KR100330733B1 - Polyethyleneglycolphosphate and methods of synthesizing the same and utilizing the same as a radioprotectant - Google Patents
Polyethyleneglycolphosphate and methods of synthesizing the same and utilizing the same as a radioprotectant Download PDFInfo
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- KR100330733B1 KR100330733B1 KR1019990053851A KR19990053851A KR100330733B1 KR 100330733 B1 KR100330733 B1 KR 100330733B1 KR 1019990053851 A KR1019990053851 A KR 1019990053851A KR 19990053851 A KR19990053851 A KR 19990053851A KR 100330733 B1 KR100330733 B1 KR 100330733B1
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Abstract
본 발명은 방사능 피해 예방 및 치료제에 관한 것으로, 방사능으로 인한 신체적 피해를 줄일 수 있는 예방제나 방사능 피해를 입은 피폭자의 사상률을 감소시킬 수 있는 치료제로 유효한 물질인 폴리에틸렌글리콜포스페이트 (polyethylene glycol phosphate)와 폴리에틸렌글리콜포스페이트를 방사능보호제로서 이용하는 방법 및 폴리에틸렌글리콜포스페이트의 합성 방법을 제공한다.The present invention relates to a radioactive damage prevention and treatment agent, polyethylene glycol phosphate (polyethylene glycol phosphate) which is effective as a prophylactic agent that can reduce the physical damage caused by radiation or a therapeutic agent that can reduce the mortality rate of the victims who have radiation damage and A method of using polyethylene glycol phosphate as a radioprotective agent and a method for synthesizing polyethylene glycol phosphate are provided.
Description
본 발명은 방사능 피해 예방 및 치료제에 관한 것으로, 보다 상세하게는 방사능으로 인한 신체적 피해를 줄일 수 있는 예방적 역할을 할 수 있고, 일단 방사능에 노출된 피해자에 대해서는 그 피해를 감소시킬 수 있는 치료제로 유효한 물질 과 그 합성 방법에 관한 것이다.The present invention relates to a radiological damage prevention and treatment agent, and more particularly, to a therapeutic agent that can play a preventive role of reducing physical damage caused by radiation, and can reduce the damage to a victim exposed to radiation once. It relates to effective substances and methods of their synthesis.
현대 문명에 있어, 원자력은 없어서는 안될 중요한 에너지원일 뿐만 아니라, 각종 질병치료나 진단, 기타 산업상의 이용 분야도 확대 일로에 있다. 그러나, 그 안전관리는 완벽하다고 할 수 없어, 방사능 노출로 인한 신체적 피해에 대한 치료제 또는 그 예방제로서 기능할 수 있는 물질의 개발에 대한 요구는 날로 증가하고 있는 실정이다.In modern civilization, nuclear power is not only an indispensable energy source, but is also expanding in the field of disease treatment, diagnosis, and other industrial uses. However, the safety management is not perfect, and there is an increasing demand for the development of a therapeutic agent or a material capable of functioning as a preventive agent for physical damage caused by radiation exposure.
