DMA（二甲基乙酰胺，N,N-dimethylacetamine）

《药用辅料手册》（四川出版社）

作用与用途：本品在药剂中用作溶剂和助溶剂。做溶剂用于溶解塑料、树脂等高分子化合物成膜、成囊材料，以制备膜剂、微囊剂等。做助溶剂多用于制备注射剂。

安全性：本品有一定毒性，小白鼠腹腔注射，LD50为3.236g/kg。本品有溶血左右，当浓度小于10%时，加入0.9%氯化钠有一定阻止效果。

Martindala：

Adverse Effects and Precautions

As for Dimethylformamide, although a disulfiram-like reaction with alcohol has not been reported. A review1 of the toxicology of dimethylacetamide with reference to its use as a vehicle for antineoplastics.

1. Kim S-N. Preclinical toxicology and pharmacology of dimethylacetamide, with clinical notes. Drug Metab Rev 1988; 19: 345–68. PubMed

Handling.

Suitable precautions should be taken to avoid skin contact with dimethylacetamide as it can penetrate skin and produce systemic toxicity.

Uses

Dimethylacetamide is used as an industrial and pharmaceutical solvent.

FDA IIG limit：

DMSO（Dimethyl Sulfoxide 二甲亚砜）

《药用辅料手册》（四川出版社）

作用与用途：作透皮促进剂、溶剂和防冻剂。

安全性：本品无毒安全，吸收后主要以原形从尿排出，少部分被氧化成二甲基碸由尿排出。本品高浓度有时产生灼烧不适感，或瘙痒、红斑，有时会引起恶心、呕吐等全身反应。

《药用辅料手册》（化工出版社）

作用与用途：溶剂、局部穿透促渗剂

安全性：具有局部毒性作用和低的全身毒性。注射、口服或经皮给药易于吸收，在体内分布广泛。主要刺激皮肤，产生红肿、灼烧等，还可引起全身症状包括恶心、呕吐、痉挛等。

LD50（狗，IV）：2.5g/kg

LD50（大鼠，IP）：8.2g/kg

LD50（大鼠，IV）：5.3g/kg

LD50（大鼠，口服）：14.5g/kg

LD50（大鼠，SC）：12g/kg

LD50（小鼠，IP）：2.5g/kg

LD50（小鼠，IV）：3.8g/kg

LD50（小鼠，口服）：7.9g/kg

法规：美国用50%DMSO溶液做灌洗剂治疗膀胱间质炎；加拿大用70%DMSO溶液做局部抗纤维药；德国用10%DMSO的局部用凝胶剂治疗肌骨骼和关节疾患；英国准许局部用于碘苷制剂。

Martindala：

Adverse Effects and Treatment

High concentrations of dimethyl sulfoxide applied to the skin may cause burning discomfort, itching, erythema, vesiculation, and urticaria. Continued use may result in scaling.

Systemic effects, including gastrointestinal disturbances, drowsiness, headache, and hypersensitivity reactions, may occur after administration by any route. A garlic-like odour on the breath and skin is attributed to the formation of dimethyl sulfide (see Pharmacokinetics, ). Intravascular haemolysis has been reported following intravenous administration. Local discomfort and spasm may occur when given by bladder instillation.

Treatment of adverse effects consists of symptomatic and supportive measures. Gastric lavage may be helpful after acute ingestion, although it should be remembered that absorption is rapid.

Reviews.

1. Brobyn RD. The human toxicology of dimethyl sulfoxide. Ann N Y Acad Sci 1975; 243: 497–506. PubMed

2. Willhite CC, Katz PI. Toxicology updates: dimethyl sulfoxide. J Appl Toxicol 1984; 4: 155–60. PubMed

Dimethyl sulfoxide given by intravenous infusion for spinal cord injury to 14 patients caused transient haemolysis and haemoglobinuria.1 Infusion strengths greater than 10% were associated with grossly discoloured urine but there was no evidence of renal damage. In 2 patients, raised liver and muscle enzyme concentrations, mild jaundice, and evidence of haemolysis developed after receiving dimethyl sulfoxide intravenously for arthritis.2 One also developed acute renal tubular necrosis, deterioration in level of consciousness, and evidence of cerebral infarction. Acute, reversible neurological deterioration in a patient has been associated with intravenous dimethyl sulfoxide.3

Serum hyperosmolality4 has been reported in a patient who had pre-existing diabetes insipidus after receiving haematopoietic stem cells cryopreserved in dimethyl sulfoxide following chemotherapy for a malignant germ-cell tumour; symptoms included severe headache, confusion, and abdominal pain.

1. Muther RS, Bennett WM. Effects of dimethyl sulfoxide on renal function in man. JAMA 1980; 244: 2081–3. PubMed

2. Yellowlees P, et al. Dimethylsulphoxide-induced toxicity. Lancet 1980; ii: 1004–6. PubMed

3. Bond GR, et al. Dimethylsulphoxide-induced encephalopathy. Lancet 1989; i: 1134–5. PubMed

4. Thomé S, et al. Dimethylsulphoxide-induced serum hyperosmolality after cryopreserved stem-cell graft. Lancet 1994; 344: 1431–2. PubMed

Precautions

When used as a penetrating basis for other drugs applied topically, dimethyl sulfoxide may enhance their toxic effects.

Since dimethyl sulfoxide has been associated with lens changes in animals, the manufacturers recommend assessment of ophthalmic function every 6 months during long-term treatment of cystitis with intravesical instillation of dimethyl sulfoxide. Hepatic and renal function should also be assessed at intervals of 6 months. Bladder instillation may be harmful in patients with urinary-tract malignancy because of vasodilatation.

Interactions

For mention of an interaction between dimethyl sulfoxide and sulindac, see .

Pharmacokinetics

Dimethyl sulfoxide is readily absorbed after administration by all routes. It is metabolised by oxidation to dimethyl sulfone and by reduction to dimethyl sulfide. Dimethyl sulfoxide and the sulfone metabolite are excreted in the urine and faeces. Dimethyl sulfide is excreted through the lungs and skin and is responsible for the characteristic odour from patients.

Uses and Administration

Dimethyl sulfoxide is a highly polar substance with exceptional solvent properties for both organic and inorganic chemicals, and is widely used as an industrial solvent.

It has been reported to have a wide spectrum of pharmacological activity including membrane penetration, anti-inflammatory effects, local analgesia, weak bacteriostasis, diuresis, vasodilatation, dissolution of collagen, and free-radical scavenging.

The principal use of dimethyl sulfoxide is as a vehicle for drugs such as idoxuridine; it aids penetration of the drug into the skin, and so may enhance the drug's effect. It is also used as a 50% aqueous solution for bladder instillation for the symptomatic relief of interstitial cystitis; doses of 50 mL are instilled and allowed to remain for 15 minutes. Treatment is repeated every 2 weeks initially.

Dimethyl sulfoxide has been administered orally, intravenously, or topically for a wide range of indications including cutaneous and musculoskeletal disorders, but evidence of beneficial effects is limited.

Dimethyl sulfoxide is used as a cryoprotectant for various human tissues.

Reviews.

1. Trice JM, Pinals RS. Dimethyl sulfoxide: a review of its use in the rheumatic disorders. Semin Arthritis Rheum 1985; 15: 45–60. PubMed

2. Swanson BN. Medical use of dimethyl sulfoxide (DMSO). Rev Clin Basic Pharm 1985; 5: 1–33. PubMed