CN106075476B - A kind of contrast agent - Google Patents

A kind of contrast agent Download PDF

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CN106075476B
CN106075476B CN201610611637.3A CN201610611637A CN106075476B CN 106075476 B CN106075476 B CN 106075476B CN 201610611637 A CN201610611637 A CN 201610611637A CN 106075476 B CN106075476 B CN 106075476B
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contrast agent
bismuth
sulfide nano
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CN106075476A (en
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陈皓
王毅
姜文兵
陈晓曙
林伟
李林锦
胡逸人
林建峰
黄时伟
吴悠扬
赵玮
朱恩强
邹贺
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Wenzhou Peoples Hospital
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    • A61K49/1824Nuclear 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
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Abstract

The present invention relates to medical preparation fields, disclose a kind of contrast agent, including poly lactic-co-glycolic acid/bismuth sulfide nano compound particle, polyethylene glycol, surfactant, stabilizer, the shell of seaear, talcum powder, rheum officinale, hairyvein agrimony, radix cynanchi atrati.Traditional Chinese medicine and modern nano material technology are combined and be used for medicine medicament, it is compound by bismuth sulfide nano particle and poly lactic-co-glycolic acid, agglomerate bismuth sulfide nano particle will not, remain the sensitivity and accuracy that bismuth sulfide nano particle itself embodies in contrast agent, simultaneously in dosage, it all makes moderate progress in toxic side effect, improve the stability of contrast agent, improve the qualitative ability and recall rate to lesion, several Chinese medicines are other than facilitating development effect, therapeutic effect can also be played, the contrast agent made is provided simultaneously with good adhesion, do not reunite, filling effect is good not to hurt gastral effect again.

Description

A kind of contrast agent
Technical field
The present invention relates to medical preparation field, more particularly to a kind of contrast agent.
Background technique
Radiography enhancing is a critically important technology in CT diagnosis, refers to and carries out again after injecting contrast agent with high pressure injector Scanning.Some CT are unenhanced to be not easy the lesion of identification or indefinite border, by the reinforcing of contrast agent, can improve pathological tissues and normal Contrast between tissue, so that lesion structure and range are more clearly shown, with the extensive use of CT scan technology, contrast agent Using more and more.
Nano material can relatively easily enter cell, and the effect of CT development can be effectively improved by making CT contrast agent with nanoparticle Fruit, while all making moderate progress in dosage, toxic side effect, it can at most be reduced especially with the current diodone of dose ratio As many as 10 times.Research finds that bismuth sulfide nano crystalline material can be applied in CT radiography the sensitivity for improving detection and accurate Property, while it all making moderate progress in dosage, toxic side effect, additionally, due to particularity possessed by nanoparticle itself, with Traditional CT iodide ion contrast agent is compared, and can also be extended the Half-life in vivo of contrast agent, be improved the stability of contrast agent, avoid The pain of biphasic injection contrast solution and the injury to human body;The good polymeric material of biodegradable and biocompatibility Material can be used as pharmaceutical carrier, have no toxic and side effect to human body, and catabolite can be excreted by human normal metabolism, Toxicity is low, raw material is cheap;Rabin et al. prepares lamella bismuth sulfide nano crystalline substance first, uses it PVP package is modified to examine as CT Contrast agent in survey, result of study show that bismuth sulfide nano crystalline material can significantly improve the sensitivity of detection and accurate Property, while all making moderate progress in dosage, toxic side effect, it is reduced especially with the current diodone concentration of dose ratio As many as 5 times.CT scan is also widely used in the diagnosis of disease of digestive tract at present, compared to traditional diodone, novel contrast agent Improve the recall rate of lesion, but at present still without one kind be provided simultaneously with good adhesion, do not reunite, filling effect it is good again Gastral contrast agent is not hurt.
Summary of the invention
In view of the deficiencies of the prior art, the present invention intends to provide it is a kind of and meanwhile have good adhesion, Do not reunite, filling effect is good and does not hurt gastral contrast agent.
To achieve the above object, the present invention provides the following technical scheme that a kind of contrast agent, including 30-40 parts by weight Poly lactic-co-glycolic acid/bismuth sulfide nano compound particle, the polyethylene glycol of 0.5-0.8 parts by weight, 0.1-2 parts by weight surface are living Property agent, the stabilizer of 0.1-3 parts by weight, the shell of seaear of 0.2-0.5 parts by weight, the talcum powder of 0.2-0.4 parts by weight, 0.1-0.3 The rheum officinale of parts by weight, the hairyvein agrimony of 0.1-0.3 parts by weight, 0.1-0.2 parts by weight radix cynanchi atrati.The polyethylene glycol of addition can increase The adhesion of contrast agent allows contrast agent to be attached on the surface of diseased organ well, and polyethylene glycol has hydrophily again, Facilitate the excretion of contrast agent again.The Chinese medicine shell of seaear clears liver and improve vision, and Chinese medicine talcum powder helps to develop, Chinese herb rhubarb Expel the heat-evil logical intestines, removing pattogenic heat from the blood and toxic material from the body, and the Chinese medicine hairyvein agrimony plays the role of astringing to arrest bleeding, and the Chinese medicine radix cynanchi atrati favorably urinates logical The effect of leaching.
As a further improvement of the present invention, the poly lactic-co-glycolic acid/bismuth sulfide nano compound particle preparation Method is as follows: the mixed solvent that 30 m L are made of chloroform and ethyl acetate is added in conical flask, at 30 DEG C, mixing speed For 1 g poly lactide-glycolide acid is added under 400 r/min, stir to being completely dissolved, by poly lactic-co-glycolic acid Solution instills in 150 m L, 1% polyvinyl alcohol water solution and obtains polymer solution;By 20 m L, 5 g/L bismuth and ammonium citrate water Solution and 10mL aqueous dispersant, which are added in flask, obtains bismuth salt aqueous solution, 30min is stirred under 90 DEG C of constant temperature, by polymer Solution pours into bismuth salt aqueous solution, is put into ultrasound 6h in Ultrasound Instrument, and 50 m L sodium sulfide solutions are added under agitation, Flask is put into microwave reactor and reacts 30min, decompression boils off chloroform and ethyl acetate, then under 10000r/min speed Be centrifuged 10 min, precipitating be washed with distilled water, be centrifuged and wash repeated several times, finally by sediment ultrasonic disperse in In 50 m L distilled water, freeze-drying obtains poly lactic-co-glycolic acid/bismuth sulfide nano compound particle under vacuum.
This preparation method simple process, easily operated, obtained poly lactic-co-glycolic acid/bismuth sulfide nano compound particle Particle is uniform, helps to make to be imaged apparent.
As a further improvement of the present invention, the molecular weight of the poly lactic-co-glycolic acid is 2000-5000.Facilitate Make poly lactic-co-glycolic acid/bismuth sulfide nano compound particle particle more evenly, the poly lactic-co-glycolic acid of this molecular weight ranges Help to make to be imaged apparent.
As a further improvement of the present invention, the dispersing agent is glucan, in polyvinylpyrrolidone, thioacetic acid It is one or more of.Addition dispersing agent helps to generate more short grained nanometer vulcanization bismuth nanoparticle.
As a further improvement of the present invention, the volume ratio of the chloroform and ethyl acetate is 2:3-2:5.
The ratio of this range can preferably dissolve poly lactide-glycolide acid, it helps more thoroughly remove.
As a further improvement of the present invention, the stabilizer is lecithin, Crodaret, gluconic acid One or more of caprolactone.These types of stabilizer facilitates the stabilization of contrast agent, avoids poly lactic-co-glycolic acid/vulcanization The generation of bismuth nano-complex particle particle is reunited.
As a further improvement of the present invention, the surfactant is lauryl sodium sulfate, sodium carboxymethylcellulose One or more of.Facilitate each effective component in contrast agent to better disperse.
As a further improvement of the present invention, the temperature setting of the microwave reactor is 40-60 DEG C.Help controlling Under the premise of nano particle size processed, accelerate reaction rate.
As a further improvement of the present invention, the shell of seaear, talcum powder, rheum officinale, hairyvein agrimony, radix cynanchi atrati granular size be 50-100 mesh.Particle is too small so that technique is complicated, and particle is unfavorable for greatly very much the filling effect in organ cavity.
The substance dosage and proportion of above steps of the present invention can be expanded or be reduced with equal proportion, without by specific weight The limitation of value.