방사능의 인체 등의 생물체에 대한 영향은 다양하겠으나, 방사능이 생물체에 영향을 미치는 기본적인 메커니즘에 대해서는 현대과학은 대부분 동의하고 있다. 즉, 감마(γ)선과 같은 방사선이 투사되면 세포내의 산소가 산소라디칼(oxygenradical)로 변화되고, 유사경로를 따라 산화수소라디칼이나 과산화수소라디칼 등을 형성하게되며, 이러한 라디칼이 DNA에 작용하여 DNA의 구조를 파괴시키는 등 형질 변환을 초래하여 돌연변이, 암의 발생, 또는 세포의 죽음을 초래하는 것으로 이해되고 있다. 그런데, 상기와 같은 류의 유리기는 평상시의 건강한 세포 내에서는 거의 자연 발생하지는 않으며, 신진 대사 중에 발생된다 하더라도 세포내의 수퍼옥사이드디스무테이즈나 카탈레이즈 같은 항산화효소의 작용으로 인하여 즉시 제거되기 때문에 세포에 악영향을 미치지는 않게 된다. 그러나, 방사선 투사시에는 과량의 라디칼이 일시적으로 발생하기 때문에 세포내의 항산화효소의 작용이 제대로 이루어지지 못하게 되고, 따라서 세포내에 여러 형태의 독성을 나타내게 되는 것이다. 한편, 라디칼은 세포벽의 구성 성분인 인지질에도 작용하여 인지질의 산화를 초래하고, 이로 인하여 인지질의 배열에 혼란을 가져오게 하는 작용도 한다. 세포막의 인지질이 정상적으로 배열되어 있지 않을 경우에는 세포막으로서의 정상적인 기능을 수행하지 못하여 세포질이 세포 밖으로 누출되는 등 세포의 죽음의 원인이 되기도 한다. 이러한 이유로 인하여 라디칼의 독성을 완화시킬 수 있거나 세포막 인지질을 보호할 수 있는 물질이 방사능 보호제로서 유효할 것이라는 기대를 갖게 하고 있는 것이다.The effects of radioactivity on living things, such as the human body, may vary, but most modern science agrees on the basic mechanism by which radiation affects living things. In other words, when radiation such as gamma (γ) rays is projected, oxygen in the cell changes to oxygen radicals and forms hydrogen oxide radicals and hydrogen peroxide radicals along with similar pathways. It is understood to cause transformation, such as destroying the structure, resulting in mutation, development of cancer, or cell death. However, free radicals of the above kind rarely occur naturally in normal healthy cells, and even if they occur during metabolism, they are immediately removed due to the action of antioxidant enzymes such as superoxide dismutase or catalase in cells, which adversely affects the cells. It will not affect. However, excessive radiation is generated temporarily during radiation projection, which prevents the proper function of antioxidant enzymes in the cell, and thus causes various forms of toxicity in the cell. On the other hand, radicals also act on phospholipids, which are components of cell walls, leading to oxidation of phospholipids, thereby causing confusion in the arrangement of phospholipids. If the phospholipids of the cell membrane are not normally arranged, they may not function as cell membranes, which may cause cell death, such as leakage of the cytoplasm out of the cell. For this reason, it is expected that a substance that can mitigate the toxicity of radicals or protect cell membrane phospholipids will be effective as a radioprotectant.
상기한 바와 같은 기술적인 배경을 토대로 하여, 1950년대 이후부터 방사능예방제 및 치료제 물질에 대한 연구는 지속적으로 이루어져 왔는데, 일례로 미국 특허 5,424,471에는 아미포스틴(amifostine)이라는 물질의 방사능보호제로의 용도에 대해 개시되어 있으며, 또 다른 미국 특허 5,227,405에는 방사능보호제로서 망간화합물이 개시되어 있고, 미국 특허 4,870,002에는 3-아미노티로신(3-amino-tyrosine)이, 미국 특허 4,657,928에서는 금속구리의 유기화합물이 각각 방사능보호제로 기재되어 있다. 이러한 기술들은 모두 상기 물질들의 항산화성에 주목하여 개발된 것으로 되어 있다.Based on the above technical background, since the 1950s, research on radiopreventive and therapeutic substances has been continuously conducted. For example, US Pat. No. 5,424,471 describes the use of amifostine as a radioprotective agent. In another US Pat. No. 5,227,405, manganese compounds are disclosed as radioprotectants, US Pat. No. 4,870,002 is a 3-amino-tyrosine, and US Pat. No. 4,657,928 is a radioactive compound of metal copper, respectively. It is described as a protective agent. All of these techniques have been developed with attention to the antioxidant properties of these materials.
그러나, 종래의 항산화성물질들의 경우 세포막 투과성이 약하여 DNA에 까지 도달하지 못하여 방사능 보호제로서의 기능을 제대로 발휘할 수 없거나, 독성이 심하여 유효량의 투약이 불가능하다는 등의 문제점이 있었다.However, in the case of conventional antioxidants, the cell membrane permeability is weak and does not reach the DNA and thus cannot function properly as a radioprotective agent, or there is a problem in that an effective amount cannot be administered due to the high toxicity.
