CN102258468A - Liposome spraying agent and its preparation method - Google Patents
Liposome spraying agent and its preparation method Download PDFInfo
- Publication number
- CN102258468A CN102258468A CN2010101891575A CN201010189157A CN102258468A CN 102258468 A CN102258468 A CN 102258468A CN 2010101891575 A CN2010101891575 A CN 2010101891575A CN 201010189157 A CN201010189157 A CN 201010189157A CN 102258468 A CN102258468 A CN 102258468A
- Authority
- CN
- China
- Prior art keywords
- liposome
- ethosome
- medicine
- spraying agent
- spray
- 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
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a novel liposome spraying agent and its preparation method. The spraying agent provided by the invention is prepared by the dispersion of medicine-loading ethosome in a solution system containing a macromolecular dispersing aid, and is used to helps raise the medicine loading capacity as well as the entrapment rate and promote medicines to penetrate through skin, mucous membrane or in vivo biomembrane barriers such that the medicines have long-acting effects. The novel liposome spraying agent has a wide medicine application range, especially is suitable for medicines of poor amphiphilicity or medicines of high molecular weight, and can be used to meet the requirement of treating local areas such as mucous membrane, skins, wounds and cavities or the whole body.
Description
[technical field]
The invention belongs to the pharmaceutical preparation field, more particularly, the present invention relates to a kind of liposome spraying agent and preparation method thereof.
[background technology]
Skin and mucous layer are a kind of barrier of human body to drug absorption, and the medicine that amphipathic difference or molecular weight are big is difficult to see through skin and mucous membrane tissue enters into deep tissues and blood circulation performance therapeutical effect.
Promote the method for biomembrane barrier in medicine transdermal, mucosa or the body mainly to rely on chemical absorbing promoter to increase drug absorption [yellow being good at present, Gao Chunsheng, prunus mume (sieb.) sieb.et zucc. is made the country prosperous. the application of penetrating agent in the macromolecular drug mucosal drug delivery system. and foreign medical science: pharmacy fascicle .2006,33 (6): 654-656].Though chemical absorbing promoter can be reduced the resistance of medicine by skin and mucosa, improve medicine and penetrate efficient.But these chemical absorbing promoter all can cause damage or stimulate biomembrane barrier in skin, mucosa or the body, its detrimental effect can manifest along with the increase of preparation consumption or the prolongation of the time of application, these chemical absorbing promoter also may react with medicine or packaging material in addition, influence the drug effect performance.
Aerosol and spray are the better dosage forms of present skin or mucosal drug delivery, but the safety of spray is better, and preparation and use are more convenient.Spray means and do not contain propellant, the preparation that content is disengaged with form such as vaporific by the pressure of manual pump.Spray is divided into single dose and multiple dose spray by using method; Be categorized as solution-type, emulsion-type and suspension type by disperse system.The solution type spray medicinal liquid should be clarified; Emulsion-type drops in the liquid medium and should be uniformly dispersed; The suspension type spray should be made stable suspensoid with fine drug powder and the abundant mixing of additives.
The advantage of spray has: (1) sprays the propellant that does not need aerosol, does not use pressure vessel, and is easy to use; (2) performance quick curing effect; (3) can accurately control dosage with quantitative valve; (4) scope of application is wider, can be used for skin, mucosa and wound surface; (5) Pen Chu droplet is thinner, the spread and good dispersion degree at skin or mucosa position, and medicinal liquid is difficult for running off.
But spray has some shortcomings: (1) multiple dose spray needs to use repeatedly, and microbiological contamination easily needs to add antibacterial; (2) though can bring into play quick-acting effects, need to add chemical absorbing promoter increase medicine and penetrate efficient; (3) duration of efficacy is short, removes very fast in the body; (4) water solution system, moldy metamorphism is unfavorable for that medicine is stable easily.
Ethosome is a kind of novel liposome, the earliest by Touitou in the nineties in 20th century middle and late stage propose, it is to be the capsule material by phospholipid or lipid materials, and the single or multiple lift vesicle of being made up of the ethanol participation structure.Compare with conventional liposome, its particle diameter is less, Stability Analysis of Structures, the envelop rate height has better flexibility, good advantage [Li Liyu such as transdermal performance, Wang Hongquan. novel percutaneous dosing carrier--Progress on ethosomes. Chinese Journal of New Drugs, 2010,19 (1): 33-38].
The patent report that liposome is applied to spray is more, and is few but ethosome is applied to the patent report of spray.Patent (CN02145124.9) discloses a kind of Camphora spray and preparation method thereof, contain high concentration ethanol solution in the spray prescription that provides, but ethanol is not applied to carriers such as liposome only as the main solvent of spray in the patent.Patent (CN200410054738.2), patent (CN200410054739.7), patent (CN200410054738.2) etc. have been used alcohol injection and have been prepared liposome, but ethanol is only as the main solvent in the liposome preparation process in these patents, finally be removed, it be not applied in the spray as the liposome key component.Patent (CN02139452.0) discloses a kind of liposome antifungal agent composition spray preparation, though comprised ethanol in this patent prescription, just as percutaneous absorption transdermal enhancers, its consumption is lower, does not participate in liposome structure and forms.Patent (CN200810061803.2) discloses ethosome preparation of a kind of antifungal drug and preparation method thereof, and the ethanol percentage by weight is 20%～45% in this patent prescription.But the ethosome of this patent preparation is long more standing time, and the ethosome microgranule is assembled easily, and it is big that particle diameter can become.
[summary of the invention]
The technical problem to be solved in the present invention is the weak point at existing liposome spraying agent and ethosome preparation, a kind of novel lipide spray-ethosome spray is provided, promote medicine to see through skin or mucosa quickly and enter into deep tissues and blood circulation, bring into play quick-acting and long-acting therapeutical effect, it is wide that this ethosome spray is suitable for the medicine scope, be particularly suitable as the medicine or the big medicine of molecular weight of amphipathic difference, can satisfy the part of mucosa, skin, wound surface, tract or the needs of whole body therapeutic.
The spray of a kind of novel lipide of the present invention not only has common spray advantage, has more following advantage: contain higher concentration ethanol in (1) prescription, not only have antibacterial preferably and mildew-proof function, and promote drug absorption, it is stable to keep medicine; (2) add the macromole dispersion aids in the prescription, help the ethosome Stability Analysis of Structures and prolong ethosome Chinese medicine action time; (3) the ethosome particle diameter is less and better flexibility is arranged, and not only helps improving medicine drug loading and envelop rate, more promotes biomembrane barrier in medicine transdermal, mucosa or the body, the performance long-acting; (4) medicine is applied widely, can use for the medicine or the big medicine of molecular weight of amphipathic difference; (3) applied range can satisfy the part of mucosa, skin, wound surface, tract or the needs of whole body therapeutic.
The inventor discovers, utilization comprises the ethosome of higher concentration (20%-45%) ethanol system and makes the ability that spray can significantly improve the transdermal or the mucosa of spray Chinese medicine, has good application prospects for the medicine and the big medicine of molecular weight that exist skin or mucosa to see through the amphipathic difference of obstacle.But this ethosome spray in storing put procedure, the preparation system instability, the ethosome microgranule is assembled easily and is become big, can not the jog redispersion, therefore can't practical application in clinical.The inventor finds through a large amount of experiments, some macromolecule polyalcohols have good suspending effect, can be used as the macromole dispersion aids and join in the ethosome spray, guarantee that the ethosome particle diameter is stable for a long time, thereby the raising stability of drug prolongs its effective acting time.
Thus, the spray of a kind of novel lipide of the present invention, this spray solution are scattered in the solution system that contains the macromole dispersion aids by the ethosome that wraps the medicine carrying thing to be formed, and ethanol accounts for the 20%-95% of spray solution cumulative volume.
Above-mentioned medicine is meant Chinese medicine, chemicals, biotech drug or the biological product of the performance cleaning that is used for mucosa, skin, wound surface, tract, sterilization, prevention, treatment, immunity, beauty treatment, healthcare applications.
Above-mentioned ethosome is meant that by known phospholipid of pharmacy or lipid materials be the capsule material, and the single or multiple lift vesicle of being made up of the ethanol participation structure.
Comprise in pharmaceutically known antioxidant, pH regulator agent or pH buffer salt, surfactant, the stabilizing agent one or more in the above-mentioned spray solution.
Above-mentioned stabilizing agent comprises propylene glycol, glycerol, PEG400, Macrogol 600 or its combination in any.
Above-mentioned macromole dispersion aids is biocompatibility or Biodegradable polymeric, comprises carbomer, hydroxypropyl emthylcellulose, polyvidone, hetastarch, poloxamer.
Ethanol accounts for the 30%-80% of spray solution cumulative volume in the above-mentioned solution system.
Above-mentioned a kind of method for preparing liposome spraying agent solution, be that one in phospholipid and the lipoid or both are dissolved in the ethanol, mix homogeneously forms organic facies, macromole dispersion aids formation water soluble in water, medicine is dissolved in organic facies or water according to the close principle of polarity, and organic facies is injected into aqueous phase, stirs, form the ethosome spray solution of bag medicine carrying thing, wherein ethanol accounts for the 20%-95% of spray solution cumulative volume.
Also be dissolved with in pharmaceutically known antioxidant, pH regulator agent or pH buffer salt, surfactant, the stabilizing agent one or more in the above-mentioned spray solution.
Above-mentioned macromole dispersion aids is biocompatibility or Biodegradable polymeric, comprises carbomer, hydroxypropyl emthylcellulose, polyvidone, hetastarch, poloxamer.
[description of drawings]
[specific embodiment]
Now further describe the present invention in conjunction with following example.
Embodiment 1:
The medicine that amphipathic difference or molecular weight are big as rubescensin, paclitaxel, curcumin, amphotericin B, dexamethasone etc., be difficult to penetrate biomembrane barrier in complete skin, mucosa or the body, so bioavailability is relatively poor, is difficult to the effective therapeutical effect of performance.It is main capsule material that first embodiment of the present invention is utilized natural phospholipid material egg yolk lecithin and cholesterol, hetastarch is the macromole dispersion aids, add surfactant Tween 80 and antioxidant vitamin C, adopt injection method to prepare rubescensin ethosome spray.
Preparation: 20mg egg yolk lecithin and 8mg cholesterol are dissolved in the 10ml ethanol, add 2mg Tween 80 and 8mg rubescensin, be heated to 60 ℃ of all dissolvings, form organic facies.Other gets 0.05g hetastarch (model 130/0.4) and is dissolved in the 20ml distilled water, is heated to 60 ℃, as water.Organic facies is injected into aqueous phase, and 1000r/min stirs 10min, forms rubescensin ethosome suspension, is chilled to room temperature, adds the 10mg vitamin C, and fill is in the spray special-purpose bottle, promptly.Ethanol accounts for the 30%-35% of spray solution cumulative volume.
Shelf-stability is investigated: rubescensin ethosome spray sample was placed 6 months for 25 ℃, and sample thief utilizes the laser particle size analyzer to observe rubescensin ethosome change of size, measures envelop rate.
Entrapment efficiency determination: get 2ml rubescensin ethosome spray sample, the centrifugal 5min of 15000r/min, get precipitation, add the 2ml anhydrous alcohol solution, the centrifugal 5min of 15000r/min, getting supernatant utilizes ultraviolet spectrophotometer to survey ultraviolet absorption value in 221nm, measure the 221nm ultraviolet absorption value of blank ethosome spray sample with method, deduction utilizes " envelop rate (%)=[(rubescensin measured quantity in the rubescensin ethosome)/rubescensin total amount] * 100 " formula to calculate the envelop rate of rubescensin ethosome as a setting.
Experimental result, the initial particle size distribution of rubescensin ethosome spray sample is at 800-1000nm, and no clustering phenomena, envelop rate are 92%.Place after 6 months for 25 ℃, particle size distribution is still at 800-1000nm, and no clustering phenomena, envelop rate are 91%, and no drug leakage phenomenon proves rubescensin ethosome spray good stability, the envelop rate height, and the medicine in the put procedure in the ethosome does not have obvious seepage.
Embodiment 2:
Implement method for making substantially with embodiment 1 for second of the present invention, but use the lipid materials glyceryl monostearate instead, preparation rubescensin ethosome spray as main material.
Preparation: the 10mg glyceryl monostearate is dissolved in the 20ml ethanol, adds 2mg Tween 80 and 8mg rubescensin, be heated to 60 ℃ of all dissolvings, form organic facies.Other gets 0.05g hetastarch (model 130/0.4) and is dissolved in the 10ml distilled water, is heated to 60 ℃, as water.Organic facies is injected into aqueous phase, and 1000r/min stirs 10min, forms rubescensin ethosome suspension, is chilled to room temperature, adds the 10mg vitamin C, and fill is in the spray special-purpose bottle, promptly.Ethanol accounts for the 60%-65% of spray solution cumulative volume.
Shelf-stability is investigated: with embodiment 1.
Experimental result, the initial particle size distribution of rubescensin ethosome spray sample is at 600-800nm, and no clustering phenomena, envelop rate are 89%.Place after 6 months for 25 ℃, particle size distribution is still at 600-800nm, and no clustering phenomena, envelop rate are 88%, no drug leakage phenomenon.The result shows rubescensin ethosome spray envelop rate height, good stability in the put procedure.
Embodiment 3:
The 3rd embodiment of the present invention is main material with the synthetic phospholipid, and polyvidone is the macromole dispersion aids, adds the stabilizing agent propylene glycol, adopts injection method to prepare curcumin ethosome spray.
Preparation: 6mg hydrogenated soya phosphatide, 2mg dipalmitoyl phosphatidyl choline (DPPC) phospholipid and 8mg cholesterol are dissolved in the 20ml ethanol, add 2mg Tween 80 and 6mg curcumin, be heated to 60 ℃ of all dissolvings, form organic facies.Other gets 50mg polyvidone (model K30) and is dissolved in the 5ml distilled water, adds the 20mg propylene glycol and is heated to 60 ℃, as water.Organic facies is injected into aqueous phase, and 1000r/min stirs 10min, forms curcumin ethosome suspension, is chilled to room temperature, and fill promptly, is faced with preceding jog mixing in the spray special-purpose bottle.Ethanol accounts for the 75%-80% of spray solution cumulative volume.
Shelf-stability is investigated: curcumin ethosome spray sample was placed 6 months for 25 ℃, and sample thief utilizes the laser particle size analyzer to observe curcumin ethosome change of size, measures envelop rate.
Entrapment efficiency determination: get 2ml curcumin ethosome spray sample, the centrifugal 5min of 15000r/min, get precipitation, add the 2ml anhydrous alcohol solution, the centrifugal 5min of 15000r/min, getting supernatant utilizes visible spectrophotometer to survey absorption value in the 427nm place, measure the 427nm place absorption value of blank ethosome spray sample with method, deduction utilizes " envelop rate (%)=[(curcumin measured quantity in the curcumin ethosome)/curcumin total amount] * 100 " formula to calculate the envelop rate of curcumin ethosome as a setting.
Experimental result, the initial particle size distribution of curcumin ethosome spray sample is at 700-900nm, and no clustering phenomena, envelop rate are 94%.Place after 6 months for 25 ℃, particle size distribution is still at 700-900nm, and no clustering phenomena, envelop rate are 93%, no significant change.The result proves curcumin ethosome spray good stability, the envelop rate height, and the medicine in the put procedure in the ethosome does not have obvious seepage.
Embodiment 4:
The 4th embodiment of the present invention utilizes the plain cyst membrane of chicken to measure the biomembranous ability that sees through of curcumin ethosome spray that embodiment 3 obtains.
The processing of the plain cyst membrane of chicken: get the plain capsule of new freshly-slaughtered poultry, clean, peel off fat deposit, be soaked in the normal saline standby.
See through the biomembrane experiment: adopt the transdermal diffusion cell, get the plain cyst membrane of chicken and be cut into suitable size, be fixed between supply chamber and the receiving chamber, in receiving chamber, inject normal saline and make the probe tube liquid level, the liquid measure that record adds a little more than film.Open magnetic stirring apparatus and constant temperature oil bath, keep constant speed to stir, 37 ℃ of constant temperature, spray 200 μ l curcumin ethosome spray solutions on the plain cyst membrane face of the chicken of supply chamber, in 5min, 10min, 30min draws receiving chamber solution 1ml from sample tap and measures, and replenishes fresh normal saline 1ml in receiving chamber, measures obtained sample with three times and adopts high-efficient liquid phase technique to measure the medicine transmitance.Performance liquid chromatographic column: C18250mm * 4.6mm (5 μ m), mobile phase: acetonitrile-4% glacial acetic acid solution (50: 50), flow velocity: 1.0ml/min, ultraviolet detection wavelength: 430nm, sampling volume: 100 μ l.
Table 1 curcumin ethosome spray sees through the experimental result of the plain cyst membrane of chicken
As shown in table 1, it is stronger that the medicine carrying ethosome sees through the biomembrane ability, and transmitance surpasses 60% in the 10min, helps medicine and enter performance drug effect in the body rapidly.
Claims (10)
1. liposome spraying agent is characterized in that: this spray solution is scattered in the solution system that contains the macromole dispersion aids by the ethosome that wraps the medicine carrying thing to be formed, and ethanol accounts for the 20%-95% of spray solution cumulative volume.
2. liposome as claimed in claim 1 spraying agent is characterized in that: described medicine is meant Chinese medicine, chemicals, biotech drug or the biological product of the performance cleaning that is used for mucosa, skin, wound surface, tract, sterilization, prevention, treatment, immunity, beauty treatment, healthcare applications.
3. liposome as claimed in claim 1 spraying agent, it is characterized in that: described ethosome is meant that by known phospholipid of pharmacy or lipid materials be the capsule material, and the single or multiple lift vesicle of being made up of the ethanol participation structure.
4. liposome as claimed in claim 1 spraying agent is characterized in that: comprise in pharmaceutically known antioxidant, pH regulator agent or pH buffer salt, surfactant, the stabilizing agent one or more in the described spray solution.
5. liposome spraying agent as claimed in claim 4, it is characterized in that: described stabilizing agent comprises propylene glycol, glycerol, PEG400, Macrogol 600 or its combination in any.
6. liposome spraying agent as claimed in claim 1, it is characterized in that: described macromole dispersion aids is biocompatibility or Biodegradable polymeric, comprises carbomer, hydroxypropyl emthylcellulose, polyvidone, hetastarch, poloxamer.
7. liposome spraying agent as claimed in claim 1, it is characterized in that: ethanol accounts for the 30%-80% of spray solution cumulative volume in the described solution system.
8. method for preparing liposome spraying agent solution, it is characterized in that: one in phospholipid and the lipoid or both are dissolved in the ethanol, mix homogeneously forms organic facies, macromole dispersion aids formation water soluble in water, medicine is dissolved in organic facies or water according to the close principle of polarity, and organic facies is injected into aqueous phase, stirs, form the ethosome spray solution of bag medicine carrying thing, wherein ethanol accounts for the 20%-95% of spray solution cumulative volume.
9. method as claimed in claim 8 is characterized in that: also be dissolved with in pharmaceutically known antioxidant, pH regulator agent or pH buffer salt, surfactant, the stabilizing agent one or more in the described spray solution.
10. method as claimed in claim 8 is characterized in that: described macromole dispersion aids is biocompatibility or Biodegradable polymeric, comprises carbomer, hydroxypropyl emthylcellulose, polyvidone, hetastarch, poloxamer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010189157.5A CN102258468B (en) | 2010-05-25 | 2010-05-25 | Liposome spraying agent and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010189157.5A CN102258468B (en) | 2010-05-25 | 2010-05-25 | Liposome spraying agent and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102258468A true CN102258468A (en) | 2011-11-30 |
| CN102258468B CN102258468B (en) | 2015-04-29 |
Family
ID=45005438
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010189157.5A Active CN102258468B (en) | 2010-05-25 | 2010-05-25 | Liposome spraying agent and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102258468B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111888469A (en) * | 2020-09-11 | 2020-11-06 | 苏州瑞微生物科技有限公司 | IgY liposome spray and preparation method thereof |
| CN114272423A (en) * | 2021-12-25 | 2022-04-05 | 蔓莎(苏州)工艺制品有限公司 | Cold fragrance lock fragrance incense |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002787A (en) * | 2006-01-20 | 2007-07-25 | 天津药物研究院 | Inhalant containing active component of methyl astragaloside |
| CN101244027A (en) * | 2008-03-20 | 2008-08-20 | 昆明制药集团股份有限公司 | Artemether percutaneous drug administration preparation for treating dermatosis |
-
2010
- 2010-05-25 CN CN201010189157.5A patent/CN102258468B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002787A (en) * | 2006-01-20 | 2007-07-25 | 天津药物研究院 | Inhalant containing active component of methyl astragaloside |
| CN101244027A (en) * | 2008-03-20 | 2008-08-20 | 昆明制药集团股份有限公司 | Artemether percutaneous drug administration preparation for treating dermatosis |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111888469A (en) * | 2020-09-11 | 2020-11-06 | 苏州瑞微生物科技有限公司 | IgY liposome spray and preparation method thereof |
| CN114272423A (en) * | 2021-12-25 | 2022-04-05 | 蔓莎(苏州)工艺制品有限公司 | Cold fragrance lock fragrance incense |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102258468B (en) | 2015-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103221040B (en) | Disulfiram preparation and purposes | |
| Cosco et al. | Gemcitabine and tamoxifen-loaded liposomes as multidrug carriers for the treatment of breast cancer diseases | |
| TWI362931B (en) | Irinotecan formulation | |
| EP3325080B1 (en) | Methods for better delivery of active agents to tumors | |
| RU2719946C2 (en) | Methods for delivering active agents into lymphatic system | |
| CN101953792B (en) | Irinotecan nano circulating liposome and preparation method thereof | |
| Jothy et al. | An overview on niosome as carrier in dermal drug delivery | |
| CN106474064B (en) | Artemether nanoliposome and preparation method and application thereof | |
| CN111195230B (en) | Method for preparing flexible liposome | |
| JP2022536222A (en) | Managing the Risk of Cation Overload and Electrolyte Imbalance with Topically Applied Buffers | |
| Oskuie et al. | Design, synthesis of novel vesicular systems using turpentine as a skin permeation enhancer | |
| Chaudhari et al. | Sphingosomes: A novel lipoidal vesicular drug delivery system | |
| CN101926770B (en) | Drug-loaded liposome and preparation method thereof | |
| CN102258468B (en) | Liposome spraying agent and its preparation method | |
| Beaven et al. | Potential of Ionic liquids to overcome physical and biological barriers to enable oral and topical administration | |
| CN104688721A (en) | Anti-rheumatoid arthritis drug gel containing paclitaxel liposome and preparation method of gel | |
| US20140328898A1 (en) | Nano-Liposomal Formulations and Methods of Use | |
| CN102188379B (en) | Preparation method of drug-carrying liposome | |
| CN104958257B (en) | A kind of Cryptotanshinone skin keratin lipoid body preparation and preparation method thereof | |
| Shakhova et al. | Niosomes: a promising drug delivery system | |
| CN110613686A (en) | Photostimulation-response liposome, pharmaceutical composition and application thereof | |
| CN105434336B (en) | Propranolol Hydrochloride external-use gel preparation and its preparation method and application | |
| CN102283807B (en) | Preparation method and application's method of liquid precursor liposome | |
| US10639372B2 (en) | Nucleic acid, medical nanoparticle, and pharmaceutical composition thereof | |
| US20220296518A1 (en) | Lipid-based nanoparticle delivery system for hydrophilic charged compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| ASS | Succession or assignment of patent right |
Owner name: ZHEJIANG HISUN PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: LU CUITAO Effective date: 20121211 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 100021 CHAOYANG, BEIJING TO: 318000 TAIZHOU, ZHEJIANG PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20121211 Address after: Jiaojiang District of Taizhou City, Zhejiang province 318000 road outside No. 46 Applicant after: Zhejiang Hisun Pharmaceutical Co., Ltd. Address before: 100021 Beijing city Chaoyang District Wu San RI 8 Building 2 403 Applicant before: Lu Cuitao |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |