CN1210023C - Carboplatin precursor liposome injection and preparing process thereof - Google Patents
Carboplatin precursor liposome injection and preparing process thereof Download PDFInfo
- Publication number
- CN1210023C CN1210023C CN 02100554 CN02100554A CN1210023C CN 1210023 C CN1210023 C CN 1210023C CN 02100554 CN02100554 CN 02100554 CN 02100554 A CN02100554 A CN 02100554A CN 1210023 C CN1210023 C CN 1210023C
- Authority
- CN
- China
- Prior art keywords
- carboplatin
- liposome injection
- precursor liposome
- weight
- organic solvent
- 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
Abstract
The present invention relates to a Carboplatin precursor liposome injection and a preparation method thereof, which aims to provide a solid Carboplatin precursor liposome injection with small toxic and side effect. The Carboplatin precursor liposome injection of the present invention is prepared from the following components: 4000 to 12000 parts by weight of Carboplatin, 500 to 1000 parts by weight of phospholipid, 50 to 100 parts by weight of cholesterin, 9000 parts by weight of sodium chloride, 100 to 1000 parts by weight of lyophilized protective agent, 500 to 700 parts by weight of organic solvent and 1000 parts by weight of distilled water. The method for producing the Carboplatin precursor liposome injection comprises the following steps that 1) the raw materials of the weight and the parts by volume are prepared; 2) the Carboplatin is dissolved in the distilled water to obtain a Carboplatin water solution isotonic with blood plasma by sodium chloride addition; 3) the phospholipid and the cholesterin are dissolved by the organic solvent and injected into the Carboplatin water solution at high speed; 4) the organic solvent is volatilized and cleanly removed; 5) the lyophilized protective agent is added and stirred; 6) the powdery solid Carboplatin precursor liposome injection is obtained by vacuum lyophilization.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation and manufacture method thereof, particularly relate to the novel form and the manufacture method thereof of cancer therapy drug carboplatin.
Background technology
The number of the infected of the annual malignant tumor in the whole world is about 1,000 ten thousand people, dead 7,000,000 people at present.According to the report of The World Health Organization (WHO), malignant tumor has become one of human underlying cause of death, occupies infectious disease and cardiovascular and cerebrovascular disease and is listed as the 3rd of the global disease cause of the death afterwards.In China, about 1,600,000 people of annual malignant tumor new cases, dead 1,300,000 people, existing disease patient more than 400 ten thousand people, the preventing and controlling of malignancy disease are shouldered heavy responsibilities.
Up to now, the effective way of treatment cancer is exactly that anticarcinogen is in conjunction with chemotherapy except operative treatment.Carboplatin is a kind of traditional anticarcinogen evident in efficacy, and the molecular formula of anticarcinogen carboplatin is a cis-1,1-cyclobutane dicarboxylic acid diamino platinum, and soluble in water for white powder or crystalline powder, dissolubility is 10mg/ml in the water, to photaesthesia, easily decomposes.The mechanism of action is the synthetic growth that suppresses tumor cell by inhibition tumor cell DNA (DNA (deoxyribonucleic acid)).
But in actual applications, when a kind of cancer is effectively treated, carboplatin and product thereof also can not be ignored grievous injuries that normal structure caused such as blood of human body, liver and kidneys, this has not only brought difficulty to treatment for cancer, has also caused serious loss and financial burden to patient.Therefore, for effectively treating cancer, improve the anticarcinogen curative effect, reduce the anticarcinogen toxic and side effects, the anticarcinogen new varieties of developing high-efficiency low-toxicity are imperative.
Liposome can improve the Drug therapy index as the anticarcinogen carrier, reduces anticarcinogen toxicity and minimizing anticancer durg side effect and reduces dosage.Liposome is fit to vivo degradation, and avirulence and non-immunogenicity, the targeting of liposome and long-acting more make liposome gain great popularity in medical science and field of biology.
Liposome commonly used is liquid condition, liposome exists many problems under liquid condition, as the oxidation under liquid condition of seepage, aggregation of particles and the phospholipid of medicine, hydrolysis etc., these have also influenced the industrialized great production of liposome, have more influenced liposome application clinically.
For solving the instability problem of liquid type liposome, this patent has been invented a kind of carboplatin precursor liposome injection stable, solid type.
Summary of the invention
The purpose of this invention is to provide the lower solid type carboplatin precursor liposome injection of a kind of toxic and side effects.
