KR102428696B1 - Hemodialysis membrane with improved phosphate adsorption ability and method for manufacturing same - Google Patents
Hemodialysis membrane with improved phosphate adsorption ability and method for manufacturing same Download PDFInfo
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- KR102428696B1 KR102428696B1 KR1020200140913A KR20200140913A KR102428696B1 KR 102428696 B1 KR102428696 B1 KR 102428696B1 KR 1020200140913 A KR1020200140913 A KR 1020200140913A KR 20200140913 A KR20200140913 A KR 20200140913A KR 102428696 B1 KR102428696 B1 KR 102428696B1
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- Prior art keywords
- membrane
- hemodialysis
- adsorption capacity
- phosphate adsorption
- dialysis membrane
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- 239000012528 membrane Substances 0.000 title claims abstract description 100
- 238000001631 haemodialysis Methods 0.000 title claims abstract description 50
- 230000000322 hemodialysis Effects 0.000 title claims abstract description 50
- 229910019142 PO4 Inorganic materials 0.000 title claims abstract description 39
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title claims abstract description 39
- 239000010452 phosphate Substances 0.000 title claims abstract description 39
- 238000001179 sorption measurement Methods 0.000 title claims abstract description 28
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 11
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 48
- 238000000502 dialysis Methods 0.000 claims abstract description 45
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims abstract description 41
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- 239000004698 Polyethylene Substances 0.000 claims description 6
- 239000004642 Polyimide Substances 0.000 claims description 6
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- 230000000694 effects Effects 0.000 abstract description 9
- 239000000126 substance Substances 0.000 abstract description 6
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 12
- 239000011574 phosphorus Substances 0.000 description 12
- 229910052698 phosphorus Inorganic materials 0.000 description 12
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- 239000011575 calcium Substances 0.000 description 6
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- 201000005991 hyperphosphatemia Diseases 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 208000020832 chronic kidney disease Diseases 0.000 description 4
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
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- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 239000007987 MES buffer Substances 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
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- NQSLZEHVGKWKAY-UHFFFAOYSA-N 6-methylheptyl 2-methylprop-2-enoate Chemical compound CC(C)CCCCCOC(=O)C(C)=C NQSLZEHVGKWKAY-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
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- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 229920012266 Poly(ether sulfone) PES Polymers 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
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- 238000010894 electron beam technology Methods 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
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- 230000002188 osteogenic effect Effects 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
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- NHARPDSAXCBDDR-UHFFFAOYSA-N propyl 2-methylprop-2-enoate Chemical compound CCCOC(=O)C(C)=C NHARPDSAXCBDDR-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000012959 renal replacement therapy Methods 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
- B01D67/0081—After-treatment of organic or inorganic membranes
- B01D67/0093—Chemical modification
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
- B01D67/0081—After-treatment of organic or inorganic membranes
- B01D67/0093—Chemical modification
- B01D67/00931—Chemical modification by introduction of specific groups after membrane formation, e.g. by grafting
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1621—Constructional aspects thereof
- A61M1/1623—Disposition or location of membranes relative to fluids
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
- B01D67/0081—After-treatment of organic or inorganic membranes
- B01D67/009—After-treatment of organic or inorganic membranes with wave-energy, particle-radiation or plasma
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
- B01D67/0081—After-treatment of organic or inorganic membranes
- B01D67/0093—Chemical modification
- B01D67/00933—Chemical modification by addition of a layer chemically bonded to the membrane
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/12—Composite membranes; Ultra-thin membranes
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/12—Composite membranes; Ultra-thin membranes
- B01D69/1216—Three or more layers
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- B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
- B01D71/06—Organic material
- B01D71/40—Polymers of unsaturated acids or derivatives thereof, e.g. salts, amides, imides, nitriles, anhydrides, esters
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01D71/40—Polymers of unsaturated acids or derivatives thereof, e.g. salts, amides, imides, nitriles, anhydrides, esters
- B01D71/401—Polymers based on the polymerisation of acrylic acid, e.g. polyacrylate
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01D2323/38—Graft polymerization
- B01D2323/385—Graft polymerization involving radiation
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- B01D2325/12—Adsorbents being present on the surface of the membranes or in the pores
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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Abstract
본 발명은 인산염 흡착능력이 향상된 혈액 투석막 및 이의 제조방법에 관한 것으로, 구체적으로 본 발명은 감마선(gamma irradiation) 동시조사법을 이용하여 투석막의 표면을 아크릴산(acrylic acid)으로 개질하고, 젤라틴(gelatin)을 화학적으로 접합하였을 때, 투석막의 인산염(phosphate) 흡착 효과가 증가하는 것을 확인하였으므로, 상기 혈액 투석막을 혈액투석 시 인산염 제거에 유용하게 이용할 수 있고, 제조과정 중 투석막에 추가적인 물질을 접합하는 방법을 인산염 이외에 다양한 물질을 제거하는데 유용하게 이용하는 것이 가능하다.The present invention relates to a hemodialysis membrane having improved phosphate adsorption capacity and a method for manufacturing the same. More specifically, the present invention relates to a hemodialysis membrane having improved phosphate adsorption capacity, and more specifically, to a surface of the dialysis membrane by using gamma irradiation simultaneous irradiation method to modify the surface of the dialysis membrane with acrylic acid, and gelatin Since it was confirmed that the phosphate adsorption effect of the dialysis membrane was increased when chemically bonded to It is possible to use it usefully to remove various substances other than phosphate.
