaconite HBr-loaded solid lipid nanoparticles (LH-SLNs) showed sustained release, with ~80% cumulative release in 24 h, while free Lappaconite HBr released nearly 100% within 4 h [2] - On H9c2 cardiomyocytes, MTT assay indicated no significant cytotoxicity for LH-SLNs or free Lappaconite HBr (0.1-10 μg/mL), with no statistical difference in cell viability (P>0.05) [2] - Flow cytometry showed significantly higher cellular uptake of LH-SLNs than free Lappaconite HBr by H9c2 cells (P<0.05) [2] - Lappaconite HBr exhibited antibacterial activity: MIC 32 μg/mL against Staphylococcus aureus, 64 μg/mL against Escherichia coli; no inhibition on Candida albicans (MIC > 128 μg/mL) [3] - In vitro analgesic activity: 10 mg/kg intraperitoneal Lappaconite HBr reduced mouse writhing by 42% (acetic acid test) and increased pain threshold by 35% at 1 h (hot plate test) [3] |
| ln Vivo |
Lappaconite Hydrobromide absorption percentage in rat stomachs after administration was 9.67%. The absorption percentages at colon, jejunum, ileum and duodenum were, 9.51%, 11.83%, 12.95%, and 19.61%, respectively. The uptake of lappaconite hydrobromide was linearly increased when the concentration was raised from 10 mg/L to 40 mg/L, whereas the absorption rate constant kept at the same level. The LD50 values are of 10.5 mg/kg (i.p. administration) and 9.9 mg/kg (i.p. administration) in mice and rat, respectively. In addition, in anesthetized rabbits injected with lappaconite up to 1 mg/kg, cardiac arrhythmia was quickly observed.
In SD rats (5 mg/kg intravenous), cardiac concentration of Lappaconite HBr in LH-SLNs group (3.2 ± 0.5 μg/g) was significantly higher than free drug group (1.6 ± 0.3 μg/g) at 2 h; no differences in other tissues (liver, kidney, spleen, lung) [2] |
| Cell Assay |
H9c2 cardiomyocytes were cultured (37°C, 5% CO2), seeded in 96-well plates overnight. LH-SLNs or free Lappaconite HBr (0.1-10 μg/mL) was added, cultured for 24 h. MTT solution was added, incubated for 4 h, DMSO dissolved formazan, and absorbance measured at 490 nm to calculate viability [2]
- H9c2 cells were seeded in 6-well plates overnight, incubated with LH-SLNs or free Lappaconite HBr for 2 h. Cells were harvested, washed with PBS, and fluorescence intensity of internalized drug was detected by flow cytometry to evaluate uptake efficiency [2] |
| Animal Protocol |
LD50: Mice 10.5mg/kg (i.p.); Rats 9.9mg/kg (i.p.)
Mice and rats SD rats (n=6/group) received 5 mg/kg intravenous free Lappaconite HBr or LH-SLNs. Blood samples were collected at 0.083-12 h, centrifuged for plasma, stored at -20°C for concentration detection [2] - For tissue distribution, SD rats were sacrificed at 2 h post-administration, tissues (heart, liver, kidney, spleen, lung) were collected, rinsed, weighed, homogenized, and stored at -20°C [2] - ICR mice received oral free Lappaconite HBr or LH-SLNs at different doses, observed for 14 days to record deaths and calculate LD50 [2] - SD rats received 5 mg/kg intravenous drug daily for 7 days, blood collected to detect serum ALT, AST, BUN, Cr [2] |
| ADME/Pharmacokinetics |
The human plasma protein binding rate of lappaconite HBr was 78.5% ± 3.2% (ultrafiltration method) [1] - In SD rats (5 mg/kg intravenous injection): the AUC0-t of the LH-SLNs group was 15.6 ± 2.3 μg·h/mL, t1/2β was 4.2 ± 0.6 h, CL was 0.32 ± 0.05 L/h/kg, and Vd was 1.9 ± 0.3 L/kg; the AUC0-t of the free drug group was 8.9 ± 1.5 μg·h/mL, t1/2β was 2.1 ± 0.3 h, CL was 0.56 ± 0.08 L/h/kg, and Vd was 1.8 ± 0.2 L/kg [2]
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| Toxicity/Toxicokinetics |
In ICR mice, the oral LD50 of free lapatinol hydrobromide was 285.6 mg/kg (95% CI: 260.3-313.2 mg/kg); the LD50 of LH-SLNs was 356.8 mg/kg (95% CI: 328.5-387.6 mg/kg) [2] In SD rats, after intravenous injection of free lapatinol hydrobromide for 7 days, serum ALT/AST was slightly increased (P<0.05); there was no significant difference in ALT/AST/BUN/Cr between LH-SLNs and the control group [2]
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| References |
Biomed Chromatogr. 1990;4(1):43-6; J Nanobiotechnology. 2015;13:47; Nat Prod. 1979;42(6):615-23.
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| Additional Infomation |
Lappaconite HBr is the hydrobromide of lapaconidine, which is an alkaloid found in aconitum sinomontanum Nakai. Its structure was identified by IR/MS/NMR, and its molecular formula is C32H44N2O8·HBr [3]
-HPLC determination of Lapaconic acid HBr in human plasma: C18 column, mobile phase methanol-water-triethylamine (65:35:0.1), detection wavelength 254 nm, linear range 0.05-10 μg/mL (r=0.9998), recovery rate 85.2%-92.6%, RSD <5% [1] -Lapaconic acid HBr-SLNs were prepared by emulsification-ultrasound method, and the lipid concentration, surfactant concentration and oil-water ratio were optimized [2] |
| Molecular Formula |
C32H45BRN2O8
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| Molecular Weight |
665.612309217453
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| Exact Mass |
664.235
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| CAS # |
97792-45-5
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| Related CAS # |
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| PubChem CID |
51346120
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
740.8ºC at 760 mmHg
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| Melting Point |
223-226ºC
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| Flash Point |
401.8ºC
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| LogP |
3.19
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
43
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| Complexity |
1120
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| Defined Atom Stereocenter Count |
11
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| SMILES |
O([C@H]1CC[C@]2(CN([C@H]3[C@]41[C@@H]1C[C@@H]5[C@H](C[C@]([C@]1([C@H]5OC)O)(O)[C@H]3C[C@@H]42)OC)CC)OC(C1C=CC=CC=1NC(=O)C)=O)C.Br
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| InChi Key |
CFFYROOPXPKMEQ-OPLXFBIMSA-N
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| InChi Code |
InChI=1S/C32H44N2O8.BrH/c1-6-34-16-29(42-28(36)18-9-7-8-10-21(18)33-17(2)35)12-11-25(40-4)31-23(29)14-20(26(31)34)30(37)15-22(39-3)19-13-24(31)32(30,38)27(19)41-5;/h7-10,19-20,22-27,37-38H,6,11-16H2,1-5H3,(H,33,35);1H/t19-,20+,22+,23-,24+,25+,26?,27+,29-,30+,31+,32+;/m1./s1
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| Chemical Name |
[(1S,2S,3S,4S,5R,6S,8S,9S,13S,16S,17S)-11-ethyl-3,8-dihydroxy-4,6,16-trimethoxy-11-azahexacyclo[7.7.2.12,5.01,10.03,8.013,17]nonadecan-13-yl] 2-acetamidobenzoate;hydrobromide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5024 mL | 7.5119 mL | 15.0238 mL | |
| 5 mM | 0.3005 mL | 1.5024 mL | 3.0048 mL | |
| 10 mM | 0.1502 mL | 0.7512 mL | 1.5024 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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