Carnitine Hydrochloride Research Articles

Pharmaco-technological research and stability of the drug for the treat-ment and prevention of vitamin and trace element deficiency in animals

The article presents the research results on the Development of manufacturing technology and the study of the stability of a solution for oral use based on carnitine hydrochloride, vitamins – E, B12, choline chloride, selenium, and zinc. “Devivit Carnitine” oral is used for the prevention of diseases of liver and muscle tissue metabolism in farm animals and poultry, nephrosis, myocarditis, prevention of stress (heat, transport, sound, food, post-vaccination, etc.), and prevention of vitamin and hypovitaminosis. When developing the drug technology, experimentally obtained pharmaco-technological properties of active substances and excipients were taken into account. The technological process of preparing an oral solution consists of four technological stages: preparation of canisters for filling, preparation of the solution, filling containers with medicine and packaging. The stability and shelf life of “Devivit Carnitine” (solution for oral use) in plastic canisters were determined. It was established that the drug sample in plastic canisters was stable, according to all quality control methods indicators, during the entire period of the study. The shelf life of the medicinal product with carnitine hydrochloride, vitamins E and B12, choline chloride, selenium, and zinc is 12 months. In the future, a study of preclinical data is planned to verify whether the drug does not reveal a particular hazard for animals based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, and developmental toxicity.

Efficacy of hepatoprotectors in prophylaxis of hepatosis of laying hens

Hepatoses of laying hens are quite common in poultry farms as a result of improper practices of poultry maintenance consisting in excessive number of protein feeds for provision of high productivity. The objective of the study was preventive efficacy of Gep-A-Stress hepatoprotectors (carnitine hydrochloride, D L methionine, sorbitol, choline chloride, magnesium sulfate heptahydrate) and Hepasan VS (L-carnitine hydrochloride, sorbitol, choline chloride, magnesium sulfate hepahydrate, betaine hydrochloride, L-arginin) against hepatosis of laying hens. To determine the efficacy of Hep-A-Stres and Hepasan-VS hepatoprotectors during production tests (n = 4,500), we monitored the parameters of survival rate (the final number of individuals as percentage of the initial number) and egg productivity of laying hens. We determined that after 30 days of using the hepatoprotectors, the content of overall protein in blood serum of laying hens of the first and the second experimental groups decreased by 21.4% and 18.9% compared with the parameters prior to providing the hepatoprotectors and by 26.3% and 23.3% compared with the control group after receiving the drug. The urea contents in blood serum increased by 19.0% and 10.5%. Compared with the control, the activity of alanine aminotransferase decreased by 43.7% and 24.1% in the first experimental group and by 23.4% and 14.9% in the second. The activity of aspartate aminotransferase in blood serum of the experimental groups decreased by 10.7%. The cholesterol concentration decreased by 50% and 58.3%. The content of triaglycerols decreased by 24.1% and 8.9% respectively. The concentrations of high-density lipoproteins after 30 days of the experiment decreased by 33.3% and 77.8% respectively, the content of low-density lipoproteins decreased by 61.3% and 40.4% and 42.3%. Population maintenance equaled respectively 97.1%, 98.3% and 98.1%. At the end of the experiment, the egg productivity of laying hens of the first and second groups increased by 4% and 3.6% compared with the control. Therefore, intake of the hepaprotectors by laying hens stimulated their metabolism, positively influenced the blood parameters, survival and egg productivity. The conducted studies confirm the benefits of using hepatoprotectors for the prohylaxis of hepatosis of hens.

Multifunctional zwitterion modified SnO2 nanoparticles for efficient and stable planar perovskite solar cells

