メントール 化学特性,用途語,生産方法
定義
本品は、次の化学式で表されるテルペンアルコールである。
解説
化学式 C10H20O 。モノテルペンアルコールの一種。多くの異性体があり,L体,DL体は薬局方に収載されている。 (1) L体 ハッカの葉や茎を水蒸気蒸留して得られる精油。はっか油の主成分で,はっか脳ともいわれる。さわやかで特異な香りがする無色針状晶。融点 43℃。エチルアルコール,エーテル,クロロホルムに易溶,水にやや溶けにくい。感覚神経末梢を刺激して冷感を起し,次いで感覚を麻痺させる作用をするため,皮膚 瘙痒,神経痛などに1~2%エチルアルコール溶液として外用される。また内服すると,胃粘膜を軽く刺激し,あるいはその芳香,清涼味により反射的に消化管の運動,分泌,吸収などの機能を亢進させる。やや多い量では,胃粘膜を鈍麻させて鎮痛,制吐作用を示す。異常発酵,胃痛,嘔吐などの際には内服される。医薬品以外に,食品,飲料,たばこ,香料品,嗜好品などにも広く使用されている。 (2) DL体 チモールの還元によって得られる。L体に比し,結晶は一般に小さい。融点 35~36℃。清涼剤,反射刺激剤,鎮痛,鎮痒剤に用いられる。
ブリタニカ国際大百科事典 小項目事典 ブリタニカ
化粧品の成分用途
変性剤、口腔衛生剤、皮膚コンディショニング剤、外用鎮痛剤、香料、香味剤
効能
外用鎮痒薬
化学的特性
Racemic menthol is a mixture of equal parts of the (1R,2S,5R)- and
(1S,2R,5S)-isomers of menthol. It is a free-flowing or agglomerated
crystalline powder, or colorless, prismatic, or acicular shiny crystals,
or hexagonal or fused masses with a strong characteristic odor and
taste. The crystalline form may change with time owing to
sublimation within a closed vessel. The USP 32 specifies that
menthol may be either naturally occurring l-menthol or syntheti-cally prepared racemic or dl-menthol. However, the JP XV and
PhEur 6.0, along with other pharmacopeias, include two separate
monographs for racemic and l-menthol.
使用
Labelled Menthol. Used for oral gel patch or film containing herb extracts or Chinese medicine, fruit extract, spearmint, and menthol for smoking cessation.
定義
ChEBI: Any secondary alcohol that is one of the eight possible diastereoisomers of 5-methyl-2-(propan-2-yl)cyclohexan-1-ol.
調製方法
Menthol occurs widely in nature as l-menthol and is the principal
component of peppermint and cornmint oils obtained from the
Mentha piperita and Mentha arvensis species. Commercially, lmenthol
is mainly produced by extraction from these volatile oils. It
may also be prepared by partial or total synthetic methods.
Racemic menthol is prepared synthetically via a number of
routes, e.g. by hydrogenation of thymol.
製法
(1)d-シトロネラールからの製法 シトロネラ油の分留で得られるd-シトロネラールにルイス酸を加えて加熱すると環化してイソプレゴールとなる。これに溶剤を加えて深冷分離すると純粋なl-イソプレゴールの結晶が収率よく得られる。これをニッケル触媒を用いて高圧水添すると、純粋なl-メントールが収率よく得られる。
(2)チモールからの製法 チモールの接触水添によりd、l-メントールとし、異性体分離、光学分割を行い、純粋なl-メントールとする。
(3)不斉合成法 ミルセンにリチウムとジエチルアミンを反応させると、ジエチルゲラニルアミンができる。これを(S)-BINAP-Ru錯体触媒を用いて不斉異性化反応を行うとシトロネラールエナミンを生じ、これを加水分解して純粋のd-シトロネラールとする。これを臭化亜鉛で閉環し、l-イソプレゴールに導き、水素添加によってl-メントールを製造する。l-メントールは医薬品(貼(は)り薬、軟膏(なんこう)、エアゾール)、タバコ、歯磨剤、育毛剤、チューインガム、キャンディー、アイスクリーム、飲料、化粧品などに用いられる。
応用例(製薬)
Menthol is widely used in pharmaceuticals, confectionery, and
toiletry products as a flavoring agent or odor enhancer. In addition
to its characteristic peppermint flavor, l-menthol, which occurs
naturally, also exerts a cooling or refreshing sensation that is
exploited in many topical preparations. Unlike mannitol, which
exerts a similar effect due to a negative heat of solution, l-menthol
interacts directly with the body’s coldness receptors. d-Menthol has
no cooling effect, while racemic menthol exerts an effect approximately
half that of l-menthol.
When used to flavor tablets, menthol is generally dissolved in
ethanol (95%) and sprayed onto tablet granules and not used as a
solid excipient.
Menthol has been investigated as a skin-penetration enhancer
and is also used in perfumery, tobacco products, chewing gum and
as a therapeutic agent. When applied to the skin, menthol dilates the
blood vessels, causing a sensation of coldness followed by an
analgesic effect. It relieves itching and is used in creams, lotions, and
ointments. When administered orally in small doses menthol has a
carminative action.
安全性
Almost all toxicological data for menthol relate to its use as a
therapeutic agent rather than as an excipient. Inhalation or
ingestion of large quantities can result in serious adverse reactions
such as ataxia and CNS depression,hypersensitivity reactions,
severe abdominal pain, nausea, vomiting, vertigo, drowsiness, and
coma.Although menthol is essentially nonirritant there have been
some reports of hypersensitivity following topical application.
In a Polish study approximately 1% of individuals were determined
as being sensitive to menthol.There have been reports of apnea
and instant collapse in infants after the local application of menthol
to their nostrils.
The WHO has set an acceptable daily intake of menthol at up to
0.4 mg/kg body-weight.
LD
50 (rat, IM): 10.0 g/kg
LD
50 (rat, oral): 3.18 g/kg
貯蔵
A formulation containing menthol 1% w/w in aqueous cream has
been reported to be stable for up to 18 months when stored at room
temperature.
Menthol should be stored in a well-closed container at a
temperature not exceeding 25°C, since it sublimes readily.
不和合性
Incompatible with: butylchloral hydrate; camphor; chloral hydrate;
chromium trioxide; b-naphthol; phenol; potassium permanganate;
pyrogallol; resorcinol; and thymol.
規制状況(Regulatory Status)
Included in the FDA Inactive Ingredients Database (dental
preparations, inhalations, oral aerosols, capsules, solutions, suspensions,
syrups, and tablets; also topical preparations). Included in
nonparenteral medicines licensed in the UK. Accepted for use in
foods and confectionery as a flavoring agent of natural origin.
Included in the Canadian List of Acceptable Non-medicinal
Ingredients.
メントール 上流と下流の製品情報
原材料
準備製品