CN102357072B - Injection preparation of T-2 lienomycin - Google Patents
Injection preparation of T-2 lienomycin Download PDFInfo
- Publication number
- CN102357072B CN102357072B CN 201110345019 CN201110345019A CN102357072B CN 102357072 B CN102357072 B CN 102357072B CN 201110345019 CN201110345019 CN 201110345019 CN 201110345019 A CN201110345019 A CN 201110345019A CN 102357072 B CN102357072 B CN 102357072B
- Authority
- CN
- China
- Prior art keywords
- toxin
- ethanol
- preparation
- injection
- cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses an injection preparation of T-2 toxin, and the injection preparation mainly comprises T-2 toxin and an ethanol solution, and is also added with one or two extended solvents such as polyvinylpyrrolidone, citric acid and the like. Experimental research shows that the injection of T-2 toxin of the invention not only improves the bioavailability of T-2 toxin, but also reduces the toxicity of T-2 toxin when administrated through intravenous injection, and increases the distribution of T-2 toxin in tumor tissues.
Description
Technical field
The present invention relates to a kind of antineoplastic pharmaceutical compositions, particularly a kind of ejection preparation that contains the T-2 toxin.
Background technology
The T-2 toxin is by multiple mycetogenetic Trichothecenes material.Its structural formula See Figure:
Recent domestic has been carried out widely research to the T-2 toxin, the toxicological action of T-2 toxin has been had more comprehensively understood.
The T-2 toxin has stronger toxic action, and directly chafe and mucosa penetrate epithelial tissue.This toxin almost can affect the activity of all subcellsular levels.It is reported that the T-2 toxin has multiple toxic effect mechanism, as, in body, can induce the generation free radical, thereby cause nucleus glutathione S-transferase activity decreased; Thymus, bone marrow and liver cell DNA and albumen synthetic that can suppress mice; Can with the endochylema film on lipid molecular and protein bound, and then affect the film function; Can suppress the IL-2 mRNA synzyme, thereby so that this mRNA growing amount minimizing; Can cause rat liver NADPH cytochrome c and NADH cytochrome b5 reductase activity decreased, and be accompanied by the active rising of lipid peroxide ability and glutathione dehydrogenase system; And can disturb the electron transfer process of rat liver cell mitochondrial respiratory chain.
Further studies show that, T-2 toxin Main Function is in the vigorous histoorgan of cell division, such as thymus, bone marrow, liver, spleen, lymph node, gonad and gastrointestinal mucosa etc., it is synthetic to suppress these organ cell's protein and DNA, and can cause dna single chain break in the lymphocyte.Toxicity to animals such as family pig, poultry, cattle is relatively strong, and adult's toxic action is lower than the child.Through respiratory tract inhalation poisoning report seldom, mainly be to cause after per os is taken in poisoning.Human long-term per os is taken in the T-2 toxin and the symptoms such as sialorrhea, vomiting, stomachache, headache, dizziness can be occurred.
Studies show that recently, although the T-2 toxin has certain toxic action, but also has significant broad-spectrum anti-tumor activity, external have extremely strong killing action to cancer cell, and the T-2 toxin of nanogram level can significantly suppress the growth of the tumor cell lines such as K562 leukaemia cells, pulmonary carcinoma NCI-460 cell strain, SMMC-7721 Cell Line, lung cancer A549 cell strain, human glioma U251 cell strain, adenocarcinoma of colon LS174-T and LOVO strain.And leukocyte had natural targeting.Experiment shows in the nude mouse body, and K562 leukaemia cells is seeded to nude mice by subcutaneous, make solid tumor models after, intratumor injection gives T-2 toxin 5mg/kg, once a day, successive administration 5 days can make that the solid tumor histiocyte is downright bad to be decomposed.The T-2 toxin has clear and definite Chemotherapy to digestive tract tumor, and chemotherapy effect is better than digestive tract First-line chemotherapy medicine 5-FU.
