/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最小流量/。如果出现低血容量的迹象，使用0.9%的生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
人类毒性摘录
紫草素具有预防或用于治疗由芳香胺引起的膀胱移行细胞癌的潜力。研究者们通过测量乙酰化2-氨基芴（AF）的量、AF-DNA加合物、N-乙酰转移酶（NAT）mRNA的变化量和NAT酶的量来评估其效果。将T24人膀胱癌细胞与30 uM AF和不同浓度的紫草素一起培养不同时间。然后用16 uM紫草素处理的T24细胞进行两个实验：1）T24细胞与22.5 uM AF和紫草素（0, 16 uM）共同处理6、12、18、24和48小时。将T24细胞与不同浓度的AF和紫草素（0, 16 uM）一起培养24小时，通过HPLC测量AF和AAF。然后在制备的人T24细胞质中添加不同浓度的AF和紫草素来测量NAT的动力学常数。接下来，检测并测量经或不经紫草素处理的T24细胞中的AF-DNA加合物。最后两个步骤包括测量经紫草素处理和未经紫草素处理的NAT Ag-Ab复合物，并评估紫草素对NAT基因的影响。更高浓度的紫草素导致AF乙酰化降低。发现培养期越长，在同一紫草素浓度下AF乙酰化的差异越大。还注意到AAF的增加与培养时间成正比。在16 uM紫草素的存在下，AF的N-乙酰化降低了72-84%。紫草素在所有检测的AF剂量下减少了人T24细胞中AAF的产生量。在细胞质中添加紫草素后，细胞质NAT的Km和Vmax值都降低了。最后，紫草素在所有检测的AF剂量下减少了人724细胞中AAF产生和AF-DNA加合物形成。经紫草素处理后，尤其是高浓度紫草素处理后，细胞染色抗体的百分比显著不同。NAT1 mRNA水平和NAT1/beta-actin比例在高浓度（16-24 uM）紫草素处理后显著降低。紫草素影响了人膀胱肿瘤T24细胞中NAT活性、基因表达（NAT1 mRNA）、AF-DNA加合物的形成和NAT Ag-Ab的形成...
/ALTERNATIVE and IN VITRO TESTS/ Shikonin has the potential to prevent, or be used in the treatment of bladder transitional cell carcinoma induced by arylamines. /Investigators/ evaluated its effectiveness by measuring the amount of acetylated 2-aminofluorene (AF), AF-DNA adducts, changes of / N-acetyltransferase (NAT)/ mRNA and the amount of NAT enzyme. T24 human bladder cancer cells were incubated with 30 uM AF with different concentrations of shikonin for various times. T24 cells treated with shikonin (16 uM) were then harvested and used in 2 experiments: 1). T24 cells were incubated with 22.5 uM AF and shikonin (0, 16 uM) (co-treatment) for 6, 12, 18, 24 and 48 hr). T24 cells were incubated with various concentrations of AF and shikonin (0, 16 uM) for 24 hr AF and AAF were measured by HPLC. Then in the prepared human T24 cell cytosols different concentrations of AF and shikonin were added to measure the kinetic constants of NAT. Next, AF-DNA adducts in human T24 cells with or without treatment with shikonin were detected and measured. The final two steps included measuring the NAT Ag-Ab complex after treatment with and without shikonin and evaluating the effect of shikonin on the NAT genes. Higher concentrations of shikonin induced decreasing AF acetylation. /It was/ found that the longer the culture period, the greater the difference in AF acetylation in the same shikonin concentrations. It was also noted that increase in AAF was proportional to incubation time. In the presence of 16 uM of shikonin, N-acetylation of AF decreased by up to 72-84%. Shikonin decreased the amount of AAF production in human T24 cells in all examined AF doses. Both Km and Vmax values in the cytosolic NAT decreased after the addition of shikonin to the cytosol. Finally, shikonin decreased the amount of AAF production and AF-DNA adducts formation in human 724 cells in all examined AF doses. The percentage of cells stained by antibody was significantly different after treatment with shikonin, especially with the higher shikonin concentrations. The NAT1 mRNA level and the NAT1/beta-actin ratio decreased significantly with higher concentrations (16-24 uM) of shikonin. Shikonin affected NAT activity, gene expression (NAT1 mRNA), AF-DNA adducts formation and formation of NAT Ag-Ab in human bladder tumor T24 cells...
/ALTERNATIVE and IN VITRO TESTS/ Shikonin isolated from the roots of the Chinese herb Lithospermum erythrorhizon has been associated with anti-inflammatory properties. /Investigators/ evaluated shikonin's chemotherapeutic potential and investigated its possible mechanism of action in a human cutaneous neoplasm in tissue culture. Shikonin preferentially inhibits the growth of human epidermoid carcinoma cells concentration- and time-dependently compared to SV-40 transfected keratinocytes, demonstrating its anti-proliferative effects against this cancer cell line. Additionally, shikonin decreased phosphorylated levels of EGFR, ERK1/2 and protein tyrosine kinases, while increasing phosphorylated JNK1/2 levels. Overall, shikonin treatment was associated with increased intracellular levels of phosphorylated apoptosis-related proteins, and decreased levels of proteins associated with proliferation in human epidermoid carcinoma cells.
