CN106420649A - Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet - Google Patents
Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet Download PDFInfo
- Publication number
- CN106420649A CN106420649A CN201611060522.6A CN201611060522A CN106420649A CN 106420649 A CN106420649 A CN 106420649A CN 201611060522 A CN201611060522 A CN 201611060522A CN 106420649 A CN106420649 A CN 106420649A
- Authority
- CN
- China
- Prior art keywords
- acetaminophen
- controlled release
- tablet
- preparation
- release tablet
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an acetaminophen press-coated controlled release tablet based on a polyelectrolyte self-assembled film and a preparation method of the acetaminophen press-coated controlled release tablet, and belongs to the technical field of medicines. The acetaminophen-pressed and coated controlled release tablet disclosed by the invention comprises not only a coating layer composed of chitosan and sodium alginate, but also a tablet core containing acetaminophen, is prepared through a pressing and coating technology, is released for 2 hours in artificial gastric juice (0.1M HCI solution) and then is released for 2 hours in simulated intestinal fluid (0.1M phosphate Buffer solution); an outer layer of the tablet can form a layer of thick polyelectrolyte compound barrier within 4 hours through self assembly to effectively control the release of medicines in the tablet core, so that the outer layer can keep a form complete within 12 hours and achieve a controlled release purpose. The acetaminophen controlled release tablet prepared by the preparation method disclosed by the invention can obliviously delay the in-vitro release time of the medicines and achieve a more stable release in vitro compared with an ordinary preparation; the preparation process is relatively simple, and a novel alternative preparation is provided for the development of the acetaminophen controlled release tablet.
Description
Technical field
The present invention relates to a kind of acetaminophen pressed coated controlled release tablet based on Polyelectrolyte Self-assembled and its system
Preparation Method, belongs to pharmaceutical technology field.
Background technology
Acetaminophen is international using the most extensive, the maximum OTC (over-the-counter) antipyretic analgesic of consumption, domestic medicine at present
Up to tens kinds of Aceta Elixir product on market, dosage form has injection, capsule, powder, electuary, syrup, suppository, drop
And injection etc..Acetaminophen has higher water solublity, and normal adult has about 2～3h phase after taking common dose
To the shorter half-life, ordinary preparation need to be taken and repeatedly could maintain drug effect, so that blood drug level produces " peak valley " phenomenon.When
When consumption is excessive, metabolite has infringement to liver, hemoglobin degeneration can be made to cause haemolysis, and take in a large number to acetyl for a long time
Amino phenols also have infringement, particularly poor kidney person to renal function, renal colic or acute renal failure easily and liver damages
Evil or cholestatic hepatitis, severe patient can cause hepatic coma even dead.For this reason, being prepared into controlled release tablet, it is possible to decrease it is in vivo
Maximum plasma concentration, the effective blood drug concentration of long period maintenance simultaneously, " peak valley " phenomenon can be prevented effectively from, there is prolongation medicine
Therapeutical effect, reduce hepatorenal damage, reduce the features such as take number of times.
Compound polyelectrolyte is novel high polymer composite developed in recent years, means with opposite charges
The macromole composite network being formed by the interaction of electrostatic attraction between cationic polymer and anionic polymer.
This composite network has special adsorptivity to water, the generally transparent gel of the hygrometric state compound polyelectrolyte after water suction and insoluble
Yu Shui, such that it is able to keep form complete for a long time, blocking medicine discharges, and reaches slow-releasing and controlled-releasing action.With chemical crosslinking formation
Complex is compared, compound polyelectrolyte relative nontoxic, good biocompatibility, clinical practice safety, and due to its raw material sources
Abundant, cheap, and in fields such as biomedicine, membrance separation, fruit freshness preserving, catalyst preparations, there is potential use, because
And its preparation, modification and applied research cause the common concern of Chinese scholars.
Because traditional packaging technique has problem of solvent residual, therefore non-solvent coating becomes the heat of researcher research
Point.Compression coated tablets refers to by secondary compacting so that internal layer label is wrapped up by outer layer macromolecule coating material completely, by outer
The corrosion of floor height molecular material, dissolve, come off etc. and realizing different drug release behaviors, such as pulsed release, slow-release etc..It is one
The packaging technique plant and do not use solvent completely, not needing heating, technology is relatively simple, and technique is simplified, and industrial cost consumes and compares
Low, there are certain Research Prospects.The medicine of the species that gets more and more in recent years achieves controlled release behavior by pressed coated, but
Dry-method coating material mostly still is cellulose derivative, such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose
Deng.
The present invention using the physical mixture of cationic polymer and anionic polymer as pressed coated technology coating
Material, when preparation contact gastric juice, surface cation type polymer can gradually protonate, and anionic polymer is in non-electrical
From state, gradually rise with Digestive system environment pH, gradually ionizing is negatively charged for the anionic polymer of dosage surface, with
Positively charged cation type polymer passes through electrostatic interaction and forms water-insoluble compound polyelectrolyte film in dosage surface, from
And the release of label Chinese medicine thing can be controlled.
Content of the invention
It is an object of the invention to provide a kind of good stability, curative effect are reliable, untoward reaction little with acetaminophen
Pressed coated controlled release tablet made for principal agent and preparation method thereof, comprise acetaminophen, cationic polymer, anion gather
, it is characterised in that the compression coated tablets of making above-mentioned material, profile is outside round convex type, piece for compound, filler and lubricant
Core diameter is 6mm, a diameter of 8mm of whole coated tablet, and smooth in appearance is complete, and during discharging in vitro, its coatings can be from dominant shape
Become compound polyelectrolyte film, form can be kept in 12h complete and with constant speed or close to the such feature of constant release medicine
Preparation.
It is framework material that the present invention selects cation and anionic polymer, and physical mixed is direct by a certain percentage for both generals
Tabletting so as to 0.1M HCl solution as dissolution medium in 2h, with 0.1M phosphate buffer as dissolution medium in 2～12h
Leaching condition under, by physical crosslinking be self-assembly of compound polyelectrolyte film.This Physical cross linking methods preparation is poly- electric
Solution matter complexes membrane is compared and is consistent with human physiological environment by being chemically crosslinked simpler feasible and required release conditions
Close.
Heretofore described outer layer coating layer is made up of cationic polymer and anionic polymer；Internal layer label is by medicine
Thing, filler and lubricant composition.Cation type polymer is selected from the different deacetylations that mean molecule quantity is not less than 100kDa
The shitosan of (70～95%), the shitosan of preferably 90.21% deacetylation；It is not little that anionic polymer is selected from molecular weight
In the sodium alginate of 100kDa, molecular weight is not less than the carrageenan of 100kDa, and molecular weight is not less than the carboxymethyl cellulose of 100kDa
One of plain sodium or combinations thereof, preferably sodium alginate；Filler is selected from one of Microcrystalline Cellulose, Lactose, starch
Or its combination in any, preferably Microcrystalline Cellulose and Lactose；Lubricant be selected from magnesium stearate, sodium stearate, in Pulvis Talci one
Plant or its combination in any, preferably magnesium stearate.
The each constituent content of acetaminophen pressed coated controlled release tablet in present invention percentage ratio by weight is as follows：
Preparation method comprises the following steps：By the acetaminophen of recipe quantity, Microcrystalline Cellulose, Lactose, magnesium stearate
Mix, direct compression obtains Paracetamol Tablets core；The shitosan of recipe quantity, sodium alginate are mixed, it mixes to take half amount
Compound is uniformly filled in punch die bottom, and label is placed in one to be refilled the mixture of other half amount after the heart and wrapped up, and two
Secondary direct compression obtains final product.
The profile of the acetaminophen pressed coated controlled release tablet in the present invention is outside round convex type, a diameter of 6mm of label,
The whole a diameter of 8mm of coated tablet, smooth in appearance is complete, and weight differential, friability all meet the requirements.
The concrete technical scheme of the present invention is as follows：
A kind of acetaminophen pressed coated controlled release tablet, mainly by outer layer coating framework material, label medicine and filling
Agent is constituted.After coating framework material is contacted with gastro-intestinal Fluid, form a strata pentalyte barrier around tablet.By adjusting
The pastille ratio of ratio, coatings and label of section coatings cation and anionic polymer, the species of filler and consumption, make
It can form compound polyelectrolyte film within the specific time, and keeps form complete during whole release, and then
Change the rate of releasing drug of label and shell, realize tablet entirety controlled release release.
The present invention is directed in existing Aceta Elixir and is mostly conventional tablet, has blood concentration fluctuation greatly, medication
Often, the problems such as, it is successfully prepared and includes 6mm pastille label, the complete 8mm acetaminophen pressed coated of smooth-shaped
Controlled release tablet, said preparation can significantly extend medicine release time in vivo, can reach more steady compared with ordinary preparation in vitro
Release, improve the oral administration biaavailability of medicine, and preparation technology be relatively easy.
Specific embodiment
With reference to example, the present invention is explained and illustrated in more detail with the embodiment it will be appreciated that given
It is illustrative, it constitutes any restriction to the scope of the present invention never in any form.
Embodiment 1 prepares 10 acetaminophen pressed coated controlled release tablet
Label：
Outer layer：
Shitosan 600mg
Sodium alginate 600mg
Preparation method：Acetaminophen is crossed 80 mesh sieves respectively with each adjuvant, weighs acetaminophen by recipe quantity
And adjuvant, it is sufficiently mixed uniformly according to equal increments method, mixing of sieving, appropriate magnesium stearate is added using outer addition, fully mixed
After even, Paracetamol Tablets core is prepared using direct powder compression.The shitosan of recipe quantity, sodium alginate are crossed respectively 80
Mesh sieve is sufficiently mixed uniformly according to equal increments method, mixing of sieving, and takes half amount coating material to be uniformly filled in punch die bottom, will
Label is placed in one and refills the coating material of other half amount after the heart, and secondary direct compression obtains final product.
Embodiment 2 prepares 10 acetaminophen pressed coated controlled release tablet
Label：
Outer layer：
Shitosan 11mg
Sodium alginate 109mg
Preparation method：Acetaminophen is crossed 80 mesh sieves respectively with each adjuvant, weighs acetaminophen by recipe quantity
And adjuvant, it is sufficiently mixed uniformly according to equal increments method, mixing of sieving, appropriate magnesium stearate is added using outer addition, fully mixed
After even, Paracetamol Tablets core is prepared using direct powder compression.The shitosan of recipe quantity, sodium alginate are crossed respectively 80
Mesh sieve is sufficiently mixed uniformly according to equal increments method, mixing of sieving, and takes half amount coating material to be uniformly filled in punch die bottom, will
Label is placed in one and refills the coating material of other half amount after the heart, and secondary direct compression obtains final product.
Embodiment 3 prepares 10 acetaminophen pressed coated controlled release tablet
Label：
Outer layer：
Acetaminophen 80mg
Shitosan 600mg
Sodium alginate 600mg
Preparation method：Acetaminophen is crossed 80 mesh sieves respectively with each adjuvant, weighs acetaminophen by recipe quantity
And adjuvant, it is sufficiently mixed uniformly according to equal increments method, mixing of sieving, appropriate magnesium stearate is added using outer addition, fully mixed
After even, Paracetamol Tablets core is prepared using direct powder compression.By the acetaminophen of recipe quantity, shitosan, sea
Sodium alginate is crossed 80 mesh sieves respectively and is sufficiently mixed uniformly according to equal increments method, and mixing of sieving takes half amount coating material uniformly to fill out
Fill in punch die bottom, label is placed in one and refills the coating material of other half amount after the heart, secondary direct compression obtains final product.
Test example：
A comparison example presented below：Commercially available Paracetamol Tablets and acetaminophen compacting according to the present invention
Release in same media for the coating sustained-release tablet is over time.According to《Chinese Pharmacopoeia》Dissolution determination in 2015 editions general rules
Method first method carries out to the dissolution in vitro of invention formulation and ordinary tablet investigating contrast, and dissolution test is at 37 DEG C, in 2h with
The 0.1M HCl solution of 900mL is with the 0.1M phosphate buffer of 900mL as solvent in solvent, 2～12h, with rotating speed is
100rpm, ultraviolet spectrophotometry is detected.Conventional tablet dissolution in 30min reaches more than 90%, the release of the present invention
Degree parameter is following (percent referenced below is percetage by weight)：
Result shows, the acetaminophen pressed coated controlled release tablet smooth in appearance of present invention preparation is complete, makes with common
Agent is compared can reach in vitro and is more stably discharged, and extends drug treating time, improves the oral administration biaavailability of medicine,
And preparation technology is relatively easy.
Claims (6)
1. a kind of acetaminophen pressed coated controlled release tablet based on Polyelectrolyte Self-assembled, said preparation includes：
(a) coatings：This coatings contains cation type polymer and anionic polymer；
(b) label：This label contains acetaminophen, filler and lubricant.
2. acetaminophen pressed coated controlled release tablet according to claim 1 it is characterised in that：Sun in coatings from
Subtype polymer is selected from the shitosan that mean molecule quantity is not less than the different deacetylations (70～95%) of 100kDa；Anionic
Polymer is selected from the sodium alginate that molecular weight is not less than 100kDa, and molecular weight is not less than the carrageenan of 100kDa, and molecular weight is not little
One of sodium carboxymethyl cellulose in 100kDa or combinations thereof；Filler is in Microcrystalline Cellulose, Lactose, starch
One kind or its combination in any；Lubricant is selected from one of magnesium stearate, sodium stearate, Pulvis Talci or its combination in any.
3. the acetaminophen pressed coated controlled release tablet according to claim 1 and 2 it is characterised in that：
A () described preparation coatings include the component of following percentage by weight：Shitosan 10～50%, sodium alginate 10～
50%；
B () described preparation label includes the component of following percentage by weight：Acetaminophen 10～30%, Microcrystalline Cellulose 5
～10%, Lactose 15～30%, magnesium stearate 0.5～2%.
4. method for preparing tablet thereof according to claim 1 is it is characterised in that label is by acetaminophen, filler and profit
Lubrication prescription direct powder compression is obtained；Compression coated tablets carries out secondary tabletting after being wrapped up label by coating layer material and is obtained.
5. the tablet according to claim 1 and 4 it is characterised in that：The profile of internal label is outside round convex type, a diameter of
6mm；After pressed coated, tablet is outside round convex type, a diameter of 8mm.
6. tablet according to claim 1 it is characterised in that：Dissolution method according to 2015 editions regulations of Chinese Pharmacopoeia
First method carries out dissolution test, under the conditions of 37 DEG C, with the 0.1MHCl solution of 900mL as dissolution medium in 2h, in 2～12h with
The 0.1M phosphate buffer of 900mL is dissolution medium, and rotating speed is 100rpm, and acetaminophen is molten from pressed coated tablet
The speed going out is：
After 2h, cumulative release percent is 5%～10%；
After 4h, cumulative release percent is 10%～30%；
After 12h, cumulative release percent is at least 80%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611060522.6A CN106420649A (en) | 2016-11-21 | 2016-11-21 | Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611060522.6A CN106420649A (en) | 2016-11-21 | 2016-11-21 | Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106420649A true CN106420649A (en) | 2017-02-22 |
Family
ID=58218733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611060522.6A Pending CN106420649A (en) | 2016-11-21 | 2016-11-21 | Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106420649A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114504561A (en) * | 2022-03-01 | 2022-05-17 | 陕西科技大学 | Water-based coating method for preparing drug osmotic pump preparation |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6372254B1 (en) * | 1998-04-02 | 2002-04-16 | Impax Pharmaceuticals Inc. | Press coated, pulsatile drug delivery system suitable for oral administration |
| CN1882316A (en) * | 2003-09-19 | 2006-12-20 | 宾韦斯特医药公司 | Delayed release dosage forms |
| CN101700235A (en) * | 2009-11-24 | 2010-05-05 | 沈阳药科大学 | Self-assembling compound film-controlled slow-release preparation and preparation method thereof |
| WO2011107750A2 (en) * | 2010-03-05 | 2011-09-09 | University Of Strathclyde | Delayed prolonged drug delivery |
| CN102988324A (en) * | 2012-11-12 | 2013-03-27 | 中国药科大学 | Preparation for glipizide compression-coated controlled-release tablets |
-
2016
- 2016-11-21 CN CN201611060522.6A patent/CN106420649A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6372254B1 (en) * | 1998-04-02 | 2002-04-16 | Impax Pharmaceuticals Inc. | Press coated, pulsatile drug delivery system suitable for oral administration |
| CN1882316A (en) * | 2003-09-19 | 2006-12-20 | 宾韦斯特医药公司 | Delayed release dosage forms |
| CN101700235A (en) * | 2009-11-24 | 2010-05-05 | 沈阳药科大学 | Self-assembling compound film-controlled slow-release preparation and preparation method thereof |
| WO2011107750A2 (en) * | 2010-03-05 | 2011-09-09 | University Of Strathclyde | Delayed prolonged drug delivery |
| CN102988324A (en) * | 2012-11-12 | 2013-03-27 | 中国药科大学 | Preparation for glipizide compression-coated controlled-release tablets |
Non-Patent Citations (3)
| Title |
|---|
| FERNA´NDEZ-HERVA´S ET AL.: "Pectin:chitosan mixtures as coatings for colon-specific drug delivery: an in vitro evaluation", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| HAIQIN HUANG ET AL.: "Compression-coated tablets of glipizide using hydroxypropylcellulose for zero-order release: In vitro and in vivo evaluation", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| LIANG LI ET AL.: "Drug release characteristics from chitosan–alginate matrix tablets based on the theory of self-assembled film", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114504561A (en) * | 2022-03-01 | 2022-05-17 | 陕西科技大学 | Water-based coating method for preparing drug osmotic pump preparation |
| CN114504561B (en) * | 2022-03-01 | 2023-08-11 | 陕西科技大学 | Aqueous coating method for preparing drug osmotic pump preparation |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI97686B (en) | A method of making beads for the purpose of producing controlled release products | |
| JP6042880B2 (en) | Controlled release solid dosage form | |
| CN101987091B (en) | Venlafaxine hydrochloride sustained-release pellet capsules | |
| CN104146976B (en) | Heavy-load valproic acid drug sustained release tablet and preparation method thereof | |
| WO2000009133A1 (en) | Sustained release oral preparations of fasudil hydrochloride | |
| CN106860430A (en) | The preparation of the skeletal muscle relaxant dosage forms of control release | |
| AU2015337779A1 (en) | Methods and compositions particularly for treatment of attention deficit disorder | |
| CN103784396A (en) | Oral ibuprofen pellet xerogel and preparation method thereof | |
| CN107308127A (en) | C14H10Cl2NNaO2 multi-unit sustained-release pellet tablet | |
| Shah et al. | A review on extended release drug delivery system and multiparticulate system | |
| CN105902500A (en) | Mesalazine enteric positioned controlled-release preparation and preparation method thereof | |
| CN106420649A (en) | Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet | |
| CN102429873A (en) | Desmethylvenlafaxine sustained-release pellet and preparation method thereof | |
| CN101411702B (en) | Nefopam hydrochloride naproxen sodium compound sustained-release preparation and preparation method thereof | |
| CN1248693C (en) | Sustained release formulation of glucosamine salt, its preparation and usage | |
| US20190240163A1 (en) | Multiparticulate including pharmaceutical or probiotic active ingredients for delivery via a shelf stable liquid dosage form | |
| CN102973533A (en) | Preparation method of famotidine gastric-floating-type pellet tablets | |
| CN103845323B (en) | Mycophenolic Acid and its salt enteric coated preparations and preparation method | |
| US9358205B2 (en) | Modified starch derivative-based matrix for colon targeting | |
| CN101507713A (en) | High bioavailability proton pump inhibitor sustained-release technique | |
| CN101040850A (en) | Colchicine sustained-release pellets and the preparing method | |
| CN102579358B (en) | A kind of drug sustained-release pellet and preparation method thereof | |
| CN102600108A (en) | Flurbiprofen sustained release capsules and preparation method thereof | |
| CN102579359B (en) | A kind of Tamsulosin sustained release pellet and preparation method thereof | |
| CN1256082C (en) | Slow-released preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170222 |
|
| RJ01 | Rejection of invention patent application after publication |