CN106075476A - A kind of contrast agent - Google Patents
A kind of contrast agent Download PDFInfo
- Publication number
- CN106075476A CN106075476A CN201610611637.3A CN201610611637A CN106075476A CN 106075476 A CN106075476 A CN 106075476A CN 201610611637 A CN201610611637 A CN 201610611637A CN 106075476 A CN106075476 A CN 106075476A
- Authority
- CN
- China
- Prior art keywords
- contrast agent
- weight portion
- bismuth
- glycolic acid
- bismuth sulfide
- 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.)
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- 239000002872 contrast media Substances 0.000 title claims abstract description 60
- NNLOHLDVJGPUFR-UHFFFAOYSA-L calcium;3,4,5,6-tetrahydroxy-2-oxohexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(=O)C([O-])=O.OCC(O)C(O)C(O)C(=O)C([O-])=O NNLOHLDVJGPUFR-UHFFFAOYSA-L 0.000 claims abstract description 26
- 239000002245 particle Substances 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 10
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 10
- 239000003381 stabilizer Substances 0.000 claims abstract description 6
- 239000004094 surface-active agent Substances 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 238000003756 stirring Methods 0.000 claims description 14
- 229910052797 bismuth Inorganic materials 0.000 claims description 13
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 239000012153 distilled water Substances 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 10
- 229920000642 polymer Polymers 0.000 claims description 10
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 5
- 230000006837 decompression Effects 0.000 claims description 5
- 239000002270 dispersing agent Substances 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 5
- 229910052979 sodium sulfide Inorganic materials 0.000 claims description 5
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 5
- 238000002604 ultrasonography Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 4
- KKMOSYLWYLMHAL-UHFFFAOYSA-N 2-bromo-6-nitroaniline Chemical compound NC1=C(Br)C=CC=C1[N+]([O-])=O KKMOSYLWYLMHAL-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 4
- 238000013019 agitation Methods 0.000 claims description 4
- 235000012208 gluconic acid Nutrition 0.000 claims description 4
- 239000000174 gluconic acid Substances 0.000 claims description 4
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 claims description 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 3
- 229920001503 Glucan Polymers 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical group CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 claims description 3
- 235000010445 lecithin Nutrition 0.000 claims description 3
- 239000000787 lecithin Substances 0.000 claims description 3
- 229940067606 lecithin Drugs 0.000 claims description 3
- 240000007594 Oryza sativa Species 0.000 claims description 2
- 235000007164 Oryza sativa Nutrition 0.000 claims description 2
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 2
- 235000009566 rice Nutrition 0.000 claims description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 241000497005 Ixophorus unisetus Species 0.000 claims 1
- BQODPTQLXVVEJG-UHFFFAOYSA-N [O].C=C Chemical group [O].C=C BQODPTQLXVVEJG-UHFFFAOYSA-N 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 26
- 239000002105 nanoparticle Substances 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 8
- 238000005516 engineering process Methods 0.000 abstract description 5
- 238000011049 filling Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 5
- 231100000331 toxic Toxicity 0.000 abstract description 5
- 230000002588 toxic effect Effects 0.000 abstract description 5
- 238000011161 development Methods 0.000 abstract description 4
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 239000002086 nanomaterial Substances 0.000 abstract description 3
- 229940126678 chinese medicines Drugs 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 23
- 241000282894 Sus scrofa domesticus Species 0.000 description 18
- 238000000338 in vitro Methods 0.000 description 18
- 229960004275 glycolic acid Drugs 0.000 description 16
- 238000002591 computed tomography Methods 0.000 description 13
- 230000010412 perfusion Effects 0.000 description 10
- 238000000034 method Methods 0.000 description 8
- 239000008157 edible vegetable oil Substances 0.000 description 6
- 239000000084 colloidal system Substances 0.000 description 5
- 239000008367 deionised water Substances 0.000 description 5
- 229910021641 deionized water Inorganic materials 0.000 description 5
- 235000013399 edible fruits Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 229920000747 poly(lactic acid) Polymers 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- PVBALTLWZVEAIO-UHFFFAOYSA-N diodone Chemical compound OC(=O)CN1C=C(I)C(=O)C(I)=C1 PVBALTLWZVEAIO-UHFFFAOYSA-N 0.000 description 3
- 229960001845 diodone Drugs 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- -1 polyoxyethylene Polymers 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 238000002601 radiography Methods 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 244000105017 Vicia sativa Species 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002707 nanocrystalline material Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 238000005987 sulfurization reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 1