SnO 2 nanoparticles (NPs) have been widely employed as electron transport layers (ETLs) in planar n-i-p perovskite solar cells (PSCs). Perfect SnO 2 ETL/perovskite interface plays a key role in high efficiency PSCs, however, the main issues caused by the self-aggregation of the SnO 2 NPs and the interface recombination limit the further improvement of device performance. Here, l -carnitine hydrochloride (L-ch) zwitterion with multiple functional groups has been incorporated into SnO 2 NP solution for high-efficiency PSCs. The results demonstrate that the unique coordination complexes assembled between L-ch zwitterion and SnO 2 NPs can inhibit the aggregation of SnO 2 NPs, benefiting for the formation of more compact film with reduced roughness. Simultaneously, the L-ch zwitterion can adjust the electronic properties of SnO 2 and promote the carrier transport between perovskite and SnO 2 ETL with well aligned energy level. Moreover, the -COO - and –N + (CH 3 ) 3 groups can passivate uncoordinated Pb 2+ and MA vacancies defects in the perovskite film, respectively. Therefore, by using SnO 2 /L-ch as the ETL, the efficiency of champion MAPbI 3 PSCs can be increased from 18.77% to 20.56%, with reduced hysteresis and improved stability. A novel multifunctional L-ch zwitterion is introduced to inhibit the aggregation of SnO 2 NPs and passivate interfacial defects in PSCs. • A novel L-ch zwitterion with multiple functional groups is introduced into SnO 2 nanoparticles (NPs). • The unique coordination complexes can inhibit the aggregation of SnO 2 NPs, benefiting for the formation of compact film. • The L-ch can adjust the electronic properties of SnO 2 and promote the carrier transport with well aligned energy level. • The -COO - and –N + (CH 3 ) 3 groups can passivate uncoordinated Pb 2+ and MA vacancies defects, respectively.

Two novel compounds of vanadium and molybdenum with carnitine exhibiting potential pharmacological use

The reaction of sodium orthovanadate with carnitine hydrochloride molecule results in the precipitation of decavanadate compound of carnitine whereas the reaction of metallic molybdenum with hydrogen peroxide and carnitine results in the peroxo-molybdenum complex of carnitine. The decavanadate compound as well as the molybdenum complex of carnitine have been characterized by means of elemental analysis, IR, electronic spectra, 1H NMR, 2D-COSY-NMR (=correlation spectroscopy) and thermo-gravimetric analysis (TGA). In addition decavanadate compound of carnitine was fully characterized by X-ray crystallography. The analytical data were in good agreement with the empirical formulae of both, decavanadate compound and molybdenum complex. The two compounds were also evaluated for cell toxicity and their anticancer activity by the MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based assay method, using primary cells and tumor cell lines of both human and murine origins and the results show that compound 1 shows an increased biological activity in comparison with compound 2. Moreover using confocal microscopy and antibodies against cleaved caspase 3 we further analyzed the cell toxicity and we conclude that the apoptotic pathway is triggered efficiently with tumor specificity by compound 1 and not by compound 2.

Lipase‐Catalyzed Enantiomer Separation of 3‐Hydroxy‐4‐(tosyloxy)butanenitrile: Synthesis of (R)‐GABOB (=(3R)‐4‐Amino‐3‐hydroxybutanoic Acid) and (R)‐Carnitine Hydrochloride (=(2R)‐3‐Carboxy‐2‐hydroxy‐N,N,N‐trimethylpropan‐1‐aminium Chloride)

AbstractEnzymatic resolution of racemic 3‐hydroxy‐4‐(tosyloxy)butanenitrile ((±)‐5) by using various lipases in different solvents were studied. The obtained optically pure (3R)‐3‐(acetyloxy)‐4‐(tosyloxy)butanenitrile ((R)‐6), upon treatment with aqueous ammonia followed by conc. HCl solution, provided (R)‐GABOB (=(3R)‐4‐amino‐3‐hydroxybutanoic acid; (R)‐1). Similarly, reaction of (R)‐6 with aqueous trimethylamine solution followed by conc. HCl solution provided (R)‐carnitine hydrochloride (=(2R)‐3‐carboxy‐2‐hydroxy‐N,N,N‐trimethylpropan‐1‐aminium chloride; (R)‐2⋅HCl) in an expeditious manner.

Isolation and Functional Characterization of a Novel Organic Solute Carrier Protein, hOSCP1

We succeeded in isolating a novel organic solute carrier from a human placenta cDNA library. The isolated cDNA consisted of 1137 base pairs that encoded a 379-amino acid protein, hOSCP1. Northern blot and reverse transcription PCR analyses revealed that the hOSCP1 mRNA is expressed in the placenta and testis and weakly expressed in the thymus and small intestine. When expressed in Xenopus laevis oocytes, hOSCP1 mediated the high affinity transport of p-aminohippurate (PAH) (K(m) = 35.0 +/- 7.5 microm) and tetraethylammonium (K(m) = 62.3 +/- 12.2 microm) in a sodium-independent manner. However, the hOSCP1-expressing oocyte did not mediate the transport of L-carnitine. The transport of PAH by hOSCP1 was sensitive to pH, but the tetraethylammonium was not transported at the high pH examined. hOSCP1 transported prostaglandin E(2), prostaglandin F(2alpha), estrone sulfate, glutarate, L-leucine, L-ascorbic acid, and tetracycline. Thus, hOSCP1 also showed broad substrate specificity. A wide range of structurally unrelated organic compounds inhibited the hOSCP1-mediated PAH uptake. Immunohistochemical analysis revealed that the hOSCP1 protein is localized in the basal membrane of the syncytiotrophoblast in the human placenta. Our results suggest that hOSCP1 is a novel polyspecific organic solute carrier protein responsible for drug clearance from the human placenta.

