CN1751741A - Nano carbon tube infusion agent, its prepn. method and application in treating cancer, cardiovascular disease and infectious disease - Google Patents
Nano carbon tube infusion agent, its prepn. method and application in treating cancer, cardiovascular disease and infectious disease Download PDFInfo
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Abstract
A carbon nanotube type perfusion for treating cancer, atherosclerosis, coronary heart disease, cerebral thrombosis, infections disease, poisoning, etc contains heavy metal (less than 0.1-10 ppm), soluble metal ions (less than 0.1-10 ppm) and ash (0-2%). It may be the granular carbon nanotube injection, activated granular carbon nanotube injection, carbon nanotube injection containing catalyst, and medicine carried carbon nanotube injection. Its advantages are high compatibility to tissue, unique curative effect and no toxic by-effect.
Description
Technical field
The present invention relates to CNT infusion solution, its preparation method and the application in diseases such as preparation treatment cancer thereof.Or rather, the present invention relates to CNT transfusion liquid, its preparation method and the application in treating cancer, cardiovascular and cerebrovascular disease, catching thereof that intravenous transfusion is used.
Background technology
Since CNT in 1991 is found, CNT owing to its exclusive structure and peculiar physics, chemical characteristic with and potential application prospect be subjected to people's attention.CNT be by in the graphite the carbon atom piped material that curls and to form, the diameter of pipe is generally several nanometers (minimum is about 1 nanometer) to tens nanometers, the thickness of pipe only is several nanometers.In fact, CNT can be regarded the length " cage 0 son " that is similar to the hollow garden column that superfine wire gauze is rolled into visually as.The diameter of CNT is very small, and tens0000 carbon bank of tubes get up just to have people's a hairline wide; And the length of CNT can arrive 100 microns, see in a sense, it be a kind of well, the thinnest fiber.Under the support of national project, nineteen ninety-five, China prepares the aligned carbon nanotube of large tracts of land, high density, Discrete Distribution finally.Uniform diameter is 20 nanometers, and tube pitch is 100 nanometers, and pipe range is about 100 microns.
CNT has been widely used in fields such as calorifics, electricity, optics, chemistry, but specifically at pharmaceutical field, also few to the research and the application of CNT, especially in infusion solution, up to now, also not with the precedent of CNT as infusion solution and carrier use.
The present invention studies show that on physicochemical property, structure, a series of carrier materials such as CNT and active carbon are essentially different, it has good organism compatibility simultaneously, therefore the present invention produces CNT diameter 35 μ m-0.5nm by research, nano-sized carbon pipe range 31 μ m-0.5nm, aperture 31 μ m-0.1nm.The CNT infusion solution, the CNT microgranule is added in traditional venous transfusion agent, import in the blood of human body again or be input in abdominal cavity, the thoracic cavity, to multiple cancer, artery is atherosis, coronary heart disease, cerebral thrombosis, infectious disease, azotemia, acute organic and inorganic toxic material poisoning etc. all have curative effect preferably.
Summary of the invention
The object of the invention provides a kind of CNT infusion solution, and it is the CNT transfusion liquid that intravenous transfusion is used.
Another object of the present invention provides the preparation method of this CNT infusion solution.
A further object of the invention provides the application of this CNT infusion solution in preparation treatment cancer drug.Activation CNT microgranule injection, the CNT injection that is adsorbed with catalyst and the agent of medicine carrying active nano carbon tube needle.
CNT infusion solution of the present invention comprises the pure charcoal CNT microgranule injection that (1) intravenous transfusion is used, (2) activation CNT microgranule injection, and (3) are adsorbed with the CNT injection and the agent of medicament-carried nano carbon tube needle of catalyst.
Above-mentioned CNT injection that is adsorbed with catalyst and the agent of medicament-carried nano carbon tube needle comprise (1) bag quilt or absorption cancer therapy drug injection; (2) bag quilt or absorption anticoagulant and pravastatin composition injection; (3) bag quilt or absorption antibiolics composition injection; (4) bag quilt or absorption antiviral agents composition injection; (5) bag quilt or absorption growth-factor medication injection.
CNT wherein meets following prescription: content of beary metal≤0.1-10ppm, other soluble metal ion≤0.1-10ppm, ash＜2%, 0.15% serge blue adsorptive value＞6-30, contained CNT diameter 35 μ m-0.5nm in this CNT infusion solution, nano-sized carbon pipe range 31 μ m-0.5nm, aperture 31 μ m-0.1nm.Main particle size distribution is diameter 6 μ m-0.5nm, and pipe range 3 μ m-0.5nm apertures 2 μ m-0.1nm account for 99%, diameter 35 μ m-7 μ m, and pipe range 4---35 μ m 3--30 μ m granule is no more than 1%.
Prove through a large amount of animal experiments, behind this CNT microgranule input blood, fabulous with histocompatibility, have no side effect, there is not bad zest, non-immunogenicity, in the using dosage scope with interior (dose therapeutically effective that is single input blood is the 0.1-5mg/kg body weight, imports 1-7 time weekly, and the adult's average cumulative always amount of storing up is below the 10g), in the preparation quality standard scope, the thromboembolism of vitals can not take place.Grasp therapeutic dose, the total amount of storing up, can be repeatedly, vein input repeatedly, find no and poison and the important organ damage; Confirm that through zootomy vein input CNT microgranule can not produce pathologic lesion to the heart, liver,kidney,spleen, lung, bone marrow, brain.
The preparation method of CNT infusion solution of the present invention is characterized in that this method comprises the steps:
(1) is prepared into CNT (CNT diameter 35 μ m-2nm, nano-sized carbon pipe range 31 μ m-2nm, aperture 31 μ m-1nm.)；
(2) make the CNT diameter 35 μ m-0.5nm of required particle diameter with cutter, nano-sized carbon pipe range 31 μ m-0.5nm, aperture 31 μ m-0.1nm.
(3) make this CNT coarse granule adsorption activation agent so that CNT activates, described activator concentration is 0.01-10%, is heated to 70-190 ℃ in high-pressure bottle, and the response time is 5-20 minute, generates oxidized form or reduced form activation CNT; Residual gas is got rid of in the cooling decompression, feeds 60-100 ℃ of steam, ammonia again under pressure respectively, generates the activatory CNT that contains charcoal-hydroxyl, charcoal-imino group or charcoal-hydrogen;
(4) carrying out the CNT medicine carrying handles;
(5) make this CNT microgranule dipping absorption bio-guide agent, carry out short time, cold drying fast then, the medication infusion agent of making different purposes then.
In above-mentioned steps (3), described activator is divided into Oxidizing and Reducing Agents, and oxidant is selected from epoxy ethers, acyl chloride, anhydrides, aldehydes oxidant, and Reducing agent is selected from LiAlH
4, NaBH
4
In above-mentioned steps (4), medicine carrying is handled can select following two kinds of methods for use: (1) selects related drugs to carry out the saturated absorption of liquid phase, cold drying then with the method and the pure CNT of physics (or chemistry); (2) CNT of making these medicines of energy special packing into (or claiming the bag quilt) according to the molecular size and the form of anticarcinogen, anticoagulant medicine, cholesterol reducing, antibiotic, antiviral drugs and growth-factor medication; Respectively anticarcinogen, anticoagulant medicine, pravastatin, antibiotic, antiviral drugs and somatomedin are packed in this specific nano carbon pipe space into the medication infusion agent of making different purposes then.
The related drugs of the selection described in the step (5) comprises: 1. traditional cancer therapy drug such as 5-FU, CTX, MTX, Ara-C/A, 6-MP, antitumor antibiotic class, suitable/carboplatin, arsenical class, paclitaxel etc.; 2. immune activation, regulate cytokine class such as IL-2,4,6, GM, G-CSF, γ-IFN, TNF, FCF-B, VECF, 4-IBB/4-IBBL, B7-1B7-2, toadpoison albumen, specificity incomplete antibody etc.; 3. catalyst class such as main metallo-organic compound benzyl/butyl lithium etc., the agent of transition metal cuprammonium, platinum, palladium agent, selenium, germanium compound etc., these conjugates have catalysis and kill the tumor dual function; 4. adsorb biological enzyme such as redox enzymes, transaminase's class, hydrolase, isomerase etc.
In above-mentioned steps (6), described bio-guide agent comprises ferrous porphyrin, or thymus pyrimidine, bird pyrimidine, uracil, thymus purine, guanine and derivant one big class material thereof, as 5-fluorouracil, hydrogen deuterium thymus pyrimidine, methotrexate and the tumor cell adhesion factor (as VCAM-1), the growth of tumour cell factor (as VEGF) etc.
