リン脂質 化学特性,用途語,生産方法
定義
本品は、複合脂質で、グリセリン(*)の水酸基の一つがリン酸とのエステル、残りの2つの水酸基は、長鎖の飽和又は不飽和脂肪酸とのエステルである。参照表示名称：グリセリン
解説
ホスファチドともいう．複合脂質の一種．リン酸エステルやホスホン酸エステルをもつ脂質の総称．グリセリンと脂肪酸とリン酸よりなるホスファチジン酸，ホスファチジングリセリン，カルジオリピン，さらに窒素化合物を含むホスファチジルコリン(レシチン)，ホスファチジルエタノールアミン，ホスファチジルセリン，1-アルケニルエーテル結合で，グリセリンの1位に結合したプラスマローゲン，脂肪酸を1個しかもっていないリゾホスホリピドなどがある．
"これらのほかに，イノシトールを含むイノシトールホスホリピドや，グリセリンのかわりにスフィンゴシンを有するスフィンゴホスホリピドもある．リン脂質は微生物界，植物界，動物界いずれにも広く分布しており，生物の細胞膜やミトコンドリア膜，神経組織などの膜構成に関与し，タンパク質とともに生体膜を構成する重要成分である．生体の各種の代謝機構への関与が知られている．リン脂質は，一般にカラムクロマトグラフィーなどを用いることにより純粋に取り出されるものが多く，生体物を構成する膜の各種機能の研究に広く用いられている．生合成経路についても解明されつつある．また，リン脂質には各エステル結合を加水分解するホスホリパーゼA(脂肪酸とグリセリンのエステル結合を1個のみ加水分解する．1位を分解するものをホスホリパーゼ A1，2位を分解するものをホスホリパーゼ A2 とよぶ)，ホスホリパーゼB(脂肪酸とグリセリンのエステル結合を2個とも加水分解する)，ホスホリパーゼC(リン酸とグリセリドとのエステル結合を加水分解する)，ホスホリパーゼD(リン酸と窒素を含む化合物，そのほかのエステル結合を加水分解する)，リゾホスホリパーゼ(リゾホスホリピドの脂肪酸エステル結合を加水分解する)が知られている．スフィンゴシンを含むリン脂質についても同様であり，作用するリン脂質に応じて，レシチナーゼ，スフィンゴミエリナーゼなどとよばれることもある．[別用語参照]グリセロリン脂質，電子伝達系(光合成)中の図
森北出版「化学辞典（第2版）
化粧品の成分用途
皮膚コンディショニング剤
説明
Lipid substances, containing a phosphate
group and one or more fatty acid residues, which are essential
components of cell membranes. Hydrolysis yields fatty acids,
phosphoric acid, and a base. They are amphoteric with a polar
and a nonpolar region. Lecithins, cephalins, and related com_x0002_pounds are based on a glycerol backbone, with a phosphate
group. In lecithin (phosphatidylcholine), R0 and Rv are fatty
acid residues, usually one saturated and the other unsaturated.
In the cephalins, ethanolamine (H2NCH2CH2OH) or serine
replaces choline. They are used in the food industry as surfactants, emulsifiers, and antioxidants. In sphingomyelins, R is a
fatty acid residue, usually tetracosanoic acid. They occur abundantly in brain tissues in association with cerebrosides, which
are similar. On hydrolysis they split into choline, sphingosine,
phosphoric acid, and a fatty acid.
化学的特性
Phospholipids occur as white powders. They are sometimes
supplied as clear, nearly colorless chloroform or methylene chloride
solutions. Phosphatidylglycerols, phosphatidic acids, and phosphatidylserines
are available as sodium or ammonium salts. Phospholipids
can be purified from natural sources, such as eggs or
soybeans, or can be chemically synthesized. Lecithins are partially
purified mixtures of naturally occurring phospholipids.
使用
phospholipids (phosphatides) is used topically as a moisturizer and emollient because of their inherent compatibility with skin lipids. In general, natural phospholipids have a short-lived effect when topically applied, and are a primary material in the manufacture of liposomes. Phospholipids are complex fat substances that, together with protein, form the membrane of all living cells.
調製方法
Phospholipids can be manufactured from naturally occurring
materials, especially soybean and egg. The manufacturing process
typically involves extraction, fractionation, and purification. They
can also be synthesized chemically by reacting glycerol phosphocholine
(PC), glycerol phosphoglycerol (PG), glycerol phosphoserine
(PS), glycerol phosphoethanolamine (PE), or glycerol phosphoinositol
(PI) with purified fatty acids.