Simultaneous separation of yttrium and lanthanide ions by isotachophoresis

An operational electrolyte system was developed for the isotachophoretic separation of fifteen rare-earth elements (yttrium and lanthanides except for Pm) by adding a helping complexing agent to an α-hydroxyisobutyric acid (HIBA) electrolyte system. As a result of testing several helping agents such as malonic acid, malic acid, tartronic acid and glycolic acid, the optimized leading electrolyte was a 20-mM ammonia solution containing 2 mM malonic acid and 7.5 mM HIBA (pH 4.8, 2-ethylbutyric acid buffer). The terminator was a 20-mM carnitine hydrochloride. According to the stability constants of rare-earth–malonate complexes evaluated by isotachophoretic method, the successful separation was due to the smaller stability constants of Y–malonate complexes compared with those of the medium lanthanide elements to be separated.

Study of isotachophoretic separation behaviour of metal cations by means of particle-induced X-ray emission VI. Selective separation of twenty metal cations using tartaric acid as a completing agent

The selective isotachophoresic (ITP) separation of twenty metal ions that form kinetically labile complexes with tartaric acid was investigated. The leading electrolyte was 20 m M ammonia solution buffered by adding acetic acid (pH 4.8) and the concentration of tartaric acid ( C Tar) was varied in the range 0–5 m M. The terminator was 20 m M carnitine hydrochloride solution. Isotachophoretic qualitative indices ( R E ) of the metal ions were measured by using a high-frequency contactless conductivity detector. An equimolar test mixture was separated by using a micro-preparative apparatus and the fractions were analysed off-line by particle-induced X-ray emission method (ITP-PIXE). When C Tar = 1 m M, the separability was good on average. The migration order was Ba 2+, (Sr 2+, Na +), Ca 2+, Mg 2+, Mn 2+, Fe 2+, Co 2+, Cd 2+, (Ni 2+ , Li +), Zn 2+, La 2+, (Ce 3+, Pb 2+), Y 3+, Gd 3+, Lu 3+, Cu 2+, where the ions in parentheses were not separated. Zr IVO 2+ was not detected. With increase in C Tar, the number of detectable elements decreased owing to the decrease in the effective mobilities of the separands. When C Tar = 5 m M, the migration order was Na +, Ba 2+, Sr 2+, Mg 2+, Li +, Ca 2+, Mn 2+, Cd 2+, CO 2+, Ni 2+ and Zn 2+. A model waste from a nuclear fuel was successfully analysed using the electrolyte system.

An efficient synthesis of (r)-carnitine

An efficient synthesis of (R)-carnitine hydrochloride is described. The starting material is obtained by microbial resolution of (Rs)-2,3-dicholoro-1-propanol.

Refinement of the crystal structure of (RS)-carnitine hydrochloride

A single crystal of (RS)-carnitine hydrochloride has been obtained, and its crystal structure has been refined by an x-ray structural experiment.

High performance liquid chromatographic determination of carnitine hydrochloride in herbal liquores used as gastrointestinal medicines.

A simple and rapid method for the quantitative analysis of carnitine hydrochloride (CH) in the herbal liquores used as gastrointestinal medicines was studied. The herbal liquores were passed through a Mega Bond Elut C18 and a Sep Pak alumina B cartridge for clean-up, and the passing solution was subjected to reversed-phase ion-pair high performance liquid chromatography on an octadecylsilylated silica-gel column (TSKgel ODS-80TM) with spectorophotometric detection at 210 nm. Standard curves were linear in the range from 0.2 to 1.0 mg/ml. The recoveries of CH added to twenty herbal liquores were obtained from 98% to 101%. The present method was appliciable to the determination of CH in the herbal liquores without interference of other principles belonging to Chinese medicinal herbs.

