ネオマイシン 化学特性,用途語,生産方法
解説
フラジオマイシンともいう．ネオマイシンA：C12H26N4O6(322.36)，BおよびC：C23H46N6O13(614.65)の3種類が知られている．アミノ配糖体抗生物質．放線菌Streptomyces fradiae，S.albogriseolusなどの培養液から，イオン交換樹脂または活性炭で吸着して分離される．塩基性の無色の結晶または粉末状物質．ネオマイシンBの分解生成物であるAの分解点250～256 ℃．
"112.8°(水)．B，Cは非結晶体であるが，ライネッケ塩などとして結晶化する．
"A：＋123°(水)，B：＋83°(0.2 mol L－1 塩酸)，C：＋121°(0.1 mol L－1 硫酸)．紫外部吸収極大は末端吸収以外ない．カナマイシン類と同様に，主としてグラム陽性菌に有効である．LD50 A：1250 mg/kg(マウス，皮下)，B：220 mg/kg(マウス，皮下)，C：290 mg/kg(マウス，皮下)．
"
森北出版「化学辞典（第2版）
用途
ネオマイシン（neomycin）は1948年にウクライナ出身のセルマン?ワクスマンにより発見されたアミノグリコシド系抗生物質である。
ネオマイシンの作用機序はカナマイシンのそれと類似し、30Sリボソームに結合することにより細菌のタンパク質合成を阻害する。
比較的広範な抗菌スペクトルを有し、グラム陰性菌、グラム陽性菌ともに強く阻害する。
分子生物学の研究においてネオマイシン耐性遺伝子は、選択マーカーとして形質細胞の分離に利用される。
効能
抗生物質, タンパク質合成阻害薬
説明
Neomycin is an antibiotic from the aminoglycoside
group, and has two isomers - neomycin Band
neomycin C. Occupational contact dermatitis mainly
occurs in workers at animal-feed mills, in veterinaries
and in health workers.
使用
Neomycin, like streptomycin, has a broad spectrum of antibacterial activity. It is effective
with respect to the majority of Gram-negative and a few Gram-positive bacteria; staphylococci, pneumococci, gonococci, meningococci, and stimulants of dysentery. It is not very
active with respect to streptococci. The antibiotic effect of neomycin with respect to many
types of bacteria is higher than that of streptomycin. At the same time, microorganisms
sensitive to neomycin become resistant to a lesser degree than streptomycin.
It is used for various gastrointestinal diseases caused by microorganisms sensitive to it,
including enteritis, which is caused by microbes that are resistant to antibiotics. However,
because of its high oto- and nephrotoxicity, its local use is preferred for infected skin diseases, infected wounds, conjunctivitis, keratitis, and others. Synonyms of this drug are
framycetin, soframycin, tautomycin, and others.
定義
An antibiotic complex obtained
from Streptomyces fradiae; it is soluble in water
and methanol but insoluble in most organic solvents. It consists of three component substances,
all of which function as antiinfective agents; some
derivatives have fungicidal properties. The three
types are A (also called neamine): C12H26N4O6; B:
C
23H46N6O13 (also available as hydrochloride and
sulfate); and C: C23H46O13
抗菌性
Among other organisms susceptible
in vitro (MIC 4–8 mg/L) are Pasteurella, Vibrio, Borrelia and
Leptospira spp. It is active against M. tuberculosis, including
streptomycin-resistant strains. Synergy has been reported
with polymyxin B. The bactericidal effect is enhanced at alkaline
pH.
獲得抵抗性
Resistance is acquired in a stepwise fashion and staphylococci
may become resistant as a result of prolonged topical use. The
use of neomycin–bacitracin–polymyxin mixtures may contribute
to this, as many strains resistant to neomycin are also
resistant to bacitracin. Resistant enterobacteria may appear
in the feces of patients treated orally and in those treated for
prolonged periods; most have been found to possess multiple
transferable antibiotic resistance. Cross-resistance with
kanamycin is often due to the synthesis of APH(3′), although
AAC(6′) some forms of AAC(3) and ANT(4′) also modify
both neomycin and kanamycin. Resistant strains of Staph.
aureus are usually more resistant to kanamycin than to neomycin.