一般的な説明
Phospholipids are a class of lipids, which helps to maintain the structural definition of cells. These lipids are key components of cell and organelle membranes, blood lipoproteins and lung surfactants. Phospholipids plays an important role in signal transduction. It is also involved in the regulation of various cellular process including cell growth.
农业用途
Phospholipids are esters of glycerol and are similar in
structure to fats. However, unlike fats, they contain only
two fatty acids. The third ester linkage involves a
phosphate group which gives phospholipids two distinct
parts: a long non-polar tail and a polar substituted
phosphate head. Because of this dual nature,
phospholipids tend to form bi-layers in an aqueous
solution, with the tails in the interior and the polar heads
interfacing with the polar water molecules.
Phospholipids form a significant portion of cell
membranes and perform two important functions. They
protect the cell from extra cellular fluids, and allow
nutrients and other chemicals to enter the cell, while
letting the waste products leave the cell. Lecithin is an
example of phospholipids.
応用例（製薬）
Phospholipids are amphiphilic molecules and are the major
component of most cell membranes.They are able to selfassociate
and form a variety of structures, including micelles and
liposomes.
Numerous pharmaceutical formulations use phospholipids to
form various types of liposomes, including unilamellar (one bilayer
membrane surrounding an aqueous chamber), multilamellar (two chamber), and multivesicular (numerous aqueous chambers joined
in a honeycomb-like arrangement) liposomes.Modified phospholipids
have been used to enhance the properties of the resulting
liposomes. The covalent attachment of polyethylene glycol (PEG) to
the phospholipid, or PEGylation, provides steric hindrance to the
surface of the liposomes, resulting in decreased uptake by the
reticuloendothelial system (RES), also known as the mononuclear
phagocyte system, and a prolonged circulation half-life following
intravenous administration; the so-called ‘stealth liposomes.’
Conjugation with antibodies produces immunoliposomes, which
are able to target specific cell types and deliver a payload of
encapsulated drug.
Phospholipids can be anionic, cationic, or neutral in charge.
Because of their amphiphilic nature, phospholipids will associate at
hydrophobic/hydrophilic interfaces. The charged lipids can be used
to provide electrostatic repulsion and physical stability to
suspended particles. Thus, they have been used to physically
stabilize emulsions and suspensions.Phospholipids have also
been used in formulations administered as lung surfactants, in
intravenous fat emulsions, and in oral solutions (e.g. Rapamune).
安全性
Generally, phospholipids have little or no acute toxicity (i.e. they are
well tolerated even when administered at doses in the g/kg
range).The clearance of most phospholipids occurs by wellknown
metabolic pathways.
Liposomes containing stearylamines (cationic liposomes) have
been found to induce cytotoxicity through apoptosis in the
macrophage-like cell line RA W2647 and inhibit the growth of
cells in vitro.In nine cancer-derived cell lines and one normal
cultured human cell line, stearylamine- and cardiolipin-containing
liposomes were toxic () at 200 μM liposomal lipid concentration
or less, whereas PG- and PS-containing liposomes were toxic in
the range 130–3000μM. Positively charged lipids such as
stearylamine can increase the toxicity of liposomes.These
studies reported an (IV) of 1.1 g/kg and 7.5 g/kg with and
without stearylamine, respectively.
The safety of phospholipids delivered by the intravenous route is
complicated by their tendency to form particles that are recognized
by macrophages of the RES. Uptake by the RES is dependent on
particle size and composition.
貯蔵
Phospholipids are stable in the solid state if protected from oxygen,
heat, and light. Chloroform or dichloromethane solutions are also
stable. Both the solid-state and solution forms should be stored at
-20°C. Liposomal phospholipids are known to degrade via
oxidation and hydrolysis. To minimize oxidation, liposomes can
be prepared under oxygen-free environments and antioxidants,
such as butylated hydroxytoluene (BHT), can be added. To
minimize hydrolysis, water can be removed from liposomes by
lyophilization. In cases where liposomes are unstable to lyophilization,
long-term storage at 2–8°C is recommended. The ester
hydrolysis of phospholipids in liposomes typically follows a Vshaped
curve, with the minimum at around pH 6.5.
規制状況(Regulatory Status)
Included in the FDA Inactive Ingredient Database (oral, otic, buccal,
vaginal, topical, epidural, intravenous, intramuscular, and inhalation
aerosol). A number of phospholipids such as DPPG and DOPC
are present in approved products in Europe and the USA.
リン脂質 上流と下流の製品情報
原材料
準備製品