Strict guarantor's autumn of domestic patent of invention CN200910019618.1(inventor, applicant Shandong University, open on 07 22nd, 2009 day for announcing, open notification number CN101485653A), strict guarantor's autumn of CN200910019619.6(inventor, applicant Shandong University, February 2 2011 Granted publication day, Granted publication CN101513399B), strict guarantor's autumn of CN200910014633.7(inventor, applicant Shandong University, March 30 2011 Granted publication day, Granted publication CN101491518B), strict guarantor's autumn of CN200910019620.9(inventor, applicant Shandong University, at 2010 Granted publication day December 8 days, Granted publication CN101485654B), strict guarantor's autumn of CN200910014627.1(inventor, applicant Shandong University, March 3 2009 applying date, open notification number CN101491517A), strict guarantor's autumn of CN201010258665.4(inventor, applicant Shandong University, March 3 2009 applying date, open notification number CN101940565A), strict guarantor's autumn of CN201010258681.3(inventor, applicant Shandong University, March 3 2009 applying date, open notification number CN101984963A), 201010258664.X(strict guarantor's autumn of inventor, applicant Shandong University, March 3 2009 applying date, notification number CN101984962A is disclosed) and strict guarantor's autumn of CN201010258682.8(inventor, applicant Shandong University, March 3 2009 applying date, open notification number CN101984964A) the T-2 toxin is disclosed respectively in the treatment leukemia, osteocarcinoma and myeloproliferative disorder, solid tumor, carcinoma of prostate, cancer of pancreas, intention in the cancer such as the cerebral tumor and renal cell carcinoma, wherein patent of invention CN200910014633.7 discloses a kind of implantation preparation of T-2 toxin, be used for the treatment of solid tumor, have desirable effect, and can avoid the toxic action of T-2 toxin.
Yet, when the T-2 toxin is used for non-solid tumor, can't adopt heeling-in administration in the tumor, and oral or intravenous administration, need to overcome that the T-2 toxin is insoluble in water, bioavailability is low, oral or there are the problems such as side effect in intravenous administration, avoid in the T-2 toxin drug administration by injection process stimulation to vascular tissue.
At present water, bioavailability are low for being insoluble in, the stronger antitumor drug of toxic and side effects after the administration, the double solvents systems that adopt improve drug bioavailability more, but solubilization-aid effect all there are significant zest in solvent such as polyoxyethylene castor oil, tween 80 etc. preferably.Therefore tend at present that water, bioavailability are low with being insoluble in, the stronger antitumor drug of toxic and side effects is prepared into the special preparations such as cyclodextrin clathrate, microball preparation after the administration, improve bioavailability and the targeting of medicine with this, reduce medicine to the zest of administration part or vascular system, but the medicine of the special preparation such as cyclodextrin inclusion compound, microball preparation preparation, price is significantly higher than ordinary preparation, so that the patient medical cost burden increases the weight of.
Therefore, preparation technique has become the key technology that hinders the clinical practice of T-2 toxin.
Summary of the invention
For above-mentioned prior art, the invention provides a kind of T-2 toxin ejection preparation that is used for the treatment of tumor.A kind of T-2 toxin injection specifically.
An aspect of of the present present invention provides a kind of T-2 toxin ejection preparation, and described T-2 toxin ejection preparation is comprised of T-2 toxin and ethanol; The consumption of described ethanol is that every 0.5mg～2mg T-2 toxin uses 1ml ethanol; The purity of described ethanol is greater than 99.4%.
Another aspect of the present invention provides a kind of T-2 toxin ejection preparation, and described T-2 toxin ejection preparation is comprised of T-2 toxin, ethanol and solubilizing agent, and the purity of described ethanol is greater than 98.0%; The consumption of described ethanol is that every 0.5mg～1mg T-2 toxin uses 1ml ethanol; The consumption of described solubilizing agent is that every 0.5mg～1.0mgT-2 toxin uses the 0.5mg solubilizing agent.
Described solubilizing agent is one or both in polyvinylpyrrolidone, citric acid, the PEG400.
Described solubilizing agent is polyvinylpyrrolidone and citric acid.
The weight ratio of used polyvinylpyrrolidone and citric acid is 1:1 in the described T-2 toxin ejection preparation.
