CN101953845B - Hepatic artery chemoembolization embolism agent containing autophagy inhibitor - Google Patents
Hepatic artery chemoembolization embolism agent containing autophagy inhibitor Download PDFInfo
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Abstract
The invention relates to the technical field of medicaments, and discloses a transcatheter arterial chemoembolization embolism agent containing an autophagy inhibitor for treating liver cancer. The embolism agent consists of a chemotherapy medicament, the autophagy inhibitor and iodized oil, wherein the chemotherapy medicament is cis-platinum; the iodized oil is liquid iodized oil; and the autophagy inhibitor is selected from bafilomycin A1 or chloroquine. The bafilomycin A1 or the chloroquine can be used as a sensitizer of the chemotherapy medicament, and can increase the sensitivity of liver cancer cells to the chemotherapy medicament in a hypoxic ischemic microenvironment after embolism and enhance the anti-cancer effect of the chemotherapy medicament. Animal experiments show that the embolism agent can achieve good curative effect for treating middle and late primary liver cancers, obviously increase the apoptosis rate and the necrosis rate of tumor cells and remarkably reduce tumors so as to improve the curative effect of transcatheter arterial chemoembolization. The invention provides the embolism agent with good curative effect and low injury for the transcatheter arterial chemoembolization.
Description
Technical field
The present invention relates to medical technical field, is a kind of hepatic arterial chemoembolization agent that contains the autophagy inhibitor for the treatment of hepatocarcinoma.
Background technology
Transarterial Chemoembolization (Transcatheter arterial chemoembolization, TACE) be to utilize iodized oil and chemotherapeutics perfusion occlusion of bone tumors feeding artery, forming the microenvironment of hypoxic-ischemic and local chemotherapy, is a kind of therapeutic modality safely and effectively of liver cancer treatment.The blood of tumor supplies more than 90% from Hepatic artery, and the blood of normal liver tissue 75% is from portal vein, can not cause big influence so carry out arterial thrombosis to normal hepatic blood supply, the main blood of but having blocked tumor supplies, therefore, cancerous node is most of downright bad, and liver function is not impaired or impaired not serious.And chemotherapeutics is delivered to the feeding artery of tumor by the conduit selectivity, tumor by local drug level height can reach 100～400 times of whole body, and this is the unapproachable level of peripheral vein administration, the first pass effect of medicine is obvious, and the whole body toxic and side effects obviously reduces.The existing suppository of being made up of chemotherapeutics and iodized oil is with chemotherapeutics and iodized oil mixing thromboembolism, can play the dual function of thromboembolism and chemotherapy.Iodized oil can prolong the action time of local chemotherapy medicine as the carrier of chemotherapeutics, simultaneously can also thromboembolism small artery and tip branch thereof, cause tumor ischemia necrosis.Yet, behind the TACE,, only have 5% to be complete necrosis, and remaining cancerous cell can have or produce stronger propagation and invasive ability though necrosis appears in the tumor tissues more than 80%.Occur many places or diffusivity behind the part patient TACE in a short time in the liver and send out in kitchen range or the lung multiple metastasis etc.And hepatoma carcinoma cell insensitive to chemotherapy, restrict the action effect of chemotherapeutics among the TACE, and then influencing the general curative effect of TACE.Because the chemotherapeutics that uses in TACE is brought into play antitumaous effect by destroying genomic dna structure of tumor cell or blocking gene expression process, therefore when there is resistance in tumor cell to chemotherapeutics, chemotherapy effect obviously weakens, and strengthen chemotherapeutic dosage serious adverse or complication can take place.Therefore, existing TACE art has its limitation, and curative effect is still satisfied inadequately.
Summary of the invention
The invention provides a kind of hepatic arterial chemoembolization agent that contains the autophagy inhibitor, that is in suppository, added the autophagy inhibitor, form chemotherapeutics, autophagy inhibitor and iodized oil three and mix thromboembolism, to improve the action effect of chemotherapeutics in the TACE art, strengthen the sensitivity of hepatoma carcinoma cell, can improve the general curative effect of TACE art to a certain extent chemotherapeutics.
The said chemotherapeutics of the present invention is a cisplatin; Iodized oil is super liquid iodophor carburetion; The autophagy inhibitor is selected from Ba Foluo mycin A1 (Bafilomycin A1) or chloroquine (Chloroquine).