In step (5) and (6), select different medicine and bio-guide agent can prepare various medicament-carried nano carbon control agent, for example adsorb the cancer therapy drug injection, absorption anticoagulant, pravastatin composition injection, absorption antibiolics composition injection, absorption antiviral agents composition injection.
The present invention also provides the application of this CNT infusion solution in preparation treatment cancer drug, it is characterized in that the dose therapeutically effective of single input blood is the 0.01-5mg/kg body weight, imports 1-7 time weekly, and the adult's average cumulative always amount of storing up is below the 10g.
The beneficial effect of CNT injection of the present invention is described as follows:
Show through long term studies, the nano-micrometre CNT of diameter in a certain size scope has the very significantly effect of alleviating cancer pain, inhibition tumor growth or kill tumor cell, this CNT microgranule be can be used for treating multiple cancer by vein input blood, and can treat that artery is atherosis, coronary heart disease, cerebral thrombosis; Also have the function of similar immune factor sample behind this CNT microgranule input blood, divide the increment function, can be used for the treatment of various refractory types, microorganism and viral infection as IgG A M, the little peptide molecule of DC, immunoglobulin superfamily.Also find to have the function that promotes that body tissue is repaired after this CNT microgranule is by vein input blood, diseases such as chronic disunion wound, osteomyelitis are had peculiar curative effect, and can treat acute organic and inorganic toxic poisoning.
Itself have outside the antitumaous effect based on pure CNT micro powder granule, the effect that also has absorption, immunomodulating, chemical catalysis, pharmaceutical carrier, pure CNT micro powder granule is carried out further chemical activation processing, medicine carrying processing and the agent of absorption bio-guide to be handled, above-mentioned effect will obtain positive and strengthen, thereby can obtain unusual therapeutic effect, this is the mechanism that CNT infusion solution of the present invention is used in preparation treatment cancer drug.To be described in more detail below:
1. pure CNT microgranule is carried out further activation processing:
CNT itself has the chemical catalysis effect, can also modify with different chemical groups simultaneously, make CNT in conjunction with the number of chemical catalytic group, these chemical groups can be the low-molecular-weight organic compounds that contains hydroxyl, carboxyl, amino, carbonyl, aromatic ring yl; Can be the enzyme Organic substance with the bonded chemism catalytic group of CNT, or select at normal temperatures and pressures, in solution, can play main metallo-organic compound, transition metal organometallic compound or the corresponding inorganic compound of catalytic action, to reach catalysis to hydrogen, oxygen, hydrocarbon, peptide, fat; The CNT adsorptive value of handling through chemical activation makes it bring into play catalysis therapeutical effect or the effect of increase medicine carrying more targetedly more obvious raising.
2. the CNT microgranule to activated processing further carries out medicine carrying processing and absorption bio-guide agent processing again:
On the CNT microgranule in conjunction with the bio-guide material, this is the effective ways that further improve CNT microgranule infusion solution curative effect, this guide material selection principle is: utilize the vigorous characteristics of growth of cancer cells, select material that growth of cancer cells demand intake Duos than the normal cell intake as guide material, be that the strong material of biting property of cancer is a guide material, this class material must be the material of non-immunogenicity, for example select to constitute DNA or the necessary base pair material of RNA (thymus pyrimidine, the bird pyrimidine, uracil, the thymus purine, guanine and derivant one big class material thereof), growth of cancer cells metabolism intake manys the material (as blood bovine) of hundred times than normal cell, or the affine material of selection tumor, the tumor cell adhesion factor (as VCAM-1) for example, the growth of tumour cell factors (as VEGF) etc. are as guide material, and these materials all have the effect of the tumor growth of promotion.Absorbing phenomenon is that tumor cell enjoys a lot to capture such CNT microgranule, and engulf these CNT microgranules in a large number up to dead or stop growing, and normal tissue cell is almost turned a blind eye to this CNT microgranule or is seldom made inquiries, this have a biting property of cancer, the CNT microgranule of tumor affinity guiding concentrates automatically around cancerous cell, CNT particle concentration in cancerous tissue inside is the hundred times of other normal structure, reach up to ten thousand times even, this creative guide material and the bonded application of CNT, break through the bio-guide material selection principle, and solved the problem that the tumor chemotherapeutic drug selectivity is not strong for a long time and to guide material produce repellence problem.