Traditional Chinese medicine and modern nano material technology are combined and are used for medicine medicament by the present invention, are received by bismuth sulfide Rice corpuscles and poly lactic-co-glycolic acid are compound, agglomerate bismuth sulfide nano particle will not, remain bismuth sulfide nano particle itself The sensitivity and accuracy embodied in contrast agent, while all making moderate progress in dosage, toxic side effect, improve radiography The stability of agent improves qualitative ability and recall rate to lesion,
Several Chinese medicines are other than facilitating development effect, moreover it is possible to play therapeutic effect, the contrast agent made is provided simultaneously with Good adhesion, do not reunite, filling effect is good and does not hurt gastral effect.
Specific embodiment
The present invention is described in further detail below in conjunction with embodiment.
Embodiment 1
30 m L are added in conical flask by chloroform and ethyl acetate by the mixed solvent that 2:3 volume ratio forms, 30 DEG C, mixing speed is that the poly lactide-glycolide acid that 1 g molecular weight is 3000 is added under 400 r/min, is stirred to complete Poly lactic-co-glycolic acid solution is instilled in 150 m L, 1% polyvinyl alcohol water solution and obtains polymer solution by fully dissolved;It will 20 m L, 5 g/L bismuth citrate aqueous ammonium and 10mL glucan aqueous solution, which are added in flask, obtains bismuth salt aqueous solution, at 90 DEG C 30min is stirred under constant temperature, polymer solution is poured into bismuth salt aqueous solution, is put into ultrasound 6h in Ultrasound Instrument, under agitation 50 m L sodium sulfide solutions are added, flask is put into microwave reactor, is 50 DEG C by temperature setting, reacts 30min, subtract Pressure boils off chloroform and ethyl acetate, then 10 min are centrifuged under 10000r/min speed, and precipitating is washed with distilled water, from The heart and washing repeated several times, finally by sediment ultrasonic disperse in 50 m L distilled water, freeze-drying is obtained under vacuum Poly lactic-co-glycolic acid/bismuth sulfide nano compound particle A.
Embodiment 2
30 m L are added in conical flask by chloroform and ethyl acetate by the mixed solvent that 1:2 volume ratio forms, 30 DEG C, mixing speed is that the poly lactide-glycolide acid that 1 g molecular weight is 2000 is added under 400 r/min, is stirred to complete Poly lactic-co-glycolic acid solution is instilled in 150 m L, 1% polyvinyl alcohol water solution and obtains polymer solution by fully dissolved;It will It is water-soluble that bismuth salt is obtained in 20 m L, 5 g/L bismuth citrate aqueous ammonium and 10mL aqueous povidone solution addition flask Liquid stirs 30min under 90 DEG C of constant temperature, and polymer solution is poured into bismuth salt aqueous solution, is put into ultrasound 6h in Ultrasound Instrument, is stirring 50 m L sodium sulfide solutions are added under the conditions of mixing, flask is put into microwave reactor, are 60 DEG C by temperature setting, reaction 30min, decompression boils off chloroform and ethyl acetate, then 10 min are centrifuged under 10000r/min speed, by precipitating distillation Water washing, centrifugation and washing repeated several times, finally freeze sediment ultrasonic disperse in 50 m L distilled water under vacuum It is dried to obtain poly lactic-co-glycolic acid/bismuth sulfide nano compound particle B.
Embodiment 3
30 m L are added in conical flask by chloroform and ethyl acetate by the mixed solvent that 2:5 volume ratio forms, 30 DEG C, mixing speed is that the poly lactide-glycolide acid that 1 g molecular weight is 5000 is added under 400 r/min, is stirred to complete Poly lactic-co-glycolic acid solution is instilled in 150 m L, 1% polyvinyl alcohol water solution and obtains polymer solution by fully dissolved;It will 20 m L, 5 g/L bismuth citrate aqueous ammonium and 10mL thioacetic acid aqueous solution, which are added in flask, obtains bismuth salt aqueous solution, 90 30min is stirred under DEG C constant temperature, polymer solution is poured into bismuth salt aqueous solution, ultrasound 6h in Ultrasound Instrument is put into, in stirring condition 50 m L sodium sulfide solutions of lower addition, flask is put into microwave reactor, is 40 DEG C by temperature setting, is reacted 30min, Decompression boils off chloroform and ethyl acetate, then 10 min are centrifuged under 10000r/min speed, and precipitating is washed with distilled water, Sediment ultrasonic disperse, is finally freeze-dried under vacuum by centrifugation and washing repeated several times in 50 m L distilled water To poly lactic-co-glycolic acid/bismuth sulfide nano compound particle C.