Suppository of the present invention is to face the time spent each component is mixed by separately dosage, and dosage separately is respectively according to the weight:
Cisplatin 2mg/kg;
Super liquid iodophor carburetion 0.2ml/kg;
Autophagy inhibitor Ba Foluo mycin A1 (Bafilomycin A1) 0.6Ug/kg or
Chloroquine (Chloroquine) 60mg/kg
Wherein, autophagy inhibitor Ba Foluo mycin A1 (Bafilomycin A1) or chloroquine (Chloroquine) all can be used as the sensitizer of chemotherapeutics, can increase in the hypoxic-ischemic microenvironment of hepatoma carcinoma cell behind thromboembolism sensitivity, strengthen the anticancer effect of chemotherapeutics chemotherapeutics.Zoopery shows that suppository of the present invention can be obtained curative effect preferably to the treatment advanced primary liver cancer, and apoptosis of tumor cells rate and necrosis rate all obviously increase, and tumor is dwindled significantly, thereby has improved the therapeutic effect of TACE.The present invention provides a kind of good effect, the little suppository of damage for hepatic arterial chemoembolization.
The specific embodiment
Now in conjunction with the embodiments and zoopery, the present invention is described in detail.
Embodiment 1. preparations contain the hepatic arterial chemoembolization agent of Ba Foluo mycin A1:
Be respectively cisplatin 2mg/kg by the body weight dosage, super liquid iodophor carburetion 0.2ml/kg, Ba Foluo mycin A1 0.6Ug/kg, with this proportioning, with cisplatin, super liquid iodophor carburetion and Ba Foluo mycin A1 mix homogeneously, the hepatic arterial chemoembolization agent.
Embodiment 2. preparations contain the hepatic arterial chemoembolization agent of chloroquine:
Be respectively cisplatin 2mg/kg by the body weight dosage, super liquid iodophor carburetion 0.2ml/kg, chloroquine 60mg/kg, with this proportioning, with cisplatin, super liquid iodophor carburetion and chloroquine mix homogeneously, the hepatic arterial chemoembolization agent.
Zoopery one. the suppository of the present invention of employing is by embodiment 1 preparation
Test of the therapeutic effect experiment of 1. suppositories of the present invention to rabbit VX2 hepatocarcinoma
1) animal: 40 of purebred new zealand white rabbits (available from The 2nd Army Medical College zoopery center, down together), male and female are not limit, body weight 2～2.5kg;
2) set up rabbit VX2 liver cancer model (down together):
Routinely VX2 liver cancer tissue piece is planted in the new zealand white rabbit leftlobe of liver with direct intercalation investment, post-transplantation two all CT scan are checked tumor in the Hepar Leporis seu Oryctolagi, confirm that rabbit VX2 liver cancer model builds up, and measure the maximum diameter and the path of tumor in the maximum aspect that CT shows;
3) grouping:
Above-mentioned VX2 liver cancer model rabbit is divided into four groups at random, 10 every group:
The A group is physiology saline control group:
Slowly inject the 0.2ml/kg normal saline by the body weight trans-hepatic artery;
The B group is super liquid iodophor carburetion+cisplatin embolization group:
Emulsifying repeatedly after will surpassing liquid iodophor carburetion 0.2ml/kg+ cisplatin 2mg/kg and mix by body weight is slowly injected Hepatic artery through connection tube again under perspective;
The C group is super liquid iodophor carburetion+Ba Foluo mycin A1 embolization group:
Under perspective, slowly inject Hepatic artery again after will surpassing liquid iodophor carburetion 0.2ml/kg+ Ba Foluo mycin A1 0.6Ug/kg and fully mix by body weight through connection tube;
The D group is the super liquid iodophor carburetion+cisplatin of the present invention+Ba Foluo mycin A1 embolization group:
After will surpassing liquid iodophor carburetion 0.2ml/kg+ cisplatin 2mg/kg+ Ba Foluo mycin A10.6Ug/kg mixing and emulsifying by body weight, under perspective, slowly inject Hepatic artery again through connection tube.
2 weeks row CT scan measurement liver neoplasm size behind the Embolization.By formula calculate gross tumor volume: V=ab
2/ 2 (wherein, V is a gross tumor volume, and a is the tumor maximum diameter, and b is the path of tumor); And calculating tumor growth rate (Growth Rate, GR): before the GR=V treatment back/V treatment * 100%; Inhibition rate of tumor growth (Growth Inhibition Rate, GIR) GIR=-1-(treatment of V administration group treatment back-V administration group is preceding)/(after the V treatment of control group-V treatment of control group before).The results are shown in Table 1:
Tumor size and tumor growth rate before and after table 1 embolotherapy
Annotate: compare with the A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05, ##P＜0.01. with the B group
By table 1 as seen, suppository of the present invention (D group) can obviously suppress the growth of rabbit VX2 hepatocarcinoma, inhibition rate of tumor growth compares with normal saline matched group (A group) not only that there were significant differences (P＜0.01), and improved 24.53% than the suppository group of forming by cisplatin and super liquid iodophor carburetion (B group), suppository of the present invention is described owing to contain autophagy inhibitor---Ba Foluo mycin A1, therefore the liver cancer treatment effect obviously is better than the suppository of existing cisplatin and super liquid iodophor carburetion composition, simultaneously by the combined therapy effect of super liquid iodophor carburetion and autophagy inhibitor Ba Foluo mycin A1 far below suppository of the present invention, the autophagy inhibitor is described---Ba Foluo mycin A1 is to the sensitization of chemotherapeutics plus cisplatin in treatment.
Test of the influence experiment of 2. suppositories of the present invention to rabbit VX2 hepatocarcinoma apoptosis
60 of purebred new zealand white rabbits, male and female are not limit, body weight 2.0-2.5kg.The VX2 liver cancer model is set up 2 weeks of back, and 60 VX2 hepatocarcinoma lotus tumor rabbits that confirm through CT scan are divided into 4 groups, 15 every group at random.Employing is carried out thromboembolism through the method for selectivity hepatic artery catheterization.
The A group is physiology saline control group: (with experiment 1)
The B group is for being super liquid iodophor carburetion+cisplatin embolization group: (with experiment 1)
The C group is super liquid iodophor carburetion+Ba Foluo mycin A1 embolization group: (with experiment 1)
The D group is the super liquid iodophor carburetion+cisplatin of the present invention+Ba Foluo mycin A1 embolization group: (with experiment 1)
2 weeks were put to death all animals behind the Embolization, took out tumor specimen 10% formalin fixed, routine paraffin wax embedding, system section.Adopt original position breach end labelling (TUNEL) method to detect the apoptotic index (AI) of respectively organizing cell, detect with immunohistochemical method and respectively organize Bax and the proteic expression of Bcl-2 in the tumor cell, the results are shown in Table 2 and table 3.
The apoptotic index of each treated animal tumor cell (%) behind table 2 Embolization
Annotate: compare with the A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05. with the B group
The expression of Bax and Bcl-2 in each treated animal tumor cell behind table 3 Embolization
Annotate: compare with the A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05, ##P＜0.01. with the B group
By table 2 as seen, suppository treatment group of the present invention (D group) TUNEL stained positive cell is maximum, apoptotic index is the highest, can obviously promote the apoptosis of rabbit VX2 hepatoma carcinoma cell, apoptotic index compares with normal saline matched group (A group) not only that there were significant differences (P＜0.01), and compare with the suppository group of forming by cisplatin and super liquid iodophor carburetion (B group), difference also has statistical significance (P＜0.05), suppository of the present invention is described owing to contain autophagy inhibitor---Ba Foluo mycin A1, therefore the hepatoma cell apoptosis index is apparently higher than the suppository of existing cisplatin and super liquid iodophor carburetion composition, the apoptotic index of super simultaneously liquid iodophor carburetion and Ba Foluo mycin A1 combination (C group) illustrates the autophagy inhibitor far below suppository of the present invention---Ba Foluo mycin A1 has promoted the apoptosis of the hepatoma carcinoma cell of chemotherapeutics cisplatin induction.
By table 3 as seen, the pro apoptotic protein Bax The positive expression rate of Bcl-2 family is the highest in the suppository treatment group of the present invention (D group), to press down apoptotic proteins Bcl-2 The positive expression rate minimum, compares obvious difference (P＜0.01) with normal saline matched group (A group); And D group compares with the suppository group of being made up of cisplatin and super liquid iodophor carburetion (B group), also has notable difference (P＜0.05).Suppository of the present invention is described owing to contain autophagy inhibitor---Ba Foluo mycin A1, so pro apoptotic protein Bax up-regulated of Bcl-2 family, anti-apoptotic proteins Bcl-2 down-regulated expression, middle Bax of super simultaneously liquid iodophor carburetion and Ba Foluo mycin A1 combination (C group) and the proteic expression of Bcl-2 also are lower than respectively and are higher than suppository D of the present invention to be organized, the autophagy inhibitor is described---Ba Foluo mycin A1 has promoted the pro apoptotic protein Bax of Bcl-2 family to express, suppress anti-apoptotic proteins Bcl-2 and expressed, finally promoted the apoptosis of the hepatoma carcinoma cell of chemotherapeutics cisplatin induction.
Test of the influence of 3. suppositories of the present invention to VX2 hepatocarcinoma Hepar Leporis seu Oryctolagi function
40 of purebred new zealand white rabbits, male and female are not limit, body weight 2.0-2.5kg.The VX2 liver cancer model is set up 2 weeks of back, and 40 VX2 hepatocarcinoma lotus tumor rabbits that confirm through CT scan are divided into 4 groups, 10 every group at random.Employing is carried out thromboembolism through the method for selectivity hepatic artery catheterization.
The A group is physiology saline control group: (with experiment 1)
The B group is for being super liquid iodophor carburetion+cisplatin embolization group: (with experiment 1)
The C group is super liquid iodophor carburetion+Ba Foluo mycin A1 embolization group: (with experiment 1)
The D group is the super liquid iodophor carburetion+cisplatin of the present invention+Ba Foluo mycin A1 embolization group: (with experiment 1)
Behind preceding 1 day of art and the embolotherapy 3,7,14 days respectively blood drawing detect alanine aminotransferase (ALT) and aspartate amino transferase (AST) in the serum, the results are shown in Table 4.
Changes of liver function before and after the table 4 rabbit VX2 hepatocarcinoma embolotherapy (U/L, Mean ± SD)
Annotate: compare with the A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05, ##P＜0.01. with the B group
By table 4 as seen, preceding 1 day of embolotherapy, the horizontal there was no significant difference of the ALT of four treated animals and AST (P＞0.05).Treat back 3 days testing result and show, the ALT of B, C, three groups of laboratory animals of D and AST value have a mistake property rising, and compare with normal saline matched group (A group) and all to have notable difference (P＜0.05); Treated back 7 days, the ALT of B, C, D three treated animals and AST level begin to descend; In the time of 14 days, the combination (C group) of super liquid iodophor carburetion and autophagy inhibitor Ba Foluo mycin A1 and A group is compared, there was no significant difference (P＞0.05), and liver function has been recovered normally, illustrates that autophagy inhibitor Ba Foluo mycin A1 itself does not have obvious influence to liver function; And 14 days the time; ALT that B, D are two groups and AST level are all apparently higher than A group (P＜0.05); and B, D compare for two groups; the ALT of D treated animal and AST value all significantly are lower than B group (P＜0.05); illustrate that the chemoembolization treatment can damage the liver function of laboratory animal; but the adding of autophagy inhibitor Ba Foluo mycin A1 does not only increase the weight of this damage, makes degree of injury reduce (P＜0.05) on the contrary, has certain liver protective effect.So suppository of the present invention both can be treated hepatocarcinoma better, suppress the growth of hepatocarcinoma, can reduce the damage of chemotherapeutics to a certain extent again to liver.
Zoopery two. the suppository of the present invention of employing is by embodiment 2 preparations
Test of the therapeutic effect experiment of 4. suppositories of the present invention to rabbit VX2 hepatocarcinoma
40 of purebred new zealand white rabbits, male and female are not limit, body weight 2.0～2.5kg.The VX2 liver cancer model is set up 2 weeks of back, and 40 VX2 hepatocarcinoma lotus tumor rabbits that confirm through CT scan are divided into 4 groups, 10 every group at random.Employing is carried out thromboembolism through the method for selectivity hepatic artery catheterization.
The A group is physiology saline control group: (with experiment 1)
The B group is super liquid iodophor carburetion+cisplatin embolization group: (with experiment 1)
The C group is super liquid iodophor carburetion+chloroquine embolization group:
To surpass liquid iodophor carburetion 0.2ml/kg+ chloroquine 60mg/kg mix homogeneously by body weight, inject Hepatic artery through the selectivity hepatic artery catheterization;
The D group is the super liquid iodophor carburetion+cisplatin of the present invention+chloroquine embolization group:
After will surpassing liquid iodophor carburetion 0.2ml/kg+ cisplatin 2mg/kg+ chloroquine 60mg/kg mixing and emulsifying by body weight, slowly inject Hepatic artery through the selectivity hepatic artery catheterization.
2 weeks row CT scan measurement liver neoplasm size behind the Embolization.By formula calculate gross tumor volume: V=ab
2/ 2 (wherein, V is a gross tumor volume, and a is the tumor maximum diameter, and b is the path of tumor); And calculating tumor growth rate (Growth Rate, GR): before the GR=V treatment back/V treatment * 100%; (Growth Inhibition Rate, GIR) GIR=-1-(treatment of V administration group treatment back-V administration group is preceding)/(after the V treatment of control group-V treatment of control group before) the results are shown in Table 5 to inhibition rate of tumor growth.
Tumor size and tumor growth rate before and after table 5 embolotherapy
Annotate: compare with the A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05, ##P＜0.01. with the B group
By table 5 as seen, suppository of the present invention (D group) can obviously suppress the growth of rabbit VX2 hepatocarcinoma, inhibition rate of tumor growth compares with A group not only that there were significant differences (P＜0.01), and improved 25.94% than B group, suppository of the present invention is described owing to contain autophagy inhibitor---chloroquine, therefore the liver cancer treatment effect obviously is better than the suppository of existing cisplatin and super liquid iodophor carburetion composition, and organize therapeutic effect far below suppository of the present invention by the C of super liquid iodophor carburetion and chloroquine combination, and the autophagy inhibitor is described---chloroquine is to the sensitization of chemotherapeutics plus cisplatin in treatment.
Test of the influence experiment of 5. suppositories of the present invention to rabbit VX2 hepatocarcinoma apoptosis
60 of purebred new zealand white rabbits, male and female are not limit, body weight 2.0～2.5kg.The VX2 liver cancer model is set up 2 weeks of back, and 60 VX2 hepatocarcinoma lotus tumor rabbits that confirm through CT scan are divided into 4 groups, 15 every group at random.Employing is carried out thromboembolism through the method for selectivity hepatic artery catheterization.
The A group is physiology saline control group: (with experiment 1)
The B group is for being super liquid iodophor carburetion+cisplatin embolization group: (with experiment 1)
The C group is super liquid iodophor carburetion+chloroquine embolization group: (with experiment 4)
The D group is the super liquid iodophor carburetion+cisplatin of the present invention+chloroquine embolization group: (with experiment 4)
2 weeks were put to death all animals behind the Embolization, took out tumor specimen 10% formalin fixed, routine paraffin wax embedding, system section.Adopt original position breach end labelling (TUNEL) method to detect the apoptotic index (AI) of respectively organizing cell, detect with immunohistochemical method and respectively organize Bax and the proteic expression of Bcl-2 in the tumor cell, the results are shown in Table 6 and table 7.
The apoptotic index of each treated animal tumor cell (%) behind table 6 Embolization
Annotate: compare with the A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05. with the B group
The expression of Bax and Bcl-2 in each treated animal tumor cell behind table 7 Embolization
Annotate: compare with the control group A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05, ##P＜0.01. with the B group
By table 6 as seen, suppository treatment group of the present invention (D group) TUNEL stained positive cell is maximum, apoptotic index is the highest, can obviously promote the apoptosis of rabbit VX2 hepatoma carcinoma cell, apoptotic index compares with A group not only that there were significant differences (P＜0.01), and compare with B group, difference also has statistical significance (P＜0.05), suppository of the present invention is described owing to contain autophagy inhibitor---chloroquine, therefore the hepatoma cell apoptosis index is apparently higher than the suppository of existing cisplatin and super liquid iodophor carburetion composition, and the apoptotic index of C group illustrates the autophagy inhibitor far below suppository of the present invention---chloroquine has promoted the apoptosis of the hepatoma carcinoma cell of chemotherapeutics cisplatin induction.
By table 7 as seen, the pro apoptotic protein Bax The positive expression rate of Bcl-2 family is the highest in the suppository treatment group of the present invention (D group), to press down apoptotic proteins Bcl-2 The positive expression rate minimum, compares obvious difference (P＜0.01) with the A group; And D group compares with the B group, also has notable difference (P＜0.05).Suppository of the present invention is described owing to contain autophagy inhibitor-chloroquine, so pro apoptotic protein Bax up-regulated of Bcl-2 family, anti-apoptotic proteins Bcl-2 down-regulated expression, and the Bax of C group and Bcl-2 protein expression also are lower than respectively and be higher than the D group, illustrate that autophagy inhibitor-chloroquine has promoted the pro apoptotic protein Bax of Bcl-2 family to express in the suppository of the present invention, suppress anti-apoptotic proteins Bcl-2 and expressed, finally promoted the apoptosis of the hepatoma carcinoma cell of chemotherapeutics cisplatin induction.
Test of the influence of 6. suppositories of the present invention to VX2 hepatocarcinoma Hepar Leporis seu Oryctolagi function
40 of purebred new zealand white rabbits, male and female are not limit, body weight 2.0～2.5kg.The VX2 liver cancer model is set up 2 weeks of back, and 40 VX2 hepatocarcinoma lotus tumor rabbits that confirm through CT scan are divided into 4 groups, 10 every group at random.Employing is carried out thromboembolism through the method for selectivity hepatic artery catheterization.
A group and B group experiment 1 together;
The C group is super liquid iodophor carburetion+chloroquine embolization group: (with experiment 4)
The D group is the super liquid iodophor carburetion+cisplatin of the present invention+chloroquine embolization group: (with experiment 4)
Behind preceding 1 day of art and the embolotherapy 3,7,14 days respectively blood drawing detect alanine aminotransferase (ALT) and aspartate amino transferase (AST) in the serum, the results are shown in Table 8.
Changes of liver function before and after the table 8 rabbit VX2 hepatocarcinoma embolotherapy (U/L, Mean ± SD)
Annotate: compare with the A group,
*P＜0.05,
*P＜0.01; Compare #P＜0.05, ##P＜0.01. with the B group
By table 8 as seen, preceding 1 day of embolotherapy, the horizontal there was no significant difference of the ALT of four treated animals and AST (P＞0.05).Treat back 3 days testing result and show, the ALT of B, C, three groups of laboratory animals of D and AST value have one to cross the property rising, and organize to compare with A and all have notable difference (P＜0.05); Treated back 7 days, the ALT of B, C, D three treated animals and AST level begin to descend; In the time of 14 days, C group is compared with the A group, there was no significant difference (P＞0.05), and liver function has been recovered normally, illustrates that autophagy inhibitor chloroquine itself does not have obvious influence to liver function; And 14 days the time; ALT that B, D are two groups and AST level all are higher than the A group; and difference has statistical significance (P＜0.05); and B, D compare for two groups; the ALT and the AST value of D group significantly are lower than B group (P＜0.05), illustrate that the chemoembolization treatment can damage the liver function of laboratory animal, but the adding of autophagy inhibitor chloroquine not only do not increase the weight of this damage; make degree of injury reduce (P＜0.05) on the contrary, illustrate to have certain liver protective effect.So suppository of the present invention both can be treated hepatocarcinoma better, suppress the growth of hepatocarcinoma, can reduce the damage of chemotherapeutics to a certain extent again to liver.
Claims (1)
1. hepatic arterial chemoembolization agent that contains the autophagy inhibitor, be made up of chemotherapeutics, autophagy inhibitor and iodized oil, said chemotherapeutics is a cisplatin, and iodized oil is super liquid iodophor carburetion, the autophagy inhibitor is selected from Ba Foluo mycin A1 or chloroquine, and the dosage of each component is respectively according to the weight:
Cisplatin 2mg/kg;
Super liquid iodophor carburetion 0.2ml/kg;
Ba Foluo mycin A1 0.6 μ g/kg or chloroquine 60mg/kg,
Facing the time spent gets final product by the dosage mixing of each component.
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| CN1547469A (en) * | 2001-09-13 | 2004-11-17 | 韩国科学技术研究院 | Paclitaxel mixed composition and water-in-oil type emulsion formulation for chemoembolization and preparation method thereof |
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| CN1547469A (en) * | 2001-09-13 | 2004-11-17 | 韩国科学技术研究院 | Paclitaxel mixed composition and water-in-oil type emulsion formulation for chemoembolization and preparation method thereof |
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| Title |
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| 周文群等.动脉内顺铂微球碘化油与抗癌药物碘化油栓塞化疗对肝癌疗效的比较.《介入放射学杂志》.1992,第1卷27-30. * |
| 王涌等.奥曲肽联合肝动脉栓塞化疗预防肝癌术后复发转移的临床研究.《中华肝胆外科杂志》.2004,第10卷(第09期),594-596. * |
| 马静等.高热碘化油-顺铂混悬剂超选择肝动脉化疗栓塞治疗中晚期肝癌的近期疗效评价.《农垦医学》.2009,第31卷(第03期),220-222. * |
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