Carboplatin precursor liposome injection of the present invention is grouped into by the one-tenth of following ratio of weight and number:
Carboplatin 4000-12000
Cholesterol 50-100
Sodium chloride 9000
Freeze drying protectant 100-1000
Wherein, the medicine that preferably is grouped into by the one-tenth of following ratio of weight and number:
Carboplatin 7500-8500
Phospholipid 750-900
Cholesterol 70-90
Sodium chloride 9000
Freeze drying protectant 400-600
Described freeze drying protectant is selected from glycine, sorbose, sorbitol, glucose, lactose, glucose or their mixture.
Another object of the present invention provides a kind of method of producing carboplatin precursor liposome injection.
A kind of method of producing carboplatin precursor liposome injection may further comprise the steps:
1) purchases the raw material of following weight and volume parts ratio
Carboplatin 4000-12000 milligram
Cholesterol 50-100 milligram
9000 milligrams in sodium chloride
Freeze drying protectant 100-1000 milligram
Organic solvent 500-700 milliliter
1000 milliliters of distilled water
2) under 10 ℃-15 ℃ condition, carboplatin is dissolved in the distilled water, adds sodium chloride, obtain and the isoosmotic carboplatin solution of blood plasma;
3), and be injected in the above-mentioned carboplatin aqueous solution at a high speed with phospholipid and cholesterol organic solvent dissolution;
4) volatilization Ex-all organic solvent;
5) inject the freeze drying protectant that is dissolved in distilled water, stirred 30-50 minute;
6) vacuum lyophilization obtains pulverous solid carboplatin precursor liposome injection.
The preferred glycine of described freeze drying protectant, sorbose, sorbitol, glucose, lactose, glucose or their mixture.The preferred chloroform of described organic solvent, ether, ethanol or any two kinds mixture.
Described carboplatin is dissolved in the distilled water, add sodium chloride and adjust solution and blood plasma etc. and ooze, the organic solvent of phospholipid and cholesterol is injected the carboplatin sodium-chloride water solution at a high speed, in the dissolved process of injection, should continue to stir always, and keep solution temperature to maintain 10 ℃-15 ℃.
In said process, described volatilization Ex-all organic solvent generally adopts the method for spending the night that stirs.
Described vacuum lyophilization is at-50 ℃～-60 ℃, carries out under 0.5～0.1mPa condition.
The solid carboplatin precursor liposome injection that obtains is Powdered for white, loose, good fluidity.Weigh, be sub-packed in the 5ml ampoule, towards nitrogen, seal, sterilization can be dispatched from the factory.
Face with preceding carboplatin precursor liposome in the ampoule is dissolved with water for injection, then be dispersed into uniform carboplatin liposome aqueous solution immediately, its effective active composition is a carboplatin liposome wherein, and concrete consumption is decided according to doctor's advice.Scanning electron microscope records the mean diameter of liposome after the carboplatin precursor liposome hydration of the present invention less than 1 μ m, and 75% particle diameter is between 200-600 μ m.
The external preparation testing conditions of carboplatin is high performance liquid chromatography (HPLC) internal standard method in the carboplatin precursor liposome injection.Chromatographic condition is: 0DS-C
18Post (250 * 4.6mm, 10 μ m) detects wavelength: 229nm, mobile phase: 5% methanol aqueous solution, flow velocity: 1.0ml/min, column temperature: room temperature, interior mark: uridnine.
The present invention has also detected carboplatin precursor liposome injection distribution situation in vivo, because carboplatin precursor liposome injection distributes extensively in vivo, carboplatin content is low in the bio-tissue, is detected by highly sensitive atomic absorption spectrophotometry so the organism inner tissue of carboplatin distributes.Testing result shows that the carboplatin in the carboplatin precursor liposome injection is compared with the carboplatin in the carboplatin water formulation, and organism inner tissue characteristic distributions has remarkable difference, shows the variation of different tissues Chinese medicine concentration.After carboplatin is made into liposome, the drug level of carboplatin in lung, spleen, hepatic tissue improved, and the drug level in kidney and blood reduce.Carboplatin is at the clinical anticarcinogen that is often used as treatment pulmonary carcinoma, and the main toxicity of carboplatin is the inhibitory action to bone marrow, make leukocyte, thrombocytopenia, the carboplatin liposome has improved the concentration of carboplatin in the target organ lung tissue, reduced the concentration of carboplatin in blood and kidney, finally reach reduction toxicity, improved the effect of therapeutic effect.
