CN1263466C - 活性炭输液剂、其制备方法及其在制备治疗癌症药中的应用 - Google Patents
活性炭输液剂、其制备方法及其在制备治疗癌症药中的应用 Download PDFInfo
- Publication number
- CN1263466C CN1263466C CNB031250904A CN03125090A CN1263466C CN 1263466 C CN1263466 C CN 1263466C CN B031250904 A CNB031250904 A CN B031250904A CN 03125090 A CN03125090 A CN 03125090A CN 1263466 C CN1263466 C CN 1263466C
- Authority
- CN
- China
- Prior art keywords
- activated carbon
- active carbon
- injection
- infusion solution
- mum
- 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.)
- Expired - Fee Related
Links
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 title claims abstract description 200
- 239000003814 drug Substances 0.000 title claims abstract description 45
- 229910052799 carbon Inorganic materials 0.000 title claims description 80
- 239000003795 chemical substances by application Substances 0.000 title claims description 15
- 206010028980 Neoplasm Diseases 0.000 title abstract description 23
- 201000011510 cancer Diseases 0.000 title abstract description 11
- 239000002245 particle Substances 0.000 claims abstract description 59
- 239000007924 injection Substances 0.000 claims abstract description 39
- 238000002347 injection Methods 0.000 claims abstract description 39
- 238000002360 preparation method Methods 0.000 claims abstract description 28
- 239000003978 infusion fluid Substances 0.000 claims abstract description 24
- 230000000694 effects Effects 0.000 claims abstract description 22
- 238000001179 sorption measurement Methods 0.000 claims abstract description 6
- 230000000274 adsorptive effect Effects 0.000 claims abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 230000003213 activating effect Effects 0.000 claims abstract description 4
- 238000010521 absorption reaction Methods 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 10
- -1 ferrous porphyrin Chemical class 0.000 claims description 9
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 8
- 239000003610 charcoal Substances 0.000 claims description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 8
- 238000011275 oncology therapy Methods 0.000 claims description 8
- 210000001541 thymus gland Anatomy 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 230000004913 activation Effects 0.000 claims description 5
- 239000012190 activator Substances 0.000 claims description 5
- 239000003560 cancer drug Substances 0.000 claims description 5
- 230000006837 decompression Effects 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229940035893 uracil Drugs 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003146 anticoagulant agent Substances 0.000 claims description 4
- 229940127219 anticoagulant drug Drugs 0.000 claims description 4
- 239000003443 antiviral agent Substances 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 4
- 229960002965 pravastatin Drugs 0.000 claims description 4
- 108090000695 Cytokines Proteins 0.000 claims description 3
- 102000004127 Cytokines Human genes 0.000 claims description 3
- 241001597008 Nomeidae Species 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000007598 dipping method Methods 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 239000004593 Epoxy Substances 0.000 claims description 2
- 229910010082 LiAlH Inorganic materials 0.000 claims description 2
- 150000001263 acyl chlorides Chemical class 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 230000005934 immune activation Effects 0.000 claims description 2
- 239000007791 liquid phase Substances 0.000 claims description 2
- 229910021645 metal ion Inorganic materials 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 150000001299 aldehydes Chemical class 0.000 claims 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims 1
- 210000004369 blood Anatomy 0.000 abstract description 18
- 239000008280 blood Substances 0.000 abstract description 18
- 239000000243 solution Substances 0.000 abstract description 7
- 230000001154 acute effect Effects 0.000 abstract description 4
- 230000005847 immunogenicity Effects 0.000 abstract description 4
- 238000001990 intravenous administration Methods 0.000 abstract description 4
- 231100000572 poisoning Toxicity 0.000 abstract description 4
- 230000000607 poisoning effect Effects 0.000 abstract description 4
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 206010008132 Cerebral thrombosis Diseases 0.000 abstract description 3
- 201000001429 Intracranial Thrombosis Diseases 0.000 abstract description 3
- 210000004204 blood vessel Anatomy 0.000 abstract description 3
- 208000029078 coronary artery disease Diseases 0.000 abstract description 3
- 208000037157 Azotemia Diseases 0.000 abstract description 2
- 208000035473 Communicable disease Diseases 0.000 abstract description 2
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 abstract 1
- 201000001320 Atherosclerosis Diseases 0.000 abstract 1
- 229910001385 heavy metal Inorganic materials 0.000 abstract 1
- 150000001455 metallic ions Chemical class 0.000 abstract 1
- 229960000907 methylthioninium chloride Drugs 0.000 abstract 1
- 239000011148 porous material Substances 0.000 abstract 1
- 230000000638 stimulation Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000001556 precipitation Methods 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 238000000703 high-speed centrifugation Methods 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 230000018044 dehydration Effects 0.000 description 8
- 238000006297 dehydration reaction Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000006555 catalytic reaction Methods 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 238000002512 chemotherapy Methods 0.000 description 6
- 210000002216 heart Anatomy 0.000 description 6
- 238000001802 infusion Methods 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 210000003462 vein Anatomy 0.000 description 6
- 210000000038 chest Anatomy 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- 230000008676 import Effects 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 229920001661 Chitosan Polymers 0.000 description 3
- 208000005189 Embolism Diseases 0.000 description 3
- 208000005228 Pericardial Effusion Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 208000001435 Thromboembolism Diseases 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000000669 biting effect Effects 0.000 description 3
- 230000005907 cancer growth Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 238000004137 mechanical activation Methods 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 239000002574 poison Substances 0.000 description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-M pravastatin(1-) Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC([O-])=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-M 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 210000000115 thoracic cavity Anatomy 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 2
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 239000003005 anticarcinogenic agent Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 125000003636 chemical group Chemical group 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
- 230000001684 chronic effect Effects 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000000640 hydroxylating effect Effects 0.000 description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 210000001989 nasopharynx Anatomy 0.000 description 2
- 231100000957 no side effect Toxicity 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000008807 pathological lesion Effects 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 239000011669 selenium Substances 0.000 description 2
- 229910052711 selenium Inorganic materials 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 208000008203 tachypnea Diseases 0.000 description 2
- 206010043089 tachypnoea Diseases 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- LAOOXBLMIJHMFO-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one;hydron;chloride Chemical compound Cl.S1C2=CC=CC=C2C(=O)C2=C1C(C)=CC=C2NCCN(CC)CC LAOOXBLMIJHMFO-UHFFFAOYSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010056377 Bone tuberculosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 description 1
- 206010058354 Bronchioloalveolar carcinoma Diseases 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 206010009208 Cirrhosis alcoholic Diseases 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010010969 Cor pulmonale acute Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000009360 Osteoarticular Tuberculosis Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 208000037114 Symptom Flare Up Diseases 0.000 description 1
- 108010046075 Thymosin Proteins 0.000 description 1
- 102000007501 Thymosin Human genes 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 102000005421 acetyltransferase Human genes 0.000 description 1
- 108020002494 acetyltransferase Proteins 0.000 description 1
- 208000022913 acute pulmonary heart disease Diseases 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000010002 alcoholic liver cirrhosis Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000003555 analeptic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003972 antineoplastic antibiotic Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- VYVRIXWNTVOIRD-LRHBOZQDSA-N ciguatoxin CTX1B Chemical compound C([C@@]12[C@@H](C)[C@@H]([C@@H]3[C@H]([C@H]([C@H](C)[C@H]4O[C@H]5C[C@@H](C)C[C@H]6O[C@@]7(C)[C@H](O)C[C@H]8O[C@H]9C=C[C@H]%10O[C@H]%11C[C@@H]%12[C@H]([C@@H]([C@H]%13O[C@H](C=CC[C@@H]%13O%12)\C=C\[C@H](O)CO)O)O[C@@H]%11C=C[C@@H]%10O[C@@H]9C\C=C/C[C@@H]8O[C@@H]7C[C@@H]6O[C@@H]5C[C@@H]4O3)O)O2)C)[C@H](O)CO1 VYVRIXWNTVOIRD-LRHBOZQDSA-N 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 150000002291 germanium compounds Chemical class 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 210000003692 ilium Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002664 inhalation therapy Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229940090459 insta-char Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 229960003350 isoniazid Drugs 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000272 myelencephalon Anatomy 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 201000003144 pneumothorax Diseases 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000001843 schistosomicidal effect Effects 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000018556 stomach disease Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940113082 thymine 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
- 231100000820 toxicity test Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/40—Peroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/44—Elemental carbon, e.g. charcoal, carbon black
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- 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
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及活性炭输液剂、其制备方法及其在制备治疗癌症药物中的应用，该活性炭输液剂包括供静脉输液用的纯活性炭微粒针剂、活化活性炭微粒针剂、吸附有催化剂的活性炭针剂以及各种载药活性炭针剂，其特征在于所用原料活性炭表面积≥400-10000m2/g或更高，重金属含量≤0.1-10ppm，其它可溶性金属离子≤0.1-10ppm，灰份＜2%，总孔容积＞0.3-6cm3/g，0.15%亚甲兰吸附值＞6-30，该活性炭输液剂中所含活性炭微粒粒径为35μm-2nm， 主要粒度分布范围为6μm-2nm，其中3μm-2nm占99%，6μm-3μm颗粒不超过1%，最大直径35μm-6μm活性炭微粒不超过2×104个/mg活性炭微粉，该活性炭微粒经静脉输入血液后，与组织相容性极好，无毒副作用，无不良刺激性，无免疫原性，安全有疗效，对癌症、血管动脉粥样硬化、冠心病、脑血栓、感染性疾病、氮质血症、急性有机和无机毒物中毒等均有超乎寻常的治疗效果。
Description
技术领域
本发明涉及活性炭输液剂、其制备方法及其在制备治疗癌症药中的应用。更确切地说，本发明涉及供静脉输液用的活性炭制剂、其制备方法及其在制备治疗癌症药物中的应用。
背景技术
在医学领域应用活性炭已有近百年历史。通常将活性炭用于中、西药针剂制备过程的纯化步骤，如下列对比文件所述：CN1377689、CN1287838、CN1068958、CN1062083，这些对比文件中提及的活性炭在吸收药剂中杂质或残留物后均被滤除，在针剂制成品中并不包含活性炭。医学研究表明，用活性炭制剂可治疗各种疾病，例如，口服活性炭制剂治疗胃部疾病；用活性炭制剂吸附进入肠胃的毒素如安眠药中毒、防酒醉等；运动员兴奋剂检查时，用活性炭作尿液吸附剂；在皮肤感染发炎时，用活性炭外敷于脓疮处吸附毒素和臭味；EP620006公开了口服活性炭制剂治疗糖尿病；JP11029485公开了口服活性炭制剂治疗肥胖症，US4152412公开了用0.5微米的活性炭吸附供动物使用的免疫疫苗、抗原和类毒素，注射后免疫疫苗效果改善，药剂被缓慢释放；SU1465052公开了将活性炭与预防、治疗动物蛔虫的药剂混合成油混悬液形式皮下注射，可以增强治疗效果并将抗虫药效延长到三个月以上；WO9108776公开了在肿瘤内注射含有1-6.8μm的非活性或略有活性的炭微粒，可在化疗和手术前标记肿瘤，也可在激光或电磁波加热等治疗中吸收能量，在肿瘤组织附近注射，让药物缓慢释放以发挥治疗作用，该炭微粒仍是在血管、血液以外的组织中起缓释作用，是外用原理的延伸，这与本发明将活性炭微粒直接输入血液，在应用途径及治疗机理方面有本质差别。本发明人经长期研究证明，将具有大比表面积，粒径主要分布在6μm-2nm的活性炭微粒加入传统的静脉输液液体中，再输入人体血液中或输入到腹腔、胸腔中，对多种癌症、血管动脉粥样硬化、冠心病、脑血栓、感染性疾病、氮质血症、急性有机和无机毒物中毒等均有超乎寻常的治疗效果。大量的动物试验结果表明，该活性炭微粒输入血液后，与组织相容性极好，无毒副作用，无不良刺激性，无免疫原性，且安全有效，不会发生器官栓塞及产生病理性损害。
发明内容
本发明目的是提供一种活性炭输液剂，它是供静脉输液用的活性炭制剂。
本发明另一个目的是提供该活性炭输液剂的制备方法，该方法工艺独特，操作简便。
本发明还有一个目的是提供该活性炭输液剂在制备治疗癌症药物中的应用。
本发明的活性炭输液剂，包括供静脉输液用的纯活性炭微粒针剂、活化活性炭微粒针剂、吸附有催化剂的活性炭针剂以及载药活性炭针剂，该载药活性炭针剂包括吸附抗癌药物针剂、吸附抗凝和降胆固醇药物针剂、吸附抗生素药物针剂、吸附抗病毒药物针剂，其特征在于所用原料活性炭符合如下质量要求：表面积≥400-10000M2/g或更高，重金属含量≤0.1-10ppm，其它可溶性金属离子≤0.1-10ppm，灰份＜2％，总孔容积＞0.3-6cm3/g，0.15％亚甲兰吸附值＞6-30，该活性炭输液剂中所含活性炭微粒粒径为35μm-2nm，主要粒度分布范围为6μm-2nm，其中3μm-2nm占99％，6μm-3μm颗粒不超过1％，最大直径35μm-6μm活性炭微粒不超过2X104个/mg活性炭微粉。
经大量的动物试验证明，该活性炭微粒输入血液后，与组织相容性极好，无毒副作用，无不良刺激性，无免疫原性，在使用剂量范围以内(即单次输入血液的有效治疗剂量为0.1-5mg/kg体重，每周输入1-7次，成人平均累计总储积量为10g以下)，在制剂质标准范围以内，不会发生重要器官的栓塞。掌握好治疗量、总储积量，可以多次、反复静脉输入，未发现有中毒及重要脏器损伤；经动物解剖证实，静脉输入这种活性炭微粒，对心、肝、肾、脾、肺、骨髓、大脑不会产生病理性损害。
本发明活性炭输液剂的制备方法，其特征在于该方法包括如下步骤：
(1)用机械方法将原料活性炭粉碎成120目的粗颗粒；
(2)使该活性炭粗颗粒吸附活化剂以使活性炭活化，所述活化剂浓度为0.01-10％，在高压容器中加热到70-190℃，反应时间为5-20分钟，生成氧化型或还原型活性炭；冷却减压，排除残余气体，再在压力下分别通入60-100C水蒸气、氨气，生成含有炭-羟基、炭-亚氨基或炭-氢的活性炭；
(3)进行活性炭载药处理，选择相关药物用经活化的活性炭或未经活化的纯活性炭进行液相饱和吸附，然后低温干燥，用空气粉碎机粉碎成所要粒径的活性炭微粒；
(4)使该活性炭微粒浸渍吸附生物导向剂，然后进行短时间、快速低温干燥。
在步骤(2)中，所述的活化剂分为氧化剂和还原剂，氧化剂选自环氧醚类、酰氯类、酸酐类、醛类氧化剂，还原剂选自LiAlH4、NaBH4。
在步骤(3)中选择的相关药物包括：①传统的抗癌药物如5-FU、CTX、MTX、Ara-C/A、6-MP、抗癌抗生素类、顺/卡铂、砷剂类、紫杉醇等；②免疫激活、调节类细胞因子类如IL-2、4、6、GM、G-CSF、γ-IFN、TNF、FCF-B、VECF、4-IBB/4-IBBL、B7-1B7-2、蟾毒蛋白、特异性半抗体等；③催化剂类如主金属有机化合物苄基/丁基锂等，过渡金属铜氨剂、铂、钯剂、硒、锗化合物等，这些结合物具有催化和杀肿瘤双重功能；④吸附生物酶类如氧化还原酶类、转氨酶类、水解酶类、异构酶类等。
在步骤(4)中，所述的生物导向剂包括卟啉铁，或胸腺嘧啶、鸟嘧啶、尿嘧啶、胸腺嘌呤、鸟嘌呤及其衍生物一大类物质，如5-氟尿嘧啶、氢氘胸腺嘧啶、甲氨喋呤以及肿瘤细胞粘附因子(如VCAM-1)、肿瘤细胞生长因子(如VEGF)等。
在步骤(3)和(4)中选择不同的药物和生物导向剂可制备各种不同的载药活性炭制剂，例如吸附抗癌药物针剂，吸附抗凝、降胆固醇药物针剂，吸附抗生素药物针剂，吸附抗病毒药物针剂。
本发明还提供了该活性炭输液剂在制备治疗癌症药物中的应用，其特征在于单次输入血液的有效治疗剂量为0.1-5mg/kg体重，每周输入1-7次，成人平均累计总储积量为10g以下。
经长期的研究表明，直径在一定大小范围内的纳米-微米活性炭具有非常明显的缓解癌症疼痛、抑制肿瘤生长或杀死肿瘤细胞的作用，将该活性炭微粒通过静脉输入血液可用于治疗多种癌症，并能治疗血管动脉粥样硬化、冠心病、脑血栓；该活性炭微粒输入血液后还具有类似免疫因子样的功能，如IgG\A\M、DC小肽分子、免疫球蛋白超家族分子样功能，可用于各种难治型、微生物及病毒感染的治疗。还发现该活性炭微粒通过静脉输入血液后具有促进机体组织修复的功能，对慢性不愈合性伤口、骨髓炎等疾病有奇特疗效，并能治疗急性有机、无机毒物中毒。
基于纯活性炭微粉颗粒本身具有抗癌作用外，还具有吸附、免疫调节、化学催化、药物载体的作用，对纯活性炭微粉颗粒进行进一步的化学活化处理、载药处理以及吸附生物导向剂处理，上述作用将得到正相强化，从而会得到超乎寻常的治疗效果，这是本发明活性炭输液剂在制备治疗癌症药物中应用的机理。下面将作更详细说明：
1.对纯活性炭微粒进行进一步活化处理：
活性炭本身具有化学催化作用，同时还可以用不同的化学基团修饰，使活性炭结合多种化学催化基团，这些化学基团可以是含有羟基、羧基、氨基、羰基、芳环基的低分子有机化合物；与活性炭结合的化学活性催化基团可为酶类有机物，或选择在常温常压下，在溶液中能起催化作用的主金属有机化合物、过渡金属有机化合物或相应的无机化合物，以达到对氢、氧、烃、肽、脂的催化；经化学活化处理的活性炭吸附值明显提高，使其更有针对性地发挥催化治疗作用或增加载药作用。
2.对经活化处理的活性炭微粒再进一步进行载药处理以及吸附生物导向剂处理：
在活性炭微粒上结合生物导向材料，这是进一步提高活性炭微粒输液剂疗效的有效方法，这种导向材料选择原则是：利用癌细胞生长旺盛的特点，选择癌细胞生长需求摄取量比正常细胞摄取量多的物质作为导向材料，即癌噬性强的物质为导向材料，这类材料必需是无免疫原性的物质，例如选择构成DNA或RNA所必需的碱基对物质(胸腺嘧啶、鸟嘧啶、尿嘧啶、胸腺嘌呤、鸟嘌呤及其衍生物一大类物质)，癌细胞生长代谢摄入量比正常细胞多几百倍的物质(如血卟啉铁)，或选择肿瘤亲和物质，例如肿瘤细胞粘附因子(如VCAM-1)、肿瘤细胞生长因子(如VEGF)等作为导向材料，这些物质都具有促进肿瘤生长作用。非常有趣的现象是肿瘤细胞非常喜欢俘获这样的活性炭微粒，并大量吞噬这些活性炭微粒直到死亡或停止生长，而正常组织细胞几乎对这种活性炭微粒熟视无睹或者很少问津，这种具有癌噬性、肿瘤亲和性导向的活性炭微粒自动浓集在癌细胞周围，在癌组织内部的活性炭微粒浓度是其它正常组织的几百倍、甚至于达到上万倍，这一创造性导向材料与活性炭结合的应用，突破生物导向材料选择原则，并解决了长期以来肿瘤化疗药物选择性不强的问题及对导向材料产生抵抗性的问题。
研究表明，在新生血管非常丰富并且紊乱的肿瘤组织内，这种带有癌噬性、癌亲和性物质的活性炭微粒或者纯活性炭微粒，会在肿瘤组织微血管内或肿瘤新生微血管盲端内形成极高浓度的堆积，并被癌细胞大量吞噬；癌组织内聚积了大量活性炭微粒，这些活性炭微粒进行着抗癌药物释放、免疫调节、化学催化、及吸附物质动态平衡来干扰肿瘤生长，完成综合杀瘤作用。
另一类抗病毒生物导向剂与载药组合选择原则为：病毒亲和剂-病毒干扰剂组合，如DNA病毒选用胸腺嘧啶碱基、RNA病毒选用尿嘧啶碱基与干扰素、IL-1、病毒转录酶抑制剂、聚合酶抑制剂类组合。
这种具有生物导向的活性炭微粉，以其巨大的比表面积，可以吸附多种抗癌药物，药物随着活性炭粉被导向并浓集于肿瘤细胞周围，所载药物可以选择不同的抗癌药，如化疗药物类、放射性核素类、免疫调节细胞因子类以及钯、铂、铜、锗、硒、钴等配位催化金属类物质，这些药物被导向肿瘤细胞，在肿瘤微血管内部和肿瘤细胞间质中，药物可以浓集到常规治疗方法的几百倍，甚至于上万倍，增强了抗肿瘤疗效，降低了化疗药物的毒副作用。挂载于活性炭上的化疗、放疗药物剂量，一般是传统治疗量的5-20％，就能够达到或超过传统治疗方案的效果，最大限度减少抗癌药物对机体正常细胞和免疫系统的损害。
本发明活性炭输液剂安全性动物实验如下：
1、大鼠毒性实验：大鼠12只，135g±10g，雌雄各半，尾静脉注射法，观察28天
| 分组 剂量 mg/KgA 0.2 2/W x5B 0.4 2/W x5C 1.6 2/W x5D 1.6 2/W x16E 30 | 动物数量(只)121212126 | 死亡数(只)00000 | LD50置信限未找到 | 蓄积量mg/Kg241625.630 |
因尾静脉连续注射困难，最多只扎2/W；D相当于最大耐受量实验，E相当于权宜性的限度实验，
A、B、C相当于动物急毒实验高中低三组，但注射次数比急毒实验多，观察天数也多。
2、病理解剖结果：随机抽样雌雄动物各2只进行病理解剖，结果如下
| 分组动物数(只)A 4B 4C 4D 4E 4 | 心 肝 肺 脾 肾 脑 脊髓 肌肉 肋骨 髂前脊 肠淋巴结 胸腺未见异常病理现象未见异常病理现象未见异常病理现象未见异常病理现象一只雄鼠有肺表面小片状淤血，但肺实体未见有出血性病理改变，其余正常 |
说明：以上动物实验资料是我们研究过程中的观察资料，未严格按照药典进行急性毒理实验或慢性毒理实验要求去作，给大鼠投药剂量大于标准实验要求，饲养观察时间也较标准要求时间长一些，而鼠的数量少于标准要求。
临床实验病例如下：
病例一：
男性，57岁，诊断为肺癌，右锁骨上淋巴结活检：腺癌，多程化疗后因胸闷、心悸、气促、不能平卧而入院。心脏B超及肺部CT显示：大量心包积液，心律120次/分，每天24小时必须坐立，抽心包积液因病人不能耐受而未成功。经静脉注射本发明活性炭制剂20mg，24小时后，胸闷、心悸、气促症状缓解，可以平卧入睡，心律90次/分。48小时复查心脏B超，心包积液完全消失。
病例二：
男性，21岁，诊断为肺泡细胞癌，经化疗症状无缓解，胸片显示，双肺布满絮状阴影，心电图呈急性肺心病改变，需间断吸氧治疗。由于患者对化疗药物产生抵抗，症状日益加重，后胸片显示，双侧气胸，右侧压缩50％，左侧压缩40％，右侧胸腔抽气一次，800ml胸透胸腔仍有大量气体。经静脉注射本发明活性炭制剂20mg加DDP 20mg和5-Fu 0.25g，每隔三天一次，共用四次，用药后一周，复查胸片，气体完全吸收。
病例三：
女性，42岁，诊断为右鼻咽非何杰金淋巴瘤T细胞型，先后给于全身化疗，鼻咽部放疗，右侧颈部1×1cm大小淋巴结不消失。经静脉注射本发明活性炭制剂20mg，二天后淋巴结消失，目前病情稳定，未进行任何其他治疗。
病例四：
女性，38岁，诊断为乳腺癌，全身骨转移，吗啡止痛无效，行走困难，经静脉注射本发明活性炭制剂20mg，7小时后疼痛明显缓解，24小时后可以自由行走，3个月后复查，体重增加2公斤，并能从事一般性家务劳动。
病例五：
男性，67岁，先后患有血吸虫性肝硬化，慢性乙型肝炎，糖尿病II型，酒精性肝硬化，肺结核，后因咳嗽咯血住院检查，诊断为右上肺癌，因患者年老多病，不能进行手术，化疗、放疗，经静脉注射本发明活性炭制剂20mg，24小时后，咯血明显减少，连续用药10天，症状消失，3个月后复查胸片肿块影较前缩小，边缘清晰，病灶无明显变化，未进行任何治疗，病情稳定。
具体实施方式
下面实施例仅为了进一步说明本发明，而不是限制本发明。
实施例1
制备纯活性炭微粒针剂：
取比表面积为6800M2的活性炭500克，机械粉碎成120目的细粉，然后输入空气粉碎机进行粉碎，控制粒径为35μm-2nm，主要粒度分布范围为61μm-2nm，其中3μm-2nm占99％，6μm-3μm颗粒不超过1％，最大直径35μm-6μm活性炭微粒不超过2×104个/mg活性炭微粉；用上述活性炭微粉作溶质，用二甲基亚砜(DMSO)作悬溶剂，配制1％活性炭混悬液5000ml，在强磁力搅拌下，分装成每瓶1ml或2ml的输液针剂。
实施例2
制备活化活性炭微粒针剂：
取比表面积为6800M2/g的活性炭100g，机械粉碎成120目的细粉，加入-10℃1％亚硫酰氯/氯仿溶液300ml，搅拌吸附反应2小时，以2万转高速离心，取沉淀；然后把沉淀物容器放入压力容器内，加热到80℃，5分钟后放气减压，生成氧化型活性炭；然后再向压力容器中分别通入活化剂，以生成几种带有不同活性基的活化活性炭：
若制备羟基化活性炭，则通入90℃水蒸汽2小时，然后减压排气，生成羟基化活性炭；
若制备亚氨基化活性炭，则通入90℃℃纯氨蒸汽2小时，生成亚氨基化活性炭；
若制备羟基、氨基活性炭，则通入90℃10-40％氨-水蒸汽，生成同时含有羟基、氨基的活性炭；
若制备炭-氢活性炭，则取比表面积为6800M2/g的活性炭100克，机械粉碎成120目的细粉，加入乙醚溶解的LiALH4，配制成1％的溶液300ml，搅拌吸附2小时，离心取沉淀；在压力容器内加热至95℃5分钟，冷却减压，制得结合有炭-氢和锂的活性炭；
将上述活化的活性炭，输入空气粉碎机进行粉碎，控制粒径为35μm-2nm，主要粒度分布范围为6μm-2nm，其中3μm-2nm占99％，6μm-3μm颗粒不超过1％，最大直径35μm-6μm活性炭微粒不超过2×104个/mg活性炭微粉；分别分装成每瓶含活化活性炭10mg或20mg输液针剂。
实施例3
制备载药活性炭针剂：
①吸附抗癌药针剂：在无药物拮抗情况，可任意选取药物进行吸附，例如，顺铂6g、5-FU 0.4g，或取顺铂6g、6-MP 0.8g溶于100ml水中，加入10g 120目活性炭或活化的羟基-氨基活性炭，搅拌下充分吸附；高速离心取沉淀，丙酮脱水，离心取沉淀，干燥；然后用0.1％几丁聚糖水溶液浸渍沉淀5分钟，用丙酮脱水，干燥；用空气粉碎机粉碎，控制粒径为35μm-2nm，主要粒度分布范围为6μm-2nm，其中3μm-2nm占99％，6μm-3μm颗粒不超过1％，最大直径35μm-6μm活性炭微粒不超过2×104个/mg活性炭微粉；将经过粉碎暴露出新断面的载药活性炭微粒，浸入20％卟啉铁丙酮溶液10分钟，高速离心取沉淀，干燥；分别分装成每瓶含相当活化活性炭10mg或20mg的输液针剂。
部分药物测定的吸附值如下：比表面积6800M2活性炭/羟、氨基炭，其吸附量测定值(活性炭吸附值mg/羟、氨基炭吸附值mg)为：尿嘧啶33/51、胸嘌呤213/260、鸟嘌呤331/378、5-氯尿嘧啶75/102、5-氟尿嘧啶20/49、胸嘧啶5/17、胸腺肽90/127、6-MP220/304、顺铂995/1105、卟啉铁283/311、CTX98/136、氯仿10/4。
②吸附抗凝、降胆固醇药物针剂：例如，取r-tPA 100mg或胆固醇乙酰转移酶80mg或烟酸220mg，加入经空气粉碎机粉碎成粒度为0.5μm以下的羟基活性炭微粒1g，进行充分水相吸附，高速离心取沉淀，丙酮脱水，干燥；然后用0.1％几丁聚糖水溶液浸渍5分钟，高速离心取沉淀，用丙酮脱水，干燥，分装成10mg/瓶输液针剂，用于治疗心、脑栓塞溶栓治疗和治疗血管硬化、高血压等。
③吸附抗生素药物针剂：例如，取异烟肼500mg或利福平200mg，用空气粉碎机粉碎成粒度为0.7μm以下的羟基、氨基活性炭微粒1g，水相吸附20分钟，高速离心取沉淀，丙酮脱水，干燥；然后用0.1％几丁聚糖水溶液浸渍5分钟，高速离心取沉淀，用丙酮脱水，干燥，分装成20mg/瓶输液针剂，用于治疗难治性骨结核、粟粒性肺结核等。
④吸附抗病毒药物针剂：例如，取IFN-γ100mg，加入空气粉碎机粉碎成粒度为0.3μm以下的羟基-氨基活性炭微粒1g，进行充分水相吸附；高速离心取沉淀，对沉淀物进行丙酮脱水，低温干燥；在丝胺酸、特异型病毒半抗体导向剂中浸渍5分钟，高速离心取沉淀，丙酮脱水，低温干燥，分装成10mg/瓶或20mg/瓶的输液针剂；用于治疗各种病毒性感染的难治疗性疾病，如EB病毒性格林巴利氏综合症、病毒脑等，也可用于HIV的治疗。
Claims (7)
1、一种活性炭输液剂，其特征在于所用原料活性炭表面积≥400-10000m2/g，重金属含量≤0.1-10ppm，其它可溶性金属离子≤0.1-10ppm，灰份＜2％，总孔容积＞0.3-6cm3/g，0.15％亚甲兰吸附值＞6-30，该活性炭输液剂中所含活性炭微粒粒径为35μm-2nm，主要粒度分布范围为6μm-2nm，其中3μm-2nm占99％，6μm-3μm颗粒不超过1％，最大直径35μm-6μm活性炭微粒不超过2×104个/mg活性炭微粉。
2、根据权利要求1所述的活性炭输液剂，是指纯活性炭微粒针剂、活化活性炭微粒针剂、吸附有催化剂的活性炭针剂或载药活性炭针剂，其中载药活性炭针剂是指吸附抗癌药物针剂、吸附抗凝和降胆固醇药物针剂、吸附抗生素药物针剂或吸附抗病毒药物针剂。
3、根据权利要求1或2所述活性炭输液剂的制备方法，其特征在于该方法包括以下步骤：
1)用机械方法将原料活性炭粉碎成120目的粗颗粒；
2)使该活性炭粗粒吸附活化剂以使活性炭活化，所述活化剂浓度为0.01-10％，在高压容器中加热至70-190℃，反应时间为5-20分钟，生成氧化型或还原型活性炭；冷却减压，排除残余气体，再在压力下分别通入60-100℃水蒸气、氨气，生成含有炭-羟基、炭-亚氨基或炭-氢的活性炭；
3)进行活性炭载药处理，选择相关药物用经活化的活性炭或未经活化的纯活性炭进行液相饱和吸附，然后低温干燥，用空气粉碎机粉碎成所要粒径的活性炭微粒；
4)使该活性炭微粒浸渍吸附生物导向剂，然后进行短时间、快速低温干燥。
4、根据权利要求3所述的活性炭输液剂的制备方法，其特征在于步骤(2)中所述的活化剂分为氧化剂和还原剂，氧化剂选自环氧醚类、酰氯类、酸酐类、醛类氧化剂，还原剂选自LiAlH4、NaBH4。
5、根据权利要求3所述的活性炭输液剂的制备方法，其特征在于步骤(3)中所述的选择相关药物是指：①传统的抗癌药物；②免疫激活、调节细胞因子类；③催化剂类；④吸附生物酶类。
6、根据权利要求3所述的活性炭输液剂的制备方法，其特征在于步骤(4)中的生物导向剂是指卟啉铁，或胸腺嘧啶、鸟嘧啶、尿嘧啶、胸腺嘌呤、鸟嘌呤及其衍生物。
7、根据权利要求1或2所述的活性炭输液剂在制备治疗癌症药物中的应用。
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031250904A CN1263466C (zh) | 2003-05-06 | 2003-05-06 | 活性炭输液剂、其制备方法及其在制备治疗癌症药中的应用 |
| PCT/CN2004/000045 WO2004098620A1 (fr) | 2003-05-06 | 2004-01-14 | Solution d'infusion de charbon actif, procede de preparation associe et son utilisation pour preparer un medicament de traitement du cancer |
| KR1020057021018A KR20060003072A (ko) | 2003-05-06 | 2004-01-14 | 정맥주사용 활성탄 주입액, 그 제조방법 및 이의 암치료약물의 사용방법 |
| EP04701884A EP1652528A1 (en) | 2003-05-06 | 2004-01-14 | Activated carbon infusion solution, preparation method therefor and use thereof for the manufacture of drug for treating cancer |
| RU2005137851/15A RU2005137851A (ru) | 2003-05-06 | 2004-01-14 | Раствор активированного угля для внутривенного введения, способ его приготовления и применение его для производства лекарственного средства для лечения злокачественных опухолей |
| CA002524924A CA2524924A1 (en) | 2003-05-06 | 2004-01-14 | Activated carbon infusion solution, preparation method therefor and use thereof for the manufacture of drug for treating cancer |
| JP2006504190A JP2006525238A (ja) | 2003-05-06 | 2004-01-14 | 活性炭輸液剤、その調製方法及び癌治療用薬物の調製におけるその使用 |
| AU2004236381A AU2004236381A1 (en) | 2003-05-06 | 2004-01-14 | Activated carbon infusion solution, preparation method therefor and use thereof for the manufacture of drug for treating cancer |
| US10/507,570 US20050123613A1 (en) | 2003-05-06 | 2004-01-14 | Activated carbon infusion solution, preparation method therefor and use thereof for the manufacture of drug for treating cancer |
| ZA200509866A ZA200509866B (en) | 2003-05-06 | 2005-12-05 | Activated carbon infusion solution, preparation method therefor and use thereof for the manufacture of drug for treating cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031250904A CN1263466C (zh) | 2003-05-06 | 2003-05-06 | 活性炭输液剂、其制备方法及其在制备治疗癌症药中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1548057A CN1548057A (zh) | 2004-11-24 |
| CN1263466C true CN1263466C (zh) | 2006-07-12 |
Family
ID=33426298
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031250904A Expired - Fee Related CN1263466C (zh) | 2003-05-06 | 2003-05-06 | 活性炭输液剂、其制备方法及其在制备治疗癌症药中的应用 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20050123613A1 (zh) |
| EP (1) | EP1652528A1 (zh) |
| JP (1) | JP2006525238A (zh) |
| KR (1) | KR20060003072A (zh) |
| CN (1) | CN1263466C (zh) |
| AU (1) | AU2004236381A1 (zh) |
| CA (1) | CA2524924A1 (zh) |
| RU (1) | RU2005137851A (zh) |
| WO (1) | WO2004098620A1 (zh) |
| ZA (1) | ZA200509866B (zh) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1964727A (zh) * | 2004-06-02 | 2007-05-16 | 株式会社吴羽 | 循环器官功能障碍因子除去剂 |
| KR100853535B1 (ko) * | 2007-03-30 | 2008-08-21 | 주식회사 돌나라한농제약 | 대한약전 규격을 만족하는 약용탄의 제조방법 |
| JP2012167030A (ja) * | 2011-02-10 | 2012-09-06 | Sony Corp | コレステロール低下薬、中性脂肪低下薬、血糖値低下薬、コレステロール吸着剤、吸着剤、中性脂肪吸着剤、健康食品、健康補助食品、栄養機能食品、特定保健用食品、医薬部外品、及び、医薬品 |
| CN103841981B (zh) * | 2011-10-07 | 2016-11-16 | 帝人制药株式会社 | 口服给药用吸附剂 |
| ES2677914T3 (es) * | 2012-03-29 | 2018-08-07 | Basf Corporation | Nanopartículas soportadas en carbono amorfo que comprenden óxidos de lantánidos y procedimiento para prepararlas |
| CN105832767B (zh) * | 2016-04-12 | 2019-03-01 | 贵州泰柏妇科疾病研究中心 | 一种纳米活性炭与石墨烯在抗hpv病毒中的应用 |
| CN105920037B (zh) * | 2016-06-20 | 2019-01-22 | 贵州泰柏妇科疾病研究中心 | 一种纳米活性炭溶胶在制备治疗疱疹病毒药物中的应用 |
| CN105998063B (zh) * | 2016-06-20 | 2019-04-26 | 贵州泰柏妇科疾病研究中心 | 一种纳米活性炭在抑制细菌中的应用 |
| TWI634891B (zh) * | 2017-08-17 | 2018-09-11 | 逢甲大學 | Medicine for treating or preventing colorectal cancer |
| KR101941871B1 (ko) * | 2017-09-05 | 2019-01-24 | 서원대학교산학협력단 | 쌀도정 부산물과 한방생약의 발효 추출물을 포함하는 항혈전용 조성물 |
| WO2020210376A1 (en) * | 2019-04-09 | 2020-10-15 | The Board Of Trustees Of The University Of Illinois | Drug adsorbed highly porous activated carbon for enhanced drug delivery |
| CN114831934B (zh) * | 2022-05-11 | 2023-05-26 | 回音必集团抚州制药有限公司 | 一种盐酸尼卡地平注射液的制备方法 |
| CN115671315B (zh) * | 2023-01-03 | 2023-04-28 | 北京弘堃医药科技有限公司 | 组织释药浓度可控的抗癌药物递送系统及其制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR215459A1 (es) * | 1976-04-02 | 1979-10-15 | Brewer J | Metodo para producir un agente terapeutico capaz de proporcionar una marca en un animal no humano para indicar la administracion del agente al animal y para proporcionar tambien un repositorio del agente a ser libeberado durante un espacio de tiempo |
| FR2655546B1 (fr) * | 1989-12-11 | 1992-03-13 | Assistance Publique | Composition pour injection intratumorale, et utilisation pour le marquage prechimiotherapique et preoperatoire, en laserotherapie et en thermotherapie. |
| RU2017492C1 (ru) * | 1991-05-14 | 1994-08-15 | Нестерова Ирина Вадимовна | Способ лечения пищевой аллергии |
-
2003
- 2003-05-06 CN CNB031250904A patent/CN1263466C/zh not_active Expired - Fee Related
-
2004
- 2004-01-14 EP EP04701884A patent/EP1652528A1/en not_active Withdrawn
- 2004-01-14 CA CA002524924A patent/CA2524924A1/en not_active Abandoned
- 2004-01-14 JP JP2006504190A patent/JP2006525238A/ja not_active Withdrawn
- 2004-01-14 RU RU2005137851/15A patent/RU2005137851A/ru not_active Application Discontinuation
- 2004-01-14 AU AU2004236381A patent/AU2004236381A1/en not_active Abandoned
- 2004-01-14 KR KR1020057021018A patent/KR20060003072A/ko not_active Application Discontinuation
- 2004-01-14 US US10/507,570 patent/US20050123613A1/en not_active Abandoned
- 2004-01-14 WO PCT/CN2004/000045 patent/WO2004098620A1/zh active Application Filing
-
2005
- 2005-12-05 ZA ZA200509866A patent/ZA200509866B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2524924A1 (en) | 2004-11-18 |
| AU2004236381A1 (en) | 2004-11-18 |
| JP2006525238A (ja) | 2006-11-09 |
| RU2005137851A (ru) | 2006-06-27 |
| CN1548057A (zh) | 2004-11-24 |
| ZA200509866B (en) | 2006-12-27 |
| EP1652528A1 (en) | 2006-05-03 |
| WO2004098620A8 (fr) | 2005-01-06 |
| US20050123613A1 (en) | 2005-06-09 |
| KR20060003072A (ko) | 2006-01-09 |
| WO2004098620A1 (fr) | 2004-11-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1263466C (zh) | 活性炭输液剂、其制备方法及其在制备治疗癌症药中的应用 | |
| CN113144179B (zh) | 乌司他丁在制备防治重症新型冠状病毒肺炎药物中的用途 | |
| CN113144180B (zh) | 乌司他丁在制备治疗新型冠状病毒肺炎药物中的用途 | |
| CN1530100A (zh) | 含有当归抽提物的食品以及药物组合物 | |
| CN1833644A (zh) | 青蒿素及其衍生物二氢青蒿素、蒿甲醚、蒿乙醚、青蒿琥酯在制药中的应用 | |
| CN100551443C (zh) | 一种纳米碳管输液剂的制备方法 | |
| CN1429558A (zh) | 甘露聚糖肽注射液及其制备方法和使用方法 | |
| CN1686165A (zh) | 药用纳米碳管组合物、制备方法及其应用 | |
| CN1748736A (zh) | 退热解毒注射剂新的给药途径及其制备工艺 | |
| CN1313099C (zh) | 炭气凝胶输液剂、其制备方法及其应用 | |
| CN1839920A (zh) | 黄芪总苷注射剂及其制备方法 | |
| CN1283272C (zh) | 一种抗癌药物及其制备方法 | |
| CN1244325C (zh) | 胆维他在制药中的应用 | |
| CN1204511A (zh) | 一种抗癌药物及其生产工艺 | |
| CN1290489C (zh) | 注射用蟾蜍提取物脂质体制剂及其制备方法 | |
| RU2342121C1 (ru) | Способ непрямой эндолимфатической антибиотикотерапии при уролитиазе у самцов домашних плотоядных | |
| RU2347573C1 (ru) | Способ коррекции эндогенной интоксикации и профилактики нежелательных побочных реакций противотуберкулезных препаратов у больных туберкулезом | |
| CN1273195C (zh) | 炭化花粉及其在制备治疗癌症药物中的应用 | |
| CN1872122A (zh) | 一种苦碟子冻干粉针剂的制备方法 | |
| CN1275591C (zh) | 一种治疗心血管疾病的中药缓释剂及其制备方法 | |
| CN1559510A (zh) | 治疗艾滋病、癌症的复方药物及其制备方法 | |
| CN111529539A (zh) | 一种原人参二醇在制备药物中的用途 | |
| CN101979047A (zh) | 生脉注射液用于copd缓解期的药物新用途 | |
| Stancioiu | Antiviral activity of L-arginine and extended-release Vitamin C | |
| CN111281893A (zh) | 注射用母牛分枝杆菌在制备用于防治covid-19的药物中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20060519 Address after: Yuhu District Xiangtan city Hunan province 411100 120 Building No. 11 No. 603 Applicant after: Chen Xiaochuan Co-applicant after: Wang Pulin Co-applicant after: Hou Xizhong Address before: Yuhu District Xiangtan city Hunan province 411100 120 Building No. 11 No. 603 Applicant before: Chen Xiaochuan Co-applicant before: Wang Pulin |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| DD01 | Delivery of document by public notice |
Addressee: Chen Xiaochuan Document name: Notification to Pay the Fees |
|
| DD01 | Delivery of document by public notice |
Addressee: Chen Xiaochuan Document name: Notification of Termination of Patent Right |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060712 Termination date: 20100506 |