The inventor is in prescription research, surprised discovery, adopt purity greater than 99.4% ethanol or adopt purity greater than the double solvents of 98.0% ethanol and some cosolvent composition solvent and the adjuvant as T-2 toxin ejection preparation, the T-2 toxin injection of making, through intravenous drip or inject reach therapeutic dose after, its blood vessel irritation and the toxic and side effects of nonneoplastic tissue significantly reduced.
Tissue distribution research further shows, purity is greater than 99.4% ethanol or adopt purity greater than the double solvents of 98.0% ethanol and some cosolvent composition solvent and the adjuvant as T-2 toxin injection, after the intravenous injection, the T-2 toxin is significantly accelerated to the speed that the vigorous tumor tissues of division distributes by blood system, be conducive to improve the bioavailability of T-2 toxin, alleviate its toxic and side effects, and this preparation process thereof is simple, be beneficial to suitability for industrialized production, possess outstanding substantive distinguishing features and significant progressive.
Description of drawings
Fig. 1 T-2 toxin positive controls organ pathological picture.
Behind Fig. 2 T-2 toxin injection intravenously administrable in tumor and blood the tissue distribution of content ratio variation diagram in the rat body.
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment:
The preparation of embodiment 1 T-2 toxin injection
Prescription:
T-2 toxin 40mg
Ethanol (purity 99.7%) 40ml
Preparation:
The T-2 toxin of recipe quantity is added in the ethanol, and after stirring was fully dissolved it, sterilization, packing, preservation got final product.
The preparation of embodiment 2 T-2 toxin injection
Prescription:
T-2 toxin 40mg
Ethanol (purity 99.5%) 50ml
Preparation:
The T-2 toxin of recipe quantity is added in the ethanol, and after stirring was fully dissolved it, sterilization, packing, preservation got final product.
The preparation of embodiment 3 T-2 toxin injection
Prescription:
T-2 toxin 12mg
Ethanol (purity 99.8%) 20ml
Preparation:
The T-2 toxin of recipe quantity is added in the ethanol, and after stirring was fully dissolved it, sterilization, packing, preservation got final product.
The preparation of embodiment 4 T-2 toxin injection
Prescription:
T-2 toxin 30mg
Ethanol (purity 99.5%) 20ml
Preparation:
The T-2 toxin of recipe quantity is added in the ethanol, and after stirring was fully dissolved it, sterilization, packing, preservation got final product.
The preparation of embodiment 5 T-2 toxin injection
Prescription:
T-2 toxin 24mg
Ethanol (purity 99.8%) 20ml
Preparation:
The T-2 toxin of recipe quantity is added in the ethanol, and after stirring was fully dissolved it, sterilization, packing, preservation got final product.
The preparation of embodiment 6 T-2 toxin injection
Prescription:
T-2 toxin 34mg
Ethanol (purity 99.7%) 20ml
Preparation:
The T-2 toxin of recipe quantity is added in the ethanol, and after stirring was fully dissolved it, sterilization, packing, preservation got final product.
The preparation of embodiment 7 T-2 toxin injection
Prescription:
T-2 toxin 38mg
Ethanol (purity 99.8%) 20ml
Preparation:
The T-2 toxin of recipe quantity is added in the ethanol, and after stirring was fully dissolved it, sterilization, packing, preservation got final product.