본 발명은 상기한 기존 방사능 보호제의 문제점을 해결하기 위한 것으로, 폴리에틸렌글리콜 유도체의 항산화성과 세포막과의 친화성에 착안하여 방사능 피해시 일어나는 세포의 죽음 경로 중의 하나인 세포막의 붕괴를 저지하여 세포막의 구조를 정상적으로 지탱할 수 있는 한편, 독성이 적은 방사능 예방 및 치료제로서의 폴리에틸렌글리콜포스페이트와 상기 물질의 신규한 합성 방법을 제공한다.The present invention is to solve the above problems of the conventional radioprotective agent, focusing on the affinity between the polyethylene glycol derivatives and the cell membrane, preventing the collapse of the cell membrane which is one of the cell death pathways occurring during radiation damage to prevent the structure of the cell membrane It provides a novel method for synthesizing polyethylene glycol phosphate and the material as a non-toxic radioactive prophylactic and therapeutic agent that can be sustained normally.
이하에서는 상기의 과제를 해결하기 위한 수단으로서의 폴리에틸렌글리콜포스페이트의 합성 방법을 실시예를 통해 살펴본 후, 방사능 보호제로서의 피해 예방 및 치료작용을 구체적인 실험예를 통하여 본 발명을 상술한다.Hereinafter, after examining the synthesis method of polyethylene glycol phosphate as a means for solving the above problems through the embodiment, the present invention will be described in detail through the experimental examples to prevent and treat the damage as a radioprotective agent.
본 발명에서 제시하는 폴리에틸렌글리콜포스페이트는 폴리에틸렌글리콜 골격의 말단에 포스페이트(-PO4)기가 결합된 것으로, 상기 폴리에틸렌글리콜 골격은 메톡시폴리에틸렌글리콜, 디올폴리에틸렌글리콜, 3지(3-arm), 4지(4-arm), 6지(6-arm), 8지(8-arm), 12지(12-arm) 등의 다지 폴리에틸렌글리콜(multi-arm polyethyleneglycol) 가운데서 선택되는 것이 가능하며, 상기 각각 포스페이트기는 모노-, 디-, 트리포스페이트의 형태로 폴리에틸렌글리콜 골격당 결합가능한 포스페이트의 수는 1, 2, 3, 4, 6, 8, 12이다. 본 발명에 의한 폴리에틸렌글리콜포스페이트는 폴리에틸렌글리콜과 디포스포글리세린산(diphosphoglyceric acid)의 반응에 의하여 합성할 수 있으며, 상기 폴리에틸렌글리콜의 골격을 제공하는 물질의 예로는 메톡시폴리에틸렌글리콜(methoxy polyethylene glycol), 디올폴리에틸렌글리콜 (diol polyethylene glycol) 등을 들 수 있다. 폴리에틸렌글리콜은 코어(core)를 중심으로 다수의 폴리에틸렌글리콜이 결합한 형태의 3지(3-arm) 또는 4지(4-arm) 등의 다지의(multi-arm) 폴리에틸렌글리콜도 이용할 수 있는데, 본 발명에서 사용하는 폴리에틸렌글리콜포스페이트의 골격이 되는 폴리에틸렌글리콜 유도체의 분자량은 300 ~ 100,000돌턴 (dalton)이 적합하다.The polyethylene glycol phosphate proposed in the present invention is a phosphate (-PO 4 ) group bonded to the terminal of the polyethylene glycol skeleton, the polyethylene glycol skeleton is methoxy polyethylene glycol, diol polyethylene glycol, 3-arm, 4- paper (4-arm), 6-arm (6-arm), 8-arm (8-arm), 12-arm (12-arm) and the like can be selected from multi-arm polyethylene glycol (multi-arm polyethyleneglycol), each of the phosphate The number of phosphates bindable per polyethyleneglycol backbone in the form of mono-, di-, triphosphates is 1, 2, 3, 4, 6, 8, 12. Polyethylene glycol phosphate according to the present invention can be synthesized by the reaction of polyethylene glycol and diphosphoglyceric acid, examples of the material providing the skeleton of the polyethylene glycol is methoxy polyethylene glycol (methoxy polyethylene glycol), Diol polyethylene glycol etc. are mentioned. Polyethylene glycol may be used as a multi-arm polyethylene glycol such as 3-arm or 4-arm in which a plurality of polyethylene glycols are bonded around a core. As for the molecular weight of the polyethyleneglycol derivative which becomes skeleton of the polyethyleneglycol phosphate used by this invention, 300-100,000 dalton is suitable.
