- Surface modification with cholesteryl acetyl carnitine, a novel cationic agent, elevates cancer cell uptake of the PEGylated liposomes
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The present study aimed to synthesize cholesteryl acetyl carnitine (CAC), and surface modify the PEGylated liposomes with the intention of enhanced cancer cell uptake. For this, CAC synthesis was performed in amine-free esterification conditions and then four liposomal formulations of unmodified, CAC/PEG, and CAC + PEG-modified were prepared by ethanol injection method. Cytotoxicity of the liposomes was investigated in A549 cells, followed by cellular uptake assessments of coumarin 6 (C6)-loaded liposomes. The results of ATR-FTIR, 1HNMR, and 13CNMR demonstrated successful formation of CAC. A molecular docking study showed efficient binding affinities rather than carnitine to the active site of four carnitine transporters. Liposomal formulations possessed spherical morphology with a mean particle size range of 112–138 nm, narrow size distribution, and negative surface charge. All formulations had low cytotoxicity at 0.5 mg/ml, but high cytotoxicity at around 2.5 mg/ml. The lowest IC50 was obtained for CAC modified liposomes. CAC + PEG-modified liposomes had the highest cellular uptake. In conclusion, CAC + PEG modification of liposomes is an effective approach for increasing A549 cellular uptake, with low cytotoxicity at commonly applied liposome concentrations. The elevated uptake may be due to the involvement of the organic cation transporter, cationic structure, and the metabolic preference of CAC in cancer cells.
- Baradaran, Behzad,Mahmoudian, Mohammad,Sarfraz, Muhammad,Shahbazi Mojarrad, Javid,Valizadeh, Hadi,Zahednezhad, Fahimeh,Zakeri-Milani, Parvin
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- A chloride process for the preparation of acetyl L-carnitine
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The invention relates to the field of medical preparations and particularly discloses a method for preparing acetyl levocarnitine hydrochloride. The method comprises the following steps: mixing levocarnitine with glacial acetic acid, dripping acetyl chloride to react, adding a first solvent at a low temperature after the reaction is completed to crystallize, filtering and drying the precipitate to obtain a crude product of the acetyl levocarnitine hydrochloride; and adding a second solvent into the crude product, heating, dripping a third solvent, filtering after the solid is dissolved, slowly cooling the filtrate to the room temperature, crystallizing at a low temperature, filtering and drying the precipitate to obtain a finished product of the acetyl levocarnitine hydrochloride. The method disclosed by the invention has the advantages that various appropriate organic solvents are combined to be used in a certain order to separate and purify the acetyl levocarnitine hydrochloride, both the contents of an impurity A and the unreacted levocarnitine raw material are reduced to be lower than 0.05% and the purity of the prepared finished product of the acetyl levocarnitine hydrochloride is up to more than 99.90%.
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Paragraph 0059; 0060; 0061; 0062
(2016/10/31)
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- Acetyl L-carnitine hydrochloride preparation method
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The present invention relates to a method for preparing (R)-acetyl carnitine hydrochloride by adopting L-carnitine hydrochloride as a raw material. According to the present invention, the problem that the high reaction temperature and the distillation operation process make the material heating time too long so as to cause side effects and produce a large amount of the glacial acetic acid-containing waste liquid in the existing process is solved, the product quality is good, and the yield is high.
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Paragraph 0017; 0018; 0019; 0020; 0021; 0022; 0023-0031
(2017/02/09)
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- Synthesis of carnitine benzyl esters as prodrugs
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The introduction of C-2 acyl groups and a benzyl ester onto L-carnitine generated a series of carnitine benzyl esters as prodrug with improved liposolubility, stability and bioavailability.
- Gong, Xiao-Wei,Li, Jin-Pei,Wu, Ji-Feng,Li, Xun,Zhai, Hai-Min,Feng, Bo,Xu, Wen-Fang,Tang, Wei
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experimental part
p. 327 - 330
(2009/05/30)
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- PROCESS FOR L-CARNITINE AND ACETYL L-CARNITINE HYDROCHLORIDE
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Provided is a process for preparing L-carnitine or acetyl L-carnitine hydrochloride. Specifically, the process comprises sequentially synthesizing racemic 4-chloro-3-hydroxybutyronitrile and racemic 4-chloro-3-hydroxy butyric acid alkyl ester under specific reaction conditions, using racemic epichlorohydrin as a starting material, preparing (R)-4-chloro-3-hydroxy butyric acid alkyl ester from stereoselective hydrolysis of the racemic 4-chloro-3-hydroxy butyric acid alkyl ester using an enzyme, and preparing L-carnitine or acetyl L-carnitine hydrochloride from the (R)-4-chloro-3-hydroxy butyric acid alkyl ester, according to the known method.
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Page/Page column 10
(2010/11/29)
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