スルファサラジン 化学特性,用途語,生産方法
外観
うすい黄色～くすんだ黄色～暗い緑色粉末～結晶
解説
[同義異語]サラゾスルファピリジン
森北出版「化学辞典（第2版）
用途
抗炎症剤です。好中球接着抑
制作用や白血球浸潤抑制作用により抗炎症作
用を示します。
用途
抗炎症剤です。好中球接着抑
制作用や白血球浸潤抑制作用を示します。
効能
抗炎症薬, 抗リウマチ薬
商品名
アザルフィジン (ファイザー); サラゾピリン (ファイザー); サラゾピリン (ファイザー)
説明
Sulfasalazine (brand name Azulfidine in the U.S., Salazopyrin and Sulazine in Europe and Hong Kong) was developed in the 1950s specifically to treat rheumatoid arthritis. It was believed at the time that bacterial infections were the cause of rheumatoid arthritis. Sulfasalazine is a sulfa drug, (a derivative of mesalazine) and is formed by combining sulfa pyridine and salicylate with an azo bond. It may be abbreviated SSZ.
化学的特性
Brownish-Yellow Crystals
使用
Sulfasalazine is an anti-inflammatory (gastrointestinal). Sulfasalazine has been used in granulomatous colitis.
定義
ChEBI: An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position.
適応症
Sulfasalazine is used in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is also indicated for use in rheumatoid arthritis and used in other types of inflammatory arthritis (e.g. psoriatic arthritis) where it has a beneficial effect. It is often well tolerated compared to other DMARDS.
In clinical trials for the treatment of chronic alcoholics, sulfasalazine has been found to reverse the scarring associated with cirrhosis of the liver .
Cells called myofibroblasts, which contribute to scar tissue in a diseased liver, also appear to secrete proteins that prevent the breakdown of the scar tissue. Sulfasalazine appears to retard this secretion.
一般的な説明
Odorless yellow or brownish-yellow to orange powder. Tasteless.
空気と水の反応
Light sensitive and may be sensitive to prolonged exposure to air. Dust can be explosive when suspended in air at specific concentrations. Insoluble in water.
火災危険
Flash point data for Salicylazosulfapyridine are not available; however, Salicylazosulfapyridine is probably combustible.
応用例（製薬）
One of the earliest and most successful sulfonamides to be
developed was sulfapyridine, which fell into disuse because
of unwanted effects such as crystalluria. Later, a number of
salicylazosulfonamides, developed because of their increased
water solubility, showed anti-inflammatory properties; one of
them, sulfasalazine (salicylazosulfapyridine), has come into
general use for ulcerative colitis.
After oral administration, some intact compound is
absorbed from the upper gastrointestinal tract, appearing in
the blood in 1–2 h, but most is cleaved by colonic bacteria
to yield sulfapyridine and 5-aminosalicylic acid (mesalamine,
mesalazine). Controlled trials have confirmed the efficacy of
5-aminosalicylic acid alone in ulcerative colitis, the sulfonamide
component merely acting as a carrier. Thus, in remarkable
extension of the good fortune that attended the discovery
of sulfanilamide as the unexpected active principle of Prontosil, a cleavage product appears to be responsible for
the beneficial effect of sulfasalazine. Since most of the side
effects associated with sulfasalazine are attributable to sulfapyridine,
there seems little reason, other than cost, to use it
in preference to mesalamine.
Sulfasalazine is also of benefit in Crohn’s disease and rheumatoid
arthritis, but the role, if any, of sulfapyridine in the
overall effect is unclear.
作用機序
Sulfasalazine is composed of sulfapyridine and 5-
ASA molecules linked by an azo bond. Sulfapyridine
has no effect on the inflammatory bowel disease, and instillation
of this agent into the colon does not heal
colonic mucosa.
薬理学
Sulfasalazine is a prodrug of which 70% is converted
by colon bacteria to two active metabolites, sulfapyridine
and 5-aminosalicylic acid (mesalamine). Sulfapyridine
has antibacterial activities, and 5-aminosalicylic
acid is antiinflammatory; however, these effects do
not account for the ability of this drug to slow the
processes of rheumatoid arthritis. Recent research suggests
additional activities of sulfasalazine that may be
relevant to these effects: its ability to increase adenosine
levels, its inhibitory effects on IL-1 and TNF-
release, and its inhibition of NF-κB.
薬物動態学
sulfasalazine is poorly absorbed, with approximately 20% of the ingested sulfasalazine
reaching the systemic circulation. The remainder of the ingested dose is metabolized by colonic bacteria into its
components, sulfapyridine and mesalamine (5-ASA). Most of the sulfapyridine metabolized from sulfasalazine
(60–80%) is absorbed in the colon following oral administration, and approximately 25% of the 5-ASA metabolized
from sulfasalazine is absorbed in the colon.
臨床応用
Sulfasalazine (2-hydroxy-5[[4-[(2-pyridinylamino)sulfonyl]phenyl]azo]benzoic acid or 5-[p-(2-pyridylsulfamoyl)phenylazo]salicylic acid) is a brownish yellow, odorlesspowder, slightly soluble in alcohol but practically insolublein water, ether, and benzene.
Sulfasalazine is broken down in the body to m-aminosalicylicacid and sulfapyridine. The drug is excreted throughthe kidneys and is detectable colorimetrically in the urine,producing an orange-yellow color when the urine is alkalineand no color when the urine is acid.
副作用
Sulfsalazine metabolizes to sulfa pyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg / l are associated with side effects. In rare cases, Sulfasalazine can cause severe depression in young males. It can also cause temporary infertility. Immune thrombocytopenia has been reported.
Sulfasalazine inhibits dihydrofolate reductase, and can cause folate deficiency and megaloblastic anemia.
Sulfasalazine can cause hemolytic anemia in people with G6PD deficiency.
予防処置
Sulfasalazine is contraindicated in individuals with hypersensitivityto salicylates, sulfonamides, sulfonylureas,and certain diuretics (furosemide, thiazides, andcarbonic anhydrase inhibitors). Because it can causekernicterus, sulfasalazine is contraindicated in infantsand children under 2 years of age. Sulfasalazine passesinto breast milk and is therefore contraindicated fornursing mothers. Similarly, pregnant women near termshould not use this drug, although it appears to be thesafest of the DMARDs during early pregnancy.Sulfasalazine can precipitate attacks of porphyria andshould not be used by individuals with bowel or urinaryobstruction.
Sulfasalazine can inhibit the absorption of cardiacglycosides and folic acid. It may displace certain drugs,including warfarin, phenytoin, methotrexate, tolbutamide,chlorpropamide, and oral sulfonylureas, fromtheir protein binding sites. Sulfasalazine can diminishthe effectiveness of penicillins and estrogen-containingoral contraceptives.
スルファサラジン 上流と下流の製品情報
原材料
準備製品