The rare enzyme AAC(1) confers resistance to neomycin
and paromomycin, but not to other aminoglycosides.
接触アレルゲン
Neomycin is an antibiotic complex of the aminoglycosides
group, extracted from Streptomyces fradiae. It is composed
of neomycin A (neamin) and an isomer neobiosamin, either neomycin B (framycetin or Soframycin?) or neomycin C.
Its use has been progressively forbidden in cosmetics and
as an additive for animal feed. Occupational contact dermatitis
occurs in workers at animal feed mills, in veterinaries,
or in health workers. Nonoccupational dermatitis mainly
concerns patients with chronic dermatitis, leg ulcers, or
chronic otitis. Cross-sensitivity is usual with other aminoglycosides
(amikacin, arbekacin, butirosin, dibekacin, gentamicin,
isepamicin, kanamycin, paromomycin,
ribostamycin, sisomycin, tobramycin), is rare with netilmicin
and streptomycin, but nonexistent with spectinomycin.
作用機序
Neomycin has a wide spectrum of antibacterial action. It is effective against both a number
of Gram-positive as well as Gram-negative microorganisms. However, it is able to bind
with cholesterol and bile salts. In combination with other bile salt-reducing drugs or nicotinic
acid, neomycin is able to block cholesterol and bile salt absorption, which significantly
increases the level of cholesterol in the plasma.
薬物動態学
C
max 0.5 g intramuscular: 20 mg/L after 1 h
Plasma half-life: 2–3 h
Volume of distribution: 0.25–0.35 L/kg
Plasma protein binding: Low
Very little is absorbed after oral administration and more
than 95% is eliminated unchanged in the feces. Peak plasma
concentrations of less than 4 mg/L have been found after an
oral dose of 3 g. Distribution and excretion resemble that of
streptomycin, but the toxicity of neomycin precludes systemic
administration except in the most extreme cases.
臨床応用
Superficial infections with staphylococci and Gram-negative bacilli
(topical; alone or in combination with bacitracin, chlorhexidine or
polymyxin)
Treatment of staphylococcal nasal carriers (topical, in combination with
chlorhexidine or bacitracin)
Eye infections (topical; alone or in combination)
Otitis externa (alone or with a corticosteroid)
Gut decontamination before abdominal surgery (oral)
Prophylaxis after urinary tract instrumentation (instillation)
Use is discouraged because of the possibility of promoting the
appearance of aminoglycoside-resistant strains, and because
of the risk of absorption with the consequent danger of systemic
toxicity or neuromuscular blockade.
副作用
Neomycin is the most likely of all the aminoglycosides to
damage the kidneys and the auditory branch of the eighth
nerve. This has almost entirely restricted it to
topical and oral use.
Irreversible deafness may develop even if the drug is
stopped at the first sign of damage. Loss of hearing may occur
as a result of topical applications to wounds or other denuded
areas, particularly if renal excretion is impaired. Instillation
of ear drops containing neomycin can result in deafness. This
generally develops in the second week of treatment and is usually
reversible.
Rashes have been described in 6–8% of patients treated
topically and these patients may be rendered allergic to
other aminoglycosides. Nausea and protracted diarrhea may
follow oral administration. Sufficient drug may be absorbed
from the gut on prolonged oral administration to produce
deafness but not renal damage. Intestinal malabsorption and
superinfection have been seen in patients receiving 4–9 g
per day and may develop in patients receiving as little as 3 g
of the drug per day. Precipitation of bile salts by the drug
may impair the hydrolysis of long-chain triglycerides. Large
doses instilled into the peritoneal cavity at operation may be absorbed, with resultant systemic toxicity, and patients concurrently
exposed to anesthetics and muscle relaxants are
liable to suffer neuromuscular blockade, which is reversible
by neostigmine.
安全性プロファイル
Poison by
intraperitoneal, intravenous, and
subcutaneous routes. Moderately toxic by
ingestion. Human systemic effects: changes
in hearing acuity, liver tubule changes, and
decreased urine volume or anuria. Mutation
data reported. When heated to
decomposition it emits acrid smoke and
irritating fumes.
ネオマイシン 上流と下流の製品情報
原材料
準備製品