Alkannin and shikonin are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, antimicrobial, anti-inflammatory, and antioxidant activities. Recently, extensive scientific effort has been focused on their effectiveness on several tumors and mechanism(s) of antitumor activity. Liposomes have been proved as adequate drug carriers offering significant advantages over conventional formulations, such as controlled release and targeted drug delivery, leading to the appearance of several liposomal formulations in the market, some of them concerning anticancer drugs. The aim of the present study was to prepare shikonin-loaded liposomes for the first time in order to enhance shikonin therapeutic index. An optimized technique based on the thin film hydration method was developed and liposomes characterization was performed in terms of their physicochemical characteristics, drug entrapment efficiency, and release profile. Results indicated the successful incorporation of shikonin into liposomes, using both 1,2-dipalmitoylphosphatidylcholine and egg phosphatidylcholine lipids. Liposomes presented good physicochemical characteristics, high entrapment efficiency and satisfactory in vitro release profile. In vitro cytotoxicity of liposomes was additionally tested against three human cancer cell lines (breast, glioma, and non-small cell lung cancer) showing a moderate growth inhibitory activity. Practical applications: Shikonin is a naturally occurring hydroxynaphthoquinone and extensive scientific research (in vitro, in vivo, and clinical trials) has been conducted during the last years, focusing on its effectiveness on several tumors and mechanism(s) of antitumor action. The purpose of this work was to prepare and characterize shikonin-loaded liposomes as a new drug delivery system for shikonin. Liposomal formulations provide significant advantages over conventional dosage forms, such as controlled release and targeted drug delivery for anticancer agents. Thus, liposomes could reduce shikonin's side effects, enhance selectivity to cancer cells and protect shikonin from internal biotransformations and instability matters (oxidization and polymerization). Furthermore, liposomal delivery helps overcome the low aqueous solubility of shikonin, which is the major barrier to its oral and internal administration, since it cannot be dissolved and further absorbed from the receptor.
A New Efficient Route for Multigram Asymmetric Synthesis of Alkannin and Shikonin
摘要：
A short and convergent approach for the synthesis of alkannin, shikonin and shikalkin is presented. A Hauser-type annulation of cyanophthalide 26 with enone 7 affords the complete aromatic system in just one step with concomitant attachment of the entire side chain. Subsequent Corey's oxazaborolidine mediated asymmetric reduction of the above advanced intermediate, leads to the required isomer in high enantiomeric excess. Finally, a selective and high yielding deprotection protocol furnishes the title compounds as pure crystalline precipitates. Thus, a multigram synthesis of shikonin, alkannin and shikalkin is achieved in high yield and enantioselectivity.
SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
申请人：Ohio State Innovation Foundation
公开号：US20140155577A1
公开（公告）日：2014-06-05
Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.
[EN] STAT DEGRADERS AND USES THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE STAT ET LEURS UTILISATIONS
申请人：KYMERA THERAPEUTICS INC
公开号：WO2020206424A1
公开（公告）日：2020-10-08
The present invention provides compounds, compositions thereof, and methods of using the same.
本发明提供了化合物、其组合物以及使用方法。
Nitric Oxide Releasing Prodrugs of Therapeutic Agents
申请人：SATYAM Apparao
公开号：US20110263526A1
公开（公告）日：2011-10-27
The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.
In certain embodiments a platform technology for the facilitating immune therapy in the treatment of cancer is provided. In certain embodiments nanocarriers are provided that facilitate delivery of an IDO inhibitor in conjunction with an inducer of cell death (ICD-inducer). In certain embodiments the IDO inhibitor is conjugated to a component of a lipid bilayer forming a nanovesicle. In still another embodiment, methods and compositions are provided where an ICD-inducing agent (e.g., doxorubicin, oxaliplatin, mitoxantrone etc.) and an IDO pathway inhibitor (e.g., an IDO inhibitor-prodrug) are integrated into a nanocarrier (e.g. a lipid-bilayer (LB)-coated nanoparticle), that allows systemic delivery to orthotopic pancreatic cancer site.
An object of the present invention is to provide skin external preparations and cosmetics which contain a branched acyl carnitine and have excellent formulation stability. A skin external preparation of the present invention includes a carnitine derivative represented by the following Formula (1) and/or a carnitine derivative salt represented by the following Formula (2), and an amphoteric surfactant.
In Formula (1), R
1
and R
2
are each independently a C1-18 optionally branched, saturated or unsaturated aliphatic hydrocarbon group. In Formula (2), R
1
and R
2
are the same as in Formula (1), X
−
is a specific anion and Y
+
is a specific cation.
