Acidulents. Like l-(14)C4 malic acid, dl-(14)C4 malic acid, when admin ip or orally to rats was extensively metabolized; 90-95% of (14)C was excreted through lungs as (14)CO2. ... Metabolized at same rate irrespective of route admin ... . /L- & dl-malic acid/
Malic acid is an intermediate in the citric acid cycle. It is formed from fumaric acid and is oxidized to oxaloacetic acid. It is also metabolized to pyruvic acid by malic enzyme which is present in many biologic systems, including bacteria and plants. L-Malic and dl-malic acid are both rapidly metabolized in the rat. Orally or ip administered l- or dl-malic acid was extensively eliminated as carbon dioxide (83 to 92%). No differences between the two forms were found in the rates (90 to 95% in 24 hr) or routes of excretion.
来源:Hazardous Substances Data Bank (HSDB)
代谢
苹果酸是人和动物饮食的正常成分，摄入后会被迅速且完全代谢成二氧化碳。/苹果酸盐/
Malates are normal constituents of the diet of humans and animals and, when ingested, are rapidly and completely metabolized to CO2. /Malates/
... Both enantiomers of malic acid are readily metabolised by laboratory animals and humans and that there was no reason to distinguish between L-malic acid and DL-malic acid when considering their safe use in food.
来源:Hazardous Substances Data Bank (HSDB)
代谢
口服和静脉注射放射性苹果酸给大鼠后，大部分放射性物质以二氧化碳的形式排出。
Upon oral and IP administration of radioactive Malic Acid to rats, most of the radioactivity was excreted as carbon dioxide.
IDENTIFICATION AND USE: Malic acid forms colorless crystals with a characteristic sour taste. It is used as a cosmetic and food ingredient. Malic acid has been tested as experimental therapy for various conditions. HUMAN EXPOSURE AND TOXICITY: Malic acid and its salts are considered as strongly irritant to the skin and mucosa and as a particular risk to the eyes. Exposure via inhalation for those handling the additives is also considered to present a risk. Malic acid was irritating in clinical tests, with less irritation seen as pH of the applied material increased. Patients patch tested with malic acid, placed on a diet that avoided foods containing malic or citric acid, and then challenged with a diet high in malic and citric acid had both immediate urticarial and delayed contact dermatitis reactions. In the absence of data on inhalation toxicity, inhalation of the malate additive should be considered as hazardous. Because of the particle size distribution of the additives and the high dusting potential of the malate salts, it is likely that handling the additives could result in a production of respirable dust that could present a risk to unprotected workers. ANIMAL STUDIES: Malic acid is a component of the Kreb's cycle. Malic acid was relatively nontoxic in acute toxicity studies using animals. In a chronic oral study, feeding malic acid to rats resulted only in weight gain changes and changes in feed consumption. Malic acid did not cause reproductive toxicity in mice, rats, or rabbits. Malic acid was a moderate to strong skin irritatant in animal tests, and was a strong ocular irritant. Malic acid was not mutagenic across a range of genotoxicity tests.
The influence of some frequent dietary constituents on gastrointestinal absorption of aluminum from drinking water and diet was investigated in mice. Eight groups of male mice received lactic (57.6 mg/kg/day), tartaric (96 mg/kg/day), gluconic (125.4 mg/kg/day), malic (85.8 mg/kg/day), succinic (75.6 mg/kg/day), ascorbic (112.6 mg/kg/day), citric (124 mg/kg/day), and oxalic (80.6 mg/kg/day) acids in the drinking water for one month. At the end of this period, animals were killed and aluminum concentrations in liver, spleen, kidney, brain, and bone were determined. All the dietary constituents significantly increased the aluminum levels in bone, whereas brain aluminum concentrations were also raised by the intake of lactic, gluconic, malic, citric, and oxalic acids. The levels of aluminum found in spleen were significantly increased by gluconic and ascorbic acids, whereas gluconic and oxalic acids also raised the concentrations of aluminum found in kidneys.
The interactions of aqueous solutions of chlorine with some fruit acids (citric acid, DL-malic acid, and L-tartaric acid) different pH values were studied diethyl ether extraction followed by GC/MS analysis indicated that a number of mutagens certain chlorinated propanones and chloral hydrate) are present as major products in some of these samples. A number of fruit juices (orange, grape, apple, pineapple, and grapefruit) were also treated with aqueous solutions of chlorine at their pH values. The products were analyzed by GC/MS. The same mutagens that were formed by the pure acids (citric acid and DL-malic acid) were identified as major products in ether extracts of these samples. All of the major products observed in the chlorination of all five fruit juices are potentially derived from reactions aqueous solutions of chlorine with citric or malic acid and with trace amounts of acetaldehyde and acetone in the juices.
The relative efficacy of citric, malic, malonic, oxalic and succinic acids, and deferoxamine mesylate (DFOA) on the toxicity, distribution and excretion in mice exposed to aluminum were compared. To determine the effect of the various chelators on the toxicity of aluminum various doses of aluminum nitrate (938-3l88 mg/kg) were administered intraperitoneally, followed by one of the chelators. Survival was recorded at the end of 14 days. Malic and succinic acids were the most effective. Malic and succinic acids were the most effective in increasing the urinary excretion of aluminum.
Eight groups of female Sprague-Dawley rats were treated with 281 mg aluminum hydroxide/kg/day by gastric intubation five times a week for fives weeks. Concurrently, animals in seven groups received ascorbic acid (56.3 mg/kg/day), citric acid (62 mg/kg/day), gluconic acid (62.7 mg/kg/day), lactic acid (28.8 mg/kg/day), malic acid (42.9 mg/kg/day), oxalic acid (28.8 mq/kg/day), and tartaric acid (48 mg/kg/day) in the drinking water. The eighth group did not receive any dietary constituent in the water and was designated as the control group. Animals were placed in plastic metabolic cages and urine was collected during the treatment period. The liver, spleen, kidney, brain and bone aluminum levels of each rat were measured, as well as the total amount of aluminun excreted into urine. All the dietary constituents significantly increased the aluminum concentrations in most of the tissues, with ascorbic and citric acids showing the highest rate of aluminum accumulation.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
口服和静脉注射放射性苹果酸给大鼠后，大部分放射性物质以二氧化碳的形式排出。
Upon oral and IP administration of radioactive malic acid to rats, most of the radioactivity was excreted as carbon dioxide.
Temperature and field dependence of critical currents, resistances and irreversibility fields of a (Tl0.6Pb0.24Bi0.16)(Ba0.1Sr0.9)2Ca2Cu3Oy film on single-crystalline lanthanum aluminate
摘要：
The temperature and magnetic field dependences of the ac resistance and the critical currents of a c-axis oriented, ab aligned (Tl0.6Pb0.24Bi0.16)(Ba0.1Sr0.9)(2)Ca2CU3Oy film on (100) single-crystalline lanthanum aluminate substrate were measured and analysed. The magnetic field and the temperature dependences of the width of the resistive transition to the superconducting state and of the irreversibility fields were analysed both within the flux-creep model and the superconducting liquid vortex state model. The temperature width of the resistive transition was explained oil the basis of the superconducting Josephson weak links model of resistance and the barrier of vortex motion. The irreversibility field was described by an exponential formula. The temperature dependence of the critical current was described by a power law; the magnetic field dependence of the critical current was fitted to a Kim-type power law as well as to an exponential relation from the percolation model. (c) 2005 Elsevier B.V. All rights reserved.
Synthesis and Properties of 2-Oxa-6-azaspiro[3.3]heptane Sulfonate Salts
作者：Richard van der Haas、Jeroen Dekker、Jorma Hassfeld、Anastasia Hager、Peter Fey、Philipp Rubenbauer、Eric Damen
DOI：10.1055/s-0036-1588733
日期：2017.6
2-oxa-6-azaspiro[3.3]heptane is presented. While this compound is often isolated as an oxalate salt, its isolation as a sulfonic acid salt yields a more stable and more soluble product. With these improved properties access to a wider range of reaction conditions with the spirobicyclic 2-oxa-6-azaspiro[3.3]heptane has been enabled. An improved synthesis of the bicyclic spiro compound 2-oxa-6-azaspiro[3.3]heptane is
Photo-triggered fluorescent theranostic prodrugs as DNA alkylating agents for mechlorethamine release and spatiotemporal monitoring
作者：Yanting Cao、Rong Pan、Weimin Xuan、Yongyi Wei、Kejian Liu、Jiahong Zhou、Wei Wang
DOI：10.1039/c5ob00500k
日期：——
However, upon photo-irradiation, the active mechlorethamine is released and induces efficient DNA cross-links, accompanied by a strong fluorescence enhancement (152 fold). Furthermore, DNA cross-linking activity from the release can be transformed into anticancer activity observed in in vitro studies of tumor cells. Importantly, the drug release progress and the movement can be conveniently monitored by
EPOTHILONE DERIVATIVES, METHOD FOR PRODUCING SAME AND THEIR PHARMACEUTICAL USE
申请人：——
公开号：US20030144523A1
公开（公告）日：2003-07-31
This invention relates to the new epothilone derivatives of general formula I,
1
in which
substituents Y, Z R
2a
, R
2b
, R
3
, R
4a
, R
4b
, D—E, R
5
, R
6
, R
7
, R
8
and X have the meanings that are indicated in more detail in the description.
The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanomas, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (psoriasis, arthritis). To avoid uncontrolled proliferation of cells and for better compatibility of medical implants, they can be applied or introduced into polymer materials.
The compounds according to the invention can be used alone or to achieve additive or synergistic actions in combination with other principles and classes of substances that can be used in tumor therapy.
Novel epothilone derivatives, method for the preparation thereof and their pharmaceutical use
申请人：——
公开号：US20040058969A1
公开（公告）日：2004-03-25
The invention relates to novel epothilone derivatives of general formula (1), wherein R
5
represents a halogen atom or a cyano group and the other substituents have the meanings as cited in the description. The novel compounds interact with tubulin by stabilizing formed microtubules. They are capable of influencing the cell division in a phase-specific manner and are well-suited for the treatment of malignant tumors, for example, ovarian, stomach, colon, adeno, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are well-suited for anti-angiogenesis therapy and for the treatment of chronic inflammable medical disorders (psoriasis, arthritis). In order to prevent uncontrolled cell growths as well as to improve the compatibility of medical implants, the inventive epothilone derivatives can be applied to or introduced into polymeric materials. The inventive compounds can be used alone or in order to obtain additive or synergistic effects, in conjunction with additional principles and substance classes that can be used in tumor therapy.
1
Effects of Gln102Arg and Cys97Gly mutations on the structural specificity and stereospecificity of the L-lactate dehydrogenase from Bacillus stearothermophilus
作者：Helmut K. W. Kallwass、Marcel A. Luyten、Wendy Parris、Marvin Gold、Cyril M. Kay、J. Bryan Jones
DOI：10.1021/ja00038a016
日期：1992.6
The L-lactatedehydrogenase of Bacillusstearothermophilus (BSLDH) is a thermostable enzyme with considerable potential for applications in asymmetric synthesis. An understanding of the factors controlling its structural specificity and stereospecificity is therefore of interest. In this paper the effects of GIn 102→Arg and Cys97→Gly mutations have been evaluated. In a survey of thirteen 2-keto acids