Description
본 발명은 인산염 흡착능력이 향상된 혈액 투석막 및 이의 제조방법에 관한 것으로, 혈액 투석막 표면에 젤라틴을 코팅하여 인산염 흡착능력이 향상된 혈액 투석막 및 이의 제조방법에 관한 것이다.The present invention relates to a hemodialysis membrane with improved phosphate adsorption capacity and a method for manufacturing the same, and to a hemodialysis membrane with improved phosphate adsorption capacity by coating gelatin on the surface of the hemodialysis membrane and a method for manufacturing the same.
만성신부전은 당뇨, 사구체 신염, 고혈압 등 다양한 원인으로 정상 신장 기능의 10 내지 15 ％ 이하로 신장 기능이 감소되는 질병으로, 정상적인 신장 기능 유지를 위하여 투석이나 신장이식수술과 같은 신 대체요법이 필요한 질환이다. 2016년 말 한국 신장학회 등록 위원회 자료수집에 따르면 신 대체요법 치료를 받는 환자는 전체 87,014명이며, 인구 백만 명당 1,689명으로 점점 증가 추세이다. 이 중 혈액투석 치료를 받는 환자는 만성신부전 환자의 72 ％를 차지하고 있으며, 매년 지속적으로 증가하는 것으로 보고되고 있다.Chronic renal failure is a disease in which renal function is reduced to less than 10 to 15% of normal renal function due to various causes such as diabetes, glomerulonephritis, and hypertension. to be. According to the data collected by the registration committee of the Korean Nephrology Association at the end of 2016, the total number of patients receiving renal replacement therapy was 87,014, and the number is increasing to 1,689 per million population. Among them, patients receiving hemodialysis treatment account for 72% of chronic renal failure patients, and it is reported that the number continues to increase every year.
혈액투석 환자는 신부전으로 인해 사구체 여과율이 저하되어 있으며, 주 2 내지 3회 혈액투석을 받음에도 불구하고 정기적인 혈액투석 치료만으로는 인의 효과적인 제거가 어려워 고인산혈증이 나타나고, 이러한 고인산혈증은 이차성 부갑상샘 항진증과 신장성 골형성 장애, 심혈관 석회화를 악화시켜 사망률을 증가시키는 중요한 요인으로 보고되고 있다. 특히, 고인산혈증으로 인한 만성신부전 환자의 사망률은 혈청 칼슘×인 값(calcium-phosphorus(Ca×P) product)이 높을수록 더욱 증가하며, 인 5.0 ㎎/㎗ 이상, 칼슘 10.0 ㎎/㎗ 이상인 경우 사망률이 더 높은 것으로 나타나고 있다. 따라서 미국 국립신장학회의 2009 지침서에는 혈청 인의 수치를 3.5 내지 5.5 ㎎/㎗, 혈청 칼슘은 8.4 내지 9.4 ㎎/㎗, Ca×P product는 55 ㎎2/㎗2 이하로 유지하도록 권고하고 혈청 인의 수치 5.5 ㎎/㎗ 이상을 고인산혈증으로 분류하고 있으며, 한국 건강보험 심사평가원에서도 혈액투석에 대한 적정성 평가 항목에 Ca×P product 충족률을 중요 평가 항목으로 지정하고 있다. 따라서 만성신부전 환자의 사망률을 증가시키는 고인산혈증에 관한 예방 및 관리가 매우 중요하며, 특히 혈액투석 환자의 고인산혈증을 관리하기 위하여 현재 권장되는 식사요법 및 인 결합제와 같은 경구 약물 요법의 병행 사용보다 편리하게 예방 및 관리할 수 있는 방법을 개발하여 제공하는 것이 무엇보다 필요한 실정이다. 또한, 인 결합제와 같은 경구 약물 요법은 환자가 소화기계 부작용을 호소한다는 점에서 부작용을 줄일 수 있는 방법을 개발하는 것이 필요하다.In hemodialysis patients, the glomerular filtration rate is lowered due to renal failure, and despite receiving hemodialysis 2-3 times a week, it is difficult to effectively remove phosphorus through regular hemodialysis treatment alone, so hyperphosphatemia appears. It has been reported as an important factor in increasing the mortality rate by exacerbating hyperthyroidism and osteogenic dysfunction and cardiovascular calcification. In particular, the mortality rate of chronic renal failure patients due to hyperphosphatemia increases as the serum calcium × phosphorus value (calcium-phosphorus (Ca × P) product) is higher, and the mortality rate is greater than 5.0 mg/dL for phosphorus and 10.0 mg/dL for calcium. appears to be higher. Therefore, in the 2009 guidelines of the American National Nephrological Association, it is recommended to maintain the serum phosphorus level at 3.5 to 5.5 mg/dL, serum calcium 8.4 to 9.4 mg/dL, and Ca×P product to be 55 mg 2 /dL 2 or less, and the serum phosphorus level Higher than 5.5 mg/dL is classified as hyperphosphatemia, and the Korean Health Insurance Review and Assessment Service also designates the Ca×P product satisfaction rate as an important evaluation item in the evaluation of adequacy for hemodialysis. Therefore, prevention and management of hyperphosphatemia, which increases the mortality rate of patients with chronic renal failure, is very important. In particular, it is more convenient than the concurrent use of dietary therapy and oral drug therapy such as phosphorus binders, which are currently recommended to manage hyperphosphatemia in hemodialysis patients. It is a situation that is most necessary to develop and provide a method to prevent and manage it. In addition, it is necessary to develop a method for reducing side effects in that oral drug therapy, such as phosphorus binders, complains of side effects in the digestive system.