이하에서는 본 발명의 방사능 보호제인 폴리에틸렌글리콜포스페이트의 가능한 형태 가운데 몇 가지 형태의 물질의 가능한 합성방법을 실시예를 통해 설명한다.Hereinafter, a possible synthesis method of some types of substances among the possible forms of polyethylene glycol phosphate which is a radioprotective agent of the present invention will be described by way of examples.
[실시예 1] 메톡시폴리에틸렌글리콜포스페이트(methoxy PEG-phosphate)의 합성방법Example 1 Synthesis Method of Methoxy Polyethylene Glycol Phosphate
메톡시폴리에틸렌글리콜(분자량 5,000)과 디포스포글리세린산을 디클로로메탄(CH2Cl2)에 녹인 후, DCC(N,N'-디사이클로헥실카보디이미드)와 DMAP(디메틸아미노피리딘)를 넣고 상온에서 1 일간 교반하였다. 반응물을 여과한 후, 여액에 증류수를 첨가하여 녹여, DCC로 추출하였다. 추출된 유기층을 황산마그네슘(MgSO4)로 건조한 후, 유기용매를 감압증류방법으로 제거하였다. 농축된 반응혼합물에 디에틸에테르를 첨가하면 메톡시폴리에틸렌글리콜포스페이트의 침전이 생성되는데, 이 침전물을 감압여과하고 건조하여 백색분말상의 메톡시폴리에틸렌글리콜포스페이트를 얻었다.Dissolve methoxy polyethylene glycol (molecular weight 5,000) and diphosphoglycerin in dichloromethane (CH 2 Cl 2 ), add DCC (N, N'-dicyclohexylcarbodiimide) and DMAP (dimethylaminopyridine) Stirred for 1 day. After the reaction was filtered, distilled water was added to the filtrate to dissolve and extracted with DCC. The extracted organic layer was dried over magnesium sulfate (MgSO 4 ), and the organic solvent was removed by distillation under reduced pressure. Diethyl ether was added to the concentrated reaction mixture to produce a precipitate of methoxy polyethylene glycol phosphate. The precipitate was filtered under reduced pressure and dried to obtain methoxy polyethylene glycol phosphate as a white powder.
이상의 반응을 반응식으로 나타내면 다음의 반응식 1과 같다.The reaction described above is represented by the following Scheme 1.
[실시예 2] 폴리에틸렌글리콜포스페이트의 합성방법Example 2 Synthesis of Polyethylene Glycol Phosphate
폴리에틸렌글리콜(분자량 3,400)과 디포스포글리세린산을 사용한 것 이외에는 실시예 1과 같은 방법으로 실험을 하여, 백색분말상의 폴리에틸렌글리콜포스페이트를 얻었다.Except having used polyethyleneglycol (molecular weight 3,400) and diphosphoglycerin acid, it experimented by the same method as Example 1, and obtained the white powdery polyethyleneglycol phosphate.
상기 반응의 반응식은 반응식 2로 나타낼 수 있다.Scheme of the reaction can be represented by Scheme 2.