Embodiment 4
By the polylactide of 30 parts by weight/bismuth sulfide nano compound particle, the dodecyl sulphur of 0.1 parts by weight Acid, the lecithin of 0.1 parts by weight, 50 mesh, the shell of seaear of 0.2 parts by weight, the talcum powder of 0.2 parts by weight, 0.1 parts by weight rheum officinale, The hairyvein agrimony of 0.1 parts by weight, 0.1 parts by weight radix cynanchi atrati mixing after ground, it is the shell of seaear, talcum powder, rheum officinale, hairyvein agrimony, white The granular size of common vetch is 50 mesh, and polyethylene glycol, 20 parts by weight of deionized water of 0.5 parts by weight are then added, are stirred to obtain Suspension is handled 3 times with high pressure homogenizer, in 60 DEG C of degassing 30min, then with colloid mill homogeneous 1 time, obtains final products.
The measurement of contrast agent CT density value: the contrast agent of preparation is put into plastic test tube, and CT scan is carried out after sealing, is surveyed Determine CT density value.The result shows that the CT density value of prepared contrast agent is -180HU, each scanning level CT density value is without bright Significant difference is different, can keep stablizing in 30min.
CT density value in measurement enteric cavity is perfused in the contrast agent perfusion of preparation in vitro chitling: prepared contrast agent is filled It infuses into one section of in vitro chitling, after excluding air, both ends is sealed with rope, in vitro chitling is immersed in edible oil, to Parenterally fat environment in analogue body, shroud gas interfacial effect interference, carries out CT scan, measures CT density value in enteric cavity, knot Fruit shows: enteric cavity CT value is -180HU or so, and image light and shade is uniform, no visible lumps.
By water be filled into vitro chitling measure enteric cavity in CT density value as a comparison: water is filled into one section of in vitro chitling In, after excluding air, both ends are sealed with rope, in vitro chitling is immersed in edible oil, to parenterally rouge in analogue body Fat environment, shroud gas interfacial effect interference, carries out CT scan, measures CT density value in enteric cavity, the results showed that enteric cavity CT value is 0, and intestinal wall is smudgy.
Embodiment 5
By the polylactide of 35 parts by weight/bismuth sulfide nano compound particle, the dodecyl sulphur of 0.5 parts by weight Acid, the Crodaret of 0.8 parts by weight, the shell of seaear of 0.3 parts by weight, the talcum powder of 0.3 parts by weight, 0.2 weight Part rheum officinale, the hairyvein agrimonies of 0.12 parts by weight, 0.1 parts by weight radix cynanchi atrati mixing after ground, the shell of seaear, talcum powder, rheum officinale, Hairyvein agrimony, radix cynanchi atrati granular size be 60 mesh, polyethylene glycol, 20 parts by weight of deionized water of 0.6 parts by weight are then added, carry out Suspension is stirred to get, is handled 3 times with high pressure homogenizer, in 60 DEG C of degassing 30min, then with colloid mill homogeneous 1 time, is obtained and finally produce Product.
The measurement of contrast agent CT density value: the contrast agent of preparation is put into plastic test tube, and CT scan is carried out after sealing, is surveyed Determine CT density value.The result shows that the CT density value of prepared contrast agent is -120HU, each scanning level CT density value is without bright Significant difference is different, can keep stablizing in 30min.
CT density value in measurement enteric cavity is perfused in the contrast agent perfusion of preparation in vitro chitling: prepared contrast agent is filled It infuses into one section of in vitro chitling, after excluding air, both ends is sealed with rope, in vitro chitling is immersed in edible oil, to Parenterally fat environment in analogue body, shroud gas interfacial effect interference, carries out CT scan, measures CT density value in enteric cavity, knot Fruit shows: enteric cavity CT value is -120HU or so, and image light and shade is uniform, no visible lumps.
Embodiment 6
By the polylactide of 40 parts by weight/bismuth sulfide nano compound particle, the carboxymethyl cellulose of 2 parts by weight Sodium, the Crodaret of 3 parts by weight, the shell of seaear of 0.5 parts by weight, the talcum powder of 0.4 parts by weight, 0.3 parts by weight Rheum officinale, the hairyvein agrimonies of 0.3 parts by weight, 0.2 parts by weight radix cynanchi atrati mixing after ground, the shell of seaear, talcum powder, rheum officinale, celestial being Crane grass, radix cynanchi atrati granular size be 60 mesh, polyethylene glycol, 20 parts by weight of deionized water of 0.8 parts by weight are then added, are stirred It mixes to obtain suspension, is handled 3 times with high pressure homogenizer, in 60 DEG C of degassing 30min, then with colloid mill homogeneous 1 time, obtain and finally produce Product.
The measurement of contrast agent CT density value: the contrast agent of preparation is put into plastic test tube, and CT scan is carried out after sealing, is surveyed Determine CT density value.The result shows that the CT density value of prepared contrast agent is -150HU, each scanning level CT density value is without bright Significant difference is different, can keep stablizing in 30min.
CT density value in measurement enteric cavity is perfused in the contrast agent perfusion of preparation in vitro chitling: prepared contrast agent is filled It infuses into one section of in vitro chitling, after excluding air, both ends is sealed with rope, in vitro chitling is immersed in edible oil, to Parenterally fat environment in analogue body, shroud gas interfacial effect interference, carries out CT scan, measures CT density value in enteric cavity, knot Fruit shows: enteric cavity CT value is -150HU or so, and image light and shade is uniform, no visible lumps.
Embodiment 7
By the polylactide of 35 parts by weight/bismuth sulfide nano compound particle, the carboxymethyl cellulose of 1 parts by weight Sodium, the gluconic acid caprolactone of 2 parts by weight, the shell of seaear of 0.4 parts by weight, the talcum powder of 0.4 parts by weight, 0.3 parts by weight it is big Huang, the hairyvein agrimony of 0.1 parts by weight, 0.1 parts by weight radix cynanchi atrati mixing after ground, the shell of seaear, talcum powder, rheum officinale, hairyvein agrimony, The granular size of radix cynanchi atrati is 60 mesh, and polyethylene glycol, 20 parts by weight of deionized water of 0.7 parts by weight are then added, are stirred To suspension, is handled 3 times with high pressure homogenizer, in 60 DEG C of degassing 30min, then with colloid mill homogeneous 1 time, obtain final products.
The measurement of contrast agent CT density value: the contrast agent of preparation is put into plastic test tube, and CT scan is carried out after sealing, is surveyed Determine CT density value.The result shows that the CT density value of prepared contrast agent is -80HU, each scanning level CT density value is without obvious Difference can keep stablizing in 30min.
CT density value in measurement enteric cavity is perfused in the contrast agent perfusion of preparation in vitro chitling: prepared contrast agent is filled It infuses into one section of in vitro chitling, after excluding air, both ends is sealed with rope, in vitro chitling is immersed in edible oil, to Parenterally fat environment in analogue body, shroud gas interfacial effect interference, carries out CT scan, measures CT density value in enteric cavity, knot Fruit shows: enteric cavity CT value is -80HU or so, and image light and shade is uniform, no visible lumps.
Embodiment 8
By the polylactide of 40 parts by weight/bismuth sulfide nano compound particle, the carboxymethyl cellulose of 2 parts by weight Sodium, the gluconic acid caprolactone of 2 parts by weight, the shell of seaear of 0.5 parts by weight, the talcum powder of 0.2 parts by weight, 0.2 parts by weight it is big Huang, the hairyvein agrimony of 0.3 parts by weight, 0.2 parts by weight radix cynanchi atrati mixing after ground, the shell of seaear, talcum powder, rheum officinale, hairyvein agrimony, The granular size of radix cynanchi atrati is 60 mesh, and polyethylene glycol, 20 parts by weight of deionized water of 0.6 parts by weight are then added, are stirred To suspension, is handled 3 times with high pressure homogenizer, in 60 DEG C of degassing 30min, then with colloid mill homogeneous 1 time, obtain final products.
The measurement of contrast agent CT density value: the contrast agent of preparation is put into plastic test tube, and CT scan is carried out after sealing, is surveyed Determine CT density value.The result shows that the CT density value of prepared contrast agent is -200HU, each scanning level CT density value is without bright Significant difference is different, can keep stablizing in 30min.