이에 본 발명자들은 경구 약물 요법의 부작용을 줄이고, 혈액투석 환자의 편리하고 효과적인 인산염 관리를 위한 방법을 개발하기 위하여 노력한 결과, 투석막의 표면을 아크릴산(acrylic acid)으로 개질하고 젤라틴(gelatin)을 이용하여 화학적으로 가교한 투석막을 혈액투석에 이용하였을 때, 투석막의 인산염(phosphate) 흡착 효과가 증가하는 것을 확인하였다. 따라서, 상기 혈액 투석막을 혈액투석 시 인산염 제거에 유용하게 이용할 수 있고, 제조과정 중 투석막에 추가적인 물질을 코팅하는 방법을 인산염 이외에 다양한 물질을 제거하는 데 유용하게 이용할 수 있다.Accordingly, the present inventors have tried to reduce the side effects of oral drug therapy and develop a method for convenient and effective phosphate management in hemodialysis patients. As a result, the surface of the dialysis membrane was modified with acrylic acid and gelatin was used. When the chemically crosslinked dialysis membrane was used for hemodialysis, it was confirmed that the phosphate adsorption effect of the dialysis membrane was increased. Therefore, the hemodialysis membrane can be usefully used to remove phosphate during hemodialysis, and a method of coating an additional material on the dialysis membrane during the manufacturing process can be usefully used to remove various substances other than phosphate.
본 발명은 인산염 흡착능력이 향상된 혈액 투석막 및 이의 제조방법에 관한 것이다.The present invention relates to a hemodialysis membrane with improved phosphate adsorption capacity and a method for manufacturing the same.
상기 목적을 달성하기 위하여, 본 발명은 인산염 흡착능력이 향상된 혈액 투석막으로서, 상기 혈액 투석막은 젤라틴이 화학적으로 접합된 것인, 혈액 투석막을 제공한다.In order to achieve the above object, the present invention provides a hemodialysis membrane with improved phosphate adsorption capacity, wherein the hemodialysis membrane is chemically bonded to gelatin.
또한, 본 발명은 1) 제1층의 소수성 투석막에 감마선 동시조사법을 이용하여 아크릴산 또는 아크릴계 고분자의 그래프트 중합체와 용매를 포함하는 용액으로 그래프트 중합반응시켜 제2층을 제조하는 단계; 및 2) 상기 제2층 상에 젤라틴을 접합하여 제3층을 제조하는 단계;를 포함하는, 인산염 흡착능력이 향상된 혈액 투석막의 제조방법을 제공한다.In addition, the present invention comprises the steps of: 1) preparing a second layer by performing a graft polymerization reaction on the hydrophobic dialysis membrane of the first layer with a solution containing a solvent and a graft polymer of acrylic acid or acrylic polymer using simultaneous gamma-ray irradiation; and 2) preparing a third layer by bonding gelatin on the second layer.
본 발명에서는 감마선(gamma irradiation)을 조사하여 투석막의 표면에 아크릴산(acrylic acid)을 도입한 후 젤라틴(gelatin)을 화학적으로 접합한 혈액 투석막이 인산염(phosphate) 흡착 효과가 증가하는 것을 확인하였으므로, 상기 젤라틴이 접합된 혈액 투석막을 혈액투석 시 인산염 제거에 유용하게 이용할 수 있고, 제조과정 중 투석막에 다양한 물질의 접합이 가능하여 인산염 이외에 다양한 물질을 제거하는데 유용하게 이용할 수 있다. In the present invention, it was confirmed that the phosphate adsorption effect was increased in the hemodialysis membrane chemically bonded with gelatin after acrylic acid was introduced to the surface of the dialysis membrane by irradiating gamma irradiation. The gelatin-conjugated hemodialysis membrane can be usefully used to remove phosphate during hemodialysis, and various substances can be bonded to the dialysis membrane during the manufacturing process, so it can be usefully used to remove various substances other than phosphate.
도 1은 본 발명에 따른 인산염 흡착능력이 증가한 혈액 투석막의 제조 과정을 나타낸 도이다.
도 2는 본 발명에 따른 투석막의 혈액 투석 시 인산염 제거 과정을 나타낸 도이다.
도 3은 본 발명에 따른 투석막의 AAc 농도에 따른 AAc의 그래프트 차이를 확인한 도이다.
도 4는 본 발명에 따른 투석막에 그래프트된 AAc의 젤라틴 결합 여부를 확인한 도이다.
도 5는 본 발명에 따른 투석막의 인 제거능을 확인한 도이다.1 is a view showing the manufacturing process of the hemodialysis membrane with increased phosphate adsorption capacity according to the present invention.
2 is a view showing a phosphate removal process during hemodialysis of the dialysis membrane according to the present invention.
3 is a diagram confirming the difference in AAc grafting according to the AAc concentration of the dialysis membrane according to the present invention.
4 is a view confirming whether AAc grafted to the dialysis membrane according to the present invention has gelatin binding.
5 is a view confirming the phosphorus removal ability of the dialysis membrane according to the present invention.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 인산염 흡착능력이 향상된 혈액 투석막으로서, 상기 혈액 투석막은 젤라틴이 화학적으로 접합된 것인, 혈액 투석막을 제공한다.The present invention provides a hemodialysis membrane with improved phosphate adsorption capacity, wherein the hemodialysis membrane is chemically bonded to gelatin.
본 발명에서, 상기 혈액 투석막은 소수성 투석막으로 이루어진 제1층; 상기 소수성 투석막에 그래프트(graft)되어 형성된 아크릴산(acrylic acid) 또는 아크릴계 고분자의 그래프트 중합체로 이루어진 제2층; 및 상기 아크릴산 또는 아크릴계 고분자에 접합된 젤라틴으로 이루어진 제3층;으로 이루어지는 것을 특징으로 하는, 인산염 흡착능력이 향상된 혈액 투석막일 수 있다.In the present invention, the hemodialysis membrane includes a first layer made of a hydrophobic dialysis membrane; a second layer made of a graft polymer of acrylic acid or an acrylic polymer, which is grafted onto the hydrophobic dialysis membrane; and a third layer made of gelatin bonded to the acrylic acid or acrylic polymer.