[실시예 3] 3지-폴리에틸렌글리콜포스페이트(3-arm polyethyleneglycol phosphate)의 합성방법Example 3 Synthesis of 3-Arm Polyethylene Glycol Phosphate
암모니아코아(NH3-core) 1.0g과 폴리에틸렌글리콜디알데히드 [polyethylene glycol-(aldehyde)2] (분자량 2,000) 를 메탄올에 녹인 후에, 수산화칼륨(KOH)을 넣고 상온에서 2일간 교반하였다. 이 반응물에 다시 소듐보로하이드라이드(NaBH4)를 넣고 상온에서 3일 동안 교반을 실시하였다. 다음에 반응물에 증류수를 첨가하여 녹인 다음 디클로로메탄으로 추출하고, 추출된 유기층을 황산마그네슘으로 건조, 유기용매를 감압증류방법으로 제거하였다. 농축된 반응물혼합물에 디에틸에테르를 첨가하면 생성물 A의 침전물이 생성되는데, 이를 감압 여과하고 건조하여 백색 분말상의 생성물 A(product A)를 얻었다.After the ammonia core (NH 3- core) 1.0g and polyethylene glycol aldehyde [polyethylene glycol- (aldehyde) 2] ( molecular weight 2,000) was dissolved in methanol, placed into a potassium hydroxide (KOH) and the mixture was stirred for 2 days at room temperature. Sodium borohydride (NaBH 4 ) was added again to the reaction and stirred at room temperature for 3 days. Next, distilled water was added to the reactant to dissolve it, followed by extraction with dichloromethane. The extracted organic layer was dried over magnesium sulfate, and the organic solvent was removed by distillation under reduced pressure. Addition of diethyl ether to the concentrated reactant mixture gave a precipitate of product A, which was filtered under reduced pressure and dried to give a white powdery product A (product A).
생성물 A(product A)와 디포스포글리세린산을 사용하는 것 이외에는, 실시예 1과 동일한 방법으로 실험을 행하여, 백색분말상의 3지-폴리에틸렌글리콜포스페이트(3-arm PEG-phosphate)를 얻었다.Except using product A and diphosphoglycerin acid, it experimented by the method similar to Example 1, and obtained tri-polyethylene glycol phosphate (3-arm PEG-phosphate) of a white powder.
[실시예 4] 4지-폴리에틸렌글리콜포스페이트(4-arm polyethyleneglycol phosphate)의 합성방법Example 4 Synthesis method of 4-arm polyethyleneglycol phosphate
에틸렌디아민(ethylene diamine) 1.0g 을 암모니아코아 대신에 사용한 것을 제외하고는 실시예 3의 방법과 동일한 방법으로 실험을 실시하여, 중간 생성물 A'(product A')를 거쳐, 백색분말상의 4지-폴리에틸렌글리콜포스페이트(4-arm PEG-phosphate)를 얻었다.The experiment was carried out in the same manner as in Example 3, except that 1.0 g of ethylene diamine was used instead of ammonia core. Polyethylene glycol phosphate (4-arm PEG-phosphate) was obtained.
상기의 폴리에틸렌글리콜포스페이트의 방사능 보호제로서의 효능을 확인하기 위하여, 상기 실시예 2에 기재한 방법에 의해 합성한 디올폴리에틸렌글리콜포스페이트를 사용하여 다음과 같은 방사능 보호제로서의 작용실험을 실시하였다.In order to confirm the efficacy of the polyethylene glycol phosphate as a radioprotective agent, a diol polyethylene glycol phosphate synthesized by the method described in Example 2 was used as the following experiment as a radioprotective agent.
[실험예 1]. 방사능 예방제로서의 폴리에틸렌글리콜포스페이트의 작용 실험[Experimental Example 1]. Experimental Study of Polyethylene Glycol Phosphate as a Radioactive Inhibitor
본 발명에서 사용하는 폴리에틸렌글리콜포스페이트가 방사능 예방제로서의 효능을 갖는지에 대한 동물 실험은 실험용 쥐에 치사량 수준의 방사능을 투사한 후의 생존율을 조사하여 실시하였으며, 구체적인 방법은 다음과 같다.Animal experiments on whether polyethylene glycol phosphate used in the present invention as an anti-radioactive agent were carried out by investigating the survival rate after projecting lethal doses of radiation in a laboratory rat, and specific methods are as follows.