The preparation of embodiment 8 T-2 toxin injection
Prescription:
T-2 toxin 20mg
Ethanol (purity 98.6%) 22ml
PEG400 19mg
Preparation:
T-2 toxin, ethanol, the PEG400 of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The preparation of embodiment 9 T-2 toxin injection
Prescription:
T-2 toxin 10mg
Ethanol (purity 99.1%) 19ml
PEG400 4mg
Citric acid 2mg
Preparation:
T-2 toxin, ethanol, PEG400 and the citric acid of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The preparation of embodiment 10 T-2 toxin injection
Prescription:
T-2 toxin 16mg
Ethanol (purity 99.7%) 24ml
Polyvinylpyrrolidone 6mg
Preparation:
T-2 toxin, ethanol and the polyvinylpyrrolidone of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The preparation of embodiment 11 T-2 toxin injection
Prescription:
T-2 toxin 30mg
Ethanol (purity 99.7%) 36ml
Polyvinylpyrrolidone 10mg
PEG400 5mg
Preparation:
T-2 toxin, ethanol, PEG400 and the polyvinylpyrrolidone of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The preparation of embodiment 12 T-2 toxin injection
Prescription:
T-2 toxin 30mg
Ethanol (purity 99.7%) 54ml
Polyvinylpyrrolidone 8mg
Citric acid 8mg
Preparation:
T-2 toxin, ethanol, citric acid and the polyvinylpyrrolidone of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The preparation of embodiment 13 T-2 toxin injection
Prescription:
T-2 toxin 30mg
Ethanol (purity 99.7%) 34ml
Polyvinylpyrrolidone 10mg
Citric acid 10mg
Preparation:
T-2 toxin, ethanol, citric acid and the polyvinylpyrrolidone of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The preparation of embodiment 14 T-2 toxin injection
Prescription:
T-2 toxin 30mg
Ethanol (purity 99.7%) 42ml
Polyvinylpyrrolidone 14mg
Citric acid 14mg
Preparation:
T-2 toxin, ethanol, citric acid and the polyvinylpyrrolidone of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The preparation of embodiment 15 T-2 toxin injection
Prescription:
T-2 toxin 30mg
Ethanol (purity 99.7%) 39ml
Polyvinylpyrrolidone 9.5mg
Citric acid 9.5mg
Preparation:
T-2 toxin, ethanol, citric acid and the polyvinylpyrrolidone of recipe quantity are mixed, and after stirring was fully dissolved the T-2 toxin, sterilization, packing, preservation got final product.
The toxicity test of embodiment 16 T-2 toxin injection
The KM mice, body weight 30 g～40g, male and female half and half are divided into 7 groups every group 20 at random.Six groups of experimental grouies, tail vein injection gives embodiment 1,5,8,9,12,14 made injection (with T-2 toxin 1mg/kg body weight dosed administration) respectively; The negative control group tail vein injection gives normal saline; The positive controls tail vein injection gives T-2 toxin alcoholic solution, and (concentration of alcohol is 95%, calculates by volume; With T-2 toxin 0.5mg/kg body weight dosed administration).Administration every day 1 time, successive administration 7 days, carry out that gross examination of skeletal muscle, hematology, blood are biochemical, the urine biochemical analysis 1-7 days every days during the administration and after the administration, and respectively organize and put to death 5 animals every day and carry out pathological anatomy the 1st, 3,5,7 day every day after the administration, carries out pathologic finding under the optical microscope.
Incidence of vomiting is 92% after the administration of gross examination of skeletal muscle discovery positive controls, and after the 4th administration, the mice food-intake significantly reduces; The experimental group incidence of vomiting is up to 3%(embodiment 8 made intravenous injections), the two compares each experimental group and matched group and all has significant difference (p＜0.05), and the experimental group symptoms of emesis is relatively light.Prompting positive controls medicine has produced stronger stimulation to gastrointestinal tract mucous system.
Observe mouse skin in the experimentation, significant hemorrhagic petechia appears in positive controls mouse tail, skin of abdomen, congestive symptom appears in eyes, experimental mice afterbody, skin of abdomen hemorrhagic petechia significantly are less than experimental group, and prompting embodiment 1,5,8,9,12,14 made T-2 toxin injection can significantly alleviate the T-2 toxin to the stimulation of vascular tissue.
Experiment finishes to put to death respectively organizes mice, gets mouse heart, liver, lungs, spleen and kidney, and gross examination of skeletal muscle finds that positive controls Mouse Liver splenomegaly is hemorrhage, and each organ is made pathological section, and microscopically is observed the pathological change of each treated animal.The result shows that all there be myocardium hemorrhage and liver, lung, kidney hemorrhagic disease phenomenon in various degree in the positive controls mice, the results are shown in Figure 1.Experimental group is not found obviously unusual.Prompting T-2 toxin injection can alleviate the T-2 toxin to the stimulation of blood vessel and other internal organs.
The tissue distribution experiment of embodiment 17 T-2 toxin injection in the tumor-bearing mice body
Age in C-57 mice 4-6 week, body weight 15-25g, male, with the Lewis lung cancer cell, it is subcutaneous to be inoculated in experiment mice right fore root veutro, every inoculation 2.0 * 10
7Individual tumor cell, cumulative volume 0.20ml.Lump is grown up after 2 weeks, is used for experiment.
