CN111956789A - 一种适用于血液净化患者的营养物的制备方法及营养物 - Google Patents
一种适用于血液净化患者的营养物的制备方法及营养物 Download PDFInfo
- Publication number
- CN111956789A CN111956789A CN202010698121.3A CN202010698121A CN111956789A CN 111956789 A CN111956789 A CN 111956789A CN 202010698121 A CN202010698121 A CN 202010698121A CN 111956789 A CN111956789 A CN 111956789A
- Authority
- CN
- China
- Prior art keywords
- nutrient
- blood
- patient
- membrane separation
- plasma
- 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.)
- Pending
Links
- 210000004369 blood Anatomy 0.000 title claims abstract description 126
- 239000008280 blood Substances 0.000 title claims abstract description 126
- 235000015097 nutrients Nutrition 0.000 title claims abstract description 77
- 238000000746 purification Methods 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000012528 membrane Substances 0.000 claims abstract description 76
- 238000000926 separation method Methods 0.000 claims abstract description 55
- 210000002381 plasma Anatomy 0.000 claims abstract description 38
- 210000002966 serum Anatomy 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims description 32
- 238000000502 dialysis Methods 0.000 claims description 28
- 239000003085 diluting agent Substances 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 9
- 238000001631 haemodialysis Methods 0.000 claims description 7
- 230000000322 hemodialysis Effects 0.000 claims description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 150000003384 small molecules Chemical class 0.000 claims description 6
- 210000000601 blood cell Anatomy 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 5
- 239000011148 porous material Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 238000003113 dilution method Methods 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 3
- 239000007853 buffer solution Substances 0.000 claims description 3
- 238000007865 diluting Methods 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 239000000644 isotonic solution Substances 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000003862 health status Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 abstract description 33
- 108090000623 proteins and genes Proteins 0.000 abstract description 33
- 239000000126 substance Substances 0.000 abstract description 19
- 208000002720 Malnutrition Diseases 0.000 abstract description 9
- 235000000824 malnutrition Nutrition 0.000 abstract description 9
- 230000001071 malnutrition Effects 0.000 abstract description 9
- 208000015380 nutritional deficiency disease Diseases 0.000 abstract description 9
- 238000002474 experimental method Methods 0.000 abstract description 5
- 230000005802 health problem Effects 0.000 abstract description 3
- 210000004379 membrane Anatomy 0.000 description 59
- 235000018102 proteins Nutrition 0.000 description 29
- 239000000306 component Substances 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 11
- 150000001413 amino acids Chemical class 0.000 description 11
- 239000012141 concentrate Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 239000011550 stock solution Substances 0.000 description 10
- 238000000108 ultra-filtration Methods 0.000 description 9
- 241000700605 Viruses Species 0.000 description 8
- 230000002779 inactivation Effects 0.000 description 8
- 238000012423 maintenance Methods 0.000 description 8
- 229940088597 hormone Drugs 0.000 description 7
- 239000005556 hormone Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 6
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 6
- 229960002478 aldosterone Drugs 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- 239000012503 blood component Substances 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002699 waste material Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 235000003715 nutritional status Nutrition 0.000 description 4
- 230000002572 peristaltic effect Effects 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 239000008176 lyophilized powder Substances 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000011573 trace mineral Substances 0.000 description 3
- 235000013619 trace mineral Nutrition 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 102400000739 Corticotropin Human genes 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- 102000000541 Defensins Human genes 0.000 description 2
- 108010002069 Defensins Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 208000028208 end stage renal disease Diseases 0.000 description 2
- 201000000523 end stage renal failure Diseases 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 2
- 229960001008 heparin sodium Drugs 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 235000004252 protein component Nutrition 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000012959 renal replacement therapy Methods 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- LVRVABPNVHYXRT-BQWXUCBYSA-N 52906-92-0 Chemical compound C([C@H](N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)C1=CC=CC=C1 LVRVABPNVHYXRT-BQWXUCBYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 1
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 1
- 102000009081 Apolipoprotein A-II Human genes 0.000 description 1
- 108010087614 Apolipoprotein A-II Proteins 0.000 description 1
- 229940122155 Bradykinin receptor antagonist Drugs 0.000 description 1
- 102000010792 Chromogranin A Human genes 0.000 description 1
- 108010038447 Chromogranin A Proteins 0.000 description 1
- 102000003780 Clusterin Human genes 0.000 description 1
- 108090000197 Clusterin Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102100024338 Collagen alpha-3(VI) chain Human genes 0.000 description 1
- 102000003706 Complement factor D Human genes 0.000 description 1
- 108090000059 Complement factor D Proteins 0.000 description 1
- 108010061635 Cystatin B Proteins 0.000 description 1
- 108010061642 Cystatin C Proteins 0.000 description 1
- 102100026891 Cystatin-B Human genes 0.000 description 1
- 102100026897 Cystatin-C Human genes 0.000 description 1
- 108010045579 Desmoglein 1 Proteins 0.000 description 1
- 102100034579 Desmoglein-1 Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102400000524 Fibrinogen alpha chain Human genes 0.000 description 1
- 101710137044 Fibrinogen alpha chain Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 101000909506 Homo sapiens Collagen alpha-3(VI) chain Proteins 0.000 description 1
- 101000869480 Homo sapiens Serum amyloid A-1 protein Proteins 0.000 description 1
- 101000637821 Homo sapiens Serum amyloid A-2 protein Proteins 0.000 description 1
- 208000003623 Hypoalbuminemia Diseases 0.000 description 1
- 206010020961 Hypocholesterolaemia Diseases 0.000 description 1
- 208000034767 Hypoproteinaemia Diseases 0.000 description 1
- 102100027403 Immunoglobulin kappa variable 3D-20 Human genes 0.000 description 1
- 101710163526 Immunoglobulin kappa variable 3D-20 Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102100027017 Latent-transforming growth factor beta-binding protein 2 Human genes 0.000 description 1
- 101710178974 Latent-transforming growth factor beta-binding protein 2 Proteins 0.000 description 1
- 102100033468 Lysozyme C Human genes 0.000 description 1
- 108050000633 Lysozyme C Proteins 0.000 description 1
- 102400001357 Motilin Human genes 0.000 description 1
- 101800002372 Motilin Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 102100038246 Retinol-binding protein 4 Human genes 0.000 description 1
- 101710137011 Retinol-binding protein 4 Proteins 0.000 description 1
- 102100021853 Secreted and transmembrane protein 1 Human genes 0.000 description 1
- 101710126682 Secreted and transmembrane protein 1 Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102100032277 Serum amyloid A-1 protein Human genes 0.000 description 1
- 102100032007 Serum amyloid A-2 protein Human genes 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- 108010046075 Thymosin Proteins 0.000 description 1
- 102000007501 Thymosin Human genes 0.000 description 1
- 102100034998 Thymosin beta-10 Human genes 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 101710100170 Unknown protein Proteins 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 102000050760 Vitamin D-binding protein Human genes 0.000 description 1
- 108700021020 Vitamin D-binding protein Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007485 conventional hemodialysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000000385 dialysis solution Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000007160 gastrointestinal dysfunction Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 102000029752 retinol binding Human genes 0.000 description 1
- 108091000053 retinol binding Proteins 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
- 108010044465 thymosin beta(10) Proteins 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 239000002441 uremic toxin Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/043—Kallidins; Bradykinins; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/085—Angiotensins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1729—Cationic antimicrobial peptides, e.g. defensins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1754—Insulin-like growth factor binding proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- A61K38/35—Corticotropin [ACTH]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Marine Sciences & Fisheries (AREA)
- Molecular Biology (AREA)
- Obesity (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Nutrition Science (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- External Artificial Organs (AREA)
Abstract
本发明属于分子生物学技术领域,具体公开了一种适用于血液净化患者的营养物的制备方法及获得的营养物。本发明的营养物的制备方法包括将正常人血液、血浆、血清中的任意一种进行膜分离,采用的分离膜的孔径为2~20nm。采用该孔径的分离膜分离得到的超滤液所含成分与血液净化患者在血液净化过程中所丢失物质成分类似,经实验证明,将该超滤液作为营养物输入到患者体内,不仅能有效地改善血液净化患者营养不良状况,特别是能维持体内低分子蛋白浓度,有效解决目前血液净化患者的健康问题。
Description
技术领域
本发明涉及分子生物学技术领域,特别是涉及一种生物制品,尤其是一种适用于血液净化患者的营养物的制备方法及获得的营养物。
背景技术
血液净化是通过清除体内的毒素和废物,移除体内过量的体液,来控制电解质和酸碱度平衡的一种临床治疗手段。血液净化能替代部分肾功能,是终末期肾脏病患者的主要替代治疗方式。对于终末期肾脏病患者,通过定时地进行维持性血液净化治疗,可以延长患者的生存期,改善生活质量,降低并发症。
但是,由于微炎症状态、毒素的蓄积和治疗并发症的药物(如铁剂、磷结合剂)等导致的食欲减退、消化不良以及胃肠功能紊乱在维持性血液净化患者中比较常见,影响了患者蛋白质-能量的摄入。虽然血液净化能清除人体内代谢产生的废物,但血液净化过程中也伴随着大量氨基酸、多肽、蛋白质、水溶性维生素、激素以及葡萄糖等营养物质的流失。例如在一次普通血液净化过程中,约丢失氨基酸10±2g。短期内,这些物质的丢失对患者健康的影响不明显,随着治疗时间的延长,维持性血液净化患者大多会出现蛋白质能量代谢异常,骨骼肌和脂肪明显消耗,表现在血液生化上为低胆固醇血症、低蛋白血症以及低前白蛋白。在维持性血液净化患者中,营养不良的患者可达到23%~76%。
血液净化过程中蛋白质的丢失以及能量摄入不足是维持性血液净化患者营养不良最重要的原因。长期透析形成的消耗状态或营养不良,会直接影响血液净化患者的死亡率和各种并发症的发病率。且营养不良还导致透析耐受性下降,出现感染以及心脑血管并发症的风险进一步增加。营养不良已成为维持性血液净化患者独立的死亡危险因素,也是预测维持性血液净化患者发病率和死亡率的重要预测因素。此外,在血液净化过程中,还存在一些功能性多肽和蛋白的流失,受患者体质状况的影响,可能这部分功能性蛋白无法自身补给,导致患者体内某些功能性蛋白缺失,从而影响患者的健康状况。
因此,提供一种适用于血液净化患者的营养物,以改善患者的营养不良状况,是一个需要亟待解决的问题。
发明内容
本发明主要解决的技术问题是提供一种适用于血液净化患者的营养物的制备方法,以及制备获得的营养物。
具体地,第一方面,本发明提供了一种适用于血液净化患者的营养物的制备方法,包括步骤:将正常血液、血浆、血清中的任意一种进行膜分离,采用的分离膜的孔径为2~20nm。采用该孔径的分离膜分离得到的超滤液所含成分与血液净化患者在血液净化过程中所丢失物质成分类似,将该超滤液作为营养物输入到患者体内,不仅能有效地改善血液净化患者营养不良状况,特别是能维持体内低分子蛋白浓度,有效解决目前血液净化患者的健康问题。
其中,所述正常血液、血浆或血清为人的正常血液、血浆或血清。
作为本发明一种优选的实施方案,所述正常血液、血浆或血清膜分离时还包括对所述正常血液、血浆或血清稀释步骤,采用的稀释液为纯水或水溶液,优选所述水溶液为生理盐水、血液透析用透析液、含葡萄糖的等渗溶液、pH值为6~8的Tris-盐酸缓冲液中的任意一种或几种的组合。
作为本发明一种优选的实施方案,稀释步骤采用的稀释方法包括两种,一种是在膜分离之前将所述稀释液与正常血液、血浆或血清混合,另一种是在膜分离过程中将所述稀释液与正常血液、血浆或血清混合。
作为本发明一种优选的实施方案,若在膜分离之前将所述稀释液与正常血液、血浆或血清混合,正常血液、血浆或血清与稀释液的混合体积比为(0.1~5):1;若在膜分离过程中将所述稀释液与正常血液、血浆或血清混合,正常血液、血浆或血清与稀释液的混合体积比为1:(0.1~10)。
作为本发明一种优选的实施方案,在进行膜分离时,进行膜分离的处理液中如含有血细胞,例如处理液是正常血液或者正常血液与稀释液的混合液时,膜分离后超滤液的收集速度为处理液流速的5~30%。如果进行膜分离的处理液中不含血细胞,例如处理液是正常血浆、正常血清、正常血浆与稀释液的混合液或者正常血清与稀释液的混合液,膜分离后超滤液的收集速度为处理液流速的5~50%。
进一步优选地,所述分离膜的孔径为3~8nm。选择该孔径的分离膜,有利于获得的营养物成分更接近于透析患者体内流失的物质成分,达到更佳的补充效果。
作为本发明一种优选的实施方案,在所述膜分离之后还包括浓缩步骤;所述浓缩步骤为冻干处理和/或除去小分子的处理。
优选地,所述除去小分子的处理是采用1kDa半透膜透析或者采用孔径为1kDa的离心管离心。
作为本发明一种优选的实施方案,所述制备方法还包括对营养物中成分进行调整步骤,优选地,所述成分调整包括对营养物中氨基酸、糖、矿物质、微量元素、维生素、激素及蛋白质中的一种或多种成分的含量进行调整。更优选地,调整后每100mL所述营养物中含有:
作为本发明一种优选的实施方案,在所述膜分离之后还包括病毒灭活步骤。由于本发明采用的分离膜的膜孔径小于20nm,因此原料中的大部分病毒不能透过膜,超滤过程中可以完成病毒的清除,因此一般获得的超滤液经病毒检测是合格的,无须进一步灭活。但在需要灭活时,可以增加该病毒灭活步骤。
第二方面,本发明提供了一种适用于血液净化患者的营养物,所述营养物由上述的制备方法获得。
其中,所述营养物成分的分子量在70kDa以内。
本发明提供的一种适用于血液净化患者的营养物,所述营养物中含有以下成分:以每100mL所述营养物计算,含有:
优选地,所述营养物中还包括以下成分:以每100mL所述营养物计算,含有:
本发明提供的营养物适用于血液净化患者,可以用于制备改善血液净化患者健康状况的药物。
本发明是采用正常血液或含有正常血液成分的液体如血浆或血清作为原料,正常血液或含有正常血液成分的液体中各种营养物质及小分子蛋白处于平衡状况,通过膜分离超滤处理后,得到的超滤液所含成分与血液净化患者在血液净化过程中所丢失物质类似,将该超滤液作为营养物输入到患者体内,不仅能有效地改善血液净化患者营养不良状况,特别是能维持低分子蛋白浓度,有效解决目前血液净化患者面临的健康问题。
本发明提供的营养物,其中含有血清蛋白,其中血清蛋白成分分子量在70kDa以内。本发明的营养物可有效改善血液净化患者的营养状况,维持血液中小分子蛋白浓度的平衡。研究发现,只单纯提高维持性血液净化患者的能量、蛋白等营养素的摄入并不能完全纠正患者的营养不良状况。本发明试验发现,采用本发明的营养物可以在治疗过程中维持血液净化患者正常的营养状况,改善患者的小分子蛋白平衡,达到维持患者健康稳定的效果。
本发明提供的营养物,可以在制备得到的超滤液的基础上,再对其成分进行调整,例如对其中患者体内需要的氨基酸、糖、矿物质、微量元素、水溶性纤维素、激素或多肽等成分的含量进行调整,可以进行增加或降低,以更好的改善维持性血液净化患者的营养状况。
具体地,本发明提供的营养物在制备时,还包括对正常血液、血浆或血清进行稀释的步骤,稀释液为纯水或水溶液。其中,所述水溶液为生理盐水、血液透析用透析液、含葡萄糖的等渗溶液、pH值为6~8的Tris-盐酸缓冲液中的一种。稀释处理有利于血液或含有血液成分的液体通过膜分离器,实现理想的超滤分离效果。
在对正常血液、血浆或血清进行稀释时,可以采用以下两种方法进行稀释。第一种方法,先将稀释液与正常血液、血浆或血清混合,制成膜分离原液,之后进行膜分离处理;第二种方法,将稀释液与正常血液、血浆或血清在膜分离器内混合进行膜分离处理。
对于第一种稀释方法,稀释液与正常血液、血浆或血清混合时,正常血液、血浆或血清与稀释液的体积比为(0.1~5):1。
对于第二种稀释方法,稀释液与正常血液、血浆或血清在膜分离器内混合时,正常血液、血浆或血清与稀释液的体积比为1:(0.1~10)。
本发明提供的营养物在制备时,膜分离采用的膜分离器可以是透析仪。
在膜分离时,将原液,或者正常血液、血浆或血清,从膜分离器一端进入,另一端流出。利用蠕动泵或真空系统或加压装置,从膜分离器中(另一侧)收集超滤液作为营养物,即通过动力装置利用压强差将超滤液分离出来。
在膜分离时,所述原液,或者正常血液、血浆或血清,可以循环通过所述膜分离器。所述超滤液也可以循环通过所述膜分离器,在血端各物质含量达到平衡后停止循环并收集,以提高分离效率。
当然,所述原液,或者正常血液、血浆或血清,也可单次通过所述膜分离器。
优选的,所述超滤液的收集速度为原液,或者,正常血液、血浆或血清流速的5~50%,可以避免膜堵塞,有利于超滤的进行。
对于含有血细胞的原液或正常血液,超滤液的收集速度优选为原液或正常血液流速的5~30%,可以避免对细胞的损坏,发生凝血。
在本发明中,将原液,或者正常血液、血浆或血清,从膜分离器一端进入,另一端流出。利用蠕动泵或真空系统或加压装置,从膜分离器另一侧收集得到超滤液。
本发明收集超滤液的量可控制与稀释液等量或大于稀释液。优选收集的超滤液的体积为稀释液体积的1~1.2倍。
在本发明中,获得的超滤液还可以进一步采用透析、低温离心超滤、分子量截留中的一种或几种方法进行处理,处理获得含有不同截留分子量的超滤液,优选所述超滤液包含分子量≥0.1kDa、≥0.3kDa、≥0.5kDa、≥1kDa、≥2kDa、≥5kDa、≥10kDa、≥15kDa和≥20kDa的成分。
本发明的制备方法还包括将制备得到的所述超滤液进行浓缩的步骤,所述浓缩方式包括透析、低温离心超滤、高压压滤、减压浓缩及冻干中的一种或多种。例如所述浓缩指将超滤液进行脱水及除去部分小分子的处理,可获得高浓度的浓缩物,还可以再冻干得到冻干粉。使用时,所述浓缩物或冻干粉经溶解复配后,直接通过静脉输入或在透析治疗结束时从回血端输入患者体内。
所得浓缩物可以根据血型不同分开,也可以将不同血型浓缩物按照任意比例混合使用。
本发明中可根据具体需要进一步调整超滤液的组成,也可进一步调整超滤液浓缩后得到的例如冻干粉的组成,使其包含不同分子量成份的浓缩物。
本发明提供的营养物可以用于制备改善血液净化患者健康状况的药物。
本发明的制备方法简便,制备得到的营养物可改善血液净化患者营养状况,维持血液中小分子蛋白浓度平衡,提高患者生存期。
附图说明
图1是本发明提供的第一种营养物制备装置的示意图;
图2是本发明提供的第二种营养物制备装置的示意图;
图3是本发明提供的第三种营养物制备装置的示意图;
图4是本发明提供的第四种营养物制备装置的示意图。
具体实施方式
下面通过具体实施例对本发明的技术方案进行详细说明。需要理解的是以下实施例的给出仅是为了起到说明的目的,并不是用于对本发明的范围进行限制。本领域的技术人员在不背离本发明的宗旨和精神的情况下,可以对本发明进行各种修改和替换。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1
本实施例提供了一种适用于血液净化患者的营养物的制备方法,具体如下:
取200mL由1.38g透析A粉与0.588g透析B粉(透析A粉和透析B粉均购自北京联合易康医疗器械公司)配置的透析液,加入到800mL正常新鲜的人血液中,再加入50IU肝素钠抗凝剂,搅拌均匀,得到膜分离原液,之后进行膜分离。
膜分离采用图1所示的装置,其中膜分离器为透析仪,透析仪采用德国费森尤斯公司的透析仪,型号为FX80,采用的分离膜的孔径为3.3nm,膜面积为1.8m2。
膜分离具体过程为:膜分离原液利用血泵以100mL/min的流速通过透析仪,在透析仪的另一侧采用蠕动泵以10mL/min速度收集超滤液,共收集超滤液200mL。所得超滤液即营养物。
采用考马斯亮蓝法(稀释200倍后)分别测试原血(正常新鲜血液)、稀释血(加入透析液后的原血)、滤后血(超滤后的血液)及超滤液中蛋白质的含量。测试结果见表1。
表1
由表1结果可以计算得出,超滤液中蛋白质总量为:0.27g/L×0.2L=0.054g。
所得超滤液经过凝胶电泳测试,主要成份分子量小于70kDa。
当然,得到的超滤液也可以循环通过膜分离器,即采用图2所示的装置,在血端各物质含量达到平衡后停止循环并收集,得到营养物,以提高分离效率。
实施例2
本实施例提供了一种适用于血液净化患者的营养物的制备方法,具体如下:
取600mL正常新鲜的人血液,加入50IU肝素钠抗凝剂,搅拌均匀,之后进行膜分离。
膜分离采用图3所示的装置,其中膜分离器为透析仪,透析仪采用德国费森尤斯公司的透析仪,型号为FX80,采用的分离膜的孔径为3.3nm,膜面积为1.8m2。
膜分离具体过程为:添加有抗凝素的正常血液利用血泵以100mL/min的流速通过透析仪,同时在透析仪的另一侧加入1200mL透析液(即稀释液,由8.28g透析A粉与3.528g透析B粉和去离子水配置而成),采用蠕动泵以200mL/min速度通过透析仪,循环交换30min,收集得到超滤液1300mL。所得超滤液即营养物。
采用考马斯亮蓝法(稀释200倍后)分别测试原血(正常新鲜血液)、滤后血(超滤后的血液)及超滤液中蛋白质的含量。测试结果见表2。
表2
由表2结果可以计算得出,超滤液中蛋白质总量为:0.04g/L×1.3L=0.052g。血液经膜分离损失的蛋白质总量为2.46g。说明透析过程中血液中存在明显的蛋白流失情况,蛋白流失量大于超滤液中蛋白总量,表明部分蛋白被吸附在透析仪上。
所得超滤液经过凝胶电泳测试,主要成份分子量小于70kDa。
当然,也可以将本实施例的超滤液循环交换改为单次通过透析仪即收集的方式进行制备,即采用图4所示的装置进行制备。
实施例3
本实施例提供了一种对制得的超滤液进行病毒灭活的方法。
取采用实施例1方法制备得到的适用于血液净化患者的营养物,进行病毒灭活,具体如下。
将采用实施例1方法制备得到的适用于血液净化患者的营养物进一步采用S/D灭活方式进行病毒灭活。具体操作为:向超滤液(即营养物)中加入三硝基丁基磷酸酯(TNBP)和Tween 80,使最终质量浓度分别为0.3%和1.0%,在25±1℃下孵育6h,即可完成病毒灭活。向灭活后的超滤液中加入相当于超滤液体积1/5的大豆油,搅拌均匀后,静置分层,重复操作3次,萃出TNBP和Tween 80,得到灭活的超滤液。
实施例4
本实施例提供了一种对制得的超滤液进行浓缩的方法。
取采用实施例1方法制备得到的适用于血液净化患者的营养物200mL,冷却至-30℃凝固后,置于低温冷冻箱中,冷冻干燥,得白色冻干粉,无菌密封后于4℃保存。
实施例5
本实施例提供了另一种对制得的超滤液进行浓缩的方法。
取采用实施例1方法制备得到的适用于血液净化患者的营养物200mL,置于1kDa半透膜中,在无菌水中透析4h,除去小分子成分,真空减压浓缩,浓缩液冷却至-30℃~-50℃凝固后,冻干,得白色粉末,无菌密封后低温保存。
实施例6
本实施例提供了又一种对制得的超滤液进行浓缩的方法。
取采用实施例1方法制备得到的适用于血液净化患者的营养物200mL,置于孔径为1kDa的离心管中,4℃左右离心浓缩,浓缩液冷却至-30℃~-50℃凝固后,真空冻干,无菌密封后低温保存。
效果实验例
本实验例进行了以下实验和研究。
分别收集了4名血液透析(HD法)患者透析废弃液各120L,采用电化学发光全自动免疫分析(罗氏:cobas e411),测试废弃液中各物质的浓度,进一步计算得到透析治疗过程中各患者血液丢失物质的总量,4名患者的透析废弃液检测结果见表3所示,其中,FX80、F14、R400分别代表透析仪的型号。
表3
注:表中“/”表示未检出。
分别收集了3名CRRT(连续性肾脏替代治疗法)患者的透析液各20L,测试透析液中各物质浓度,计算CRRT治疗过程中血液中丢失物质的量,检测结果如表4所示。
表4
由表3、表4的检测结果可知,血液净化过程中激素和小分子蛋白等具有重要生理功能的物质流失在各透析方式不同时虽存在差异,但流失现象均十分明显。
取实施例1制备得到的营养物,采用孔径为1kDa的膜,将营养物进行超滤浓缩,经胰蛋白酶酶解成多肽。通过UPLC/QTOF-MS方法对肽段进行序列分析,并通过已有蛋白质库进行数据比对,分析出实施例1获得的营养物中已知蛋白的种类,结果如表5所示。
表5
纤维蛋白原α链 | 载脂蛋白A2 |
β微球蛋白 | 溶菌酶C |
血清胱抑素C | 补体成分 |
视黄醇结合蛋白4 | D2前列腺素合成酶 |
视黄醇结合蛋白前体 | 白蛋白 |
免疫球蛋白卡帕尔 | 半胱氨酸蛋白酶抑制剂B |
半胱氨酸蛋白酶抑制素 | 丝氨酸肽酶抑制剂 |
血清淀粉样蛋白A1 | 潜在转化生长因子贝塔结合蛋白2 |
前纤维蛋白1抗体 | 胶原型VI阿尔法3链 |
免疫球蛋白 | 胸腺素β10 |
载脂蛋白A1 | 桥粒糖蛋白1抗体 |
补充因子D | 嗜铬粒蛋白A |
胰岛素 | 血管紧张肽原前体 |
丛生蛋白 | 胃动蛋白 |
肌动蛋白 | 胸腺素4 |
血清淀粉样蛋白A2 | 甲朊酸亚单位阿尔法前体 |
免疫球蛋白卡帕尔可变3D-20 | 胶原蛋白I阿尔法2链 |
促甲状腺激素 | 防御素1 |
白细胞介素6 | 促肾上腺皮质激素 |
基底膜聚糖 | 分泌和跨膜蛋白1 |
微球蛋白前体 | 硫氧还蛋白 |
1-抗胰蛋白酶 | 胰岛素样生长因子结合蛋白 |
通过数据库比对,确定了营养物中已知蛋白有42种,其中包括部分尿毒症毒素分子,而未知蛋白种类超过100多种。
通过商用专一性ELISA检测试剂盒对实施例1获得的200mL营养物中部分已知蛋白进行了定量分析。在包被一抗的96孔板中加入营养物,检测目标蛋白与固相抗体结合,再加入酶标记的二抗,使之与目标蛋白结合,反应后加入底物显色,颜色的深浅与目标蛋白的量成正比,通过酶标仪测定具体数值,结果如表6所示。
表6
蛋白种类 | 含量 |
醛固酮 | 1.5μg |
白蛋白 | 5.0mg |
血管紧张素 | 0.93μg |
血管舒缓激肽 | 1.7μg |
防御素 | 3.2μg |
胰岛素样生长因子结合蛋白 | 4.5μg |
黏蛋白 | 0.5μg |
维生素D结合蛋白 | 1.3μg |
对以上选择的4名血液透析(HD法)患者和3名CRRT(连续性肾脏替代治疗法)患者进行情况分析,患者基本情况如下表7所示。
表7
患者基本情况: | 4男,3女 |
年龄(岁) | 49(25-60) |
透析时间(月) | 20(14-40) |
体重(kg) | 60(52-75) |
BMI(kg/m<sup>2</sup>) | 22(19-30) |
白蛋白(g/L) | 37(34-42) |
按照常规血液透析对选取的患者进行透析,分析透析前后血液中物质流失情况。透析完成后,取按照实施例5方法制备得到的营养物冻干粉,并对其成分进行调整,得到浓缩物,每个患者体内输入浓缩物100mL,之后检测患者体内血液成分的变化情况。
其中成分调整的方法为:取按照实施例5方法制备得到的营养物冻干粉0.5g,将其溶于按照表8所示的成分和浓度配置的氨基酸溶液中,之后添加葡萄糖和部分激素以及蛋白成分,制备成100mL的浓缩物。
表8
每100mL的浓缩物中含有氨基酸总量2.87g,总蛋白量1.5g,葡萄糖5g,还含有激素、微量元素、维生素及矿物质等。其中激素的代表性成分含量见表9。
表9
成分 | 含量 |
促肾上腺皮质激素 | 1.0μg |
睾酮 | 1.0μg |
肾上腺糖皮质激素 | 2.0mmol |
促甲状腺激素 | 0.85mIU |
甲状腺激素T3 | 15.1pmol |
维生素B12 | 250ng |
胰岛素 | 5.2μU |
生长激素 | 1.0μg |
胆固醇 | 10mmol |
甘油三脂 | 3mmol |
选取的7名患者在输入以上浓缩物之后,患者血浆氨基酸浓度的结果对比见表10。患者血浆代表性物质浓度变化的结果对比见表11。
表10
从表10结果可以看出,透析后氨基酸流失非常明显,总流失量大;通过添加营养物后,血液中的氨基酸得到补充,使得透析前后的变化较小,大部分氨基酸浓度保持平稳。当然,针对部分特异性氨基酸可以基于患者进行个体化调整,从而达到更好的效果。
表11如下。
表11
从表11结果中可以看出,通过检测几种代表性物质浓度变化,可以发现,透析前后小分子物质浓度变化较大,如胰岛素和醛固酮。尤其是醛固酮,透析后浓度不到透析前的一半。通过流加营养物后,醛固酮的浓度明显得到提升,几乎恢复到透析前的含量,保证了透析患者的健康水平。
虽然,上文中已经用一般性说明、具体实施方式及试验,对本发明作了详尽的描述,但在本发明基础上,可以对之作一些修改或改进,这对本领域技术人员而言是显而易见的。因此,在不偏离本发明精神的基础上所做的这些修改或改进,均属于本发明要求保护的范围。
Claims (10)
1.一种适用于血液净化患者的营养物的制备方法,其特征在于,包括步骤:将正常血液、血浆、血清中的任意一种进行膜分离,采用的分离膜的孔径为2~20nm。
2.根据权利要求1所述的制备方法,其特征在于,所述正常血液、血浆或血清膜分离时还包括对所述正常血液、血浆或血清稀释步骤,采用的稀释液为纯水或水溶液,优选所述水溶液为生理盐水、血液透析用透析液、含葡萄糖的等渗溶液、pH值为6~8的Tris-盐酸缓冲液中的任意一种或几种的组合;进一步优选地,稀释方法为在膜分离之前将所述稀释液与正常血液、血浆或血清混合,或者在膜分离过程中将所述稀释液与正常血液、血浆或血清混合;在膜分离之前将所述稀释液与正常血液、血浆或血清混合时,正常血液、血浆或血清与稀释液的混合体积比为(0.1~5):1;或,在膜分离过程中将所述稀释液与正常血液、血浆或血清混合时,正常血液、血浆或血清与稀释液的混合体积比为1:(0.1~10)。
3.根据权利要求1或2所述的制备方法,其特征在于,进行膜分离的处理液中含有血细胞时,膜分离后超滤液的收集速度为处理液流速的5~30%;或,膜分离的处理液中不含血细胞时,膜分离后超滤液的收集速度为处理液流速的5~50%;和/或,收集的超滤液的体积为稀释液体积的1~1.2倍。
4.根据权利要求1~3任意一项所述的制备方法,其特征在于,所述分离膜的孔径为3~8nm。
5.根据权利要求1~4任意一项所述的制备方法,其特征在于,所述膜分离之后还包括浓缩步骤;所述浓缩步骤为冻干处理和/或除去小分子的处理。
6.根据权利要求5所述的制备方法,其特征在于,所述除去小分子的处理是采用1kDa半透膜透析或者采用孔径为1kDa的离心管离心。
8.一种适用于血液净化患者的营养物,其特征在于,所述营养物由权利要求1~7任意一项所述的制备方法获得;优选地,所述营养物成分的分子量在70kDa以内。
10.权利要求8或9所述的适用于血液净化患者的营养物在制备改善血液净化患者健康状况的药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010698121.3A CN111956789A (zh) | 2020-07-20 | 2020-07-20 | 一种适用于血液净化患者的营养物的制备方法及营养物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010698121.3A CN111956789A (zh) | 2020-07-20 | 2020-07-20 | 一种适用于血液净化患者的营养物的制备方法及营养物 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111956789A true CN111956789A (zh) | 2020-11-20 |
Family
ID=73360448
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010698121.3A Pending CN111956789A (zh) | 2020-07-20 | 2020-07-20 | 一种适用于血液净化患者的营养物的制备方法及营养物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111956789A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116625772A (zh) * | 2023-05-25 | 2023-08-22 | 安徽九陆生物科技有限公司 | 一种微量血液过滤的方法及应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1569031A (zh) * | 2004-04-26 | 2005-01-26 | 巫山 | 病毒灭活/超滤膜分段筛分法制备的血浆组分系列制剂 |
US20150056363A1 (en) * | 2012-03-09 | 2015-02-26 | Shanghai Genon Biological Products Co., Ltd | Method for producing low-ash poultry plasma protein powder by utilizing poultry blood |
CN107261234A (zh) * | 2017-05-18 | 2017-10-20 | 李建中 | 一种透析液的再生方法及血液净化系统 |
-
2020
- 2020-07-20 CN CN202010698121.3A patent/CN111956789A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1569031A (zh) * | 2004-04-26 | 2005-01-26 | 巫山 | 病毒灭活/超滤膜分段筛分法制备的血浆组分系列制剂 |
US20150056363A1 (en) * | 2012-03-09 | 2015-02-26 | Shanghai Genon Biological Products Co., Ltd | Method for producing low-ash poultry plasma protein powder by utilizing poultry blood |
CN107261234A (zh) * | 2017-05-18 | 2017-10-20 | 李建中 | 一种透析液的再生方法及血液净化系统 |
Non-Patent Citations (1)
Title |
---|
林元藻等: "超滤", 《生物制药学》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116625772A (zh) * | 2023-05-25 | 2023-08-22 | 安徽九陆生物科技有限公司 | 一种微量血液过滤的方法及应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20180243376A1 (en) | Methods and non-immunogenic compositions for treating inflammatory disorders | |
Berggård | On a γ-globulin of low molecular weight in normal human plasma and urine | |
CN105153297B (zh) | 一种从Cohn组分Ⅳ沉淀中分离纯化α2-巨球蛋白的方法 | |
US20140271589A1 (en) | Treatment of collagen defects using protein solutions | |
KR20110036001A (ko) | 분비 면역글로블린이 풍부한 우유 분획 제조방법 | |
US10729156B2 (en) | Methods of purifying exosomes | |
CN106699869A (zh) | 血管生成素富集的乳级分 | |
CN104328101A (zh) | 一种凝血酶的制备方法 | |
CN111956789A (zh) | 一种适用于血液净化患者的营养物的制备方法及营养物 | |
CN113215079B (zh) | 一种从牛奶中提取细胞外囊泡的方法 | |
CN105177097A (zh) | 一种具有促进成骨细胞增殖活性的乳铁蛋白肽的制备方法及应用 | |
Ronco et al. | Basic mechanisms and definitions for continuous renal replacement therapies | |
US7214319B2 (en) | Method of separating protein from animal milk | |
EP3411384B1 (en) | Extraction process from colostrum | |
CN110538196A (zh) | 一种富血小板血浆和提取富血小板血浆的方法 | |
Casillas et al. | Chromatographic behaviour of clotting factors | |
Kobayashi et al. | Nitrogen metabolism in patients on peritoneal dialysis | |
CN112410323B (zh) | 一种羔羊皱胃凝乳酶标准品的制备方法 | |
US20030080056A1 (en) | Extraction of biological components from body fluids | |
CN107303385B (zh) | 一种脑蛋白水解物溶液的制备方法 | |
CN105586330B (zh) | 一种尖吻蝮蛇凝血酶及其制备方法 | |
RU2799637C1 (ru) | Способ получения биологически активного пептидно-аминокислотного препарата на основе плазмы крови человека | |
Kawai-Harada et al. | Scalable Isolation of Surface-Engineered Extracellular Vesicles and Separation of Free Proteins via Tangential Flow Filtration and Size Exclusion Chromatography (TFF-SEC) | |
RU2719152C1 (ru) | Линия клеток C-HAlb, секретирующих рекомбинантный альбумин человека | |
RU2308286C1 (ru) | Способ получения альфа-фетопротеина |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201120 |