Organic reactions at surfaces: A study of carnitine by secondary ion mass spectrometry

AbstractCarnitine inner salt, (CH3)3N+ CH2CH(OH)CH2COO−, and carnitine hydrochloride, (CH3)3N+CH2CH (OH)CH2COOH Cl−, in the solid state undergo ion‐beam‐induced intermolecular methyl transfer reactions as shown by (CH3)3N+ CH2CH(OH)CH2COOCH3 ions at m/z 176 in their positive ion spectra. In the case of carnitine HCl, the product ion is three times as abundant as the intact cation. For the inner salt however, the product is less than one‐tenth as abundant as [M + H] +. In both cases, the reaction can be precluded by dissolution of the sample, supporting an intermolecular mechanism. The negative ion spectra for these compounds contain no [M − CH3]− ions, suggesting that simple transmethylation does not occur. Rather it is proposed that the inner salt abstracts a methyl group from the intact carnitine cation to yield [M + CH3]+ and a neutral species, the driving force being a minimization of the total number of charges desorbed into the gas phase. Thermodynamic data favor this mechanism as do data for other carnitine salts. The reaction appears to be inhibited when one reactant is present in excess. This is the case for carnitine HNO3 and CH3SO3H, which tend to liberate the intact cation since the anions are large and polarizable. It is also the case for small, hard anions like fluoride, which appear to favor release of the inner salt, hence the cation at m/z 162 is of low abundance and the transmethylation product (m/z 176) is absent. The extent of the reaction is also dependent on the methods of preparation of the sample, and deposition of the salts from solution greatly reduces the extent of methyl transfer. [M − CH3]− is observed when glycerol is used as a matrix, possibly due to a matrix‐analyte methyl transfer reaction.

(-)-β-Pinene as chiral promoter. Stereospecific access to (-)-γ-amino-β( [formula omitted])-hydroxybutyric acid (gabob) and ( [formula omitted])-carnitine.2

The stereochemical correlation between the ene adducts 2 and 4a and their products of alkaline hydrolysis is reported. Starting from 2, by using a degradative sequence, a stereocontrolled approach to γ-amino-β( R )-hydroxybutyric acid (GABOB) 8f and ( R )-carnitine hydrochloride 8g is described.

Crystal and Molecular Structure of ω-Amino Acids, ω-Amino-Sulfonic Acids and Their Derivatives. VII. The Crystal and Molecular Structure of Dl-Carnitine Hydrochloride

Abstract The crystal structure of Dl-carnitine hydrochloride, C7H15NO3·HCl, was determined by the heavy atom method using X-ray diffraction data on a Weissenberg photograph, and refined by the least-squares method to an R-factor of 0.13 for 1969 independent reflections. The crystals are monoclinic space group P21⁄c, Z=4, with a=6.77(1), b=11.41(2), c=15.10(3) Å and β=120.1(1)°. By protonation at carboxyl oxygen atom, carnitine molecule has the cationic form, N+(CH3)3CH2CH(OH)CH2COOH, with trans-zigzag skeletal configuration as similar as γ-amino-β-hydroxybutyric acid. The Cl− ion mediates between adjacent carnitine cations by two O–H···Cl− hydrogen bonds to form infinite chain elongated along the c-axis. The correlation between molecular structure and biological activity was also discussed.

Studies on Carnitine. I. Hydrolysis of Carnitine-nitrile Chloride with Concentrated Hydrochloric Acid.

It became questionable that Dechamps, et al.8) obtained carnitine-carnitate (IV) in their hands as the hydrolysis product of carnitine-nitrile chloride (II), since in our hands the latter, when heated with conc. hydrochloric acid at 130°, yielded mainly apocarnitine hydrochloride (V) containing a certain amount of carnitine hydrochloride (III). By carrying out the hydrolysis of (II) at boiling water-bath temperature the formation of (V) was practically suppressed to give (III) in a satisfactory yield, the formation of (IV) was altogether not observed.

The ineffectiveness of carnitine preventing the twitchings of striated frog muscle in 0.7 per cent sodium chloride solution.

The spontaneous twitchings of isolated frog sartorius muscles in 0.7% NaCl solution have been studied. Addition of 1 mg./ml. of (+/-)-carnitine hydrochloride, or of (+/-)-carnitine base, to the bath fluid had no influence on the spontaneous activity of the muscles, their excitability or their ability to liberate potassium. This indicates that carnitine is not a natural inhibitor of striated frog muscle. Fluids enriched with potassium either from twitching muscle or by addition of KCl inhibited the activity of muscles reversibly.