본 발명에서, 상기 소수성 투석막은 통상의 투석막에서 지지체의 성분으로 사용되는 화합물의 경우 제한없이 사용될 수 있으나, 바람직하게는 폴리비닐리덴 플루오라이드(polyvinylidene fluoride, PVDF), 폴리카보네이트(polycarbonate, PC), 폴리설폰(polysulfone, PSF), 폴리에테르술폰(polyethersulfone, PES), 폴리 에테르이미드(polyetherimide, PEI), 폴리이미드(polyimide, PI), 폴리에틸렌(polyethylene, PE), 폴리프로필렌(polypropylene, PP) 및 폴리아미드(polyamide, PA)로 이루어진 군으로부터 선택되는 어느 하나 이상일 수 있고, 구체적으로 플루오라이드 및 폴리카보네이트로 이루어진 군으로부터 선택되는 어느 하나 이상일 수 있으며, 더욱 구체적으로 플루오라이드일 수 있으나, 이에 한정되지 않으며 투석막의 용도에 따라 성분을 변경할 수 있다.In the present invention, the hydrophobic dialysis membrane may be used without limitation in the case of a compound used as a component of a support in a conventional dialysis membrane, but preferably polyvinylidene fluoride (PVDF), polycarbonate (PC), Polysulfone (PSF), polyethersulfone (PES), polyetherimide (PEI), polyimide (PI), polyethylene (PE), polypropylene (PP) and poly It may be any one or more selected from the group consisting of amide (PA), specifically, may be any one or more selected from the group consisting of fluoride and polycarbonate, and more specifically may be fluoride, but is not limited thereto. The composition can be changed according to the use of the dialysis membrane.
본 발명에서, 아크릴계 고분자는 아크릴 단량체가 중합반응하여 제조되는 고분자로서, 예를 들면, 아크릴산, 메틸아크릴레이트, 에틸아크릴레이트, n-부틸아크릴레이트, 에틸부틸아크릴레이트, 메타크릴레이트, 메틸 메타크릴레이트, 에틸 메타크릴레이트, 프로필 메타크릴레이트, 부틸아크릴레이트, 이소옥틸메타크릴레이트 등이 있으나, 이에 한정되는 것은 아니다.In the present invention, the acrylic polymer is a polymer prepared by polymerization of an acrylic monomer, for example, acrylic acid, methyl acrylate, ethyl acrylate, n-butyl acrylate, ethyl butyl acrylate, methacrylate, methyl methacryl rate, ethyl methacrylate, propyl methacrylate, butyl acrylate, isooctyl methacrylate, and the like, but is not limited thereto.
본 발명에서, 상기 소수성 투석막은 감마선을 조사함으로써 친수성 투석막으로 개질될 수 있으나, 이에 한정되지 않는다. 보다 구체적으로, 본 발명에서 소수성 투석막에 아크릴산 또는 아크릴계 고분자 용액에 함침한 후 감마선을 조사함으로써 친수성 투석막으로 개질될 수 있다. 친수성 투석막으로 개질됨으로써 젤라틴과의 결합이 용이해질 수 있으며, 제1층 내지 제3층이 화학적으로 결합되어 다른 물질의 투석에 영향없이 인산염 흡착능력이 향상될 수 있다.In the present invention, the hydrophobic dialysis membrane may be modified into a hydrophilic dialysis membrane by irradiating gamma rays, but is not limited thereto. More specifically, in the present invention, the hydrophobic dialysis membrane can be modified into a hydrophilic dialysis membrane by irradiating gamma rays after impregnating the hydrophobic dialysis membrane with acrylic acid or an acrylic polymer solution. By modifying the hydrophilic dialysis membrane, binding to gelatin may be facilitated, and the first to third layers may be chemically bonded to improve phosphate adsorption capacity without affecting dialysis of other materials.
또한, 상기 감마선은 1 내지 30 kGy의 선량으로 조사될 수 있고, 구체적으로 5 내지 20 kGy의 선량으로 조사될 수 있으며, 보다 구체적으로 10 kGy의 선량으로 조사될 수 있으나, 이에 한정되지 않으며 선량에 따른 효과의 차이를 보이는 경우 이를 적절히 조절할 수 있다.In addition, the gamma rays may be irradiated at a dose of 1 to 30 kGy, specifically, may be irradiated at a dose of 5 to 20 kGy, and more specifically, may be irradiated at a dose of 10 kGy, but is not limited thereto. If there is a difference in the effect according to the result, it can be appropriately adjusted.
또한, 상기 감마선은 6 내지 180분간 조사될 수 있고, 구체적으로 30 내지 120분간 조사될 수 있으며, 보다 구체적으로 60분간 조사될 수 있으나, 이에 한정되지 않으며 조사 시간에 따른 차이를 보이는 경우 이를 적절하게 조절할 수 있다.In addition, the gamma rays may be irradiated for 6 to 180 minutes, specifically for 30 to 120 minutes, and more specifically for 60 minutes, but is not limited thereto. can be adjusted
본 발명에서, 상기 그래프트는 상기 소수성 투석막에 아크릴산을 처치하여 카르복실기(carboxy group)를 부착할 수 있으나, 이에 한정되지 않는다.In the present invention, the graft may be treated with acrylic acid to attach a carboxy group to the hydrophobic dialysis membrane, but is not limited thereto.
또한, 상기 아크릴산은 0.01 내지 20 중량％의 농도일 수 있고, 구체적으로 0.1 내지 10％의 농도일 수 있으며, 더욱 구체적으로 1 내지 5％의 농도일 수 있으나, 이에 한정되지 않으며 아크릴산 농도에 따른 차이를 보이는 경우 이를 적절하게 조절할 수 있다.In addition, the acrylic acid may have a concentration of 0.01 to 20% by weight, specifically, may have a concentration of 0.1 to 10%, and more specifically, may have a concentration of 1 to 5%, but is not limited thereto, and the difference according to the concentration of acrylic acid If it is shown, it can be adjusted appropriately.
본 발명에서, 상기 젤라틴은 20 내지 2000 ㎍/㎖의 농도일 수 있고, 구체적으로 100 내지 1000 ㎍/㎖의 농도일 수 있으며, 더욱 구체적으로 200 ㎍/㎖의 농도일 수 있으나, 이에 한정되지 않으며 젤라틴 농도에 따른 차이를 보이는 경우 이를 적절하게 조절할 수 있다.In the present invention, the gelatin may have a concentration of 20 to 2000 μg/ml, specifically 100 to 1000 μg/ml, and more specifically 200 μg/ml, but is not limited thereto. If there is a difference according to the gelatin concentration, it can be appropriately adjusted.
본 발명은the present invention
1) 제1층의 소수성 투석막에 감마선 동시조사법을 이용하여 아크릴산 또는 아크릴계 고분자의 그래프트 중합체와 용매를 포함하는 용액으로 그래프트 중합반응시켜 제2층을 제조하는 단계;1) preparing a second layer by performing a graft polymerization reaction on the hydrophobic dialysis membrane of the first layer with a solution containing a solvent and a graft polymer of acrylic acid or an acrylic polymer using simultaneous gamma-ray irradiation;
2) 상기 제2층 상에 젤라틴을 접합하여 제3층을 제조하는 단계;를 포함하는, 인산염 흡착능력이 향상된 혈액 투석막의 제조방법을 제공한다.2) preparing a third layer by bonding gelatin on the second layer;
본 명세서에서 감마선 동시조사법은 방사선 조사법의 하나로써, 두 가지 이상의 상이한 물질을 혼합한 상태에서 감마선을 조사하는 것을 의미한다. 본 발명에서, 감마선 동시조사법을 통해 두 가지 이상의 상이한 물질을 결합시킬 수 있으며, 감마선의 높은 물질 투과력으로 상이한 두 물질을 내외부에 전체적으로 고르게 결합시킬 수 있다. 또한, 그래프트 중합반응 이후 제3층을 결합하기 위하여, 상대적으로 투과력이 적은 전자선보다 감마선이 바람직하며, 전조사법보다 동시조사법이 바람직할 수 있다.In the present specification, the simultaneous gamma-ray irradiation method is one of the radiation irradiation methods, and means irradiating gamma rays in a state in which two or more different materials are mixed. In the present invention, two or more different materials can be combined through simultaneous gamma-ray irradiation, and the two different materials can be uniformly combined inside and outside due to the high material penetrating power of gamma rays. In addition, in order to bond the third layer after the graft polymerization reaction, gamma rays are preferable to electron beams having relatively low penetrating power, and simultaneous irradiation may be preferable than pre-irradiation.
본 발명에서, 그래프트 중합반응을 위하여 가교용액을 이용할 수 있다. 가교용액은 1-에틸-3-(3-디메틸 아미노프로필)카보디이미드 [1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide; EDC], N-하이드록시숙신이미드(hydroxysuccinimide; NHS)를 포함할 수 있으나, 이에 한정되지 않는다. 가교용액을 통해 화학적으로 가교됨으로써, 고체상에서도 높은 가교밀도를 형성할 수 있다.In the present invention, a crosslinking solution may be used for the graft polymerization reaction. The crosslinking solution was 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide [1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide; EDC] and N-hydroxysuccinimide (NHS), but is not limited thereto. By chemically crosslinking through a crosslinking solution, a high crosslinking density can be formed even in the solid phase.
상기 소수성 투석막, 아크릴계 고분자, 감마선, 그래프트 및 젤라틴은 상기 인산염 흡착능력이 향상된 혈액 투석막에 대한 설명과 동일한 바, 구체적인 설명은 상기 내용을 원용한다.The hydrophobic dialysis membrane, acrylic polymer, gamma ray, graft, and gelatin are the same as the description of the hemodialysis membrane with improved phosphate adsorption capacity, and detailed descriptions thereof are incorporated herein by reference.
본 발명의 구체적인 실시예에서, 본 발명자들은 인산염 흡착능력이 향상된 혈액 투석막을 제조하였다.In a specific embodiment of the present invention, the present inventors prepared a hemodialysis membrane with improved phosphate adsorption capacity.
또한, 본 발명자들은 투석막에 감마선을 조사하여 아크릴산으로 표면을 개질하고, 젤라틴을 화학적으로 접합하여 본 발명에 따른 혈액 투석막을 제조하였고, 이를 이용한 혈액투석 시 인산염 흡착 효과가 증가하는 것을 확인하였다.In addition, the present inventors irradiated the dialysis membrane with gamma rays, modified the surface with acrylic acid, and chemically bonded gelatin to prepare the hemodialysis membrane according to the present invention. It was confirmed that the phosphate adsorption effect was increased during hemodialysis using the same.
따라서, 본 발명에 따른 혈액 투석막 및 이의 제조방법을 투석막에 추가적인 물질을 접합하는 방법으로 인산염 이외에도 다양한 물질을 제거하는데 유용하게 이용할 수 있다.Therefore, the hemodialysis membrane and the method for manufacturing the same according to the present invention can be effectively used to remove various substances other than phosphate as a method of bonding additional substances to the dialysis membrane.