우선, 몸무게 150~250g정도의 쉬프라그-도올리(Sprague-dawley)쥐를 실험동물로 선택하여, 10 마리씩을 세개의 군으로 나누었다. 첫 번째 군은 대조군으로 아무런 처치도 받지 않고 방사능에 노출시켰으며, 두 번째 군(실험군 1)과 세 번째 군(실험군 2)은 각각 폴리에틸렌글리콜포스페이트(실시예 2에 기재된 형태로 분자량 20,000정도의 것)를 실험동물의 몸무게 ㎏당 250㎎과 500㎎을 정맥주사하고 1시간 경과 후에 방사능에 노출시켜 시간이 경과함에 따른 실험 동물의 생존율을 조사하였다. 실험에 있어 사용한 방사선은 40Gy의 세슘(Cs)방사선이며, 폴리에틸렌글리콜포스페이트는 생리식염수에 5% 농도로 용해시킨 것을 사용하여 주사하였다.First, Sprague-dawley rats weighing 150-250 g were selected as experimental animals, and 10 animals were divided into three groups. The first group was exposed to radiation without any treatment as a control group, and the second group (experimental group 1) and the third group (experimental group 2) each had polyethylene glycol phosphate (molecular weight of about 20,000 in the form described in Example 2). ) Were injected intravenously with 250 mg and 500 mg / kg body weight and exposed to radiation after 1 hour to investigate the survival rate of the test animals over time. The radiation used in the experiment was 40Gy of cesium (Cs) radiation, and polyethylene glycol phosphate was injected using 5% dissolved in physiological saline.
이상의 실험 조건에 대한 실험결과는 표 1에 나타내었다.The experimental results for the above experimental conditions are shown in Table 1.
상기 실험결과에 의하면 폴리에틸렌글리콜포스페이트를 주사받지 않은 대조군은 시간의 경과에 따라 생존율이 급격히 감소하여, 4주째에 이르러서는 생존율이 0 %를 기록한 반면에, 폴리에틸렌글리콜포스페이트를 주사받은 실험군의 경우에는500㎎/㎏을 주사받은 실험군 2의 생존율이 방사능 노출로 부터 8주 경과 후에도 80%, 250㎎/㎏을 주사받은 실험군 1도 8주 후 생존율 60%를 기록함으로써, 폴리에틸렌글리콜포스페이트가 방사선 피해에 대한 예방효과가 있음을 알 수 있었다.According to the experimental results, the control group that was not injected with polyethylene glycol phosphate rapidly reduced the survival rate over time, and by the fourth week, the survival rate was 0%, whereas in the experimental group injected with polyethylene glycol phosphate, 500 The survival rate of experimental group 2 injected with mg / kg recorded 80% after 8 weeks of radiation exposure and 60% after 8 weeks of experimental group 1 injected with 250 mg / kg, indicating that polyethylene glycol phosphate It was found that there is a preventive effect.
[실험예 2] 방사능 치료제로서의 폴리에틸렌글리콜포스페이트의 작용 실험Experimental Example 2 Experiment of Action of Polyethylene Glycol Phosphate as Radiotherapy
본 발명이 방사능 치료제로서의 효능을 갖는지에 대한 동물 실험은 실험용 쥐에 치사량 수준의 방사능을 투사한 후, 실험 물질인 폴리에틸렌글리콜포스페이트를 정맥주사하여 대조군과의 생존율을 대비 조사하여 실시하였으며, 구체적인 방법은 다음과 같다.Animal experiments on whether the present invention has efficacy as a radiopharmaceutical agent were carried out by projecting a lethal dose of radioactivity to a rat, and then intravenously injecting polyethylene glycol phosphate, a test substance, to compare the survival rate with a control group. As follows.