CT density value in measurement enteric cavity is perfused in the contrast agent perfusion of preparation in vitro chitling: prepared contrast agent is filled It infuses into one section of in vitro chitling, after excluding air, both ends is sealed with rope, in vitro chitling is immersed in edible oil, to Parenterally fat environment in analogue body, shroud gas interfacial effect interference, carries out CT scan, measures CT density value in enteric cavity, knot Fruit shows: enteric cavity CT value is -200HU or so, and image light and shade is uniform, no visible lumps.
The above is only a preferred embodiment of the present invention, protection scope of the present invention is not limited merely to above-mentioned implementation Example, all technical solutions belonged under thinking of the present invention all belong to the scope of protection of the present invention.It should be pointed out that for the art Those of ordinary skill for, several improvements and modifications without departing from the principles of the present invention, these improvements and modifications It should be regarded as protection scope of the present invention.

Claims (3)

1. a kind of contrast agent, it is characterised in that: the compound grain of poly lactic-co-glycolic acid/bismuth sulfide nano including 30-40 parts by weight Son, the polyethylene glycol of 0.5-0.8 parts by weight, 0.1-2 parts surfactant, the stabilizer of 0.1-3 parts by weight, 0.2-0.5 The shell of seaear of parts by weight, the talcum powder of 0.2-0.4 parts by weight, the rheum officinale of 0.1-0.3 parts by weight, 0.1-0.3 parts by weight red crowned crane The radix cynanchi atrati of grass, 0.1-0.2 parts by weight;
The poly lactic-co-glycolic acid/bismuth sulfide nano compound particle the preparation method is as follows:
Prepare the mixed solvent that 30mL is made of chloroform and ethyl acetate, at 30 DEG C, mixing speed is that 1g is added under 400r/min Poly lactide-glycolide acid, stirring instill 150mL1% polyethylene to being completely dissolved, by poly lactic-co-glycolic acid solution Polymer solution is obtained in alcohol solution;20mL5g/L bismuth citrate aqueous ammonium and 10mL aqueous dispersant are mixed to get Bismuth salt aqueous solution stirs 30min under 90 DEG C of constant temperature, and polymer solution is poured into bismuth salt aqueous solution, is put into Ultrasound Instrument and surpasses 50mL sodium sulfide solution is added under agitation, flask is put into microwave reactor and reacts 30min by sound 6h, and decompression is steamed Chloroform and ethyl acetate are removed, then is centrifuged 10min under 10000r/min speed, precipitating is washed with distilled water, is centrifuged and washs Repeated several times, finally by sediment ultrasonic disperse in 50mL distilled water, freeze-drying obtains polylactic acid-glycolic base second under vacuum Acid/bismuth sulfide nano compound particle;
The molecular weight of the poly lactic-co-glycolic acid is 2000-5000;
The dispersing agent is one or more of glucan, polyvinylpyrrolidone, thioacetic acid;
The volume ratio of the chloroform and ethyl acetate is 2:3-2:5;
The stabilizer is one or more of lecithin, Crodaret, gluconic acid caprolactone;The table Face activating agent is one or more of lauryl sodium sulfate, sodium carboxymethylcellulose.
2. a kind of contrast agent according to claim 1, it is characterised in that: the temperature setting of the microwave reactor is 40- 60℃。
3. a kind of contrast agent according to claim 2, it is characterised in that: the shell of seaear, talcum powder, rheum officinale, hairyvein agrimony, The granular size of radix cynanchi atrati is 50-100 mesh.
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CN1147206A (en) * 1994-04-21 1997-04-09 耐克麦德英梅金公司 X-ray contrast compositions contg. pharmaceutically acceptable clays
CN1215342A (en) * 1996-02-20 1999-04-28 耐克麦德英梅金公司 Contrast medium
CN103977429A (en) * 2014-04-28 2014-08-13 石德强 Gastrointestinal tract contrast agent

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CN1147206A (en) * 1994-04-21 1997-04-09 耐克麦德英梅金公司 X-ray contrast compositions contg. pharmaceutically acceptable clays
CN1215342A (en) * 1996-02-20 1999-04-28 耐克麦德英梅金公司 Contrast medium
CN103977429A (en) * 2014-04-28 2014-08-13 石德强 Gastrointestinal tract contrast agent

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"Silica-coated bismuth sulfide nanorods as multimodal contrast agents for a non-invasive visualization of the gastrointestinal tract";Xiaopeng Zheng等;《Nanoscale》;20150619(第7期);摘要

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