이하, 본 발명을 실시예 및 실험예에 의하여 상세히 설명한다.Hereinafter, the present invention will be described in detail by way of Examples and Experimental Examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 의하여 한정되는 것은 아니다.However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.
<실시예 1> 인산염 흡착 효과가 증가한 혈액 투석막의 제조<Example 1> Preparation of hemodialysis membrane with increased phosphate adsorption effect
<1-1> 감마선 동시조사법을 이용한 아크릴산(acrylic acid, AAc) 그래프트(graft)<1-1> Acrylic acid (AAc) graft using simultaneous gamma-ray irradiation
혈액 투석막으로 두께 100 ㎛, 기공 크기(pore sizs) 10 ㎛의 폴리비닐리덴 플루오라이드(Polyvinylidene fluoride, PVDF)를 와츠맨(Whatman®)에서 구입하여 5 × 10 ㎝ 크기로 자르고, 70 ％ 에탄올에 담지하여 적신 후 500 ㎖의 증류수에 재담지하여 에탄올 성분을 완전히 제거하였다. 그다음, 상기 PVDF 막을 1 및 5 중량％(wt％)의 아크릴산(AAc) 수용액에 각각 함침하고, Co60에서 발생되는 감마선(gamma ray, γ-ray)을 상온에서 10 kGy의 선량으로 60분 동안 조사하여 상기 PVDF 막 표면에 아크릴산을 도입해 친수성으로 개질하였다. 이후, AAc로 그래프팅(grafting)된 PVDF 막을 증류수 500 ㎖로 3번 헹구어 그래프트되지 않은 AAc를 제거하고, 1일 동안 진공건조하였다. Polyvinylidene fluoride (PVDF) with a thickness of 100 μm and a pore size of 10 μm as a hemodialysis membrane was purchased from Whatman ® , cut into 5 × 10 cm, and loaded in 70% ethanol. After re-wetting in 500 ml of distilled water, the ethanol component was completely removed. Then, the PVDF film is impregnated with 1 and 5 wt% (wt%) of acrylic acid (AAc) aqueous solution, respectively, and gamma ray (γ-ray) generated from Co 60 is applied at a dose of 10 kGy at room temperature for 60 minutes. Acrylic acid was introduced to the surface of the PVDF membrane by irradiation and modified to be hydrophilic. Thereafter, the PVDF membrane grafted with AAc was rinsed 3 times with 500 ml of distilled water to remove ungrafted AAc, and vacuum dried for 1 day.
<1-2> 젤라틴 결합<1-2> Gelatin binding
상기 실시예 <1-1>에서 수득된 AAc가 그래프트된 PVDF 막을 1 mM의 EDC/NHS가 용해되어 있는 pH 5.0의 MES 완충액(MES buffer, Sigma Aldrich)에 담지한 후, 상온에서 30분 동안 교반하여 카르복실기(carboxy group)를 활성화하였다. 그다음, 상기 카르복실기가 활성된 PVDF 막을 200 ㎍/㎖의 젤라틴이 용해된 pH 8.5의 중탄산 나트륨 완충액(sodium bicarbonate buffer, Sigma Aldrich)에 담지하고 120분간 교반하여 젤라틴을 막 표면에 코팅하는 형태로 접합하였다. 이후, 상기 젤라틴이 코팅된 PVDF 막을 증류수 500 ㎖로 3번 헹구어 미 접합된 젤라틴을 제거하고, 동결건조한 다음 포장하여 보관하였다.The AAc-grafted PVDF membrane obtained in Example <1-1> was supported in an MES buffer (MES buffer, Sigma Aldrich) of pH 5.0 in which 1 mM EDC/NHS was dissolved, followed by stirring at room temperature for 30 minutes. Thus, a carboxy group was activated. Then, the carboxyl group-activated PVDF membrane was supported in sodium bicarbonate buffer (Sigma Aldrich) of pH 8.5 in which 200 μg/ml of gelatin was dissolved, and stirred for 120 minutes to coat the gelatin on the membrane surface. . Thereafter, the gelatin-coated PVDF membrane was rinsed 3 times with 500 ml of distilled water to remove unconjugated gelatin, lyophilized, and then packaged and stored.
<실험예 1> PVDF 막의 AAc 농도에 따른 AAc 그래프트 차이 확인<Experimental Example 1> Confirmation of AAc graft difference according to AAc concentration of PVDF membrane
동일한 감마선 조사량에서 AAc 농도에 따른 PVDF 막에 대한 AAc 그래프트 정도를 확인하기 위하여 본 실험을 진행하였다. 구체적으로, 상기 <실시예 1-1>에 따른 AAc가 그래프트된 PVDF 막을 제조하여 FTIR 스펙트럼 분석을 수행하였다. 대조군으로 AAc 수용액 대신 순수한 물을 이용한 PVDF 막을 사용하였다.This experiment was conducted to confirm the degree of AAc grafting on the PVDF film according to the AAc concentration at the same gamma-irradiation dose. Specifically, an AAc-grafted PVDF film according to <Example 1-1> was prepared and FTIR spectral analysis was performed. As a control, PVDF membrane using pure water instead of AAc aqueous solution was used.
그 결과, 도 3에서 나타낸 바와 같이, 대조군을 제외한 실험군에서 AAc의 도입에 따른 수산기(―OH)의 흡수가 3300 ㎝-1에서 관찰되는 것을 확인하였고(도 3A), 그래프트된 AAc에서 유래한 카보닐기(C＝O)의 흡수 피크가는 1650 ㎝-1에서 관찰되는 것을 확인하였다(도 3B). 상기 결과를 통해 동일한 감마선 선량에서는 아크릴산의 농도에 따른 그래프트 차이가 미미한 것을 확인하였다.As a result, as shown in FIG. 3 , it was confirmed that the absorption of hydroxyl group (—OH) according to the introduction of AAc was observed at 3300 cm −1 in the experimental group except for the control group ( FIG. 3A ), and the grafted AAc-derived carbo It was confirmed that the absorption peak value of the nyl group (C═O) was observed at 1650 cm −1 ( FIG. 3B ). Through the above results, it was confirmed that the graft difference according to the concentration of acrylic acid was insignificant at the same gamma-ray dose.
<실험예 2> PVDF 막에 그래프트된 AAc에 결합하는 젤라틴 확인<Experimental Example 2> Confirmation of gelatin binding to AAc grafted to PVDF membrane
상기 <실시예 1>에서 제조된 Acc가 그래프트된 PVDF 막에 젤라틴 접합 여부를 확인하기 위하여 본 실험을 진행하였다. 구체적으로, 상기 <실시예 1-2>에 따라 제조한 카르복실기가 활성화된 PVDF 막을 젤라틴 접합 유무에 따라 FTIR 스펙트럼 분석을 수행하였다. This experiment was conducted to confirm whether gelatin was bonded to the PVDF membrane grafted with Acc prepared in <Example 1>. Specifically, FTIR spectral analysis was performed on the PVDF membrane with activated carboxyl groups prepared according to <Example 1-2> according to the presence or absence of gelatin bonding.
그 결과, 도 4에서 나타낸 바와 같이, AAc가 그래프트된 PVDF 막에 젤라틴을 접합한 경우 그래프트된 AAc에서 관찰되었던 카르복실기의 ―OH group에 대한 흡수가 감소한 것을 확인하였다(도 4A). 또한, AAc 도입 및 젤라틴 단백질 구조에서 기인하는 C＝O의 흡수 피크가 겹쳐 관찰되는 것을 확인하였고, 젤라틴의 N―H 굽힘에 대한 흡수가 1520 ㎝-1에서 관찰되는 것을 확인하였다(도 4B). 상기 결과를 통해 본 발명의 젤라틴이 감마선 조사를 이용해 그래프트된 AAc의 카르복실기를 통하여 PVDF 막에 화학적으로 접합된 것을 알 수 있다.As a result, as shown in FIG. 4 , it was confirmed that when gelatin was bonded to the AAc-grafted PVDF membrane, the absorption of the carboxyl group to the —OH group observed in the grafted AAc was reduced ( FIG. 4A ). In addition, it was confirmed that the absorption peak of C = O resulting from the introduction of AAc and the structure of the gelatin protein was observed overlapping, and it was confirmed that the absorption of gelatin for N-H bending was observed at 1520 cm -1 (FIG. 4B). From the above results, it can be seen that the gelatin of the present invention was chemically bonded to the PVDF membrane through the carboxyl group of AAc grafted using gamma irradiation.
<실험예 3> 젤라틴이 접합된 PVDF 막의 인 제거능 확인<Experimental Example 3> Confirmation of phosphorus removal ability of PVDF membrane bonded with gelatin
상기 <실시예 1>에서 제조한, 젤라틴이 접합된 PVDF 막의 인 제거능을 확인하기 위하여 본 실험을 진행하였다. 구체적으로, 상기 <실시예 1-1>에 따라 제조한 감마선 조사를 통해 AAc가 그래프트된 PVDF 막, 및 상기 <실시예 1>에 따라 제조한 젤라틴이 접합된 PVDF 막을 이용하여 혈액투석의 샘플링을 행하고, 인 농도를 측정하였다. 대조군으로 감마선 조사 및 젤라틴을 처리하지 않은 PVDF 막, 즉 젤라틴이 접합되지 않은 기존의 투석막을 사용하였다. This experiment was conducted to confirm the phosphorus removal ability of the PVDF membrane to which the gelatin was bonded, prepared in <Example 1>. Specifically, hemodialysis sampling was performed using a PVDF membrane grafted with AAc through gamma irradiation prepared according to <Example 1-1>, and a PVDF membrane conjugated with gelatin prepared according to <Example 1>. and the phosphorus concentration was measured. As a control, a PVDF membrane not treated with gamma-irradiation and gelatin, that is, a conventional dialysis membrane not bonded with gelatin was used.
그 결과, 도 5에서 나타낸 바와 같이, 기존의 투석막 및 AAc가 도입된 투석막의 잔존 인산염을 기준으로 젤라틴이 접합된 PVDF 막은 약 85 ％의 인산염만이 잔존하여 대조군 대비 인 제거율이 약 15 ％ 증가하는 것을 확인하였다. 상기 결과를 통해 젤라틴이 접합된 혈액 투석막은 혈액투석 시 인산염 제거 능력이 향상되는 것을 확인하였다. 또한, 본 발명에 따라 감마선을 이용하여 소수성을 갖는 혈액 투석막 표면에 AAc를 그래프트하고, 이를 이용하여 젤라틴을 화학적으로 접합함으로써, 투석막의 인산염(phoshate) 흡착 능력이 향상된 것을 확인하였다.As a result, as shown in FIG. 5, based on the residual phosphate of the conventional dialysis membrane and the AAc-introduced PVDF membrane, only about 85% of the phosphate remained in the PVDF membrane bonded with gelatin, and the phosphorus removal rate was increased by about 15% compared to the control. confirmed that. From the above results, it was confirmed that the gelatin-conjugated hemodialysis membrane had improved phosphate removal ability during hemodialysis. In addition, according to the present invention, it was confirmed that the phosphate adsorption capacity of the dialysis membrane was improved by grafting AAc to the hydrophobic hemodialysis membrane surface using gamma rays and chemically bonding the gelatin using this.
Claims (17)
상기 혈액 투석막은 젤라틴이 코팅된 것이고,
상기 혈액 투석막은
소수성 투석막으로 이루어진 제1층;
상기 소수성 투석막에 그래프트(graft)되어 형성된 아크릴산(acrylic acid) 또는 아크릴계 고분자의 그래프트 중합체로 이루어진 제2층; 및
상기 아크릴산 또는 아크릴계 고분자에 접합된 젤라틴으로 이루어진 제3층;으로 이루어지는 것을 특징으로 하는, 인산염 흡착능력이 향상된 혈액 투석막.
A hemodialysis membrane with improved phosphate adsorption capacity, comprising:
The hemodialysis membrane is gelatin-coated,
The hemodialysis membrane is
a first layer made of a hydrophobic dialysis membrane;
a second layer made of a graft polymer of acrylic acid or an acrylic polymer, which is grafted onto the hydrophobic dialysis membrane; and
A hemodialysis membrane with improved phosphate adsorption capacity, characterized in that it comprises; a third layer made of gelatin bonded to the acrylic acid or acrylic polymer.
According to claim 1, wherein the hydrophobic dialysis membrane is polyvinylidene fluoride (polyvinylidene fluoride, PVDF), polycarbonate (PC), polysulfone (PSF), polyethersulfone (polyethersulfone, PES), polyetherimide (polyetherimide, PEI), polyimide (polyimide, PI), polyethylene (PE), polypropylene (polypropylene, PP) and polyamide (polyamide, PA) characterized in that at least one selected from the group consisting of, Hemodialysis membrane with improved phosphate adsorption capacity.
The hemodialysis membrane with improved phosphate adsorption capacity according to claim 1, wherein the hydrophobic dialysis membrane is modified into a hydrophilic dialysis membrane by irradiating gamma rays.
[Claim 5] The hemodialysis membrane with improved phosphate adsorption capacity according to claim 4, wherein the gamma rays are irradiated with a dose of 1 to 30 kGy.
[Claim 5] The hemodialysis membrane with improved phosphate adsorption capacity according to claim 4, wherein the gamma rays are irradiated for 6 to 180 minutes.
The hemodialysis membrane with improved phosphate adsorption capacity according to claim 1, wherein the graft is characterized in that a carboxy group is attached to the hydrophobic dialysis membrane by treatment with acrylic acid.
The hemodialysis membrane with improved phosphate adsorption capacity according to claim 7, wherein the acrylic acid has a concentration of 0.1 to 10 wt%.
The hemodialysis membrane with improved phosphate adsorption capacity according to claim 1, wherein the gelatin has a concentration of 20 to 2000 μg/ml.
2) 상기 제2층 상에 젤라틴을 접합하여 제3층을 제조하는 단계;를 포함하는, 인산염 흡착능력이 향상된 혈액 투석막의 제조방법.
1) preparing a second layer by performing a graft polymerization reaction on the hydrophobic dialysis membrane of the first layer with a solution containing a solvent and a graft polymer of acrylic acid or an acrylic polymer using simultaneous gamma-ray irradiation;
2) manufacturing a third layer by bonding gelatin on the second layer;
The method of claim 10, wherein the hydrophobic dialysis membrane is polyvinylidene fluoride (PVDF), polycarbonate (PC), polysulfone (PSF), polyethersulfone (polyethersulfone, PES), polyetherimide (polyetherimide, PEI), polyimide (polyimide, PI), polyethylene (PE), polypropylene (polypropylene, PP) and polyamide (polyamide, PA) characterized in that at least one selected from the group consisting of, A method for manufacturing a hemodialysis membrane with improved phosphate adsorption capacity.
11. The method of claim 10, wherein the hydrophobic dialysis membrane is modified into a hydrophilic dialysis membrane by irradiating gamma rays.
The method of claim 10, wherein the gamma rays are irradiated with a dose of 1 to 30 kGy.
11. The method of claim 10, wherein the gamma rays are irradiated for 6 to 180 minutes.
[Claim 11] The method of claim 10, wherein the graft is treated with acrylic acid to attach a carboxy group to the hydrophobic dialysis membrane.
[16] The method of claim 15, wherein the acrylic acid has a concentration of 0.1 to 10 wt%.
11. The method of claim 10, wherein the gelatin has a concentration of 20 to 2000 μg/ml.
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| KR1020200140913A KR102428696B1 (en) | 2020-10-28 | 2020-10-28 | Hemodialysis membrane with improved phosphate adsorption ability and method for manufacturing same |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070125709A1 (en) * | 2005-09-02 | 2007-06-07 | Alok Nigam | Extracorporeal Renal Dialysis System |
| KR100859995B1 (en) | 2002-05-09 | 2008-09-25 | 헤모텍 아게 | Compounds and method for coating surfaces in a hemocompatible manner |
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- 2020-10-28 KR KR1020200140913A patent/KR102428696B1/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100859995B1 (en) | 2002-05-09 | 2008-09-25 | 헤모텍 아게 | Compounds and method for coating surfaces in a hemocompatible manner |
| US20070125709A1 (en) * | 2005-09-02 | 2007-06-07 | Alok Nigam | Extracorporeal Renal Dialysis System |
Non-Patent Citations (2)
| Title |
|---|
| Scientific Reports, Vol. 7, Article number: 2721, 2017. 6. 2. |
| Separation and Purification Technology, 207, 2018.6.19., 83~91 |
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| Publication number | Publication date |
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| KR20220056382A (en) | 2022-05-06 |
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