Disodium succinate   中文名称: 琥珀酸钠

Microbial Metabolite; Endogenous Metabolite; Flavoring Agents; Alters several flavor and/or taste characteristics; Food additives; Fragrance Ingredients; Cosmetics -> Buffering; Environmental transformation -> Pesticide transformation products (metabolite, successor)

琥珀酸被认为是一种重要的平台化学品。采用响应面法（RSM）通过中心复合设计（CCD）优化了产琥珀酸放线杆菌BE-1菌株的琥珀酸发酵。预测了琥珀酸的优化生产，并研究了葡萄糖、酵母提取物和碳酸镁之间的相互作用。因此，开发了一个预测琥珀酸生产浓度的模型。方差分析（ANOVA）证实了模型的准确性，验证实验进一步证明了模型的有效性，实验表明实际值和预测值之间的百分比误差在3.02%到6.38%之间。此外，观察到酵母提取物和碳酸镁之间的相互作用具有统计学意义。综上所述，RSM是优化培养基成分和研究相互作用效应的有效和有用的方法，可以为使用产琥珀酸A.菌株BE-1进行琥珀酸放大发酵提供有价值的信息[1]。

给予琥珀酸（3、6 mg/kg；口服）的雄性小鼠进入张臂的比例更高，停留时间也更长[3]。分娩后 5 至 40 分钟内，琥珀酸（3、6、12 mg/kg；腹腔注射）可显着提高食物摄入量。测量直肠温度，发现 1.5 mg/kg 的琥珀酸可以预防应激引起的体温过高 [3]。

The putative anxiolytic activity of succinic acid was examined in male mice by using a number of experimental paradigms of anxiety and compared with that of the known anxiolytic compound diazepam. Use of the elevated plus-maze test revealed that diazepam (1.0, 2.0 and 4.0 mg/kg, PO) or succinic acid (3.0 or 6.0 mg/kg, PO) increased the percentage of entries into open arms and of time spent on open arms. In novel food consumption test, succinic acid (3.0, 6.0, and 12.0 mg/kg, IP) caused significant increases in food intake during 5 min when compared with the vehicle. In the stress-induced hyperthermia test, 40 min after drug administration rectal temperature was measured, succinic acid at dose of 1.5 mg/kg, inhibited stress-induced hyperthermia. Thus, these findings indicated that, in contrast with diazepam, succinic acid exhibits anxiolytic-like effect.[3]

Absorption, Distribution and Excretion
Succinic acid occurs normally in human urine (1.9-8.8 mg/L).

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Metabolism / Metabolites
Succinic acid is a normal intermediary metabolite and a constituent of the citric acid cycle. It is readily metabolized when administered to animals, but may be partly excreted unchanged in the urine if large doses are fed.

Succinic acid can be converted into fumaric acid by oxidation via succinate dehydrogenase.

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Agrochemical Transformations
Butanedioic acid is a known environmental transformation product of Sulcotrione.
Succinic acid is a known environmental transformation product of Linuron.

mouse LD50 intravenous 4500 mg/kg Merck Index; an Encyclopedia of Chemicals, Drugs, and Biologicals, 11th ed., Rahway, NJ 07065, Merck & Co., Inc. 1989, 11(1368), 1989

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Toxicity Summary
Succinate can inhibit the activities of α-KG–dependent oxygenases (KDMs) and the TET family of 5-methlycytosine (5mC) hydroxylases. Succinate also mediates allosteric inhibition of hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs). Inhibition of HIF PHDs leads to activation of HIF-mediated pseudohypoxic response, whereas inhibition of KDMs and TET family of 5mC hydroxylases causes epigenetic alterations that ultimately cause cancer. Succination of KEAP1 in FH deficiency results in the constitutive activation of the antioxidant defense pathway mediated by NRF2, conferring a reductive milieu that promotes cell proliferation. Succination of the Krebs cycle enzyme Aco2 impairs aconitase activity in Fh1-deficient MEFs. Succination also causes irreversible inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

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Health Effects
At acute doses or exposures succinic acid is a skin irritant. Chronically high doses of succinate can lead to succinylation or succination of a variety of enzymes. Partial succinate dehydrogenase deficiency (15% to 50% of normal reference enzyme activity) in skeletal muscle leads to elevated succinate levels and causes mitochondrial myopathy with various symptoms, for example, brain involvement, cardiomyopathy, and/or exercise intolerance.

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Exposure Routes
Eye contact, Inhalation, Ingestion.

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Symptoms
Acute Exposure: the clinical signs of acute toxicity are weakness and diarrhea.

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Adverse Effects
Neurotoxin - Other CNS neurotoxin

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Toxicity Data
Acute oral toxicity (LD50): 2260 mg/kg [Rat].

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Treatment
EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

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Human Toxicity Excerpts
/OTHER TOXICITY INFORMATION/ Primary irritant effects are present with a number of ... /aliphatic dicarboxylic/ acids, particularly in concentrated solution or as dusts- sensitization is rare. /Aliphatic dicarboxylic acids/ International Labour Office. Encyclopedia of Occupational Health and Safety. Volumes I and II. New York: McGraw-Hill Book Co., 1971., p. 30

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Non-Human Toxicity Excerpts /LABORATORY ANIMALS: Acute Exposure/ Succinic acid is slight skin irritant and a strong eye irritant in rats. Application of 750 ug of succinic acid as a 15% solution produced severe damage in rabbit eyes. The clinical signs of acute toxicity in rats are weakness and diarrhea.

/LABORATORY ANIMALS: Acute Exposure/ Large iv doses of sodium succinate produced vomiting and diarrhea in cats... .

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Rats/Fischer (F344) males and females,10 per group /were exposed for/ 13 weeks ad libitum /to/ 0, 0.3, 0.6, 1.25, 2.5, 5, 10% monosodium succinate, purity 100.2%. ...Severe suppression of body weight gain occurred in rats in the 10% group, and all of the rats in this group died during the first 4 weeks of the experiment. However, in the other dose groups all of the rats survived to the end of the experiment. Suppression of body weight gain was observed at >/=2.5%. The volume of drinking water consumed was very small in the highest dose groups, although it was larger in the 5% group than in the other groups. No specific dose-related changes were observed in any parameters in the hematological and biochemical investigations. Rats that died during the experiment were severely emaciated. However, no toxic lesions caused by the test substance were found in any organs of these rats histopathologically, although atrophy of the organs was observed. No specific lesions were observed histologically in any of the other test groups. On the basis of body weight depression, the maximum tolerated dose of monosodium succinate was determined to be approximately 2-2.5% when given in the drinking water.

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Non-Human Toxicity Values
LD50 Rat oral 2260 mg/kg

[1]. Optimization of succinic acid fermentation with Actinobacillus succinogenes by response surface methodology (RSM). J Zhejiang Univ Sci B. 2012 Feb;13(2):103-10.

[2]. Johns A T. The production of propionic acid by decarboxylation of succinic acid in a bacterial fermentation. The Biochemical journal, 1948, 42(1): ii.

[3]. Chen SW, Xin Q, Kong WX, Min L, Li JF. Anxiolytic-like effect of succinic acid in mice. Life Sci. 2003 Nov 7;73(25):3257-64. doi: 10.1016/j.lfs.2003.06.017. PMID: 14561530.

[4]. Microbial succinic acid, its polymer poly (butylene succinate), and applications. Plastics from bacteria: Natural functions and applications, 2010: 347-388.

[5]. Succinic acid: a new platform chemical for biobased polymers from renewable resources. Chemical Engineering & Technology: Industrial Chemistry‐Plant Equipment‐Process Engineering‐Biotechnology, 2008, 31(5): 647-654.

Sodium succinate (anhydrous) is a sodium salt that is the disodium salt of succinic acid. The hexahydrate form is used as an ingredient of topical preparations for the treatment of cataract. It contains a succinate(2-).
See also: Succinic Acid (has active moiety).

C4H4NA2O4

162.05

161.99

C, 29.65; H, 2.49; Na, 28.37; O, 39.49

150-90-3

9020

White to off-white solid powder

110.9ºC

0.0165mmHg at 25°C

80.26

0

4

1

10

81.6

0

ZDQYSKICYIVCPN-UHFFFAOYSA-L

InChI=1S/C4H6O4.2Na/c5-3(6)1-2-4(7)8;;/h1-2H2,(H,5,6)(H,7,8);;/q;2*+1/p-2

disodium;butanedioate

CCRIS-3700; Disodium succinate; 150-90-3; SODIUM SUCCINATE; Disodium butanedioate; Succinic acid disodium salt; Butanedioic acid, disodium salt; FEMA No. 3277; Sodium succinate dibasic; CCRIS 3700; Butanedioic acid, disodium salt

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。