CN101322849A - Radioactive sustained-release particle and preparation and use thereof - Google Patents
Radioactive sustained-release particle and preparation and use thereof Download PDFInfo
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- CN101322849A CN101322849A CNA2008100221140A CN200810022114A CN101322849A CN 101322849 A CN101322849 A CN 101322849A CN A2008100221140 A CNA2008100221140 A CN A2008100221140A CN 200810022114 A CN200810022114 A CN 200810022114A CN 101322849 A CN101322849 A CN 101322849A
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Abstract
The invention discloses a radioactive slow-release particle, a preparation method and the application thereof, pertaining to the field of radiation medicine. The particle mainly consists of <32> P-chromium phosphate and poly-L-lactic acid and can better solve the problem of targeted delivery of drugs in the treatment of tumors. The transplant of the particles in a tumor body or around a tumor can increase the local concentration of the drug, prolong the time of drug action and reduce systemic toxicity and side effects.
Description
Technical field:
The invention belongs to the radiological medicine field, relate to a kind of radioactive sustained-release particle and its production and application.
Background technology:
Radiopharmaceutical
32The P-chromium phosphate (
32P-chromic phosphate,
32P-CP) colloid is used to the pernicious hydrops treatment of intracavity, interstitial curitherapy and lymph treatment in one's early years
[1-4] 32P is pure β
-Emitter, average energy is 0.695MeV (ceiling capacity is 1.71Mev), half-life is 14.28d, organize medium range average out to 3~4mm (maximum range reaches 7.6mm), can observe body radioactivity roughly by the bremstrahlen video picture and distribute, be easy to radiation protection in the clinical practice, and the source easily, moderate cost is ideal treatment nucleic.
32P-CP colloidal solid size about 20~50nm (accounting for 60%), physicochemical property is stable, belongs to the nanoscale nucleic, is ideal internal-radiation therapy medicine.
Matter irradiation at short distance therapy (brachytherapy) treatment entity tumor is a kind of rapidly new technique of development in recent years between radionuclide, its method is that the point-like radioactive source is placed around diseased region or its, and the ray that sends by radioactive source continues to make the atrophy of tumor tissues generation blood vessel, apoptosis and necrosis in its effective range.
32P-CP colloid mesenchyma stroma of tumors injection for curing solid tumor becomes studies focus in recent years both at home and abroad, has reported that at present this radiopharmaceutical has obtained good tumor and the lymph metastasis kitchen range therapeutic effect of pressing down in to the experiment of solid tumor such as primary hepatocarcinoma, cancer of pancreas, ovarian cancer, cerebral glioma, tumor of head and neck and metastasis thereof and clinical research
[5-8],
32The P colloid obviously is better than
125I, 1. its reason is
32P linear energy transfer (LET) is about the pure gamma-rays of emission
125The twice of I, therefore by the β ray the relative biological effectiveness (RBE) of inductive apoptosis of tumor cells than corresponding χ ray, gamma-rays height; 2.
32The P-CP colloid is more easily migrated along lymph or microcirculation, the double lymphatic channel micrometastasis kitchen range of controlling; 3.
125The permanent transplanting of I titanium particle is made troubles to the patient, even viscera perforation takes place, migrates to matters of aggravation such as lungs along blood circulation, and the medical expense costliness.But this seminar increases in expection
32The P-CP dosage is to find in the research that improves the tumor by local curative effect, the distribution of systemic drug is especially assembled obviously increase in the liver spleen, appreciable impact the dosage of tumor and normal structure effectively distribute target spot effective half life when, and obviously increased toxic and side effects, the untoward reaction such as concurrent rawhide bleed bottom point that lose weight than matched group of the heavy dose of group of laboratory animal to histoorgans such as liver, spleen and bone marrow
[9]Therefore, clinical administration is still many at present decides and each tame differing with the body tolerance dose, fails all the time to solve by increasing dose to strengthen
32The local biological effect of P, control its in the external distribution of tumor, lower problem such as toxic and side effects.Thereby significant limitation its clinical practice at the tumor the field of nuclear medicine.
Poly (l-lactic acid) (poly (L-lactide), PLLA) be a kind of have good biocompatibility, certain mechanical strength and can be by the macromolecular material of human body degraded and absorbed, catabolite lactic acid and hydroxyacetic acid can participate in the metabolism of human body, final formation carbon dioxide and water are excreted, as the pharmaceutic adjuvant of multiple slow releasing pharmaceutical clinically, being the skeleton implantation made from PLLA is ratified to enter clinical research by state food and Drug Administration with chemotherapeutics such as release fluoride uracil, cisplatin and biodegradable PLLA pharmaceutic adjuvant
[10-12]Wherein implant and be identified as high-tech achievement (certificate number: 2002-004) with the release fluoride uracil, compare with glass microsphere and titanium alloy, PLLA is mainly reflected in as the carrier advantage: 1. biological degradability: PLLA effectively improves topical medications dosage during treating, and degraded gradually, the double micrometastasis kitchen range of controlling of the medicine that slowly disengages, and glass microsphere etc. can only be brought into play local therapeutic effects, and permanent delay the in the injection body, can cause the functional lesion of corresponding organ, increase the weight of tissue fibering; 2. complication is few: the glass microsphere particle diameter is little, easily branch to target organ outer (as normal hepatocytes, lung or backflow) after the administration and cause complication such as liver failure, lungs fibrosis and digestive tract hemorrhage, the using dosage of radioactivity microsphere is very limited into gastroduodenal artery.Still do not have at present adopt PLLA with
32The bonded radioactivity antitumor drug of P-CP gel phase.
Summary of the invention:
The purpose of this invention is to provide a kind of radioactive chromic phosphate colloid sustained-release particle.
Another object of the present invention provides the application of radioactive chromic phosphate colloid sustained-release particle.
The objective of the invention is to realize by following technical measures:
A kind of radioactive sustained-release particle, this particle mainly by
32P-chromium phosphate and poly (l-lactic acid) are formed.
Described radioactive sustained-release particle, wherein the poly (l-lactic acid) molecular weight is 7000~12000Da.
Described radioactive sustained-release particle, wherein in
32The consumption of P-chromium phosphate and poly (l-lactic acid) is that every gram poly (l-lactic acid) binding radioactivity activity is 3750~37500MBq (promptly 100~1000mci)
32The P-chromium phosphate.
The preparation method of described radioactive sustained-release particle comprises the following steps:
0.75~1.25g PLLA and 10~20mg magnesium stearate are inserted in the dismembyator, and adding 4.5~7.5ml radioactive concentration is 1875~5625MBq/ml's
32P-CP colloid solution adds 2~3ml dehydrated alcohol, and 50 ℃ are stirred 30min, and dry 5h is ground to Powderedly, is pressed into granule.
The application of described radioactive sustained-release particle in the preparation anti-tumor drug.
Beneficial effect of the present invention:
The present invention constitutes with the blend operation, is carrier with biodegradable PLLA in can body, and physical property is evenly sneaked into
32The local implantation of P-CP colloid for preparing used radioactivity
32The P-CP-PLLA sustained-release particle.Investigate the rate of disengaging in its physicochemical property and the external different release medium, biodegradation and the radiolabeled biotin observed after normal mouse sustained-release particle body is implanted into distribute, understanding radiopharmaceutical distribution and dynamic metabolism measures, radioactive particle cancer of pancreas mice with tumor model tumor body is implanted into back different time points row SPECT video picture, separate tumor body and each internal organs, carry out radiocounting and tumor soma morphological observation.Confirm that the particle physicochemical property is stable, have excellent biological compatibility and self degradability, particle accumulative total weight-loss ratio reached 7% in 30 days, and it is about 10% that radioactivity accumulative total is disengaged,
32P-CP's slowly disengages and the slow degraded of carrier PLLA, the basic match synchronization of corrosion of particle, has effectively improved radioactivity
32P-CP obviously improves implant site/surrounding tissue (as organizing in tumor body/tumor week) radioactive dosage distribution ratio and implant site (in the tumor body) radioactivity effective half life in implant site such as the intravital distribution of tumor, and part is slowly disengaged
32P-CP can go into blood and be distributed in liver and spleen through lymphatic drainage, and increased radioactivity is few in other internal organs.The tumor bulk-growth suppresses curve and exists obvious amount-effect positive correlation, and tumor body volume promptly organizes the increase of absorbed dose to reduce with implanting tumor body corpuscular radiation activity, therefore
32P sustained-release particle dosage form can increase local curative effect of implantation and follow-up biological effect by increasing corpuscular radiation dosage, more effectively kill and wound the various tumor cells of implant site, because range is short, a little less than surrounding tissue ionization, to whole body, especially less to the toxic and side effects of important organs such as liver, spleen and bone marrow.
The invention provides radioactivity
32The P-CP-PLLA sustained-release particle can solve the targeted delivery of drugs problem in the oncotherapy preferably, with its action time of implanting the tumor body or tumor week can increase local drug concentration, prolong drug, reduces the general toxic and side effects.Radioactivity
32The P-CP-PLLA sustained-release particle does not change
32The physicochemical property of P and biological effect thereof, main dependence
32The biological action of P in effective range, tumor cell around the particle of β radiation-sensitive all produced preferably kill and wound, applicable to the treatment of testing with solid tumor such as the primary hepatocarcinoma of clinical proof, cancer of pancreas, ovarian cancer, cerebral glioma, tumor of head and neck and metastasis thereof
[5-8]By the degraded of PLLA, the corrosion of particle, avoided the permanent implanted and serious complication of existing seed source and glass microsphere simultaneously, matter irradiation at short distance targeted therapy between the solid tumor radionuclide has been had huge application advantage and prospect.
Description of drawings:
Fig. 1 is a radioactivity
32Disengage rate curve in the external serum of P-CP-PLLA sustained-release particle.
Fig. 2 is a radioactivity
32Involve the weight-loss ratio curve in the P-CP-PLLA sustained-release particle body.
Fig. 3 is a radioactivity
32The tumor bulk-growth of P-CP-PLLA sustained-release particle various dose group suppresses curve.
Fig. 4 is a radioactivity
32P-CP-PLLA sustained-release particle tumor body is implanted into the morphology performance of tumor soma.Under the light microscopic, the oncocyte volume increases, edema; After birth is still complete, and karyopycnosis, karyorrhexis, karyolysis are seen more, and with the increase of corpuscular radiation dosage and the prolongation of time, above-mentioned change significantly.A. (0MBq) empty particle matched group Pc-3 oncocyte is arranged fine and close, neat; After particle tumor body essence was implanted, b. (7.4MBq) cell was arranged loose, the part membranolysis, and the most of tumor tissues of c. (37.5MBq) destroys, and is replaced (HE * 400) by fibrous connective tissue.
The specific embodiment:
The invention will be further elaborated by the following examples.
General explanation:
32P-CP is provided by Atom High Tech Co., Ltd., is a kind of aseptic, green colloid solution, bacteria endotoxin content<15EU/ml, uclear purity>99.9%, radiochemicsl purity 〉=98%, granularity 20~50nm (60%), specific radioactivity 〉=1850MBq/ml, PH6.0~8.0; PLLA, molecular weight 7000, white powder, lot number 20000910 is provided by HeFei University of Technology controlled release chamber; The video picture instrument is the two detector SPECT instrument of GE Millennium VG Hawkeye, and well type gamma detector is available from good company in the Hefei; BS-110S type electronic balance is available from Sartorius company; Cancer of pancreas transplanted tumor model is by being provided by institute of oncology, Shanghai Experimental Animal Center.
Embodiment 1:
32The preparation of P-CP-PLLA sustained-release particle and general form thereof, particle diameter are investigated.
0.75~1.25g PLLA and 10~20mg magnesium stearate are inserted in the dismembyator, add 4.5~7.5ml
32(radioactive concentration is 1875~5625MBq/ml) to P-CP colloid solution, as dispersant, low speed (150r/min) stirs 30min in constant temperature (50 ℃) agitator with the 2ml dehydrated alcohol, inserts the dry 5h of vacuum drying oven, in dismembyator, it is ground to Powderedly, is pressed into radioactivity
32The P-CP-PLLA sustained-release particle.Gained
32P-CP-PLLA particle specification is as follows: particle is the light green cylinder bodily form, diameter 0.85mm~0.9mm, long 2.2mm~2.5mm, the form rounding, there is micro-pore on the surface, and quality is hard, quality 0.9-1.1mg/ grain, radioactivity 11.25~37.5MBq/ grain, the sub-sealed packaging of individual particle is preserved.
Embodiment 2: radioactivity
32P-CP-PLLA sustained-release particle external beam radiotherapy disengages rate research.
Select 90 quality and radioactivity more uniform
32The P-CP-PLLA sustained-release particle (quality is 1 ± 0.05mg, and radioactivity is 33.75 ± 1.6875MBq), is divided into 9 groups at random, 10 every group, measure every group of particle gross activity activity respectively, and be designated as A
(n0)(n is a group, is designated as 1~9 group) places 9 culture dishs, and per 3 culture dishs are one group, adds release medium normal saline, RPMI-1640, each 5.0ml of human serum respectively.It is put in the water bath chader 37 ℃ of temperature, 100 times/min of frequency of oscillation.Respectively get release medium 1.0ml in the culture dish in 1,3,7,15,21,30 day (representing that by t time point is designated as 1~6), measure radiocounting, be designated as B by the enhancement mode activity meter
(nt), radioactivity is designated as C behind the correction for attenuation
(nt)=λ
t* B
(nt)(annotate: 1~6 attenuation correction coefficient λ is respectively 0.953,0.865 by time point, 0.712,0.483,0.361,0.233) calculates the t time point respectively, n group corpuscular radiation disengages rate=particle and disengages radioactivity total amount/primary radioactivity total amount, i.e. RR
(nt)={ 5C
(nt)+ ∑ C
[n (t-1)]}/A
(n0), mend the synthermal fresh release medium of 1.0ml then.
The results are shown in Table 1, one factor analysis of variance shows that three kinds of release medium are right
32The no difference of science of statistics that influences of P-CP-PLLA particle release rate (F=0.07, P=0.9373), disengage rate curve and see Fig. 1 by the external time in human serum-accumulative total.Prolong in time and the degraded of PLLA, particle disengages rate slowly to be increased, and it is relatively large that preceding 3d disengages the rate curve slope, considers more relevantly with the medium contact area with particle, slows down later on and the rate of disengaging continues more steadily, and total is disengaged rate nearly 10% during 30d.The result shows: the sustained-release particle physicochemical property is stable, and external beam radiotherapy disengages slowly, and not having obviously dashes forward releases phenomenon, significantly improves the part
32P dosage and be detained time of contact is avoided being subjected to stronger radiation damage in the drain zone short time.
In the different release medium of table 1
32The external in time rate result of disengaging of P-CP-PLLA
Embodiment 3:
32P-CP-PLLA sustained-release particle mice body is implanted into biodegradation and reaches
32The P biodistribution.
Select 35 of BALB/c mouse, body weight 20 ± 2g is divided into 7 groups at random, 5 every group, measures and select quality and radioactivity more uniform
32(quality is 1 ± 0.05mg to 35 of P-CP-PLLA sustained-release particles, radioactivity is 33.75 ± 1.6875MBq), measuring radiocounting and percutaneous puncture method respectively implants in the left back leg muscle of mice, one of every Mus, particle implantation part and whole body ordinary circumstance in the mice body are dynamic observed, and respectively at implanting back 0.5,1,3,7,14,21,30d gets one group of mice socket of the eye vein and gets blood 1ml, taking off cervical vertebra then puts to death, core respectively, liver, spleen, lung, kidney, pancreas, stomach, intestinal, brain, right rear leg muscle, main organs and tissues such as muscle and femur around the particle, claim weight in wet base and measure its radiocounting, calculate %ID/g (every gram tissue radiation counting/every mice is implanted corpuscular radiation counting * 100%) after the radiation decay correction down.Biological degradation rate is represented with percentage loss of weight, promptly takes out the particle clean surface respectively, and the vacuum drying oven inner drying is used scales/electronic balance weighing to constant weight, is calculated as follows: percentage loss of weight (%)=(w
0-w
t)/w
0(w in the formula
0And w
tBe respectively the weight that particle is just implanted preceding weight and implanted t particle during the time).
32After P-CP-PLLA sustained-release particle muscle was implanted, diet, implant site active situation and the fur outward appearance of observing animal were all better, and body weight does not have significant change.
32The P-CP-PLLA sustained-release particle back accumulative total weight-loss ratio curve that implants is seen Fig. 2,0.5,1,3,7,14,21, the 30d average is respectively 1.49%, 2.51%, 4.26%, 5.28%, 5.67%, 6.72%, 7.20%, show that PLLA constantly degrades with implanting time lengthening in vivo.Slowly disengage
32Bio distribution the results are shown in Table 2 in the P-CP mice body.Implant by the visible intramuscular of table 2
32Behind the P-CP-PLLA, in the time of 30 days about 90%
32P is trapped in sustained-release particle and implants the target spot position, and effective half life reaches 13 days, and different time points is disengaged
32P-CP mainly is distributed in muscular tissue around the particle in the mice body, secondly be spleen and liver, and heart, blood, lungs, kidney, brain, skeletal bones amount are few.The result shows:
32Biocompatibility in the P-CP-PLLA body, sustained release performance are better, radioactivity is disengaged with the particle biological degradation rate and is the concordance variation substantially, all be in reduced levels, obviously increase and implant target spot and normal structure dose distribution ratio and target spot position effective half life, to whole body and important organ, especially less to the toxic and side effects of the abundant important organs such as liver, spleen and bone marrow of reticuloendothelial cell.And particle can self be degraded in vivo, has avoided the appearance of interior permanent delay of seed source bodies such as permanent implantation and severe complication.
