CN102302477A - Cinobufagin dry power inhaler and preparation method and application thereof - Google Patents
Cinobufagin dry power inhaler and preparation method and application thereof Download PDFInfo
- Publication number
- CN102302477A CN102302477A CN201110147795A CN201110147795A CN102302477A CN 102302477 A CN102302477 A CN 102302477A CN 201110147795 A CN201110147795 A CN 201110147795A CN 201110147795 A CN201110147795 A CN 201110147795A CN 102302477 A CN102302477 A CN 102302477A
- Authority
- CN
- China
- Prior art keywords
- cinobufagin
- lactose
- powder
- adjuvant
- formoterol fumarate
- 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.)
- Granted
Links
Abstract
The invention relates to a cinobufagin dry power inhaler, in particular to a dry power inhaler made of cinobufagin, a preparation method of the dry power inhaler and application of the dry power inhaler in preparation of drugs for treating tumors of lung. The cinobufagin dry power inhaler is characterized by consisting of the cinobufagin and medically acceptable auxiliary materials, and the mass ratio of the cinobufagin to the medically acceptable auxiliary materials is 1: 0.03 - 1:110. The cinobufagin is prepared to be the dry powder inhaler, therefore, the cinobufagin can be directly acted on pulmonary lesions, the happening of adverse actions is reduced, the bioavailability of the drug is enhanced, the defects of oral formulation including slow effect, liver first-pass effect to liver, low bioavailability and the like are overcome, and synchronously the problems of injection including inconvenience for use, bad compliance of patients and the like are also solved.
Description
Technical field:
The present invention relates to Foradil Aerolizer formoterol fumarate, specifically the method for preparing of the Foradil Aerolizer formoterol fumarate processed of cinobufagin, said Foradil Aerolizer formoterol fumarate and the application in preparation treatment lung tumors medicine.
Background technology:
Cinobufagin is the main effective ingredient in the Venenum Bufonis, belongs to the cardiac glycoside material, is liposoluble substance, and molecular formula is: C
26H
34O
6, have antitumor, pharmacological actions such as analgesia heart tonifying, antiinflammatory and enhance immunity.The oral formulations that contains cinobufagin at present has been applied to clinical, hepatocarcinoma, pulmonary carcinoma, gastric cancer etc. is had curative effect preferably, and chemotherapy and radiation is had synergism.But oral formulations need pass through the first pass effect of liver, and onset is slow, and the preparation bioavailability is lower.Though the antitumous effect of cinobufagin is better,, understands because of the bigger toxicity of cinobufagin, and cause bigger general toxicity if be that effective ingredient prepares oral formulations with the cinobufagin separately.After cinobufagin processed inhalant, medicine will directly act on patient part, reduce because of the oral general toxic and side effects that produces.
Lung has great surface area, make drug molecule very easily get into blood, so the lung inhalation has plurality of advantages such as rapid-action, that untoward reaction is little.(the drypowder inhalers of Foradil Aerolizer formoterol fumarate in the lung inhalation; DPIs) do not use propellant and solvent; The air-flow that leans on patient's autonomous respiration to produce makes the medicine powder atomization, and then makes drug powder be delivered to pulmonary, over past ten years; Foradil Aerolizer formoterol fumarate because its targeting, efficient, quick-acting, toxic and side effects is little and characteristics such as pollution-free, development is rapidly.
Employing can directly act on cinobufagin the focus of pulmonary carcinoma through the inhalant of lung administering mode; Improve the curative effect of the anti-pulmonary carcinoma of cinobufagin; Reduce its toxic and side effects simultaneously, the primary pulmonary carcinoma of the treatment cancer cause of the death is had great clinical value normal structure.The research that has the cinobufagin Foradil Aerolizer formoterol fumarate of resisting tumor of lung effect does not at present appear in the newspapers.
Summary of the invention:
Goal of the invention: an object of the present invention is to provide pulmonary's dry powder inhaler formulations of cinobufagin and preparation method thereof.Another object of the present invention provides the application of Foradil Aerolizer formoterol fumarate according to the invention in preparation treatment lung tumors medicine.
To the foregoing invention purpose, the present invention provides following technical scheme:
A kind of cinobufagin Foradil Aerolizer formoterol fumarate is characterized in that it is made up of cinobufagin and medically acceptable adjuvant, and the mass ratio of cinobufagin and described adjuvant is 1: 0.03-1: 110.
Described cinobufagin Foradil Aerolizer formoterol fumarate is characterized in that it is to use powder by the suction that cinobufagin adding adjuvant is processed, and the particle diameter of powder is with D
50Meter is between the 0.1-1300 micron.
Described adjuvant is selected one or more mixture in sugar, alcohol, aminoacid, phospholipid, surfactant, cyclodextrin, biodegradable polymer substance, magnesium stearate, stearic acid, hard ester fumaric acid sodium, micropowder silica gel, the Pulvis Talci for use.
Described sugar can be selected one or more mixture in galactose, lactose, glucose, fructose, sucrose, trehalose, the Raffinose for use; Described alcohol can be selected one or more mixture in mannitol, xylitol, maltose alcohol, the sorbitol for use; Described aminoacid can be selected in glycine, Aspartic Acid, alanine, tryptophan, isoleucine, threonine, glutamic acid, phenylalanine, leucine, cystine, lysine, proline, the arginine one or more for use; Described phospholipid can be selected in soybean phospholipid, lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, the synthetic phospholipid one or more for use; Described surfactant can be selected one or more mixture in pulmonary surfactant such as dipalmitoyl phosphatidyl choline, two Laurel phosphatidyl cholines, the cholesterol for use; Described polymer substance; Can select the macromolecule that meets safety requirements for use, preferred biodegradable polymer substance is one or more mixture in albumin, starch, polylactic acid, polylactic acid-glycolic guanidine-acetic acid, Polyethylene Glycol, poloxamer, hyaluronic acid, hyaluronate sodium, the sodium alginate for example.
Preferred mode is that said adjuvant is the mixture of different-grain diameter lactose; Preferred mode is that said adjuvant is for sucking the mixture with lactose granule and micronization lactose; Wherein the lactose granule mean diameter is the 80-250 micron; Micronization lactose mean diameter is the 1-10 micron, and the mass ratio of lactose granule and micronization lactose is 1050: 1-1: 1, and most preferred mode is that the mass ratio of lactose granule and micronization lactose is 100: 1-11: 1.
Described cinobufagin Foradil Aerolizer formoterol fumarate, its preparation process is following:
Cinobufagin is processed powder through pulverizing or spray drying, and powder and adjuvant mix homogeneously are processed to suck and are used powder, are packaged in capsule or bubble-cap or the Diskus; Perhaps, process suction through pulverizing or spray drying and use powder, be packaged in capsule or bubble-cap or the Diskus cinobufagin and adjuvant mix homogeneously; Perhaps with partial supplementary material mix homogeneously in cinobufagin and the prescription, through pulverizing or spray drying is processed powder, residue adjuvant mix homogeneously is processed to suck and is used powder in powder and the prescription, is packaged in capsule or bubble-cap or the Diskus.
Preferred cinobufagin Foradil Aerolizer formoterol fumarate, its preparation process is following:
Cinobufagin through pulverizing or spray drying is processed powder, is mixed with the lactose of different-grain diameter or the mixture of lactose granule and micronization lactose is evenly processed suction and used powder, be packaged in capsule or bubble-cap or the Diskus.
The application of described cinobufagin Foradil Aerolizer formoterol fumarate in preparation lung tumors medicine.
Beneficial effect:
1, lung has great surface area, and alveolar wall is made up of cell monolayer, make drug molecule very easily get into blood, so the lung inhalation has plurality of advantages such as rapid-action, that untoward reaction is little.(the drypowder inhalers of Foradil Aerolizer formoterol fumarate in the lung inhalation; DPIs) do not use propellant and solvent; The air-flow that leans on patient's autonomous respiration to produce makes the medicine powder atomization; And then make drug powder be delivered to pulmonary, and have convenient in application, absorb the first mistake of rapid, no liver, rapid release and the localized characteristics of targeting, be a kind of novel drug-supplying system.At present be used for treating the infection of respiratory tract and pulmonary more, but do not see treatment at lung tumors relevant for Foradil Aerolizer formoterol fumarate.Simultaneously, the research that has the cinobufagin Foradil Aerolizer formoterol fumarate of resisting tumor of lung effect does not appear in the newspapers yet.The oral formulations that contains cinobufagin at present has been applied to clinical, and hepatocarcinoma, pulmonary carcinoma, gastric cancer etc. are had curative effect preferably, and comprehensive effective percentage is 80.74%, and chemotherapy and radiation is had synergism.Though the antitumous effect of cinobufagin is better,, understands because of the bigger toxicity of cinobufagin, and cause bigger toxicity if be that effective ingredient prepares oral formulations with the cinobufagin separately.With the cinobufagin is that main Foradil Aerolizer formoterol fumarate mainly is to lung tumors, directly acts on affected part, does not have the first pass effect of liver simultaneously; Can improve bioavailability of medicament, reduce the generation of toxicity, overcome medicine is processed the first pass effect that oral formulations need pass through liver; Onset is slow; Shortcomings such as toxicity is big, and the preparation bioavailability is lower have very big prospect to new drug development.
2, cinobufagin needs to be mixed into Foradil Aerolizer formoterol fumarate with adjuvant; Find in the practical operation; Because of influence such as electrostatic interaction, cohesiveness between the powder, medicine was easy to reunite, and therefore need carry out proportioning with adjuvant when cinobufagin was crushed to certain particle size; Overcome the problem that medicine is reunited; The applicant knows that through a large amount of experiments cinobufagin and ratio of adjuvant are controlled in the particular range, and particularly adjuvant selects for use the mixture of lactose granule and micronization lactose can make the good Foradil Aerolizer formoterol fumarate of intake performance.
The specific embodiment
Below in conjunction with instance the present invention is done further explain, but scope of the present invention does not receive any restriction of these instances.
Embodiment 1
The preparation of inhalant: adopt comminution by gas stream to D cinobufagin
90Below=5 microns, mix at 1: 9 by mass ratio, drug powder is packaged in capsule or bubble-cap or the Diskus, obtain inhalant with the lactose of particle diameter at the 80-110 micron.
Embodiment 2
The preparation of inhalant: adopt comminution by gas stream to D cinobufagin
90=4 microns, mix in 10: 90: 3 ratio at the leucine of 35-70 micron with lactose, the particle diameter of particle diameter at the 80-125 micron, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 3
The preparation of inhalant: adopt comminution by gas stream to D cinobufagin
90=4 microns, mix in 1: 9 ratio with the leucine of particle diameter 80-150 micron, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 4
The preparation of inhalant: with cinobufagin powder, lactose, mannitol, glycine, two Laurel phosphatidyl cholines, lecithin, magnesium stearate in 1: 3: 4: 3: 0.4: 0.5: 0.2 ratio was mixed, and comminution by gas stream is to powder D
90=7 microns, drug powder is packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 5
The preparation of inhalant: cinobufagin, lactose, cholesterol are mixed in 1: 9: 2 ratio, and comminution by gas stream is to powder D
50=5 microns, drug powder is packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 6
The preparation of inhalant: in cinobufagin, add lactose, polyethylene glycol 6000, the albumin of 5 times, 2 times, 2 times of quality respectively, spray drying, powder D
50=8 microns, drug powder is packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 7
The preparation of inhalant: cinobufagin drug powder, particle diameter are mixed in 15: 80: 5 ratio at mannitol, the micronization silica gel of 4-100 micron, be packaged into behind the mix homogeneously in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 8
The preparation of inhalant: cinobufagin drug powder, mannitol, leucine are mixed in 10: 95: 4 ratio, and it is an amount of to add water after the mixing, and spray drying obtains D
90Be 5 microns powder, add mean diameter and be 135 microns lactose granule mixing, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 9
The preparation of inhalant: cinobufagin powder, mannitol, glycine are mixed in 10: 95: 4 ratio, and it is an amount of to add water after the mixing, and spray drying obtains D
90Be 7 microns powder, add mean diameter and be 145 microns lactose granule mixing, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 10
1, the preparation of inhalant: cinobufagin powder, German U.S. agent are found pleasure in
70 lactose, micronization lactose (D
90=4.8 microns) mix in 10: 75: 5 ratio, be packaged into behind the mix homogeneously in capsule or bubble-cap or the Diskus, obtain inhalant.
2, inhalant pulmonary deposition rate is investigated
Investigate according to People's Republic of China's version pharmacopeia in 2010 prescriptive procedure, the pulmonary deposition rate of cinobufagin reaches 33.1%, and the room temperature condition held is after 18 months, and the pulmonary deposition rate of cinobufagin does not have significant change.
Embodiment 11
1, the preparation of inhalant: cinobufagin powder, German U.S. agent are found pleasure in
70 lactose, micronization lactose (D
90=5.2 microns) mix in 3: 97: 2 ratio, be packaged into behind the mix homogeneously in capsule or bubble-cap or the Diskus, obtain inhalant.
2, inhalant pulmonary deposition rate is investigated
Investigate according to People's Republic of China's version pharmacopeia in 2010 prescriptive procedure, the pulmonary deposition rate of cinobufagin reaches 29.1%, and the room temperature condition held is after 18 months, and the pulmonary deposition rate of cinobufagin does not have significant change.
Embodiment 12
1, the preparation of inhalant: cinobufagin powder, German U.S. agent are found pleasure in
70 lactose, micronization lactose (D
90=5.7 microns) mix in 2: 85: 1 ratio, be packaged into behind the mix homogeneously in capsule or bubble-cap or the Diskus, obtain inhalant.
2, inhalant pulmonary deposition rate is investigated
Investigate according to People's Republic of China's version pharmacopeia in 2010 prescriptive procedure, the pulmonary deposition rate of cinobufagin reaches 28.9%, and the room temperature condition held is after 18 months, and the pulmonary deposition rate of cinobufagin does not have significant change.
Embodiment 13
The preparation of inhalant: cinobufagin powder, leucine are mixed in 1: 9 ratio, mix the particulate D in back
50Be 257 microns, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 14
The preparation of inhalant: cinobufagin is mixed comminution by gas stream, powder D with leucine in 1: 1 ratio
90Below 5 microns, this powder is mixed with the mannitol of 9 times of amounts again, mix the particulate D in back
50Be 286 microns, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 15
The preparation of inhalant: cinobufagin is mixed comminution by gas stream, powder D with poloxamer in 5: 1 ratio
90Below 5 microns, this powder is mixed with the lactose granule of 9 times of amounts, the magnesium stearate of 1 times of amount again, mix the particulate D in back
50Be 312 microns, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 16
The preparation of inhalant: with the cinobufagin comminution by gas stream, powder D
90=5 microns, this powder is mixed with the lactose granule of 14 times of amounts again, mix the particulate D in back
50Be 254 microns, be packaged in capsule or bubble-cap or the Diskus, obtain inhalant.
Embodiment 17
Obtain inhalant according to embodiment 1-16, carry out pharmacodynamic experiment.
Effect experiment:
The method of benzopyrene percutaneous puncture pulmonary injection is set up the induced lung animal model for tumour, gets 180 of modeling rats, is divided into 18 groups at random, 10 every group.Every day 1 time, medication 7 days.The inhalant inhalation that administering mode: 1-16 group obtains for embodiment 1-16, dosage is 1mg cinobufagin/kg; Irritate stomach for the 17th group and give cinobufagin, dosage is 1mg cinobufagin/kg; The 18th group is that the normal saline that contains 0.5% sodium carboxymethyl cellulose contrasts carefully lumbar injection 10mL/kg.Next day is put to death rat in drug withdrawal, dissects the rat lungs, observes the lung lesion situation.
Experimental result: it is 17% that the pulmonary of rat of each group of inhalant administration the incidence rate of lump or tuberosity pathological changes occurs minimum, is up to 34%; It is 52% that cinobufagin is irritated the stomach group, and the normal saline group is 100%, and each group of inhalant administration is irritated the stomach group with cinobufagin, the normal saline group has significant difference (P＜0.05) on the pulmonary lesion incidence rate.
Embodiment 18
Obtain inhalant according to embodiment 1-16, carry out pharmacodynamic experiment.
1, the foundation of rabbit VX2 original position lung cancer model
1) the freezing cell suspension of the conventional recovery VX2 tumor of the making of lotus tumor kind rabbit processes 10
6The living cells suspension of/mL is got 1mL and is inoculated in 1 rabbit right rear leg outside intramuscular, 3 week the back can lay one's hand on and the lump of the about 30cm of a diameter in inoculation position, promptly process lotus tumor kind rabbit.
2) cut the intramuscular tumor in the lotus tumor kind rabbit leg outside under the preparation aseptic condition of piece of tissue suspension, get to be and oppress the eugonic tumor tissues of appearance, be cut into the mud shape.30 mesh sieves were descended in the flushing of RPMI RPMI-1640, removed individual cells and too small piece of tissue, and 20 mesh sieves were descended in the flushing of RPMI RPMI-1640 in sieve top, removed excessive piece of tissue.Get the lower part of screen branch, after the centrifugation, taking precipitate 2mL adds the RPMI RPMI-1640 and is mixed with piece of tissue suspension 20mL.
3) all rabbit right thoracic wall depilations of inoculation in the lung; Intramuscular injection speed is slept and is fixed after new mixture 0.8mL/kg anaesthetizes; Routine disinfection; Get aseptic three way cock, connecing No. 12 injection needles, suctions respectively has the 1mL syringe of rabbit self blood clot and the syringe that suction has VX2 tumor tissue suspension or cell suspension 1mL.Under X line perspective, No. 12 syringe needles are thrust in the rabbit inferior lobe of right lung, behind the resorption depletion of blood, inject 0.4mL piece of tissue suspension or cell suspension, inject 0.2mL rabbit self blood clot then, extract syringe needle, inoculation finishes.
4) the whole rabbit of the observation of growth of xenografted situation are from inoculating back the 3rd day, and carry out layer wide, bed thickness be 5mm CT scan to chest every day, observes transfer case in tumor growth, the thoracic cavity.
5) rabbit VX2 original position lung cancer model is set up as a result rabbit all has tumor growth in the lung, success ratio of inoculation 100%.
2, pharmacodynamic experiment
Get successfully 180 of modeling rabbit, be divided into 18 groups at random, 10 every group.Every day 1 time, medication 12 days.The inhalant inhalation that administering mode: 1-16 group obtains for embodiment 1-16, dosage is 1mg cinobufagin/kg; Irritate stomach for the 17th group and give cinobufagin, dosage is 1mg cinobufagin/kg; The 18th group is the normal saline matched group that contains 0.5% sodium carboxymethyl cellulose, lumbar injection 10mL/kg.Next day is put to death rabbit in drug withdrawal, dissects the rabbit lungs, peels off tumor tissues, weighs.
Experimental result: the tumour inhibiting rate minimum of the rabbit of each group of inhalant administration is 49.4%, is up to 62.8%; The tumour inhibiting rate that cinobufagin is irritated the stomach group is 29.5%, and normal saline is to almost unrestraint effect of tumor, and each group of inhalant administration heavily has significant difference (P＜0.05) with the tumour inhibiting rate that cinobufagin is irritated stomach group, normal saline group.
Claims (10)
1. cinobufagin Foradil Aerolizer formoterol fumarate is characterized in that it is made up of cinobufagin and medically acceptable adjuvant, and the mass ratio of cinobufagin and described adjuvant is 1: 0.03-1: 110.
2. a kind of cinobufagin Foradil Aerolizer formoterol fumarate according to claim 1 is characterized in that it is to use powder by the suction that cinobufagin adding adjuvant is processed, and the particle diameter of powder is with D
50Meter is between the 0.1-1300 micron.
3. a kind of cinobufagin Foradil Aerolizer formoterol fumarate according to claim 1 is characterized in that described adjuvant selects one or more mixture in sugar, alcohol, aminoacid, phospholipid, surfactant, cyclodextrin, biodegradable polymer substance, magnesium stearate, stearic acid, hard ester fumaric acid sodium, micropowder silica gel, the Pulvis Talci for use.
4. a kind of cinobufagin Foradil Aerolizer formoterol fumarate according to claim 3 is characterized in that described sugar, selects one or more mixture in galactose, lactose, glucose, fructose, sucrose, trehalose, the Raffinose for use; Described alcohol is selected one or more mixture in mannitol, xylitol, maltose alcohol, the sorbitol for use; Described aminoacid is selected in glycine, Aspartic Acid, alanine, tryptophan, isoleucine, threonine, glutamic acid, phenylalanine, leucine, cystine, lysine, proline, arginine, the methionine one or more for use; Described phospholipid can be selected in soybean phospholipid, lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, the synthetic phospholipid one or more for use; Described surfactant is selected one or more mixture in pulmonary surfactant such as dipalmitoyl phosphatidyl choline, two Laurel phosphatidyl cholines, the cholesterol for use; Biodegradable polymer substance is one or more mixture in albumin, starch, polylactic acid, polylactic acid-glycolic guanidine-acetic acid, Polyethylene Glycol, poloxamer, hyaluronic acid, hyaluronate sodium, the sodium alginate.
5. a kind of cinobufagin Foradil Aerolizer formoterol fumarate according to claim 3 is characterized in that said adjuvant is the mixture of different-grain diameter lactose or lactose and micronization lactose.
6. a kind of cinobufagin Foradil Aerolizer formoterol fumarate according to claim 5; It is characterized in that said adjuvant is for sucking the mixture with lactose granule and micronization lactose; Wherein the lactose granule mean diameter is the 80-250 micron; Micronization lactose mean diameter is the 1-10 micron, and the mass ratio of lactose granule and micronization lactose is 1050: 1-1: 1.
7. adjuvant according to claim 6, the mass ratio that it is characterized in that lactose granule and micronization lactose is 100: 1-11: 1.
8. method for preparing the described a kind of cinobufagin Foradil Aerolizer formoterol fumarate of claim 1, its preparation process is following:
Cinobufagin is processed powder through pulverizing or spray drying, and powder and adjuvant mix homogeneously are processed to suck and are used powder, are packaged in capsule or bubble-cap or the Diskus; Perhaps, process suction through pulverizing or spray drying and use powder, be packaged in capsule or bubble-cap or the Diskus cinobufagin and adjuvant mix homogeneously; Perhaps with partial supplementary material mix homogeneously in cinobufagin and the prescription, through pulverizing or spray drying is processed powder, residue adjuvant mix homogeneously is processed to suck and is used powder in powder and the prescription, is packaged in capsule or bubble-cap or the Diskus.
9. method for preparing the described cinobufagin Foradil Aerolizer formoterol fumarate of claim 1, its preparation process is following:
Cinobufagin through pulverizing or spray drying is processed powder, is processed suction with the mixture mix homogeneously of the lactose of different-grain diameter or lactose granule and micronization lactose and used powder, be packaged in capsule or bubble-cap or the Diskus.
10. the application of a kind of cinobufagin Foradil Aerolizer formoterol fumarate of claim 1 in preparation treatment lung tumors medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110147795 CN102302477B (en) | 2011-06-02 | 2011-06-02 | Cinobufagin dry power inhaler and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110147795 CN102302477B (en) | 2011-06-02 | 2011-06-02 | Cinobufagin dry power inhaler and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102302477A true CN102302477A (en) | 2012-01-04 |
| CN102302477B CN102302477B (en) | 2013-08-28 |
Family
ID=45376467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110147795 Active CN102302477B (en) | 2011-06-02 | 2011-06-02 | Cinobufagin dry power inhaler and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102302477B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016030524A1 (en) * | 2014-08-29 | 2016-03-03 | Algipharma As | Inhalable powder formulations of alginate oligomers |
| CN114903907A (en) * | 2022-05-31 | 2022-08-16 | 合肥师范学院 | Application of arenobufagin and derivatives thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1458164A (en) * | 2003-06-05 | 2003-11-26 | 王利忠 | Purifying technology for lipid bufalin genin and cino-bufagin in fresh senso |
| CN1686183A (en) * | 2005-03-25 | 2005-10-26 | 张海峰 | Toad cake freeze dried powder injection agent and its preparation method |
| CN101176739A (en) * | 2006-11-08 | 2008-05-14 | 山东绿叶制药有限公司 | Toadpoison ligand extract as well as preparation method and application thereof |
| CN101683359A (en) * | 2008-09-28 | 2010-03-31 | 上海秀新臣邦医药科技有限公司 | Traditional Chinese medicine composition for treating tumours and preparation method thereof |
-
2011
- 2011-06-02 CN CN 201110147795 patent/CN102302477B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1458164A (en) * | 2003-06-05 | 2003-11-26 | 王利忠 | Purifying technology for lipid bufalin genin and cino-bufagin in fresh senso |
| CN1686183A (en) * | 2005-03-25 | 2005-10-26 | 张海峰 | Toad cake freeze dried powder injection agent and its preparation method |
| CN101176739A (en) * | 2006-11-08 | 2008-05-14 | 山东绿叶制药有限公司 | Toadpoison ligand extract as well as preparation method and application thereof |
| CN101683359A (en) * | 2008-09-28 | 2010-03-31 | 上海秀新臣邦医药科技有限公司 | Traditional Chinese medicine composition for treating tumours and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 王隶书等: "华蟾毒精气雾剂的研制", 《中成药》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016030524A1 (en) * | 2014-08-29 | 2016-03-03 | Algipharma As | Inhalable powder formulations of alginate oligomers |
| CN106659689A (en) * | 2014-08-29 | 2017-05-10 | 阿尔吉法玛公司 | Inhalable powder formulations of alginate oligomers |
| US20180235879A1 (en) * | 2014-08-29 | 2018-08-23 | Algipharma As | Inhalable powder formulations of alginate oligomers |
| AU2015308381B2 (en) * | 2014-08-29 | 2020-10-22 | Algipharma As | Inhalable powder formulations of alginate oligomers |
| CN113384538A (en) * | 2014-08-29 | 2021-09-14 | 阿尔吉法玛公司 | Inhalable powder formulations of alginate oligomers |
| CN114903907A (en) * | 2022-05-31 | 2022-08-16 | 合肥师范学院 | Application of arenobufagin and derivatives thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102302477B (en) | 2013-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102078312A (en) | Curcumin compound dry powder inhaler as well as preparation method and application thereof | |
| CN102058566A (en) | Dry powder inhaler with constituent rubescensin A as well as preparation method and application thereof | |
| CN103833713B (en) | Nicousamide brilliant type III, its method for making and its pharmaceutical composition and purposes | |
| CN102247335B (en) | Bufalin dry powder inhalant as well as preparation method and application thereof | |
| WO2010111807A1 (en) | A polysaccharide liposome, the preparation method and use of it | |
| CN102302477B (en) | Cinobufagin dry power inhaler and preparation method and application thereof | |
| CN102302475B (en) | Resibufogenin dry powder inhalant and preparation method and application thereof | |
| CN101322681B (en) | Method for preparing nano micelle formulation of anthracene nucleus antineoplastic antibiotic | |
| CN102961409B (en) | Toad skin extract dry powder inhaler | |
| CN102210712B (en) | Bufo bufo gargarizans cantor skin extract dry powder inhalant and preparation method and use thereof | |
| CN102247337B (en) | Bufotalin dry powder inhalers and preparation method as well as application thereof | |
| CN102210711B (en) | Senso fat-soluble extract dry powder inhalation, preparation method and application thereof | |
| CN102247336B (en) | Bufothionine dry powder inhaler, and its preparation method and application | |
| CN102526038B (en) | Temozolomide brain-targeting pharmaceutical composition and application thereof | |
| CN103083286B (en) | Toad venom lipophilic extract dry powder inhaler, as well as preparation method and application thereof | |
| CN102961406B (en) | Toad skin extract dry powder inhaler, as well as preparation method and application thereof | |
| CN102302476B (en) | Dehydrobufotenine dry power inhaler and preparation method and application thereof | |
| CN103142652B (en) | Venenum bufonis fat-soluble extract dry powder inhaler, and preparation method and application thereof | |
| CN102309469A (en) | Baohuoside I dry powder inhalant as well as preparation method and application thereof | |
| CN102961407B (en) | Toad skin extract dry powder inhaler, as well as preparation method and application thereof | |
| CN102961408B (en) | Toad skin extract dry powder inhaler | |
| CN103070885B (en) | Toad skin extract dry-powder inhalant and its preparation method and use | |
| CN103070886B (en) | Toad skin extract dry-powder inhalant and its preparation method and use | |
| CN102988419A (en) | Toad skin extract powder inhalant, and preparation method and application thereof | |
| CN102973604B (en) | Toad skin extract dry powder inhalant and preparation method and applications thereof |
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 | ||
| ASS | Succession or assignment of patent right |
Owner name: JIANGSU POMOCELL BIOTECHNOLOGY CO., LTD. Free format text: FORMER OWNER: ZHANG ZHENHAI Effective date: 20131212 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 210028 NANJING, JIANGSU PROVINCE TO: 214434 WUXI, JIANGSU PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20131212 Address after: Dongsheng Road 214434 Jiangsu city of Jiangyin province No. 6 Yangtze biomedical accelerator C2 building Patentee after: Jiangsu Pu Nuosheng bio tech ltd Address before: 210028, cross street, Hongshan Road, Jiangsu, Nanjing, 100 Patentee before: Zhang Zhenhai Effective date of registration: 20131212 Address after: Dongsheng Road 214434 Jiangsu city of Jiangyin province No. 6 Yangtze biomedical accelerator C2 building Patentee after: Jiangsu Pu Nuosheng bio tech ltd Address before: 210028, cross street, Hongshan Road, Jiangsu, Nanjing, 100 Patentee before: Zhang Zhenhai |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20200513 Address after: 211100 floor 3, building B, Ruihong Biotechnology Park, 2289 Tianyuan East Road, Jiangning District, Nanjing City, Jiangsu Province Patentee after: Nanjing NANYAO Pharmaceutical Technology Co., Ltd Address before: Dongsheng Road 214434 Jiangsu city of Jiangyin province No. 6 Yangtze biomedical accelerator C2 building Patentee before: JIANGSU PROMOCELL BIOTECHNOLOGY Co.,Ltd. |
|
| TR01 | Transfer of patent right |