The irritation test of carboplatin precursor liposome injection and hemolytic result of the test show that carboplatin precursor liposome injection is safe and reliable, nonirritant, and do not have hemolytic reaction.
Because after the carboplatin precursor liposome injection hydration of the present invention, the particle diameter of carboplatin liposome is little, lung, spleen tissue are had natural targeting, and concentration reduces relatively in kidney, therefore improved the accumulation of anticarcinogen carboplatin in lung tissue, reduced the toxicity of carboplatin kidney.Therefore carboplatin precursor liposome injection of the present invention is a kind of low toxicity, cancer therapy drug novel form efficiently.Simultaneously,, face with preceding adding disperse medium and disperse to form the solution-type liposome, not only made things convenient for storage, transportation, and fundamentally solved the instability problem of liquid type liposome because carboplatin precursor liposome is stored with solid form.
The method technology that the present invention produces carboplatin precursor liposome injection is simple, does not need special equipment, thereby production cost is low, is suitable for large-scale industrial production.
The present invention will be further described below in conjunction with drawings and the specific embodiments.
Description of drawings
Fig. 1 is carboplatin concentration-time changing curve figure in the lung
Fig. 2 is carboplatin concentration-time changing curve figure in the spleen
Fig. 3 is carboplatin concentration-time changing curve figure in the liver
Fig. 4 is carboplatin concentration-time changing curve figure in the kidney
Fig. 5 is carboplatin concentration-time changing curve figure in the blood
The specific embodiment
The production carboplatin precursor liposome injection may further comprise the steps:
1, purchases the raw material of following weight and volume
8000 milligrams of carboplatins
800 milligrams in phospholipid
80 milligrams in cholesterol
9000 milligrams in sodium chloride
500 milligrams of glycines
600 milliliters of chloroforms
1000 milliliters of distilled water
2, the carboplatin aqueous solution 800ml of preparation 8.0mg/ml places the 1000ml large beaker, adds 9.0g sodium chloride and adjusts the carboplatin aqueous solution to oozing with blood plasma etc., and magnetic stirring apparatus 500rpm stirs, and keeps solution temperature to maintain 13 ℃;
3, phospholipid and cholesterol are fully dissolved with chloroform, inject the carboplatin aqueous solution of magnetic agitation at a high speed, can obtain transparent carboplatin liposome solutions with the gradation of 10ml syringe;
4, magnetic agitation is spent the night, and extremely the chloroform with remnants volatilizes;
5, with redistilled water 200ml the freeze drying protectant glycine is dissolved, inject the carboplatin liposome solutions that has made with the 10ml syringe, solution continued magnetic agitation 40 minutes, promptly got the translucent liposome turbid liquor of the milky that contains freeze drying protectant;
6, the carboplatin liposome turbid liquor that will contain freeze drying protectant places the large diameter Flat bottom container of wide-mouth, and-55 ℃, vacuum lyophilization is 24 hours under the 0.3mPa condition, promptly gets Powdered carboplatin precursor liposome injection white, loose, good fluidity.
Embodiment 2, production carboplatin precursor liposome injection
Identical with the step of embodiment 1, the prescription of different is raw material is as follows:
11000 milligrams of carboplatins
00 milligram of phosphatidase 14
90 milligrams in cholesterol
9000 milligrams in sodium chloride
The mixture of sorbic acid and sorbitol (sorbic acid: sorbitol=4: 6) 900 milligrams
600 milliliters of ether
1000 milliliters of distilled water
Embodiment 3, production carboplatin precursor liposome injection
Identical with the step of embodiment 1, the prescription of different is raw material is as follows:
3000 milligrams of carboplatins
950 milligrams in phospholipid
60 milligrams in cholesterol
9000 milligrams in sodium chloride
200 milligrams of glucoses
The mixture of ethanol and ether (ethanol: ether=5: 5) 550 milliliters
1000 milliliters of distilled water
Embodiment 4, carboplatin precursor liposome are to the carboplatin influence of tissue distribution in vivo
Experiment is provided with two groups of carboplatin precursor liposome experimental group and carboplatin aqueous solution matched groups, experimental subject is a mice, carboplatin precursor liposome injection and carboplatin aqueous solution mouse tail vein injection with identical carboplatin active component, respectively the different organs tissue (liver, spleen, lung, kidney) of mice is taken out at different time points, with sensitive, the most advanced aas determination medicament contg situation over time wherein, also monitored the situation of change of mice blood Chinese medicine concentration simultaneously, result such as Fig. 1, Fig. 2, Fig. 3, Fig. 4, shown in Figure 5.
From Fig. 1-5, as can be seen, after carboplatin is made into carboplatin precursor liposome injection, changed carboplatin distribution in vivo, the bioavailability of carboplatin in lung, spleen, liver improved, and reduce in the bioavailability of kidney and blood Chinese medicine.
The irritation test of embodiment 5, carboplatin precursor liposome injection
1, white big ear rabbit rabbit ear edge hypodermic injection
Test method: select 6 of healthy earless disease white big ear rabbits, body weight 2.0-3.0kg divides two groups at random.Administration group ear edge subcutaneous injection carboplatin precursor liposome injection 0.05ml, matched group white big ear rabbit ear edge subcutaneous injection 0.9% normal saline solution.Observed one hour.
Observation index: during injection, the rabbit peace and quiet do not have because of the action of shaking the head due to stimulating, and after the injection, rabbit ear edge is subcutaneous a medicinal liquid bulge, white, and the administration rabbit ear does not have redness, irriate phenomenons such as hyperemia.After one hour, can see that the administration rabbit ear is compared with the matched group rabbit ear, rabbit ear administration topical remedy absorbs good, does not have knot lump or downright bad phenomenon.
Conclusion: carboplatin precursor liposome injection is organized non-stimulated damaging action to the rabbit ear after giving tame rabbit ear edge subcutaneous injection.
2. white big ear rabbit eye dripping method
Test method: select 6 of healthy no ophthalmic white big ear rabbits, body weight 2.0-3.0kg.Drip carboplatin precursor liposome injection 0.2ml in the one-sided eye of rabbit, splash into 0.9% normal saline solution 0.2ml in the offside man lagophthalmos.Observed 30 minutes.
Observation index: before dripping medicine, lagophthalmos is limpid, asecretory foreign body in the eye.One-sided lagophthalmos drips medicine, when the offside lagophthalmos drips normal saline, the rabbit peace and quiet do not have because of the action of shaking the head due to stimulating.After one-sided lagophthalmos drips medicine, observed 30 minutes, compare with the offside lagophthalmos, lagophthalmos anophthalmia excess secretion, redness, abnormal phenomenas such as nictation take place.
Conclusion: carboplatin precursor liposome injection is organized non-stimulated damaging action to lagophthalmos after giving the rabbit eye drip.
3, white mice intravenous injection
Test method: select 10 of healthy Kunming kind white mice, body weight 20.0-25.0g divides two groups at random.One group of 5 mice, tail vein injection 0.2ml carboplatin precursor liposome injection, 5 mices of matched group, tail vein injection is with dosage 0.9% normal saline.
Observation index: in one hour, observe the administration mice and do not have any Deviant Behavior after the administration, the nonirritant reaction, mice is movable and diet is unaffected, and the carboplatin precursor liposome injection of being injected is to the blood vessel nonirritant.
Conclusion: carboplatin precursor liposome injection is organized non-stimulated damaging action to the mice vascular venous after giving mouse tail vein injection.
4, mice by intraperitoneal injection method
Test method: select 10 of healthy Kunming kind white mice, body weight 20.0-25.0g divides two groups at random.One group of 5 mice, lumbar injection 0.3ml carboplatin precursor liposome injection, 5 mices of matched group, lumbar injection is with dosage 0.9% normal saline.
Observation index: in one hour, observe the administration mice and do not have any Deviant Behavior to the administration after the administration, the nonirritant writhing response, mice is movable and diet is unaffected, the carboplatin precursor liposome injection nonirritant of being injected.
Conclusion: carboplatin precursor liposome injection is organized non-stimulated damaging action to mouse peritoneal after injecting to mouse peritoneal.
In above-mentioned each experiment, experimental animal there is no stimulates the sexual abnormality reaction.Result of the test shows that carboplatin precursor liposome injection is safe and reliable.
The haemolysis of embodiment 6, carboplatin precursor liposome injection and hemagglutination test (HA test)
Test method: get one of rabbit, heart extracting blood 10ml, Glass rod stirs except that Fibrinogen, makes into defibrinated blood, adds the 100ml normal saline and shakes up, centrifugal, remove supernatant, sedimentary erythrocyte reuse normal saline washs 4 times to the apparent redness of supernatant, with gained erythrocyte 3ml, add normal saline 150ml, be prepared into 2% red blood cell suspension and substitute.
Get 7 in test tube, indicate the according to the form below parallelism 1-7 number, add 2% red blood cell suspension and normal saline successively, put 37 ℃ of calorstats interior 30 minutes, add not commensurability carboplatin precursor liposome injection then, the negative control tube of the 6th pipe, the positive haemolysis sample of the 7th pipe.After shaking up, put in 37 ℃ of calorstats and observed once every 20 minutes approximately, observe to 6 hours, the 1-5 pipe is compared with 6 pipes, and the clarity of supernatant is identical, transparent red normal complexion rufous flocky precipitate all do not occur, 7 pipe hemocyte complete hemolysis, the 1-5 pipe is compared with 7 pipes, and phenomenon is opposite fully.Result of the test sees Table 1:
Table 1 carboplatin lipid freeze-dry powder injection haemolysis, agglutination test
Test tube numbers 1234567
Be subjected to reagent liquid (ml) 0.1 0.2 0.3 0.4 0.5 00
Normal saline (ml) 2.4 2.3 2.2 2.1 2.0 2.5 0
Deionized water (ml) 000000 2.5
2% red blood cell suspension (ml) 2.5 2.5 2.5 2.5 2.5 2.5 2.5
The result judges: the 1-5 pipe is in 2-6 hour, and its supernatant is compared basic identical with 6 pipes, the brown flocky precipitate of transparent red normal complexion all do not occur.The 1-5 pipe was compared with 7 pipes in 2-6 hour, and then phenomenon is opposite fully, and whole red haemolysises has appearred in 7 pipes.
Conclusion: carboplatin precursor liposome injection does not have blood coagulation, no erythroagglutination, and injection is safe and reliable, can supply the clinical injection medication.
Claims (9)
1, carboplatin precursor liposome injection is grouped into by the one-tenth of following ratio of weight and number:
Carboplatin 4000-12000
Phosphatidase 15 00-1000
Cholesterol 50-100
Sodium chloride 9000
Freeze drying protectant 100-1000
2, carboplatin precursor liposome injection according to claim 1 is characterized in that: described injection is grouped into by the one-tenth of following ratio of weight and number:
Carboplatin 7500-8500
Phospholipid 750-900
Cholesterol 70-90
Sodium chloride 9000
Freeze drying protectant 400-600
3, carboplatin precursor liposome injection according to claim 1 and 2 is characterized in that: described freeze drying protectant is glycine, sorbose, sorbitol, glucose, lactose, glucose or their mixture.
4, a kind of method of producing carboplatin precursor liposome injection may further comprise the steps:
1) purchases the raw material of following weight and volume parts ratio
Carboplatin 4000-12000 milligram
Phosphatidase 15 00-1000 milligram
Cholesterol 50-100 milligram
9000 milligrams in sodium chloride
Freeze drying protectant 100-1000 milligram
Organic solvent 500-700 milliliter
1000 milliliters of distilled water
2) under 10 ℃-15 ℃ condition, carboplatin is dissolved in the distilled water, adds sodium chloride, obtain and the isoosmotic carboplatin solution of blood plasma;
3), and be injected in the above-mentioned carboplatin aqueous solution at a high speed with phospholipid and cholesterol organic solvent dissolution;
4) volatilization Ex-all organic solvent;
5) inject the freeze drying protectant that is dissolved in distilled water, stirred 30-50 minute;
6) vacuum lyophilization obtains pulverous solid carboplatin precursor liposome injection.
5, a kind of method of producing carboplatin precursor liposome injection according to claim 4 is characterized in that: described freeze drying protectant is glycine, sorbose, sorbitol, glucose, lactose, glucose or their mixture.
6, a kind of method of producing carboplatin precursor liposome injection according to claim 4 is characterized in that: described organic solvent is chloroform, ether, ethanol or any two kinds mixture.
7, according to claim 4 or 5 or 6 described a kind of methods of producing carboplatin precursor liposome injection, it is characterized in that: described carboplatin is dissolved in the distilled water, add sodium chloride, and inject with the phospholipid of organic solvent dissolution and the process of cholesterol at a high speed, stir always.