Table 2
32The radioactive uptake mark of each internal organs of P-CP different time points (x ± s, n=5) (%ID/g)
Embodiment 4:
32Matter is implanted radiolabeled biotin distribution and dose response studies experiment between P-CP-PLLA sustained-release particle lotus human pancreas cancer (Pc-3):
42 tumor bearing nude mices, tumor body volume are (0.50 ± 0.05) cm
3(the about 1cm of major diameter) is divided into 7 groups at random, implants through the rind gall plastid stroma respectively
32One on P-CP-PLLA particle, each is organized every Mus and on average implants corpuscular radiation activity and be respectively 0MBq (empty particle group), 7.4MBq, 14.8MBq, 29.6MBq, 37.5MBq, 59.2MBq and 74MBq, be designated as the 1st~7 group, particle is implanted the back different time points by SPECT bremsstrahlung video picture (the universal collimator of mental retardation, energy peak 70KeV, window width 20%, acquisition time 20min), after the observation particle is implanted
32P is the bio distribution situation in the mice body.Particle is implanted the back every 2d, and close observation tumor body surface is seen and changed, and with the maximum diameter (a, b) on two vertical direction of each Mus tumor body of vernier caliper measurement, according to formula V=ab
2/ 2 calculate tumor body volume, and the time dependent tumor growth of tumor body volume average of drawing each dosage group suppresses curve and sees Fig. 3.The 21d mice takes off cervical vertebra puts to death, and separates the tumor body and formulates tissue slice, by om observation tumor somatic cell morphological change.
The visible radioactivity of SPECT bremsstrahlung video picture is mainly assembled at implant site (tumor body region), organizes beyond the tumor body and does not see few increased radioactivity is only arranged obvious development, the region of interest of painting respectively, the record radiocounting is calculated corresponding site increased radioactivity percentage ratio, i.e. A%=(At/2
-t/14.28)/A0 * 100%.(A
0, A
tBe respectively 0, the radiocounting of region of interest during t, t is that particle is implanted the back time, unit is the sky), calculate tumor body region radioactivity effective half life and reach 13d.
The 2nd~5 dosage group tumor bulk-growth suppresses curve and exists obvious amount-effect positive correlation, and tumor body volume promptly organizes the increase of absorbed dose to reduce with implanting tumor body corpuscular radiation activity.
32P is by the obvious killing tumor cell of radiation effects, and the tumor body dwindles even disappears, and gross examination of skeletal muscle sees that empty particle matched group tumor body increases obviously, matter is nodositas firmly, and epidermis attenuation, bright is rendered as the red meat color, the tumor body surface skin generation ulcer that has; Congestion, diabrosis, incrustation take place in the 7th day the earliest beginning surface of the tumor body of 2~7 treatment groups.Light microscopic undertissue section pathological examination is seen Fig. 4, and the oncocyte of the 1st group of visible active proliferation, Pc-3 cell are arranged closely, rich blood vessel; Particle implantation group has shown necrosis in different degree, fibrosis and has been wrapped to form, the 2nd~4 group average oncocyte necrosis rate increases gradually, showing as sheet solidifies the sample necrosis or shows as remaining oncocyte arrangement loose or not loose, and the oncocyte of good differentiation appears, the 5th~7 group most of, and tumor cell is destroyed is replaced by fibrous connective tissue, the tumor body day by day dwindles, shrivelled, incrustation also finally comes off, and does not see tumor tissues under the light microscopic.It is obviously downright bad that the dosage of prompting 37.5MBq is enough to make diameter to be that tumor about 1cm takes place, and on this basis, the increase of dosage will no longer cause the corresponding raising of necrosis rate.For the bigger tumor of volume, can adopt the multiple spot particle to implant, so that tumor tissues receives enough radiant energy at one in during short, reach the purpose of rapid control tumor growth.
32The P-CP-PLLA particle is implanted and is made the implant site tumor tissues obtain higher amount of radiation, and whole-body radiation dose is low, and particle is implanted and can be made the main dense coalescence long period of radionuclide be trapped in performance direct killing effect in the Pc-3 tumor tissue.Morphological examination shows that most of Pc-3 cell is destroyed, and the oncocyte of good differentiation occurs.To gross tumor volume the greater, can be by the increase number of particles, effective killing tumor cell in the ray range, and to the harmless effect of normal surrounding tissue beyond the range.
List of references:
1.Dempke?W,Firusian?N.Treatment?of?malignant?pericardial?effusion?with?
32P-colloid.Br?JCancer,1999,80:1955-1967.
2.DeNittis?AS,Stambaugh?MD,Lang?P,et?al.Complete?remission?of?nonesectable?pancreaticcancer?after?infusional?colloidal?phosphorus-32?brachytherapy,external?beam?radiationtherapy,and?5-fluorouracil:preliminary?report.Am?J?Clin?Oncol,1999,22:355-360.
3.Firusian?N,Dempke?W.An?early?phase?II?study?of?intratumoral?P-32?chromic?phosphateinjection?therapy?for?patients?with?refractory?solid?tumors?and?solitary?metastases.Cancer,1999,85:980-987.
4. Zheng Jia is female, Lin Xiaocong, and Wang Chaoyang, etc.
32Radiotherapy adds the observation of curative effect of the VM26 perfusion combination therapy 55 routine cerebral tumors in the P. practical cancer magazine, 2002,17:302-303.
5.Zhang?DS,Liu?L,Jin?LQ,et?al.Effect?of?phosphorus-32?glass?microspheres?on?humanhepatocellular?carcinoma?in?nude?mice.World?J?Gastroenterol.2004?Jun?1;10(11):1551-4.
6.Alimi?KA,Firusian?N,Dempke?W.Effects?of?intralesional?32-P?chromic?phosphate?inrefractory?patients?with?head?and?neck?tumours.Anticancer?Res.2007Jul-Aug;27(4C):2997-3000.
7.Firusian?N,Dempke?W.An?early?phase?II?study?of?intratumoral?P-32?chromic?phosphateinjection?therapy?for?patients?with?refractory?solid?tumors?and?solitary?metastases.Cancer.1999?Feb?15;85(4):980-7.
8.Daozhen?C,Lu?L,Guansheng?T,Zhiyong?L,Xudong?L,Ying?H.Preventing?and?treatinglymphatic?minute?metastasis?with(32)p-chromic?phosphate?during?an?operation.CancerBiother?Radiopharm.2007?Feb;22(1):24-32.
9. Gao Wen, Liu Lu, Yin Qihua, etc.
32The administration of P glue plastid stroma is biodistribution and morphology performance in the body of lotus human pancreas cancer nude mice. Chinese radiological medicine and protection magazine, 2004,24 (1): 23-25.
10. Du Weidong, Yuan Zurong, Ni Quanxing waits the experimentation of .5-fluorouracil slow release agent intratumor injection treatment cancer of pancreas. surgery theory and practice, 2004,9 (3): 204-207.
11. rather appoint, Wu Zhiquan, Fan Jia, etc. the tumor-inhibiting action of implanted mitomycin controlled release agent. Chinese experimental surgery magazine, 2003,20 (4): 367-368.
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Claims (5)
1, a kind of radioactive sustained-release particle, it is characterized in that be this particle mainly by
32P-chromium phosphate and poly (l-lactic acid) are formed.
2, radioactive sustained-release particle according to claim 1 is characterized in that the poly (l-lactic acid) molecular weight is 7000~12000Da.
3, radioactive sustained-release particle according to claim 1 is characterized in that
32The consumption of P-chromium phosphate and poly (l-lactic acid) is that every gram poly (l-lactic acid) binding radioactivity activity is 3750~37500MB's
32The P-chromium phosphate.
4, the preparation method of the described radioactive sustained-release particle of claim 1 is characterized in that comprising the following steps:
0.75~1.25g PLLA and 10~20mg magnesium stearate are inserted in the dismembyator, and adding 4.5~7.5ml radioactive concentration is 1875~5625MBq/ml's
32P-CP colloid solution adds 2~3ml dehydrated alcohol, and 50 ℃ are stirred 30min, and dry 5h is ground to Powderedly, is pressed into granule.
5, the application of the described radioactive sustained-release particle of claim 1 in the preparation anti-tumor drug.
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