실험예 1에서와 같이, 실험동물을 세개의 군으로 나눈 후, 각각 방사능을 조사하고, 실험군 1과 실험군 2에는 방사능 조사 후 1시간이 경과한 시점에서 각각 250㎎/㎏와 500㎎/㎏의 실험물질을 투여하였으며, 대조군에는 아무런 조치도 취하지 않았다. 기타 실험조건은 실험예 1에서와 같이 하여, 시간이 경과함에 따른 실험동물의 생존율 변화를 조사하였는데, 그 결과는 표 2에 정리하였다.As in Experiment 1, the test animals were divided into three groups, and then irradiated with radioactivity. Experimental groups 1 and 2, respectively, showed 250 mg / kg and 500 mg / kg at 1 hour after irradiation. The test substance was administered, and no control was taken. Other experimental conditions, as in Experimental Example 1, and examined the change in survival rate of the experimental animals over time, the results are summarized in Table 2.
상기 표에 따르면, 실험물질인 폴리에틸렌글리콜포스페이트를 주사받지 않은 대조군은 5주째에 이른 시점에서 치사율이 100%에 달한 반면에, 실험군의 동물들은8주 후에도 각각 40%와 50%의 생존율을 기록하였다.According to the table, the control group not injected with the experimental polyethylene glycol phosphate reached a mortality rate of 100% at the beginning of the 5th week, whereas the animals of the experimental group recorded survival rates of 40% and 50% after 8 weeks, respectively. .
이상의 결과에서, 방사선에 노출된 후 1시간이 경과한 시점에서 실험물질인 폴리에틸렌글리콜포스페이트를 치료용으로 주사받은 때에는 그렇지 않은 경우에 대비하여 현저한 생존율의 증가가 있음을 알 수 있었다. 따라서, 본 발명의 물질이 방사선 피해에 대한 예방 효과 뿐만 아니라, 치료 효과도 있음을 알 수 있는 것이다.In the above results, it was found that when one hour elapsed after exposure to radiation, when the experimental substance polyethylene glycol phosphate was injected for treatment, there was a significant increase in survival rate compared to the other cases. Therefore, it will be appreciated that the material of the present invention has a therapeutic effect as well as a preventive effect on radiation damage.
본 발명에 의한 방사능보호제인 폴리에틸렌글리콜포스페이트는 항산화적 기능과 세포막을 안정화시키는 작용으로 인하여, 생체의 방사능 노출시의 피해에 대한 예방제로서의 효능과 방사능 피폭자에 대한 피해를 감소시키는 치료제로서의 효능을 갖는다.Polyethylene glycol phosphate, a radioprotective agent according to the present invention, has an effect as a preventive agent against damage upon exposure to radiation of a living body and as a therapeutic agent for reducing damage to radiation exposure due to its antioxidant function and stabilizing action.
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| US3284297A (en) * | 1961-12-22 | 1966-11-08 | Thiokol Chemical Corp | 2-n-methylammoniumethylthiosulfuric acid and its use as a radioprotective agent |
| US5028715A (en) * | 1989-02-06 | 1991-07-02 | Southwest Research Institute | Radioprotective agents and their method of manufacture |
| JPH1072356A (en) * | 1996-08-30 | 1998-03-17 | Cci Corp | Radioprotective agent |
| US5961955A (en) * | 1997-06-03 | 1999-10-05 | Coulter Pharmaceutical, Inc. | Radioprotectant for peptides labeled with radioisotope |
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| US3284297A (en) * | 1961-12-22 | 1966-11-08 | Thiokol Chemical Corp | 2-n-methylammoniumethylthiosulfuric acid and its use as a radioprotective agent |
| US5028715A (en) * | 1989-02-06 | 1991-07-02 | Southwest Research Institute | Radioprotective agents and their method of manufacture |
| JPH1072356A (en) * | 1996-08-30 | 1998-03-17 | Cci Corp | Radioprotective agent |
| US5961955A (en) * | 1997-06-03 | 1999-10-05 | Coulter Pharmaceutical, Inc. | Radioprotectant for peptides labeled with radioisotope |
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