8, according to claim 4 or 5 or 6 described a kind of methods of producing carboplatin precursor liposome injection, it is characterized in that: described volatilization Ex-all organic solvent adopts the method for spending the night that stirs.
9, according to claim 4 or 5 or 6 described a kind of methods of producing carboplatin precursor liposome injection, it is characterized in that: described vacuum lyophilization is at-50 ℃～-60 ℃, carries out under 0.5～0.1mPa condition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02100554 CN1210023C (en) | 2002-01-31 | 2002-01-31 | Carboplatin precursor liposome injection and preparing process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02100554 CN1210023C (en) | 2002-01-31 | 2002-01-31 | Carboplatin precursor liposome injection and preparing process thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1435167A CN1435167A (en) | 2003-08-13 |
| CN1210023C true CN1210023C (en) | 2005-07-13 |
Family
ID=27627147
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02100554 Expired - Fee Related CN1210023C (en) | 2002-01-31 | 2002-01-31 | Carboplatin precursor liposome injection and preparing process thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1210023C (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525931A (en) * | 2012-03-07 | 2012-07-04 | 中国药科大学 | Pentaplatin liposome preparation and preparation method thereof |
| AU2014204733B2 (en) * | 2013-01-14 | 2016-09-08 | Clinics Operations Limited | Cancer drug and uses |
| CN104473874B (en) * | 2014-11-21 | 2017-09-12 | 辽宁大学 | A kind of preparation method of cordycepin proliposome |
| CN107260674A (en) * | 2016-04-06 | 2017-10-20 | 广州英特基因科技有限公司 | Carboplatin aggregation and preparation method thereof |
| CN105748458B (en) * | 2016-04-12 | 2018-06-19 | 张佃梅 | A kind of freeze-drying composition for injection for treating advanced ovarian cancer and preparation method thereof |
-
2002
- 2002-01-31 CN CN 02100554 patent/CN1210023C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1435167A (en) | 2003-08-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1246039C (en) | Moxilfloxacin formulation containing common salt | |
| CN1709248A (en) | Lansoprazole lyophilized powder injection and its preparing method | |
| CN1210023C (en) | Carboplatin precursor liposome injection and preparing process thereof | |
| CN101032512A (en) | Medicine composition for expanding blood volume and the preparing method thereof | |
| CN1931874A (en) | Prepn process, medicine prepn and medicinal use of ginseng glycopeptide | |
| CN1429558A (en) | Mannosan peptide injection and its preparation and use method | |
| CN101049337A (en) | Medication for curing furuncle, sore, and carbuncle, and preparation method | |
| CN1864666A (en) | Lyophilized powder injection of levofloxacin mesylate and preparation method thereof | |
| CN100336507C (en) | Nimoldipine new nano liposome, its precursor freeze dryed matter and its preparing method | |
| CN1274366C (en) | Medicinal nano carbon microsphere and its application for preparing medicine to treat cancer | |
| CN1939328A (en) | Puerarin injection | |
| CN1772020A (en) | Freeze dried pubescent holly powder for injection and its prepn | |
| CN1748758A (en) | Dragon's blood gel preparation and its preparing method | |
| CN1780824A (en) | Compositions and methods for preventing and treating endotoxin-related diseases and conditions. | |
| CN1107501C (en) | Albendazole emulsion | |
| CN1176655C (en) | Refapentine or rifampin liposome perfusate, injection and preparation process thereof | |
| CN1194696C (en) | Medicinal composition for injection, preparation containing said medicinal composition and its preparing process | |
| CN1278676C (en) | Curcumin injection and method for preparing the same | |
| CN1555805A (en) | Ortho diphenylhydratoin freeze dried powder for injection and its preparation method | |
| CN1475266A (en) | Production method of injection agent used for treating cardio and cerebro vascular diseases and its product | |
| CN1247196C (en) | Solid prepn. of sodium vitamin C for injection and its prepn. method | |
| CN1327047A (en) | Method for cultivating variotin pecilocin with silkworm and medicinal use | |
| CN1211088C (en) | Application of emodin analog EMD-31 for curing tumor | |
| CN1224386C (en) | Fumagucin injection against cancers and its preparing method | |
| CN1768762A (en) | Novel drug administering route of pantocrine injection, its preparation process and novel indications |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| 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 | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |