CN106727306A - A kind of preparation method of high drug load Triamcinolone acetonide micella - Google Patents
A kind of preparation method of high drug load Triamcinolone acetonide micella Download PDFInfo
- Publication number
- CN106727306A CN106727306A CN201611135650.2A CN201611135650A CN106727306A CN 106727306 A CN106727306 A CN 106727306A CN 201611135650 A CN201611135650 A CN 201611135650A CN 106727306 A CN106727306 A CN 106727306A
- Authority
- CN
- China
- Prior art keywords
- triamcinolone acetonide
- poly
- preparation
- polycaprolactone
- ethyleneglycol
- 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.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Dental Preparations (AREA)
- Materials For Medical Uses (AREA)
- Steroid Compounds (AREA)
Abstract
A kind of preparation method of high drug load Triamcinolone acetonide micella, compared to traditional polymer micelle preparation method, thing useful load is higher, stability is stronger.Micellar preparation prepared by the present invention has preparation process and method simple, without using organic solvent in preparation process, the advantages of drug load is high.
Description
Technical field
Present invention relates particularly to technical field of medicine, and in particular to a kind of preparation of high drug load Triamcinolone acetonide micella
Method.
Background technology
Triamcinolone acetonide is a kind of water-insoluble steroid hormone medicine, is artificial synthesized a kind of fluorine-containing long-acting sugared cortical hormone
Element.Various disease treatments are had been used for as a kind of long-acting steroidal anti-inflammatory drugses（Inflammation of eye section, arthritis etc.）, and show one
Fixed curative effect and preferable security.But the poorly water-soluble of the medicine, significantly limit it the shortcomings of toxic and side effect is big and faces
Bed prolonged application.The toxic and side effect for how improving medicine water solubility and reducing medicine turns into the focus and problem of research at present.
In order to solve these problems, researcher uses high molecular polymer to carry medicine for drug molecule is disperseed wherein to build by pharmaceutical carrier
Micellar preparation, it is water-soluble and reduce poisonous side effect of medicine to improve medicine, is that clinical disease treatment is carried and laid a good foundation.Such as Araz
It is pharmaceutical carrier that the researchers such as Sabzevari use PLGA, and Triamcinolone acetonide/PLGA nanometers is prepared for using emulsion volatility process
Treatment of the grain for eye uveitis（European Journal of Pharmaceutics and
Biopharmaceutics, 2013, 84(1): 63-71）;The researchers such as Wai-Leung Langston Suen use
Modified with folic acid polymer is that carrier is used to wrap up Triamcinolone acetonide to improve targeting of the medicine for retinal pigment epithelium,
Strengthen its anti-new vessels curative effect (Journal of Controlled Release, 2013,167 (1): 21-28).
Prepare at present and generally need in the method for medicine high molecular polymer micella using organic solvent as solvent, easily
Remained in micellar preparation preparation process, introduce related toxic and side effect.Meanwhile, using traditional polymer micelle preparation side
, also there is the shortcomings of drug load is not high, stability is poor in method.
The content of the invention
In order to solve the low shortcoming of Triamcinolone acetonide poorly water-soluble, drug load, the clinical practice demand of medicine is met.This
Invention is prepared for a kind of preparation method of high drug load Triamcinolone acetonide micella.The preparation method has preparation process with method letter
It is single, without using organic solvent, the advantages of drug load is high.
The present invention use technical solution be：A kind of preparation method of high drug load Triamcinolone acetonide micella, including with
Lower step：
（1）Triamcinolone acetonide-butanedioic acid derivative is scattered in PBS, added and Triamcinolone acetonide-succinic acid derivatives
The aqueous sodium carbonate of biological equivalent, obtains Triamcinolone acetonide hydrogel；；
（2）Poly- second two is formed during Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) is dissolved in into the aqueous solution or PBS
Alcohol-polycaprolactone-polyethylene glycol solution, is placed in 0-20 DEG C of condition and preserves；；
（3）By physical mixed under the conditions of 0-20 DEG C of Triamcinolone acetonide hydrogel and Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) solution,
It is heated to more than 20 DEG C systems and the Triamcinolone acetonide micellar preparation that self assembly obtains clear occurs.
Described step（1）With（2）In PBS PH be 7.4.
Described step（2）The Mw of middle Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) is 3500.
Described step（2）Middle Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) solution concentration is 40 wt%.
Described step（3）Middle Triamcinolone acetonide hydrogel and the mixing of Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) solution
Volume ratio is 1：1.
The beneficial effects of the invention are as follows：The invention provides a kind of preparation method of high drug load Triamcinolone acetonide micella, phase
Compared with traditional polymer micelle preparation method, thing useful load is higher, stability is stronger.Micellar preparation prepared by the present invention has
Preparation process and method are simple, without using organic solvent in preparation process, the advantages of drug load is high.
Brief description of the drawings
Fig. 1 is Triamcinolone acetonide micellar preparation of the present invention schematic diagram under the conditions of 37 DEG C.
Fig. 2 is Triamcinolone acetonide micella of the present invention（2 wt% TA and 20 wt%PECE physical mixeds）Grain size distribution.
Fig. 3 is Triamcinolone acetonide micella of the present invention（2 wt% TA and 20 wt%PECE physical mixeds）Transmission electron microscope picture.
Specific embodiment
Example 1 (with PBS as solution, 2 wt% Triamcinolone acetonides micellas is prepared at 37 DEG C of temperature):
(1) by Triamcinolone acetonide-butanedioic acid derivative, it is scattered in PBS（pH=7.4）In, add the carbon of equivalent
Acid sodium aqueous solution（1mM）, obtain 4 wt% Triamcinolone acetonide hydrogels；
（2）By Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol)（PECE；Mw=3500）It is dissolved in the aqueous solution or phosphate-buffered is molten
Liquid（pH=7.4）60 wt% solution are formed, 4 DEG C of conditions is placed in and is preserved；
（3）By under the conditions of 4 DEG C of Triamcinolone acetonide hydrogel and the Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) aqueous solution according to 1:1 grade body
Product physical mixed, is heated to 37 DEG C of 2 wt% Triamcinolone acetonide micellar preparations of acquisition clear.
Example 2 (with PBS as solution, 2 wt% Triamcinolone acetonides micellas is prepared at 37 DEG C of temperature):
(1) by Triamcinolone acetonide-butanedioic acid derivative, it is scattered in PBS（pH=7.4）In, add the carbon of equivalent
Acid sodium aqueous solution（1mM）, obtain 4 wt% Triamcinolone acetonide hydrogels；
（2）By Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol)（PECE；Mw=3500）It is dissolved in the aqueous solution or phosphate-buffered is molten
Liquid（pH=7.4）40 wt% solution are formed, 4 DEG C of conditions is placed in and is preserved；
（3）By under the conditions of 4 DEG C of Triamcinolone acetonide hydrogel and the Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) aqueous solution according to 1:1 grade body
Product physical mixed, is heated to 37 DEG C of 2 wt% Triamcinolone acetonide micellar preparations of acquisition clear.
Example 3 (with PBS as solution, 2 wt% Triamcinolone acetonides micellas is prepared at 37 DEG C of temperature):
(1) by Triamcinolone acetonide-butanedioic acid derivative, it is scattered in PBS（pH=7.4）In, add the carbon of equivalent
Acid sodium aqueous solution（1mM）, obtain 4 wt% Triamcinolone acetonide hydrogels；
（2）By Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol)（PECE；Mw=3500）It is dissolved in the aqueous solution or phosphate-buffered is molten
Liquid（pH=7.4）20 wt% solution are formed, 4 DEG C of conditions is placed in and is preserved；
（3）By under the conditions of 4 DEG C of Triamcinolone acetonide hydrogel and the Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) aqueous solution according to 1:1 grade body
Product physical mixed, is heated to 37 DEG C of 2 wt% Triamcinolone acetonide micellar preparations of acquisition clear.
Example 4 (with PBS as solution, 2 wt% Triamcinolone acetonides micellas is prepared at 37 DEG C of temperature):
(1) by Triamcinolone acetonide-butanedioic acid derivative, it is scattered in PBS（pH=7.4）In, add the carbon of equivalent
Acid sodium aqueous solution（1mM）, obtain 4 wt% Triamcinolone acetonide hydrogels；
（2）By Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol)（PECE；Mw=3500）It is dissolved in the aqueous solution or phosphate-buffered is molten
Liquid（pH=7.4）10 wt% solution are formed, 4 DEG C of conditions is placed in and is preserved；
（3）By under the conditions of 4 DEG C of Triamcinolone acetonide hydrogel and the Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) aqueous solution according to 1:1 grade body
Product physical mixed, is heated to 37 DEG C of 2 wt% Triamcinolone acetonide micellar preparations of acquisition clear.
Example 5 (with PBS as solution, 3 wt% Triamcinolone acetonides micellas is prepared at 37 DEG C of temperature):
(1) by Triamcinolone acetonide-butanedioic acid derivative, it is scattered in PBS（pH=7.4）In, add the carbon of equivalent
Acid sodium aqueous solution（1mM）, obtain 6 wt% Triamcinolone acetonide hydrogels；
（2）By Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol)（PECE；Mw=3500）It is dissolved in the aqueous solution or phosphate-buffered is molten
Liquid（pH=7.4）40 wt% solution are formed, 4 DEG C of conditions is placed in and is preserved；
（3）By under the conditions of 4 DEG C of Triamcinolone acetonide hydrogel and the Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) aqueous solution according to 1:1 grade body
Product physical mixed, is heated to 37 DEG C of 3 wt% Triamcinolone acetonide micellar preparations of acquisition clear.
Example 6 (with PBS as solution, prepares 3 wt% Triamcinolone acetonides micellas) under temperature 50 C:
(1) by Triamcinolone acetonide-butanedioic acid derivative, it is scattered in PBS（pH=7.4）In, add the carbon of equivalent
Acid sodium aqueous solution（1mM）, obtain 6 wt% Triamcinolone acetonide hydrogels；
（2）By Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol)（PECE；Mw=3500）It is dissolved in the aqueous solution or phosphate-buffered is molten
Liquid（pH=7.4）40 wt% solution are formed, 4 DEG C of conditions is placed in and is preserved；
（3）By under the conditions of 4 DEG C of Triamcinolone acetonide hydrogel and the Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) aqueous solution according to 1:1 grade body
Product physical mixed, is heated to 50 DEG C of 3 wt% Triamcinolone acetonide micellar preparations of acquisition clear.
Example 7 (with PBS as solution, 3 wt% Triamcinolone acetonides micellas is prepared at 80 DEG C of temperature):
(1) by Triamcinolone acetonide-butanedioic acid derivative, it is scattered in PBS（pH=7.4）In, add the carbon of equivalent
Acid sodium aqueous solution（1mM）, obtain 6 wt% Triamcinolone acetonide hydrogels；
（2）By Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol)（PECE；Mw=3500）It is dissolved in the aqueous solution or phosphate-buffered is molten
Liquid（pH=7.4）40 wt% solution are formed, 4 DEG C of conditions is placed in and is preserved；
（3）By under the conditions of 4 DEG C of Triamcinolone acetonide hydrogel and the Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) aqueous solution according to 1:1 grade body
Product physical mixed, is heated to 80 DEG C of 3 wt% Triamcinolone acetonide micellar preparations of acquisition clear.
The grain size distribution of the Triamcinolone acetonide micella according to Fig. 2, can obtain Triamcinolone acetonide micella average grain diameter for 20nm.
The transmission electron microscope picture micella of the Triamcinolone acetonide micella according to Fig. 3 is spherical in shape, average grain diameter 20nm.
The above is only the preferred embodiment of the present invention, and protection scope of the present invention is not limited merely to above-mentioned implementation
Example, all technical schemes belonged under thinking of the present invention belong to protection scope of the present invention.It should be pointed out that for the art
Those of ordinary skill for, some improvements and modifications without departing from the principles of the present invention, these improvements and modifications
Should be regarded as protection scope of the present invention.
Claims (5)
1. a kind of preparation method of high drug load Triamcinolone acetonide micella, it is characterised in that comprise the following steps：
（1）Triamcinolone acetonide-butanedioic acid derivative is scattered in PBS, added and Triamcinolone acetonide-succinic acid derivatives
The aqueous sodium carbonate of biological equivalent, obtains Triamcinolone acetonide hydrogel；；
（2）Poly- second two is formed during Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) is dissolved in into the aqueous solution or PBS
Alcohol-polycaprolactone-polyethylene glycol solution, is placed in 0-20 DEG C of condition and preserves；；
（3）By physical mixed under the conditions of 0-20 DEG C of Triamcinolone acetonide hydrogel and Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) solution,
It is heated to more than 20 DEG C systems and the Triamcinolone acetonide micellar preparation that self assembly obtains clear occurs.
2. the preparation method of a kind of high drug load Triamcinolone acetonide micella according to claim 1, it is characterised in that described
Step（1）With（2）In PBS PH be 7.4.
3. the preparation method of a kind of high drug load Triamcinolone acetonide micella according to claim 1, it is characterised in that described
Step（2）The Mw of middle Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) is 3500.
4. the preparation method of a kind of high drug load Triamcinolone acetonide micella according to claim 1, it is characterised in that described
Step（2）Middle Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) solution concentration is 40 wt%.
5. the preparation method of a kind of high drug load Triamcinolone acetonide micella according to claim 1, it is characterised in that described
Step（3）Middle Triamcinolone acetonide hydrogel is 1 with the volume ratio of the mixing of Poly(ethylene glycol)-Polycaprolactone-Poly(ethyleneglycol) solution：1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611135650.2A CN106727306A (en) | 2016-12-12 | 2016-12-12 | A kind of preparation method of high drug load Triamcinolone acetonide micella |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611135650.2A CN106727306A (en) | 2016-12-12 | 2016-12-12 | A kind of preparation method of high drug load Triamcinolone acetonide micella |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106727306A true CN106727306A (en) | 2017-05-31 |
Family
ID=58879769
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611135650.2A Pending CN106727306A (en) | 2016-12-12 | 2016-12-12 | A kind of preparation method of high drug load Triamcinolone acetonide micella |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106727306A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002045689A1 (en) * | 2000-12-07 | 2002-06-13 | Samyang Corporation | Compositions for sustained delivery of hydrophobic drugs and process for the preparation thereof |
| CN1429120A (en) * | 2000-05-17 | 2003-07-09 | 株式会社三养社 | Stable polymeric micelle-type drug composition and method for preparation thereof |
| CN1164675C (en) * | 1999-08-14 | 2004-09-01 | 株式会社三养社 | Polymeric compsn. for solubilizing poorly water soluble drugs and process for prepn. thereof |
| CN1813770A (en) * | 2005-11-21 | 2006-08-09 | 咸阳步长医药科技发展有限公司 | Gel of triamcinolone acetonide and econazole nitrate, its preparing and quality control method |
| CN1899292A (en) * | 2005-07-22 | 2007-01-24 | 上海医药工业研究院 | Triamcinolone benetonide local film forming gel composition |
| CN104055728A (en) * | 2014-06-16 | 2014-09-24 | 温州医科大学 | Preparation method of ophthalmic triamcinolone acetonide hydrogel preparation |
-
2016
- 2016-12-12 CN CN201611135650.2A patent/CN106727306A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1164675C (en) * | 1999-08-14 | 2004-09-01 | 株式会社三养社 | Polymeric compsn. for solubilizing poorly water soluble drugs and process for prepn. thereof |
| CN1429120A (en) * | 2000-05-17 | 2003-07-09 | 株式会社三养社 | Stable polymeric micelle-type drug composition and method for preparation thereof |
| WO2002045689A1 (en) * | 2000-12-07 | 2002-06-13 | Samyang Corporation | Compositions for sustained delivery of hydrophobic drugs and process for the preparation thereof |
| CN1899292A (en) * | 2005-07-22 | 2007-01-24 | 上海医药工业研究院 | Triamcinolone benetonide local film forming gel composition |
| CN1813770A (en) * | 2005-11-21 | 2006-08-09 | 咸阳步长医药科技发展有限公司 | Gel of triamcinolone acetonide and econazole nitrate, its preparing and quality control method |
| CN104055728A (en) * | 2014-06-16 | 2014-09-24 | 温州医科大学 | Preparation method of ophthalmic triamcinolone acetonide hydrogel preparation |
Non-Patent Citations (1)
| Title |
|---|
| WAI-LEUNG ET AL: "Specific uptake of folate-decorated triamcinolone-encapsulating nanoparticles by retinal pigment epithelium cells enhances and prolongs antiangiogenic activity", 《JOURNAL OF CONTROLLED RELEASE》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Duong et al. | Preparation of solid lipid nanoparticles and nanostructured lipid carriers for drug delivery and the effects of preparation parameters of solvent injection method | |
| Li et al. | New nanomicelle curcumin formulation for ocular delivery: improved stability, solubility, and ocular anti-inflammatory treatment | |
| Hao et al. | Fabrication of an ionic-sensitive in situ gel loaded with resveratrol nanosuspensions intended for direct nose-to-brain delivery | |
| Gao et al. | Preparation and characterization of intravenously injectable curcumin nanosuspension | |
| CN102824356A (en) | Baicalin nano crystal suspension, nano crystal dry powder and methods for preparing baicalin nano crystal suspension and nano crystal dry powder | |
| CN107929235B (en) | Tacrolimus ophthalmic preparation and preparation method thereof | |
| Yuan et al. | Encapsulation and delivery of curcumin in cellulose nanocrystals nanoparticles using pH-driven method | |
| Huang et al. | Preparation and pharmacodynamics of low-molecular-weight chitosan nanoparticles containing insulin | |
| Osman et al. | Novel fatty acid-based pH-responsive nanostructured lipid carriers for enhancing antibacterial delivery | |
| CN1771910A (en) | Nanometer particle of insoluble medicine and its prepn | |
| CN101843582B (en) | taxol nano suspension and preparation method thereof | |
| CN113197852A (en) | Cannabidiol nano micelle preparation and preparation method thereof | |
| Wei et al. | The characterisation, pharmacokinetic and tissue distribution studies of TPGS modified myricetrin mixed micelles in rats | |
| CN101612121A (en) | The preparation of microemulsion containing paclitaxel method | |
| Morteza-Semnani et al. | Green formulation, characterization, antifungal and biological safety evaluation of terbinafine HCl niosomes and niosomal gels manufactured by eco-friendly green method | |
| JP5784619B2 (en) | Method for wetting powders containing benzoyl peroxide | |
| CN103099785A (en) | Method for preparing hydrophobic medicament nuclear shell granule-type solid dispersion by static electricity spraying method | |
| Sampathi et al. | Pharmacokinetics and anti-diabetic studies of gliclazide nanosuspension | |
| Zhao et al. | Controlled fabrication of drug‐loaded protein nanoparticles via flash nanoprecipitation | |
| CN108025080A (en) | Containing cyclosporin and nonirritant eye medicine combination and convenient preparation method | |
| CN107137350A (en) | A kind of taxol polymer micelle and preparation method thereof | |
| CN106727306A (en) | A kind of preparation method of high drug load Triamcinolone acetonide micella | |
| CN104188904B (en) | Eye use voriconazole nanocrystal preparation and preparation method thereof | |
| CN110604747A (en) | Propolis nanoparticle, preparation method and application thereof, and preparation method of freeze-dried powder of propolis nanoparticle | |
| CN103070836B (en) | Ciclesonide nanometer freeze-dried powder and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170531 |