Tumor-bearing mice is divided into 4 groups at random, and experimental group single tail vein injection gives the made T-2 toxin injection (with T-2 toxin 0.5mg/kg body weight dosed administration) of embodiment 1.The positive controls tail vein injection gives T-2 toxin alcoholic solution, and (concentration of alcohol is 95%, calculates by volume; With T-2 toxin 0.5mg/kg body weight dosed administration).Each treated animal administration every day 1 time, successive administration 3 days.The the 1st, 2,8,12,16,24 hour every group of 5 mices after the administration, after the blood sampling, put to death, take out tumor tissues, measure the relative amount of blood plasma and tumor tissues T-2 toxin, calculate in the tumor tissues ratio of T-2 content of toxins in the T-2 content of toxins and blood plasma [T-2 content of toxins in the T=(tumor tissues)/(T-2 content of toxins in the blood plasma), the results are shown in Figure 2.
As seen from Figure 2, can significantly improve the T-2 toxin in the distribution of tumor tissues behind the T-2 toxin injection intravenous administration, and can make that the T-2 toxin maintained high concentration large 40 hours in the tumor tissues.And the T-2 toxin is lower in the distribution of tumor tissues behind the T-2 toxin alcoholic solution intravenous administration.Prompting T-2 toxin injection can improve T-2 toxin bioavailability, and can improve the tissue distribution of T-2 toxin.
The stability experiment of embodiment 18 T-2 toxin injection
Embodiment 1,3,7,11,14 gained T-2 toxin injection are carried out stability experiment.
(1) strong illumination test: T-2 toxin injection is observed after placing respectively 5 days and 10 days under the 4 000 lx illumination, be found that, and compare before the placement, injection still keeps clear.
(2) high humility test: T-2 toxin injection is placed in the airtight vessel respectively at placing 5 days and 10 days afterwards investigation stability under 25 %, the 75% and 92 .5 % relative humidity conditions.With place before compare, intravenous injection still keeps clear, has no medicine and separates out.
(3) hot test: T-2 toxin injection is placed in the airtight vessel and places respectively under 40,60,80 ℃ of conditions, investigated afterwards stable in 5 days and 10 days.With place before compare, still keep clear, have no medicine and separate out.
(4) accelerated test: with centrifugal 10 min of T-2 toxin injection 4000rpm, still keep clear, have no medicine and separate out.
(5) the room temperature investigation that keeps sample: T-2 toxin injection was placed respectively 1,2,3,6,12,24 month under 25 ℃ of temperature, relative humidity 75 % conditions, still kept clear, have no medicine and separate out.
Because of the T-2 toxin this under illumination and hot conditions, can stable existence.Therefore, the stability experiment of T-2 toxin injection mainly is to observe the T-2 toxin in selected solvent system, under the conditions such as high light, high temperature, high humidity, medicine whether can occur and the formulation problems such as separate out.By experimental result as seen, T-2 toxin injection stability is stronger, meets the preparation technique requirement, even under super-humid conditions, and still can the stable existence certain hour.
Embodiment 19 T-2 toxin cell in vitro poison reaches the inhibitory action to growth of tumour cell
(1) cell
Normal cell: L929 (l cell), CHL(hamster pneumonocyte)
Human tumor cell line: MCF-7 (breast carcinoma), HepG-2(hepatocarcinoma), the K562(leukemia), A549(pulmonary carcinoma), U251 (human glioma), DU145(carcinoma of prostate), the RPMI8226(multiple myeloma).
(2) positive control: mitomycin for inj
(3) method: " sulphonyl rhodamine staining (srb assay) detects to adopt cell toxicant class antineoplastic.
Test sample preparation: get T-2 toxin injection 1ml, add 9ml DMSO, being mixed with the solution that concentration is 0.5mg/ml, is the working concentration of 0.025ng/ml, 0.25ng/ml, 2.5ng/ml, 25ng/ml, 250ng/ml, 2500ng/ml, 25000ng/ml with the dilution of RPMI 1640 complete mediums again.
