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JPH0515574A - Production of aseptic phospholipid and/or phospholipid aqueous dispersion by radiation seterilization - Google Patents

Production of aseptic phospholipid and/or phospholipid aqueous dispersion by radiation seterilization

Info

Publication number
JPH0515574A
JPH0515574A JP3170136A JP17013691A JPH0515574A JP H0515574 A JPH0515574 A JP H0515574A JP 3170136 A JP3170136 A JP 3170136A JP 17013691 A JP17013691 A JP 17013691A JP H0515574 A JPH0515574 A JP H0515574A
Authority
JP
Japan
Prior art keywords
phospholipid
aqueous dispersion
aseptic
aqueous
ionizing radiation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
JP3170136A
Other languages
Japanese (ja)
Other versions
JP3320430B2 (en
Inventor
Tamikazu Kume
民和 久米
Isao Ishigaki
功 石垣
Yoshiaki Aikawa
義明 相川
Akio Nozawa
昭男 野沢
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NIHON SURFACTANT KOGYO KK
NIPPON SAAFUAKUTANTO KOGYO KK
Japan Atomic Energy Agency
Original Assignee
NIHON SURFACTANT KOGYO KK
NIPPON SAAFUAKUTANTO KOGYO KK
Japan Atomic Energy Research Institute
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by NIHON SURFACTANT KOGYO KK, NIPPON SAAFUAKUTANTO KOGYO KK, Japan Atomic Energy Research Institute filed Critical NIHON SURFACTANT KOGYO KK
Priority to JP17013691A priority Critical patent/JP3320430B2/en
Publication of JPH0515574A publication Critical patent/JPH0515574A/en
Application granted granted Critical
Publication of JP3320430B2 publication Critical patent/JP3320430B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Apparatus For Disinfection Or Sterilisation (AREA)

Abstract

PURPOSE:To obtain aseptic phospholipid and or a phospholipid aqueous dispersion generating no deterioration by irradiating phospholipid and or a phospholipid aqueous dispersion with ionizing radiation to easily sterilize the same. CONSTITUTION:Phospholipid and/or a phospholipid aqueous dispersion unstable against heat or ultraviolet rays are sterilized by the irradiation with ionizing radiation to obtain aseptic phospholipid and/or an aseptic phospholipid aqueous dispersion generating no deterioration. As phospholipid, soybean licithin, yolk lecithin, hydrogenated soybean lecithin, hydrogenated yolk lecithin and one of phosphatidylcholine, phosphatidylserine and sphingomyeline or a mixture of two or more kinds of them are designated. As the dispersing medium of the aqueous dispersion, water or a liposome is used and, as ionizing radiation, gamma rays, electron beam or X-rays are used in an irradiation dose of 1-50kGy.

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【産業上の利用分野】本発明は、リン脂質及び/又はリ
ン脂質水性分散液に放射線を照射することにより滅菌
し、無菌のリン脂質及び/又はリン脂質の水性分散液の
製造法に関するものである。さらに詳しくは、望ましく
ない微生物が存在しないことを保証した化粧品、医薬部
外品及び医薬品の分野において利用されるリン脂質及び
/又はりん脂質の水性分散液を提供するものである。
TECHNICAL FIELD The present invention relates to a method for producing a sterile phospholipid and / or phospholipid aqueous dispersion by sterilizing the phospholipid and / or phospholipid aqueous dispersion by irradiation. is there. More specifically, the present invention provides an aqueous dispersion of phospholipids and / or phospholipids used in the fields of cosmetics, quasi drugs and pharmaceuticals, which is guaranteed to be free of undesirable microorganisms.

【0002】[0002]

【従来の技術】化粧品に使用される原料は、油脂、エス
テル、界面活性剤、粉体、色素、天然動植物抽出物、天
然ガム質、水溶性高分子、多価アルコール、水等多岐に
わたっており、微生物による一次汚染の原因となってい
る。特に、天然抽出物や水溶液又は水分散液については
微生物汚染の可能性が高い。一般に、化粧品、医薬部外
品及び医薬品分野で使用されている素材の微生物除去対
策としては、微生物による汚染や品質の劣化を防止する
目的で防腐・殺菌剤を添加する方法、高圧で加熱滅菌す
る方法、エチレンオキサイドガスにより滅菌する方法、
滅菌フィルターによりろ過して滅菌する方法、紫外線を
照射して滅菌する方法、無菌環境下で製造する方法等が
ある。
2. Description of the Related Art Raw materials used for cosmetics include oils and fats, esters, surfactants, powders, pigments, natural animal and plant extracts, natural gums, water-soluble polymers, polyhydric alcohols, water, etc. Causes primary contamination by microorganisms. Especially, natural extracts, aqueous solutions or aqueous dispersions are highly likely to be contaminated with microorganisms. In general, as a measure for removing microorganisms from materials used in the fields of cosmetics, quasi drugs, and pharmaceuticals, a method of adding an antiseptic / bactericidal agent for the purpose of preventing contamination by microorganisms and deterioration of quality, and heat sterilization under high pressure Method, a method of sterilizing with ethylene oxide gas,
There are a method of sterilizing by filtering with a sterilizing filter, a method of sterilizing by irradiating with ultraviolet rays, a method of manufacturing in a sterile environment, and the like.

【0003】[0003]

【発明が解決しようとする課題】防腐・殺菌剤としては
多くのものが開発されているが、多用な微生物に対して
広く効力がある、少量で有効である、製品の機能や外観
を損なわない、生体に対して無毒、無刺激であること等
の条件を全て満足するものがなく、問題点が多い。高温
で加熱滅菌する場合には、熱により原料の品質が劣化し
たり、有害分解物が生成する等の問題点が指摘される。
特に、酵素、リン脂質等の天然動植物抽出物の中には熱
に不安定なものが多く、加熱滅菌することは実際上出来
ない。エチレンオキサイドガスによる滅菌は熱がかから
ないので耐熱性のない原料の滅菌には有効であるが、吸
着あるいは残留するガスの毒性をはじめ、原料とエチレ
ンオキサイドとの化学反応により、好ましくない不純物
が生成する可能性がある等の問題点がある。フィルター
によるろ過滅菌は水や低粘性の液体には有効であるが、
粉体や高粘性の液体原料の滅菌には利用できない。又、
紫外線滅菌やろ過滅菌は、その効果を一定に維持するた
めに、装着の保守管理に多大のコストがかかるという問
題点を指摘できる。なお、化粧品原料として使用される
原材料の中には、エマルションやリポソームのように不
安定なコロイド分散状態のものも多く、上記のような滅
菌操作によりコロイド状態が変化したり破壊されてしま
う場合が多い。さらに、原料そのもの以外に、充填・包
装時における微生物汚染や容器による微生物汚染等への
対策も講じる必要がある。
Although many antiseptic / bactericidal agents have been developed, they are widely effective against various microorganisms, effective in a small amount, and do not impair the function or appearance of the product. However, none of them satisfy all the conditions such as being non-toxic and non-irritating to the living body, and there are many problems. It is pointed out that when heat sterilization is performed at a high temperature, the quality of the raw material is deteriorated by heat and a harmful decomposition product is generated.
In particular, many natural animal and plant extracts such as enzymes and phospholipids are unstable to heat and cannot be sterilized by heating. Sterilization with ethylene oxide gas does not generate heat, so it is effective for sterilizing raw materials that do not have heat resistance, but undesired impurities are generated due to the toxicity of the adsorbed or residual gas and the chemical reaction between the raw material and ethylene oxide. There is a problem such as possibility. Filter sterilization with a filter is effective for water and low-viscosity liquids,
It cannot be used to sterilize powders or highly viscous liquid raw materials. or,
It can be pointed out that ultraviolet sterilization and filter sterilization require a great deal of cost to maintain and manage the attachment in order to keep the effect constant. Many of the raw materials used as cosmetic raw materials are in an unstable colloidal dispersion state such as emulsions and liposomes, and the colloidal state may be changed or destroyed by the above sterilization operation. Many. Furthermore, in addition to the raw materials themselves, it is necessary to take measures against microbial contamination during filling and packaging and microbial contamination in containers.

【0004】本発明は、以上のような従来の技術の問題
点を解決した、熱や紫外線などに不安定な原材料にたい
する滅菌方法を提案し、微生物汚染のないリン脂質及び
/又はリン脂質分散液の提供を目的とする。
The present invention proposes a sterilization method for raw materials unstable to heat and ultraviolet rays, which solves the problems of the conventional techniques as described above, and provides a phospholipid and / or phospholipid dispersion liquid free from microbial contamination. For the purpose of providing.

【0005】[0005]

【課題を解決するための手段】本発明者らは、上記の問
題点を考慮して、熱や光を加えることなく、品質劣化が
少なく、2次汚染の可能性がなく、汎用性の高いリン脂
質及び/又はリン脂質の水性分散液の滅菌方法を見い出
すべく鋭意検討を重ねた結果、リン脂質及び/又はリン
脂質の水性分散液に電離放射線を照射することにより、
リン脂質及び/又はリン脂質の水性分散液の品質を全く
変化させることなく、効果的に滅菌処理することを見い
出し本発明を完成するにいたった。
In view of the above-mentioned problems, the present inventors have high general versatility without adding heat or light, with little quality deterioration, and without the possibility of secondary contamination. As a result of extensive studies to find a sterilization method for phospholipids and / or aqueous dispersions of phospholipids, by irradiating the phospholipids and / or aqueous dispersions of phospholipids with ionizing radiation,
The present invention has been completed by finding effective sterilization treatment without changing the quality of the phospholipid and / or the aqueous dispersion of the phospholipid at all.

【0006】リン脂質及びリン脂質の水分散液は熱や酸
化に対して不安定なものが多く、リン、窒素等の微生物
の栄養源になる元素で構成されているため汚染された微
生物が繁殖しやすい。また、天然物であり皮膚に対する
安全性が高いばかりでなく、皮膚をすこやかな状態に保
つ作用に優れているため、合成の滅菌・防腐剤の高濃度
使用による滅菌対策は好ましくない。本発明は、これら
リン脂質及びその水性分散液を、その品質や機能を損な
うことなく効果的に滅菌する方法を提供するものであ
る。
Many phospholipids and aqueous dispersions of phospholipids are unstable to heat and oxidation, and are composed of elements such as phosphorus and nitrogen that are nutrient sources for microorganisms, so that contaminated microorganisms propagate. It's easy to do. In addition, since it is a natural product and not only highly safe to the skin, but also excellent in the action of keeping the skin in a healthy state, sterilization countermeasures by using a high concentration of a synthetic sterilization / preservative are not preferable. The present invention provides a method for effectively sterilizing these phospholipids and their aqueous dispersions without impairing their quality or function.

【0007】以下、本発明の具体的展開態様について述
べる。
Hereinafter, a specific mode of development of the present invention will be described.

【0008】○リン脂質が、大豆レシチン、卵黄レシチ
ン、水素添加大豆レシチン、水素添加卵黄レシチン、ホ
スファチジルコリン、ホスファチジルエタノールアミ
ン、ホスファチジルイノシトール、ホスファチジルセリ
ン及びスフィンゴミエリンの1種又は2種以上の混合物
であること。
The phospholipid is one or a mixture of two or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and sphingomyelin. .

【0009】○水性分散液の分散媒が水であること。The dispersion medium of the aqueous dispersion is water.

【0010】○水性分散液がリポソームの水分散液であ
ること。
The aqueous dispersion is an aqueous dispersion of liposomes.

【0011】○ここでの電離放射線とはガンマ線、電子
線、エックス線であること。
The ionizing radiation here means gamma rays, electron rays, and X-rays.

【0012】○照射線量は1〜50kGyであること。The irradiation dose should be 1 to 50 kGy.

【0013】さらに詳細に本発明を説明する。The present invention will be described in more detail.

【0014】本発明に使用するリン脂質とは、天然の大
豆や卵黄から抽出した大豆レシチン、卵黄レシチン及び
/又はこれらを水素添加した水素添加大豆レシチン、水
素添加卵黄レシチン及び/又はホスファチジルコリン、
ホスファチジルエタノールアミン、ホスファチジルイノ
シトール、ホスファチジルセリン、スフィンゴミエリン
をさす。具体的にはリン脂質単独でも、あるいは2種以
上を混合して使用してもよい。
The phospholipid used in the present invention means soybean lecithin extracted from natural soybean or egg yolk, egg yolk lecithin and / or hydrogenated soybean lecithin hydrogenated from these, hydrogenated egg yolk lecithin and / or phosphatidylcholine,
Refers to phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingomyelin. Specifically, the phospholipids may be used alone or in combination of two or more.

【0015】本発明で使用するリン脂質水性分散液と
は、上記リン脂質の1種又は2種以上の混合物を水に分
散させたものをさす。さらに具体的には、上記リン脂質
の1種又は2種以上の混合物を0.1−20.0重量
%、好ましくは0.1−10.0重量%、さらに好まし
くは0.5−5.0重量%の濃度となるように、ホモミ
キサー、超音波ホモジナイザー等により水に分散懸濁さ
せたものをさす。また、リン脂質2分子膜からなる閉鎖
小胞体であるリポソームの水分散液をさす。
The phospholipid aqueous dispersion used in the present invention refers to a dispersion of one or more of the above phospholipids in water. More specifically, one or a mixture of two or more of the above phospholipids is 0.1-20.0% by weight, preferably 0.1-10.0% by weight, more preferably 0.5-5. The dispersion is suspended in water with a homomixer, an ultrasonic homogenizer or the like so that the concentration becomes 0% by weight. It also refers to an aqueous dispersion of liposomes, which are closed vesicles composed of a phospholipid bilayer.

【0016】さらに、リン脂質水分散液中には通常化粧
品や医薬品に使用される界面活性剤、油分、多価アルコ
ール、水溶性高分子、無機及び有機粉体、キレート剤、
酸化防止剤、皮膚に対する有効成分等が添加してあって
も差し支えない。
Furthermore, in the aqueous dispersion of phospholipids, surfactants, oils, polyhydric alcohols, water-soluble polymers, inorganic and organic powders, chelating agents, which are commonly used in cosmetics and pharmaceuticals,
An antioxidant, an active ingredient for skin, etc. may be added.

【0017】滅菌に必要な放射線量は、原材料の汚染の
程度によって異なるが、50kGyでもリン脂質及び水
性分散液の品質に変化は認められないことから1〜50
kGyが適当である。また、通常の製造環境においては
汚染菌数は少なく、このような場合には1〜5kGy程
度の照射で十分である。
The radiation dose required for sterilization varies depending on the degree of contamination of the raw materials, but the quality of the phospholipid and the aqueous dispersion does not change even at 50 kGy, and therefore 1 to 50.
kGy is suitable. Further, in a normal manufacturing environment, the number of contaminating bacteria is small, and in such a case, irradiation of about 1 to 5 kGy is sufficient.

【0018】[0018]

【実施例】次に実施例に従って本発明をさらに詳細に説
明するが、本発明の範囲はこれら実施例に限定されるも
のではない。また、特に限定しない限り、実施例中の
「%」は「重量%」を表す。
The present invention will now be described in more detail with reference to examples, but the scope of the present invention is not limited to these examples. In addition, "%" in the examples represents "% by weight" unless otherwise specified.

【0019】実施例1−実施例5 水素添加大豆レシチンに線量の異なるガンマ線を照射し
たときの菌数と過酸化物価(POV)及び外観変化を第
1表に示した。本実験で用いた試料は大腸菌群は陰性で
あったが、カビ・酵母及び一般細菌が検出された。1k
Gy照射で一般細菌、カビ・酵母いずれも検出限界以下
となり、十分な殺菌効果が得られた。また、50kGy
までの線量では、リン脂質の品質にはほとんど変化が認
められなかった。脂質は一般に放射線の照射により酸化
され易いが、顕著な酸化変化は認められなかった。
Examples 1 to 5 Table 1 shows the number of bacteria, peroxide value (POV) and appearance change when hydrogenated soybean lecithin was irradiated with gamma rays having different doses. The samples used in this experiment were negative for coliform bacteria, but mold / yeast and general bacteria were detected. 1k
With Gy irradiation, both general bacteria, mold and yeast were below the detection limit, and a sufficient bactericidal effect was obtained. Also, 50kGy
There was little change in phospholipid quality at doses up to. Lipids are generally easily oxidized by radiation, but no significant oxidative change was observed.

【0020】 [0020]

【0021】実施例6−実施例10 第2表に、リポソーム水性分散液に線量の異なるガンマ
線を照射した時の菌数と酸価、pH,粒子径及び外観変
化を示した。本試料中の汚染微生物は、大腸菌群、カビ
・酵母は検出されず、一般細菌のみが検出された。これ
らの菌は1kGyの線量で検出限界以下にまで殺菌でき
ることが明らかとなった。また、使用した線量範囲では
成分変化はほとんど認められず、品質を損なうことなく
滅菌する有効な手段であることが示された。
Example 6 to Example 10 Table 2 shows the bacterial count, acid value, pH, particle size and appearance change when the liposome aqueous dispersion was irradiated with gamma rays having different doses. Regarding the contaminating microorganisms in this sample, coliforms, molds and yeasts were not detected, and only general bacteria were detected. It was revealed that these bacteria can be sterilized at a dose of 1 kGy below the detection limit. In addition, almost no change in the composition was observed within the dose range used, indicating that it is an effective means of sterilization without compromising quality.

【0022】 [0022]

【0023】[0023]

【発明の効果】以上のように、汚染菌数が少ない場合に
は1〜5kGy程度の照射で殺菌が可能であるが、汚染
菌数が高い場合あるいは放射線抵抗性の微生物が含まれ
る場合にはさらに高線量の照射が滅菌のために必要であ
る。50kGyまでの高線量照射しても品質劣化はな
く、必要に応じて1〜50kGyの適当な線量を選ぶこ
とにより、効果的に滅菌することができる。
As described above, when the number of contaminated bacteria is small, it is possible to sterilize by irradiation of about 1 to 5 kGy, but when the number of contaminated bacteria is high or when radiation resistant microorganisms are contained. Higher doses of irradiation are required for sterilization. Even if a high dose of up to 50 kGy is irradiated, the quality does not deteriorate, and it is possible to effectively sterilize by selecting an appropriate dose of 1 to 50 kGy as necessary.

───────────────────────────────────────────────────── フロントページの続き (72)発明者 相川 義明 栃木県宇都宮市平出工業団地7−14 日本 サーフアクタント工業株式会社宇都宮事業 所内 (72)発明者 野沢 昭男 栃木県宇都宮市平出工業団地7−14 日本 サーフアクタント工業株式会社宇都宮事業 所内   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Yoshiaki Aikawa             7-14 Hiraide Industrial Park, Utsunomiya City, Tochigi Prefecture Japan             Surf actant industry Utsunomiya business             In-house (72) Inventor Akio Nozawa             7-14 Hiraide Industrial Park, Utsunomiya City, Tochigi Prefecture Japan             Surf actant industry Utsunomiya business             In-house

Claims (5)

【特許請求の範囲】[Claims] 【請求項1】 電離放射線を照射することによる無菌リ
ン脂質及び/又はリン脂質水性分散液の製造法。
1. A method for producing a sterile phospholipid and / or phospholipid aqueous dispersion by irradiating with ionizing radiation.
【請求項2】 リン脂質が、大豆レシチン、卵黄レシチ
ン、水素添加大豆レシチン、水素添加卵黄レシチン、ホ
スファチジルコリン、ホスファチジルエタノールアミ
ン、ホスファチジルイノシトール、ホスファチジルセリ
ン及びスフィンゴミエリンの1種又は2種以上の混合物
である請求項1に記載の無菌リン脂質及び/又はリン脂
質水性分散液の製造法。
2. The phospholipid is one or a mixture of two or more of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and sphingomyelin. The method for producing the sterile phospholipid and / or phospholipid aqueous dispersion according to claim 1.
【請求項3】 水性分散液の分散媒が水である請求項1
に記載の無菌リン脂質及び/又はリン脂質水性分散液の
製造法。
3. The dispersion medium of the aqueous dispersion is water.
The method for producing a sterile phospholipid and / or an aqueous phospholipid dispersion according to 1.
【請求項4】 水性分散液がリポソームである請求項1
に記載の無菌リン脂質及び/又はリン脂質水性分散液の
製造法。
4. The aqueous dispersion is a liposome.
The method for producing a sterile phospholipid and / or an aqueous phospholipid dispersion according to 1.
【請求項5】 ガンマ線、電子線、エックス線などの電
離放射線を1〜50kGy照射することによる請求項1
に記載の無菌リン脂質及び/又はリン脂質水性分散液の
製造法。
5. The method according to claim 1, wherein the ionizing radiation such as gamma ray, electron beam and X-ray is irradiated at 1 to 50 kGy.
The method for producing a sterile phospholipid and / or an aqueous phospholipid dispersion according to 1.
JP17013691A 1991-07-10 1991-07-10 Method for producing sterile phospholipid, aqueous phospholipid dispersion or aqueous liposome dispersion by radiation sterilization Expired - Fee Related JP3320430B2 (en)

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US8431550B2 (en) 2000-10-27 2013-04-30 Johnson & Johnson Consumer Companies, Inc. Topical anti-cancer compositions and methods of use thereof
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