- 241001415959 Grus japonensis Species 0.000 description 1
- 241000446313 Lamella Species 0.000 description 1
- 244000299790 Rheum rhabarbarum Species 0.000 description 1
- 235000009411 Rheum rhabarbarum Nutrition 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000004438 eyesight Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
- A61K49/1857—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
-
- 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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/12—Magnesium silicate
-
- 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
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/27—Asclepiadaceae (Milkweed family), e.g. hoya
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/708—Rheum (rhubarb)
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
- A61K49/126—Linear polymers, e.g. dextran, inulin, PEG
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- Natural Medicines & Medicinal Plants (AREA)
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- Chemical & Material Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Alternative & Traditional Medicine (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Radiology & Medical Imaging (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention relates to medical preparation field, disclose a kind of contrast agent, including polylactic-co-glycolic acid/bismuth sulfide nano compound particle, Polyethylene Glycol, surfactant, stabilizer, Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, Herba Agrimoniae, Radix Cynanchi Atrati.Chinese medicine material and modern nano material technology are combined for medical science medicament, it is combined by bismuth sulfide nano particle and polylactic-co-glycolic acid, bismuth sulfide nano particle is made to condense, remain bismuth sulfide nano particle this sensitivity embodied in contrast agent and accuracy, simultaneously at using dosage, all make moderate progress in toxic and side effects, improve the stability of contrast agent, improve the qualitative ability to focus and recall rate, several Chinese medicines are in addition to contributing to development effect, therapeutic effect can also be played, the contrast agent obtained is made to be provided simultaneously with good adhesion, do not reunite, filling effect does not the most hinder gastral effect.
Description
Technical field
The present invention relates to medical preparation field, a kind of contrast agent.
Background technology
It is a critically important technology in CT diagnosis that radiography strengthens, and carries out after referring to inject contrast agent with high pressure injector again
Scanning.Some CT is unenhanced is difficult to identification or the pathological changes of indefinite border, by the strengthening of contrast agent, can improve pathological tissues with normal
Contrast between tissue, thus more clearly show lesion structure and scope, along with the extensive application of CT scan technology, contrast agent
Use get more and more.
Nano material can relatively easily enter cell, makees CT contrast agent with nanoparticle and can be effectively improved the effect of CT development
Really, all make moderate progress in using dosage, toxic and side effects simultaneously, at most can reduce especially with the current diodone of dose ratio
10 times more than.Research finds that bismuth sulfide nano crystalline material may apply to improve in CT radiography the sensitivity of detection with accurate
Property, all make moderate progress in using dosage, toxic and side effects simultaneously, the particularity being had additionally, due to nanoparticle itself, with
Traditional CT iodide ion contrast agent is compared, it is also possible to extend the Half-life in vivo of contrast agent, improves the stability of contrast agent, it is to avoid
The misery of biphasic injection contrast solution and the injury to human body；The polymeric material that biodegradable and biocompatibility is good
Material can be as pharmaceutical carrier, and to human non-toxic's side effect, and catabolite can be excreted by human normal metabolism,
Toxicity is low, cheaper starting materials；It is brilliant that first Rabin et al. prepares lamella bismuth sulfide nano, examines with PVP parcel is modified it as CT
Contrast agent in survey, its result of study shows that bismuth sulfide nano crystalline material can significantly improve the sensitivity of detection with accurate
Property, all make moderate progress in using dosage, toxic and side effects simultaneously, reduce especially with dose ratio current diodone concentration
5 times more than.The most widely used CT scan of diagnosis of digestive tract disease, compares traditional diodone, novel contrast agent at present
Improve the recall rate of focus, but still do not have at present a kind of be provided simultaneously with good adhesion, do not reunite, filling effect the most again
Do not hinder gastral contrast agent.
Summary of the invention
The deficiency existed for prior art, it is an object of the invention to provide a kind of have simultaneously good adhesion,
Do not reunite, filling effect does not the most hinder gastral contrast agent.
For achieving the above object, the technical scheme is that a kind of contrast agent, including 30-40 weight portion
Live in poly lactic-co-glycolic acid/bismuth sulfide nano compound particle, the Polyethylene Glycol of 0.5-0.8 weight portion, 0.1-2 weight portion surface
Property agent, the stabilizer of 0.1-3 weight portion, the Concha Haliotidis of 0.2-0.5 weight portion, the Pulvis Talci of 0.2-0.4 weight portion, 0.1-0.3
The Radix Et Rhizoma Rhei of weight portion, the Herba Agrimoniae of 0.1-0.3 weight portion, the Radix Cynanchi Atrati of 0.1-0.2 weight portion.The Polyethylene Glycol added can increase
The adhesion of contrast agent so that contrast agent can be attached on the surface of diseased organ well, Polyethylene Glycol has again hydrophilic,
Contribute to again the excretion of contrast agent.Chinese medicine Concha Haliotidis has the effect of liver heat removing and eyesight improving, Chinese medicine Pulvis Talci to contribute to development, Chinese herb rhubarb
Having the effect of expel the heat-evil logical intestinal, removing pathogenic heat from blood and toxic substance from the body, described Chinese medicine Herba Agrimoniae to have anastaltic effect, described Chinese medicine Radix Cynanchi Atrati favorably urinates logical
The effect drenched.
As a further improvement on the present invention, the preparation of described poly lactic-co-glycolic acid/bismuth sulfide nano compound particle
Method is as follows: the mixed solvent being made up of chloroform and ethyl acetate by 30 m L adds in conical flask, at 30 DEG C, and mixing speed
Being under 400 r/min, add 1 g Poly(D,L-lactide-co-glycolide, stirring is to being completely dissolved, by poly lactic-co-glycolic acid
Solution instills in 150 m L 1% polyvinyl alcohol water solutions and obtains polymer solution；By 20 m L 5 g/L bismuth and ammonium citrate water
Solution and 10mL aqueous dispersant addition flask obtain bismuth saline solution, under 90 DEG C of constant temperature, stirs 30min, by polymer
Solution is poured in bismuth saline solution, puts into ultrasonic 6h in Ultrasound Instrument, adds 50 m L sodium sulfide solutions under agitation,
Flask is put into reaction 30min in microwave reactor, and decompression boils off chloroform and ethyl acetate, then under 10000r/min speed
Centrifugal 10 min, by precipitation distilled water wash, centrifugal and washing repeated several times, finally by precipitate ultrasonic disperse in
In 50 m L distilled water, under vacuum, lyophilization obtains poly lactic-co-glycolic acid/bismuth sulfide nano compound particle.
The poly lactic-co-glycolic acid that this preparation method technique is simple, easily operated, obtain/bismuth sulfide nano compound particle
Granule is uniform, contributes to making imaging apparent.
As a further improvement on the present invention, the molecular weight of described poly lactic-co-glycolic acid is 2000-5000.Contribute to
Make poly lactic-co-glycolic acid/bismuth sulfide nano compound particle granule evenly, the poly lactic-co-glycolic acid of this molecular weight ranges
Contribute to making imaging apparent.
As a further improvement on the present invention, during described dispersant is glucosan, polyvinylpyrrolidone, TGA
One or more.Add dispersant to contribute to generating more short grained nanometer sulfuration bismuth nanoparticle.
As a further improvement on the present invention, the volume ratio of described chloroform and ethyl acetate is 2:3-2:5.
The ratio of this scope can preferably dissolve Poly(D,L-lactide-co-glycolide, it helps removes more up hill and dale.
As a further improvement on the present invention, described stabilizer is lecithin, polyoxyethylene hydrogenated Oleum Ricini, gluconic acid
One or more in caprolactone.These several stabilizers contribute to stablizing of contrast agent, it is to avoid poly lactic-co-glycolic acid/sulfuration
Bismuth nano-complex particle granule generation is reunited.
As a further improvement on the present invention, described surfactant is sodium lauryl sulphate, sodium carboxymethyl cellulose
In one or more.Contribute to each effective ingredient in contrast agent preferably to disperse.
As a further improvement on the present invention, the temperature of described microwave reactor is set to as 40-60 DEG C.Contribute in control
On the premise of nano-particle size processed, accelerate reaction rate.
As a further improvement on the present invention, described Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, Herba Agrimoniae, the granular size of Radix Cynanchi Atrati are
50-100 mesh.The least meeting of granule makes technique complicate, and granule is unfavorable for the most greatly filling effect in organ cavity.
The material consumption of above steps of the present invention and proportioning can expand with equal proportion or reduce, and not by concrete weight
The restriction of value.
Chinese medicine material and modern nano material technology are combined for medical science medicament by the present invention, are received by bismuth sulfide
Rice corpuscles and poly lactic-co-glycolic acid are combined, and make bismuth sulfide nano particle to condense, remain bismuth sulfide nano particle itself
The sensitivity embodied in contrast agent and accuracy, all make moderate progress in using dosage, toxic and side effects simultaneously, improves radiography
The stability of agent, improves the qualitative ability to focus and recall rate,
Several Chinese medicines are in addition to contributing to development effect, moreover it is possible to play therapeutic effect so as to get contrast agent be provided simultaneously with well
Adhesion, do not reunite, filling effect does not the most hinder gastral effect.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1
The mixed solvent that 30 m L are made up of by 2:3 volume ratio chloroform and ethyl acetate is added in conical flask, at 30 DEG C, stirs
Mixing speed is under 400 r/min, and adding 1 g molecular weight is the Poly(D,L-lactide-co-glycolide of 3000, and stirring is to the most molten
Solve, poly lactic-co-glycolic acid solution is instilled in 150 m L 1% polyvinyl alcohol water solutions and obtain polymer solution；By 20 m
L 5 g/L bismuth citrate aqueous ammonium and 10mL glucan aqueous solution addition flask obtain bismuth saline solution, at 90 DEG C of constant temperature
Lower stirring 30min, pours into polymer solution in bismuth saline solution, puts into ultrasonic 6h in Ultrasound Instrument, add under agitation
50 m L sodium sulfide solutions, put into flask in microwave reactor, and temperature is set to 50 DEG C, react 30min, and decompression is steamed
Go chloroform and ethyl acetate, more centrifugal 10 min under 10000r/min speed, by precipitation distilled water wash, centrifugal and
Washing repeated several times, finally by precipitate ultrasonic disperse in 50 m L distilled water, under vacuum, lyophilization obtains poly-breast
Acid-hydroxyacetic acid/bismuth sulfide nano compound particle A.
Embodiment 2
The mixed solvent that 30 m L are made up of by 1:2 volume ratio chloroform and ethyl acetate is added in conical flask, at 30 DEG C, stirs
Mixing speed is under 400 r/min, and adding 1 g molecular weight is the Poly(D,L-lactide-co-glycolide of 2000, and stirring is to the most molten
Solve, poly lactic-co-glycolic acid solution is instilled in 150 m L 1% polyvinyl alcohol water solutions and obtain polymer solution；By 20 m
L 5 g/L bismuth citrate aqueous ammonium and 10mL aqueous povidone solution addition flask obtain bismuth saline solution,
Stir 30min under 90 DEG C of constant temperature, polymer solution is poured in bismuth saline solution, put into ultrasonic 6h in Ultrasound Instrument, at stirring bar
Add 50 m L sodium sulfide solutions under part, flask is put in microwave reactor, temperature is set to 60 DEG C, reaction
30min, decompression boils off chloroform and ethyl acetate, more centrifugal 10 min under 10000r/min speed, precipitation is distilled
Water washs, centrifugal and washing repeated several times, finally by precipitate ultrasonic disperse in 50 m L distilled water, freezing under vacuum
It is dried to obtain poly lactic-co-glycolic acid/bismuth sulfide nano compound particle B.
Embodiment 3
The mixed solvent that 30 m L are made up of by 2:5 volume ratio chloroform and ethyl acetate is added in conical flask, at 30 DEG C, stirs
Mixing speed is under 400 r/min, and adding 1 g molecular weight is the Poly(D,L-lactide-co-glycolide of 5000, and stirring is to the most molten
Solve, poly lactic-co-glycolic acid solution is instilled in 150 m L 1% polyvinyl alcohol water solutions and obtain polymer solution；By 20 m
L 5 g/L bismuth citrate aqueous ammonium and 10mL TGA aqueous solution addition flask obtain bismuth saline solution, 90 DEG C of perseverances
Stir 30min under temperature, polymer solution is poured in bismuth saline solution, put into ultrasonic 6h in Ultrasound Instrument, add under agitation
Enter 50 m L sodium sulfide solutions, flask is put in microwave reactor, temperature is set to 40 DEG C, react 30min, decompression
Boil off chloroform and ethyl acetate, more centrifugal 10 min under 10000r/min speed, by precipitation distilled water wash, centrifugal
With washing repeated several times, finally by precipitate ultrasonic disperse in 50 m L distilled water, under vacuum, lyophilization is gathered
Lactic-co-glycolic acid/bismuth sulfide nano compound particle C.
Embodiment 4
By the polylactide of 30 weight portions/bismuth sulfide nano compound particle, the lauryl sulphate acid of 0.1 weight portion,
The lecithin of 0.1 weight portion 50 mesh, the Concha Haliotidis of 0.2 weight portion, the Pulvis Talci of 0.2 weight portion, the Radix Et Rhizoma Rhei of 0.1 weight portion, 0.1
The Herba Agrimoniae of weight portion, 0.1 weight portion Radix Cynanchi Atrati mixing after be ground, Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, Herba Agrimoniae, Radix Cynanchi Atrati
Granular size is 50 mesh, is subsequently adding the Polyethylene Glycol of 0.5 weight portion, 20 parts by weight of deionized water, is stirred being suspended
Liquid, processes 3 times with high pressure homogenizer, at 60 DEG C of 30min that deaerate, then with colloid mill homogenizing 1 time, obtains final products.
The mensuration of contrast agent CT density value: put in plastic test tube by the contrast agent of preparation, carries out CT scan after sealing, survey
Determine CT density value.Result shows that the CT density value of prepared contrast agent is-180HU, and each scanning aspect CT density value is without bright
Significant difference is different, can keep stable in 30min.
The contrast agent perfusion of preparation in vitro Intestinum Sus domestica perfusion is measured CT density value in enteric cavity: filled by prepared contrast agent
Note in one section of in vitro Intestinum Sus domestica, after getting rid of air, with rope, two ends are sealed, in vitro Intestinum Sus domestica is immersed in edible oil, in order to
Parenterally fat environment in analogue body, shroud gas interfacial effect is disturbed, and carries out CT scan, measures CT density value in enteric cavity, knot
Fruit shows: enteric cavity CT value is about-180HU, and image light and shade is uniform, without visible lumps.
In water is filled in vitro Intestinum Sus domestica mensuration enteric cavity, CT density value is as a comparison: water is filled into one section of in vitro Intestinum Sus domestica
In, after getting rid of air, with rope, two ends are sealed, in vitro Intestinum Sus domestica is immersed in edible oil, in order to parenterally fat in analogue body
Fat environment, shroud gas interfacial effect is disturbed, and carries out CT scan, measures CT density value in enteric cavity, and result shows: enteric cavity CT value is
0, and intestinal wall is smudgy.
Embodiment 5
By the polylactide of 35 weight portions/bismuth sulfide nano compound particle, the lauryl sulphate acid of 0.5 weight portion,
The polyoxyethylene hydrogenated Oleum Ricini of 0.8 weight portion, the Concha Haliotidis of 0.3 weight portion, the Pulvis Talci of 0.3 weight portion, 0.2 weight portion
Radix Et Rhizoma Rhei, the Herba Agrimoniae of 0.12 weight portion, the Radix Cynanchi Atrati of 0.1 weight portion are ground after mixing, Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, red crowned crane
Grass, the granular size of Radix Cynanchi Atrati are 60 mesh, are subsequently adding the Polyethylene Glycol of 0.6 weight portion, 20 parts by weight of deionized water, are stirred
Obtain suspension, process 3 times with high pressure homogenizer, at 60 DEG C of 30min that deaerate, then with colloid mill homogenizing 1 time, obtain final products.
The mensuration of contrast agent CT density value: put in plastic test tube by the contrast agent of preparation, carries out CT scan after sealing, survey
Determine CT density value.Result shows that the CT density value of prepared contrast agent is-120HU, and each scanning aspect CT density value is without bright
Significant difference is different, can keep stable in 30min.
The contrast agent perfusion of preparation in vitro Intestinum Sus domestica perfusion is measured CT density value in enteric cavity: filled by prepared contrast agent
Note in one section of in vitro Intestinum Sus domestica, after getting rid of air, with rope, two ends are sealed, in vitro Intestinum Sus domestica is immersed in edible oil, in order to
Parenterally fat environment in analogue body, shroud gas interfacial effect is disturbed, and carries out CT scan, measures CT density value in enteric cavity, knot
Fruit shows: enteric cavity CT value is about-120HU, and image light and shade is uniform, without visible lumps.
Embodiment 6
By the polylactide of 40 weight portions/bismuth sulfide nano compound particle, the sodium carboxymethyl cellulose of 2 weight portions, 3
The polyoxyethylene hydrogenated Oleum Ricini of weight portion, the Concha Haliotidis of 0.5 weight portion, the Pulvis Talci of 0.4 weight portion, 0.3 weight portion big
Huang, the Herba Agrimoniae of 0.3 weight portion, 0.2 weight portion Radix Cynanchi Atrati mixing after be ground, Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, Herba Agrimoniae,
The granular size of Radix Cynanchi Atrati is 60 mesh, is subsequently adding the Polyethylene Glycol of 0.8 weight portion, 20 parts by weight of deionized water, is stirred
To suspension, process 3 times with high pressure homogenizer, at 60 DEG C of 30min that deaerate, then with colloid mill homogenizing 1 time, obtain final products.
The mensuration of contrast agent CT density value: put in plastic test tube by the contrast agent of preparation, carries out CT scan after sealing, survey
Determine CT density value.Result shows that the CT density value of prepared contrast agent is-150HU, and each scanning aspect CT density value is without bright
Significant difference is different, can keep stable in 30min.
The contrast agent perfusion of preparation in vitro Intestinum Sus domestica perfusion is measured CT density value in enteric cavity: filled by prepared contrast agent
Note in one section of in vitro Intestinum Sus domestica, after getting rid of air, with rope, two ends are sealed, in vitro Intestinum Sus domestica is immersed in edible oil, in order to
Parenterally fat environment in analogue body, shroud gas interfacial effect is disturbed, and carries out CT scan, measures CT density value in enteric cavity, knot
Fruit shows: enteric cavity CT value is about-150HU, and image light and shade is uniform, without visible lumps.
Embodiment 7
By the polylactide of 35 weight portions/bismuth sulfide nano compound particle, the sodium carboxymethyl cellulose of 1 weight portion, 2
The gluconic acid caprolactone of weight portion, the Concha Haliotidis of 0.4 weight portion, the Pulvis Talci of 0.4 weight portion, the Radix Et Rhizoma Rhei of 0.3 weight portion,
The Herba Agrimoniae of 0.1 weight portion, 0.1 weight portion Radix Cynanchi Atrati mixing after be ground, Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, Herba Agrimoniae, white
The granular size of common vetch is 60 mesh, is subsequently adding the Polyethylene Glycol of 0.7 weight portion, 20 parts by weight of deionized water, is stirred obtaining
Suspension, processes 3 times with high pressure homogenizer, at 60 DEG C of 30min that deaerate, then with colloid mill homogenizing 1 time, obtains final products.
The mensuration of contrast agent CT density value: put in plastic test tube by the contrast agent of preparation, carries out CT scan after sealing, survey
Determine CT density value.Result shows that the CT density value of prepared contrast agent is-80HU, and each scanning aspect CT density value is without substantially
Difference, can keep stable in 30min.
The contrast agent perfusion of preparation in vitro Intestinum Sus domestica perfusion is measured CT density value in enteric cavity: filled by prepared contrast agent
Note in one section of in vitro Intestinum Sus domestica, after getting rid of air, with rope, two ends are sealed, in vitro Intestinum Sus domestica is immersed in edible oil, in order to
Parenterally fat environment in analogue body, shroud gas interfacial effect is disturbed, and carries out CT scan, measures CT density value in enteric cavity, knot
Fruit shows: enteric cavity CT value is about-80HU, and image light and shade is uniform, without visible lumps.
Embodiment 8
By the polylactide of 40 weight portions/bismuth sulfide nano compound particle, the sodium carboxymethyl cellulose of 2 weight portions, 2
The gluconic acid caprolactone of weight portion, the Concha Haliotidis of 0.5 weight portion, the Pulvis Talci of 0.2 weight portion, the Radix Et Rhizoma Rhei of 0.2 weight portion,
The Herba Agrimoniae of 0.3 weight portion, 0.2 weight portion Radix Cynanchi Atrati mixing after be ground, Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, Herba Agrimoniae, white
The granular size of common vetch is 60 mesh, is subsequently adding the Polyethylene Glycol of 0.6 weight portion, 20 parts by weight of deionized water, is stirred obtaining
Suspension, processes 3 times with high pressure homogenizer, at 60 DEG C of 30min that deaerate, then with colloid mill homogenizing 1 time, obtains final products.
The mensuration of contrast agent CT density value: put in plastic test tube by the contrast agent of preparation, carries out CT scan after sealing, survey
Determine CT density value.Result shows that the CT density value of prepared contrast agent is-200HU, and each scanning aspect CT density value is without bright
Significant difference is different, can keep stable in 30min.
The contrast agent perfusion of preparation in vitro Intestinum Sus domestica perfusion is measured CT density value in enteric cavity: filled by prepared contrast agent
Note in one section of in vitro Intestinum Sus domestica, after getting rid of air, with rope, two ends are sealed, in vitro Intestinum Sus domestica is immersed in edible oil, in order to
Parenterally fat environment in analogue body, shroud gas interfacial effect is disturbed, and carries out CT scan, measures CT density value in enteric cavity, knot
Fruit shows: enteric cavity CT value is about-200HU, and image light and shade is uniform, without visible lumps.
The above is only the preferred embodiment of the present invention, and protection scope of the present invention is not limited merely to above-mentioned enforcement
Example, all technical schemes belonged under thinking of the present invention belong to protection scope of the present invention.It should be pointed out that, for the art
Those of ordinary skill for, some improvements and modifications without departing from the principles of the present invention, these improvements and modifications are also
Should be regarded as protection scope of the present invention.
Claims (9)
1. a contrast agent, it is characterised in that: include that the poly lactic-co-glycolic acid/bismuth sulfide nano of 30-40 weight portion is combined
Particle, the Polyethylene Glycol of 0.5-0.8 weight portion, 0.1-2 parts surfactant, the stabilizer of 0.1-3 weight portion, 0.2-
The Concha Haliotidis of 0.5 weight portion, the Pulvis Talci of 0.2-0.4 weight portion, the Radix Et Rhizoma Rhei of 0.1-0.3 weight portion, the celestial being of 0.1-0.3 weight portion
Crane grass, the Radix Cynanchi Atrati of 0.1-0.2 weight portion.
A kind of contrast agent the most according to claim 1, it is characterised in that: described poly lactic-co-glycolic acid/bismuth sulfide is received
The preparation method of rice compound particle is as follows:
Preparing the mixed solvent that 30 m L are made up of chloroform and ethyl acetate, at 30 DEG C, mixing speed is under 400 r/min, adds
Entering 1 g Poly(D,L-lactide-co-glycolide, poly lactic-co-glycolic acid solution, to being completely dissolved, is instilled 150 m L by stirring
1% polyvinyl alcohol water solution obtains polymer solution；By 20 mL 5g/L bismuth citrate aqueous ammonium and 10mL dispersant water
Solution is mixed to get bismuth saline solution, stirs 30min, poured into by polymer solution in bismuth saline solution, put under 90 DEG C of constant temperature
Enter ultrasonic 6h in Ultrasound Instrument, add 50 m L sodium sulfide solutions under agitation, flask is put in microwave reactor anti-
Answer 30min, decompression to boil off chloroform and ethyl acetate, more centrifugal 10 min under 10000r/min speed, precipitation is steamed
Distilled water is washed, centrifugal and washing repeated several times, finally by precipitate ultrasonic disperse in 50 m L distilled water, cold under vacuum
Freeze and be dried to obtain poly lactic-co-glycolic acid/bismuth sulfide nano compound particle.
A kind of contrast agent the most according to claim 2, it is characterised in that: the molecular weight of described poly lactic-co-glycolic acid is
2000-5000。
A kind of contrast agent the most according to claim 3, it is characterised in that: described dispersant is glucosan, polyvinyl pyrrole
One or more in alkanone, TGA.
A kind of contrast agent the most according to claim 4, it is characterised in that: the volume ratio of described chloroform and ethyl acetate is 2:
3-2:5.
6. according to a kind of contrast agent described in any one of claim 1-5, it is characterised in that: described stabilizer is lecithin, gathers
One or more in oxygen ethylene hydrogenation Oleum Ricini, gluconic acid caprolactone.
A kind of contrast agent the most according to claim 6, it is characterised in that: described surfactant is lauryl sulphate acid
One or more in sodium, sodium carboxymethyl cellulose.
A kind of contrast agent the most according to claim 7, it is characterised in that: the temperature of described microwave reactor be set to for
40-60℃。
A kind of contrast agent the most according to claim 8, it is characterised in that: described Concha Haliotidis, Pulvis Talci, Radix Et Rhizoma Rhei, Herba Agrimoniae,
The granular size of Radix Cynanchi Atrati is 50-100 mesh.
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| CN111885844A (en) * | 2020-08-20 | 2020-11-03 | 深圳市明正宏电子有限公司 | Gold plating process for PCB secondary circuit |
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|---|---|---|---|---|
| CN1147206A (en) * | 1994-04-21 | 1997-04-09 | 耐克麦德英梅金公司 | X-ray contrast composition containing medicinal clay |
| CN1215342A (en) * | 1996-02-20 | 1999-04-28 | 耐克麦德英梅金公司 | contrast agent |
| CN103977429A (en) * | 2014-04-28 | 2014-08-13 | 石德强 | Gastrointestinal tract contrast agent |
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2016
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1147206A (en) * | 1994-04-21 | 1997-04-09 | 耐克麦德英梅金公司 | X-ray contrast composition containing medicinal clay |
| CN1215342A (en) * | 1996-02-20 | 1999-04-28 | 耐克麦德英梅金公司 | contrast agent |
| CN103977429A (en) * | 2014-04-28 | 2014-08-13 | 石德强 | Gastrointestinal tract contrast agent |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111885844A (en) * | 2020-08-20 | 2020-11-03 | 深圳市明正宏电子有限公司 | Gold plating process for PCB secondary circuit |
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