Cell culture: will put 37 ℃, 5%CO with the required corresponding complete medium of cell behind the cell recovery
2Cultivate in the incubator, go down to posterity, be cultured to exponential phase.
The cell inoculation: will be cultured to cell 0.25% trypsinization of exponential phase, and add complete culture medium and blow and beat into cell suspension, and get a little cell suspension and add the rear microscopically counting of equivalent 0.4% trypan blue dye liquor dyeing, attached cell is adjusted concentration to 2 * 10
5Individual/ml, suspension cell is adjusted concentration to 5 * 10
5Individual/ml, be inoculated in 96 orifice plates with 100 μ l/ holes, put 37 ℃, 5%CO
2Cultivated 24 hours in the incubator.
Tested material is processed cell: the every hole of experimental group adds the test sample liquid of 100 each concentration of μ l, and negative control adds the complete medium of equivalent, and blank is not for adding the complete medium of cell, every group establish 6 parallel, put 7 ℃, 5%CO
2Continue in the incubator to cultivate 24 hours.
Attached cell detects (srb assay): behind the cell culture 24h, take out culture plate, add 50% trichloroacetic acid (TCA) of 50 μ l pre-coolings in every hole, final concentration is 10%, plate put 4 ℃ 1 hour.Take out with distillation washing 5 times, remove trichloroacetic acid, culture fluid, low-molecular-weight metabolite, serum albumin, air drying.Every hole adds 0.4% SRB100 μ l of 1% acetic acid preparation behind bone dry, and 15～30min dyes under the room temperature.Outwell dye liquor, wash 5 times with 1% acetic acid, remove unconjugated dyestuff, use the non-buffering Tris alkali liquor 150 μ l dissolving of the 10mmol/L of pH 10.5 behind the air drying.Shake 5min at oscillator plate, in wavelength 490nm place, the enzyme linked immunological monitor is measured the absorbance value in each hole.Record numerical value draws the growth inhibition ratio of each concentration cell, uses SPSS13.0 software to draw the IC50 value.
Suspension cell detects (srb assay): cell culture took out culture plate after 24 hours, added 80% trichloroacetic acid (TCA) of 50 μ l pre-coolings in every hole, and final concentration is 16%, left standstill 5 minutes, plate put 4 ℃ 1 hour.Take out with distillation washing 5 times, remove trichloroacetic acid, culture fluid, low-molecular-weight metabolite, serum albumin, air drying.Every hole adds 0.4% SRB100 μ l of 1% acetic acid preparation behind bone dry, and 15～30min dyes under the room temperature.Outwell dye liquor, wash 5 times with 1% acetic acid, remove unconjugated dyestuff, use the non-buffering Tris alkali liquor 150 μ l dissolving of the 10mmol/L of pH 10.5 behind the air drying.Shake 5min at oscillator plate, in wavelength 490nm place, the enzyme linked immunological monitor is measured the absorbance value in each hole.Record numerical value draws the growth inhibition ratio of each concentration cell, uses SPSS13.0 software to draw the IC50 value.
(4) as a result the T-2 toxin to suppression ratio and the IC50 value of normal cyto-inhibition:
Table 1 T-2 toxin is to suppression ratio and the IC50 value of inhibiting tumour cells effect
The experiment of T-2 vitro cytotoxicity shows that ng level level gets final product obvious cell growth inhibiting; It is the leukemia K 562 strain that IC50 is lower than the 100ng/ml cell strain.And mitomycin need reach 2 * 10 when reaching the obvious inhibitory action of cell growth
5Ng/ml.
Claims (3)
1. T-2 toxin ejection preparation, it is characterized in that: be comprised of T-2 toxin and ethanol, the purity of described ethanol is greater than 99.4%; The consumption of described ethanol is that every 0.5mg ~ 2mg T-2 toxin uses 1ml ethanol.
2. T-2 toxin ejection preparation is characterized in that: be comprised of T-2 toxin, ethanol and solubilizing agent, the purity of described ethanol is greater than 98.0%, and the consumption of described ethanol is that every 0.5mg ~ 1mg T-2 toxin uses 1ml ethanol; Described solubilizing agent is one or both in polyvinylpyrrolidone, citric acid, the PEG400, and the consumption of described solubilizing agent is that every 0.5mg ~ 1.0mg T-2 toxin uses the 0.5mg solubilizing agent.