Studies show that, in the very abundant and disorderly tumor tissues of new vessels, this CNT microgranule or the pure CNT microgranule that has biting property of cancer, cancer affinity substance, can form the accumulation of high concentration in the tumor tissues blood capillary or in the tumor neogenetic blood capillary cecum, and be engulfed in a large number by cancerous cell; Built up a large amount of CNT microgranules in the cancerous tissue, these CNT microgranules are carrying out cancer therapy drug release, immunomodulating, chemical catalysis and adsorbent dynamic equilibrium and are disturbing tumor growth, finish the comprehensive tumor effect of killing.
Agent of another kind of antiviral bio-guide and medicine carrying combination selection principle are: viral affinity agent-viral agent interfering combination, and select for use thymine alkali bases, RNA viruses to select for use uracil base and interferon, IL-1, virus transcription enzyme inhibitor, AG14361 class to make up as DNA viruses.
This CNT microgranule with bio-guide, with its huge specific surface area, can adsorb multiple cancer therapy drug, medicine is directed to along with the CNT microgranule and concentrates around tumor cell, contained medicine can be selected different anticarcinogens, as the chemotherapeutics class, the radionuclide class, immunomodulating cytokines class and palladium, platinum, copper, germanium, selenium, coordination catalysis metal species materials such as cobalt, these medicines are directed to tumor cell, between tumor blood capillary inside and tumor cell in the matter, can the concentrate hundred times of conventional treatments of medicine, up to ten thousand times even, strengthened antitumor curative effect, reduced the toxic and side effects of chemotherapeutics.Chemotherapy, the radiotherapy drug dose of carry on CNT generally is the 2--50% of traditional treatment amount, just can meet or exceed the effect of traditional treatment scheme, reduces cancer therapy drug to greatest extent to organism normal cell and immune infringement.
CNT infusion solution safety zoopery of the present invention is as follows:
1, rat toxicity experiment: 60 of rats, 135g ± 10g, male and female half and half, the tail vein injection method was observed 28 days
Grouping dosage mg/Kg size of animal (only) death toll (only) LD
50Confidence limit accumulation mg/Kg
A 0.1 3/W * 7W 12 0 does not find 2.1
B 0.3 3/W×7W 12 0 --- 6.3
C 1.6 3/W×7W 12 0 --- 31.5
D 1.6 3/W×14W 12 0 --- 72
E 30 1/W 12 0 --- 30
Because of the continuous injections difficult of tail vein, at most only prick 3/W; D is equivalent to the maximum tolerated dose experiment, and E is equivalent to the limit experiment of expedient property, and A, B, C are equivalent to high, normal, basic three groups of the anxious poison experiment of animal, but frequency injection is more than anxious poison experiment, and it is also many to observe natural law.
2, pathological anatomy result: each 6 of the female toms of stochastic sampling carry out pathological anatomy, and the result is as follows
Ridge colic lymph nodes thymus before grouping number of animals (only) the conscience lung spleen kidney marrowbrain muscle rib ilium
A 6------------the no abnormality seen pathological phenomenon-----------------------
B 6------------the no abnormality seen pathological phenomenon-----------------------
C 6------------the no abnormality seen pathological phenomenon-----------------------
D 6------------the no abnormality seen pathological phenomenon-----------------------
E 6------------the no abnormality seen pathological phenomenon-----------------------
Illustrate: above animal data is the observations in our research process, not carrying out acute toxicological experiment or chronic toxicological experiment requirement in strict accordance with pharmacopeia goes to do, to rat dispensing dosage overgauge requirement of experiment, the breeding observing time is also longer than the standard-required time, and the quantity of Mus is less than standard-required.
Under the clinical trial for example:
Case one:
The women, 45 years old, behind the carcinoma simplex radical correction of diagnosis mammary gland right side, recurrence and lung, lymph node, rib metastatic carcinoma after 3 years, the NVB+DDP chemotherapy is invalid, and appearance is coughed, dyspnea, hydrothorax, left costalgia, last oxygen, antitussive, pain management effect are bad, symptom day by day increases the weight of, and the state of an illness is critically ill.CNT 20mg/ days+the DDP+5-Fu combined chemotherapy.Cough after 24 hours, dyspnea, pain symptom are alleviated, and stop to go up oxygen after 3 days, the walking of can leaving the bed after 10.The check lung CT shows after January: lung metastasis, lymph node, hydrothorax disappear.This shows that the effect that adds with the CNT treatment is fabulous.
Case two:
The male, 68 years old, be diagnosed as carcinoma of prostate lung, bone transfer, do not carry out any treatment, the cough dyspnea, give above oxygen, 3 lumbar vertebras, the 6th, 7 right costalgias unbearably, take bucinnazine, morphine slow releasing tablet poor effect, can not stand up and walking, night can not be fallen asleep, give pure CNT 20mg through intravenous injection once, pain is obviously alleviated after 8 hours, the cough symptom is clearly better, can walking freely after 24 hours, check after 3 months, pulmonary's metastasis is obviously dwindled, 3 kilograms of weight increase, and can be engaged in general housework.As seen CNT not only has therapeutical effect, also has pain-relieving functions.
Case three:
Wu women, 54 years old, because of colporrhagia, lower abdominal pain was gone to a doctor in three months, be diagnosed as cervical cancer, sick inspection: low differentiated squamous-cell carcinomas, abdominal CT: pelvic cavity is found 6 * 7cm size lump and several 3 * 3,3 * 4cm lump gynecological consultation of doctors suggestion: because of the extensive adhesion formation of tumor and pelvic cavity frozen pelvis, lose the surgical engine meeting.Award systemic chemotherapy earlier, 0.5 * 5 day+CF0.1 of 5-Fu * 5 days DDP30mg * 3 day ADM30mg * 2 days treatment one-period.The state of an illness does not have improvement, still colporrhagia, and lower abdominal pain, check abdominal CT tumor does not have and dwindles.Use CNT 20mg absorption DDP30mg intravenous injection * 0.5 * 5 day+CF0.1 of 3 days absorption 5-Fu * 5 days instead, absorption ADM30mg * 2 day are simultaneously in absorption guide material-hemoporphyrin treatment one-period.Stomachache disappears after 20 hours, and colporrhagia reduces; Colporrhagia stops after 3 days, checks abdominal CT after 15 days: 1 of the visible 1 * 1cm lump of pelvic cavity.Stable disease is not carried out any other treatment at present.The CNT infusion solution that the absorption medicine is described has better therapeutic effect.
Case four
Chen male 65 years old goes to a doctor because of the cough chest pain bimester, and rabat, lung CT are shown the right upper lung occupying lesion, and the pulmonary carcinoma probability is big.In April, 2004 row excision art, phymatosis inspection: poorly differentiated adenocarcinoma, the capable adjuvant chemotherapy DDP+NVB of postoperative treats and finds left axillary gland enlargement 3 * 2cm size in June, 2004 one-period, lung CT: a plurality of metastasis of lung and hilar lymph node enlargement proof NP scheme loses curative effect, adds this moment with the CNT 30mg venoclysis that is coated with DDP * 3 days.The back axillary gland disappearance of one week, check lung CT after 15 days: metastasis dwindles 75% in the lung, and hilar lymph node disappears.And no tangible digestive tract reaction in therapeutic process.As seen the CNT therapeutic effect that passes through drug coated is fabulous, and does not have tangible toxicity.
Case five
Male Liu 53 years old is uncomfortable in chest repeatedly, cardiopalmus increased the weight of to be admitted to hospital in a week in 4 years.The admission examination blood fat increases, electrocardiogram: ST-T moves down, and the T ripple is inverted, and the heart B ultrasonic: arterial elasticity goes down, and left locular wall is paradoxical movement.Be diagnosed as coronary heart disease, angina pectoris gives coronary dilating, anticoagulant, to protect myocardium microcirculation improvement therapeutic effect not obvious.Venoclysis CNT 30mg, uncomfortable in chest after 17 hours, cardiopalmus remission, week back check electrocardiogram, the heart B ultrasonic is normal.Stable disease, normally work every day over one year.
Case six
Abscess 5 years appears in the left back of what certain male 51 years old portion repeatedly, and repeatedly operation and anti-infective therapy are still invalid, the pure CNT 30mg of venoclysis, and left two days later back abscess disappears, and sleep is stood up freely, does not existingly recur over 5 months.
The specific embodiment
Following embodiment is only in order to further specify the present invention, rather than limits the scope of the invention.
Embodiment 1
Prepare pure CNT microgranule injection:
Get 0.5 kilogram of CNT, diameter 2nm wherein, nano-sized carbon pipe range 100 μ m, aperture 1nm.The input air cutting machine cuts then, and controlling main particle size distribution is diameter 2nm, pipe range 3 μ m-1nm, and aperture 1nm accounts for 99%.Use the CNT micropowder and make solute, make outstanding solvent, prepare 1% CNT 5000ml, under strong magnetic agitation, be distributed into the infusion solution of every bottle of 1ml or 2ml with dimethyl sulfoxide (DMSO).
Embodiment 2
Preparation activation CNT microgranule injection:
CNT 100g adds-10 ℃ of 1% thionyl chloride/chloroformic solution 300ml, and stirring and adsorbing reaction 2 hours with 20,000 commentaries on classics high speed centrifugations, is got precipitation; Then the precipitate container is put into pressure vessel, be heated to 80 ℃, the venting decompression generates the oxidized form CNT after 5 minutes; And then in pressure vessel, feed activator respectively, to generate several activation CNTs that have the different activities base:
If preparation hydroxylating CNT then fed 90 ℃ of water vapour 2 hours, decompression exhaust generates the hydroxylating CNT then;
If preparation imino group CNT then fed 90 ℃ of ℃ of pure ammonia steam 2 hours, generate the imino group CNT;
If preparation hydroxyl, amino CNT then feed 90 ℃ of 10-40% ammonia-water vapour, generate the CNT that contains hydroxyl, amino simultaneously;
If preparation charcoal-hydrogen CNT is then got CNT 100 grams,
The LiALH that adds ether dissolution
4, be mixed with 1% solution 300ml, stirring and adsorbing 2 hours, centrifuging and taking precipitation; Pressure vessel internal heating to 95 ℃ 5 minutes, the cooling decompression made the CNT that is combined with charcoal-hydrogen and lithium;
With above-mentioned activatory CNT, the input cutter is prepared, control particle diameter 35 μ m-0.5nm, nano-sized carbon pipe range 31 μ m-0.5nm, aperture 31 μ m-0.1nm.Main particle size distribution is diameter 6 μ m-0.5nm, and pipe range 3 μ m-0.5nm apertures 2 μ m-0.1nm account for 99%.CNT diameter 35 μ m-7 μ m, pipe range 4---35 μ m 3--30 μ m granule is no more than 1%.Be distributed into every bottle of infusion solution that contains CNT 10mg or 20mg respectively.
Embodiment 3
The agent of preparation medicament-carried nano carbon tube needle:
1. adsorb the anticarcinogen infusion solution: in no drug antagonism situation, can choose medicine arbitrarily adsorbs, for example, cisplatin 6g, 5-FU 0.4g, or get cisplatin 6g, 6-MP 0.8g and be dissolved in the 100ml water, add 10g 120 order CNTs or activatory hydroxyl-amino CNT, stir down fully absorption; High speed centrifugation is got precipitation, acetone dehydration, centrifuging and taking precipitation, drying; Use 0.1% chitosan aqueous solution dipper precipitation 5 minutes then, with acetone dehydration, drying; Pulverize with the air pulverizer, the control particle diameter is 35 μ m-2nm, and main particle size distribution is 6 μ m-2nm, and wherein 3 μ m-2nm account for 99%, 6 μ m-3 μ m granule and are no more than 1%; To immerse 20% ferrous porphyrin acetone soln 10 minutes through pulverizing the medicament-carried nano carbon pipe microgranule that exposes the section that makes new advances, high speed centrifugation is got precipitation, drying; Be distributed into every bottle of infusion solution that contains suitable activation CNT 10mg or 20mg respectively.
2. adsorb anticoagulant, anticholesteremic agent infusion solution: for example, get r-tPA 100mg or cholesterol acetyl transferase 80mg or nicotinic acid 220mg, it is hydroxyl CNT microgranule 1g below the 0.5 μ m that adding is ground into granularity through the air pulverizer, carry out abundant water absorption, high speed centrifugation is got precipitation, the acetone dehydration, drying; Flooded 5 minutes with 0.1% chitosan aqueous solution then, high speed centrifugation is got precipitation, and with the acetone dehydration, drying is distributed into 10mg/ bottle infusion solution, is used for the treatment of the heart, cerebral embolism thromboembolism treatment and treatment sclerosis of blood vessels, hypertension etc.
3. adsorb the antibiotic medicine infusion solution: for example, get isoniazid 500mg or rifampicin 200mg, being ground into granularity with the air pulverizer is following hydroxyl, amino CNT microgranule 1g of 0.7 μ m, water absorption 20 minutes, high speed centrifugation is got precipitation, acetone dehydration, drying; Flooded 5 minutes with 0.1% chitosan aqueous solution then, high speed centrifugation is got precipitation, with acetone dehydration, drying, is distributed into the infusion solution of 20mg/ bottle, is used for the treatment of intractable bone tuberculosis, phthisis miliaris etc.
4. adsorb the antiviral drugs infusion solution: for example, get IFN-γ 100mg, it is the following hydroxyl-amino CNT microgranule 1g of 0.3 μ m that adding air pulverizer is ground into granularity, carries out abundant water absorption; High speed centrifugation is got precipitation, and precipitate is carried out acetone dehydration, cold drying; Dipping is 5 minutes in silk amino acid, Idiotype virus incomplete antibody directed agents, and high speed centrifugation is got precipitation, the acetone dehydration, and cold drying is distributed into the infusion solution of 10mg/ bottle or 20mg/ bottle; The difficult therapeutic disease that is used for the treatment of various viral infections as Epstein-Barr virus personality Lin Bali syndrome, viral brain etc., also can be used for the treatment of HIV.
The CNT of present embodiment can also be made according to the molecular size of anticarcinogen, anticoagulant medicine, cholesterol reducing, antibiotic, antiviral drugs and growth-factor medication and form can special dress (or claim bag by) these medicines; Then respectively anticarcinogen, anticoagulant medicine, pravastatin, antibiotic, antiviral drugs and somatomedin are packed in this specific nano carbon pipe space into the medication infusion agent of making different purposes.
Claims (10)
1. CNT infusion solution is characterized in that the pure CNT microgranule injection that comprises that (1) intravenous transfusion is used, (2) activation CNT microgranule injection, and (3) are adsorbed with the CNT injection and the agent of medicament-carried nano carbon tube needle of catalyst.
2. CNT infusion solution as claimed in claim 1 is characterized in that wherein CNT injection that is adsorbed with catalyst and the agent of medicament-carried nano carbon tube needle, comprises (1) bag quilt or absorption cancer therapy drug injection; (2) bag quilt or absorption anticoagulant and pravastatin composition injection; (3) bag quilt or absorption antibiolics composition injection; (4) bag quilt or absorption antiviral agents composition injection; (5) bag quilt or absorption growth-factor medication injection.
3. CNT infusion solution as claimed in claim 1 or 2, it is characterized in that CNT wherein meets following prescription: content of beary metal≤0.1-10ppm, other soluble metal ion≤0.1-10ppm, ash＜2%, 0.15% serge blue adsorptive value＞6-30, contained CNT diameter 35 μ m-0.5nm in this CNT infusion solution, nano-sized carbon pipe range 31 μ m-0.5nm, aperture 31 μ m-0.1nm.Main particle size distribution is diameter 6 μ m-0.5nm, and pipe range 3 μ m-0.5nm apertures 2 μ m-0.1nm account for 99%, diameter 35 μ m-7 μ m, and pipe range 4---35 μ m 3--30 μ m granule is no more than 1%.
4. as the preparation method of any described CNT infusion solution of claim 1-3, it is characterized in that this method may further comprise the steps:
(1) is prepared into CNT (CNT diameter 35 μ m-2nm, nano-sized carbon pipe range 31 μ m-2nm, aperture 31 μ m-1nm.)；
(2) make the CNT diameter 35 μ m-0.5nm of required particle diameter with cutter, nano-sized carbon pipe range 31 μ m-0.5nm, aperture 31 μ m-0.1nm.
(3) make this CNT coarse granule adsorption activation agent so that CNT activates, described activator concentration is 0.01-10%, is heated to 70-190 ℃ in high-pressure bottle, and the response time is 5-20 minute, generates oxidized form or reduced form activation CNT; Residual gas is got rid of in the cooling decompression, feeds 60-100 ℃ of steam, ammonia again under pressure respectively, generates the activatory CNT that contains charcoal-hydroxyl, charcoal-imino group or charcoal-hydrogen;
(4) carrying out the CNT medicine carrying handles;
(5) make this CNT microgranule dipping absorption bio-guide agent, carry out short time, cold drying fast then, the medication infusion agent of making different purposes then.
The preparation method of 5 CNT infusion solutions as claimed in claim 4 is characterized in that: medicine carrying is handled can select following method for use: molecular size and the form according to anticarcinogen, anticoagulant medicine, cholesterol reducing, antibiotic, antiviral drugs and growth-factor medication made special packing into the CNT of (or claiming the bag quilt) these medicines; Respectively anticarcinogen, anticoagulant medicine, pravastatin, antibiotic, antiviral drugs and somatomedin are packed into then in this specific nano carbon pipe space, make the medicine injection of different purposes.
The preparation method of 6 CNT infusion solutions as claimed in claim 4 is characterized in that the related drugs of selecting comprises: 1. traditional cancer therapy drug such as 5-FU, CTX, MTX, Ara-C/A, 6-MP, antitumor antibiotic class, suitable/carboplatin, arsenical class, paclitaxel; 2. immune activation, regulate cytokine class such as IL-2,4,6, GM, G-CSF, γ-IFN, TNF, FCF-B, VECF, 4-IBB/4-IBBL, B7-1B7-2, toadpoison albumen, specificity incomplete antibody: 3. catalyst class such as main metallo-organic compound benzyl/butyl lithium, the agent of transition metal cuprammonium, platinum, palladium agent, selenium, germanium compound, these conjugates have catalysis and kill the tumor dual function; 4. adsorb biological enzyme such as redox enzymes, transaminase's class, hydrolase, isomerase.
The preparation method of 7 CNT infusion solutions as claimed in claim 4, it is characterized in that: described bio-guide agent comprises ferrous porphyrin, or thymus pyrimidine, bird pyrimidine, uracil, the fast mountain range of thymus, guanine and derivant one big class material thereof, as 5-fluorouracil, hydrogen deuterium thymus pyrimidine, methotrexate, the tumor cell adhesion factor such as VCAM-1 and the growth of tumour cell factor such as VEGF.
The application of 8 CNT infusion solutions as claimed in claim 1 in preparation treatment cancer drug.
9 CNT infusion solutions as claimed in claim 1 are in the application of preparation treatment cardiovascular and cerebrovascular disease
10 CNT infusion solutions as claimed in claim 1 are treated in the application aspect the infection in preparation.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100468215A CN100551443C (en) | 2004-09-22 | 2004-09-22 | A kind of preparation method of CNT infusion solution |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100468215A CN100551443C (en) | 2004-09-22 | 2004-09-22 | A kind of preparation method of CNT infusion solution |
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| Publication Number | Publication Date |
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| CN1751741A true CN1751741A (en) | 2006-03-29 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008063157A3 (en) * | 2006-10-25 | 2009-03-19 | Us Gov Health & Human Serv | A nanoparticle-based anticoagulant |
| CN101209349B (en) * | 2006-12-27 | 2010-09-01 | 中国科学院大连化学物理研究所 | Application of carbon nano-tube as carrier in transferring anti-cancer medicine |
| CN101433720B (en) * | 2007-11-16 | 2011-08-31 | 中国科学院大连化学物理研究所 | Tumor-targeted carbon nano-tube medicament carrier and preparation thereof |
| CN102885778A (en) * | 2012-10-29 | 2013-01-23 | 中国人民解放军军事医学科学院毒物药物研究所 | Active carbon paclitaxel nano-drug delivery system, and preparation method and application thereof |
| CN103083661A (en) * | 2008-03-20 | 2013-05-08 | 中国医学科学院基础医学研究所 | Application of carbon nanotube in preparation of immunostimulant of anti-tumor immunotherapy medicine |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120007139A (en) * | 2010-07-14 | 2012-01-20 | 주식회사 파미니티 | Composition for preventing and treating brain diseases comprising carbon nanotube as an active ingredient |
-
2004
- 2004-09-22 CN CNB2004100468215A patent/CN100551443C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008063157A3 (en) * | 2006-10-25 | 2009-03-19 | Us Gov Health & Human Serv | A nanoparticle-based anticoagulant |
| CN101209349B (en) * | 2006-12-27 | 2010-09-01 | 中国科学院大连化学物理研究所 | Application of carbon nano-tube as carrier in transferring anti-cancer medicine |
| CN101433720B (en) * | 2007-11-16 | 2011-08-31 | 中国科学院大连化学物理研究所 | Tumor-targeted carbon nano-tube medicament carrier and preparation thereof |
| CN103083661A (en) * | 2008-03-20 | 2013-05-08 | 中国医学科学院基础医学研究所 | Application of carbon nanotube in preparation of immunostimulant of anti-tumor immunotherapy medicine |
| CN102885778A (en) * | 2012-10-29 | 2013-01-23 | 中国人民解放军军事医学科学院毒物药物研究所 | Active carbon paclitaxel nano-drug delivery system, and preparation method and application thereof |
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