3. T-2 toxin ejection preparation according to claim 2, it is characterized in that: described solubilizing agent is polyvinylpyrrolidone and citric acid; The weight ratio of described polyvinylpyrrolidone and citric acid is 1:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110345019 CN102357072B (en) | 2011-11-04 | 2011-11-04 | Injection preparation of T-2 lienomycin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110345019 CN102357072B (en) | 2011-11-04 | 2011-11-04 | Injection preparation of T-2 lienomycin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102357072A CN102357072A (en) | 2012-02-22 |
| CN102357072B true CN102357072B (en) | 2013-01-16 |
Family
ID=45582491
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110345019 Expired - Fee Related CN102357072B (en) | 2011-11-04 | 2011-11-04 | Injection preparation of T-2 lienomycin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102357072B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101984962B (en) * | 2009-03-03 | 2011-12-07 | 山东大学 | Application of T-2 toxin to preparing drugs for treating brain tumors |
| CN101491518B (en) * | 2009-03-03 | 2011-03-30 | 山东大学 | Combination for treating tumor |
-
2011
- 2011-11-04 CN CN 201110345019 patent/CN102357072B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN102357072A (en) | 2012-02-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101254308B (en) | Biogastrone acid-polyethyleneglycol /chitosan liver target composite drug administration system and preparation thereof | |
| CN110545820B (en) | Application of kelimycin and pharmaceutically acceptable salt thereof in preparing medicaments for treating and/or preventing tumors | |
| CN103221373A (en) | Methods and compositions for treating lung cancer | |
| CN104042567A (en) | Ampelopsin nano-micelle and application thereof | |
| CN109998996A (en) | Lipid composition and the method for improving Antitumor Activity of Drugs | |
| CN110054659A (en) | The method for improving Antitumor Activity of Drugs | |
| WO2020177748A1 (en) | Quaternized modified taxane derivative, and pharmaceutical composition and use thereof | |
| CN110938032A (en) | Organic selenium compound and use thereof | |
| CN102526073A (en) | Application of mogrol H9 for preparing antitumor drugs | |
| CN104666247A (en) | Heparin-modified cleavable adriamycin liposome preparation and preparation method thereof | |
| CN110092808A (en) | A kind of sterol compound and pharmaceutically acceptable salt or prodrug and its application | |
| JP2018513130A (en) | HSP90 inhibitory peptide conjugate and its application in tumor therapy | |
| CN102357072B (en) | Injection preparation of T-2 lienomycin | |
| CN102525954B (en) | Lyophilized emulsion preparation for injection of levo-gossypol and acetate of levo-gossypol | |
| CN102475698A (en) | Application of salvianolic acid L in preparation of medicines used for treating tumor | |
| CN106974908A (en) | Pharmaceutical composition and purposes containing hdac inhibitor and IRE1 inhibitor | |
| CN103893168A (en) | Application of isopimpinellin in preparation of antitumor drugs and anticancer reversal agents | |
| CN102336904A (en) | Multivalent polyglycol (PEG) modifier for camptothecin and derivatives thereof and application of multivalent PEG modifier | |
| CN106822129B (en) | Application of the aloperine derivative in the drug of preparation treatment tumour | |
| CN105287612A (en) | Salinomycin sodium and adriamycin co-loaded nano-liposome as well as preparation method and application thereof | |
| CN102688228B (en) | Pharmaceutical composition containing apigenin, apigenin derivative, rubescensin and rubescensin derivative, and application thereof | |
| CN102210668B (en) | Application of cantharidin and derivants thereof in preparation of tumor chemotherapy sensitivity enhancing medicine | |
| CN104225611B (en) | The conjugate of Dasatinib and non-linear configurations polyethylene glycol | |
| CN102940651B (en) | A kind of method and application thereof utilizing tumor-targeting bacterium activation prodrug | |
| CN103054802A (en) | Procationic/ cationic liposome curcumin preparation for interventional treatment of hepatic carcinoma and preparation method of preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130116 Termination date: 20181104 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |