CN109172533A - A kind of xylitol grains of directly compressible and preparation method thereof - Google Patents
A kind of xylitol grains of directly compressible and preparation method thereof Download PDFInfo
- Publication number
- CN109172533A CN109172533A CN201811366053.XA CN201811366053A CN109172533A CN 109172533 A CN109172533 A CN 109172533A CN 201811366053 A CN201811366053 A CN 201811366053A CN 109172533 A CN109172533 A CN 109172533A
- Authority
- CN
- China
- Prior art keywords
- xylitol
- preparation
- adhesive
- wetting agent
- grains
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/20—Agglomerating; Granulating; Tabletting
- A23P10/28—Tabletting; Making food bars by compression of a dry powdered mixture
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses xylitol grains of a kind of directly compressible and preparation method thereof, the mass percent ingredients of the xylitol grains are as follows: Determination of Xylitol is 98~99%, and binder content is 1~2%.The xylitol grains are that xylitol and adhesive are sprayed wetting agent after mixing, are granulated by boiling granulator, are then directly pressed into tablet with tablet press machine.The present invention produces the big particle of direct tablet compressing hardness by adjusting binder dosage, wetting agent type and the indexs such as dosage, prilling temperature and time, drying temperature and time, granule size, water content in production process.Adhesive dry powder is directly mixed with material, and without still further being dissolved, and material is mixed, pelletized, drying carries out in the same device, and production process simple operations are convenient.Adhesive therefor amount of pelletizing is few, and in addition addition will not be had to when its tabletting and assists substance in blocks, particle and tabletting xylitol purity is improved, reduces production cost.
Description
Technical field
The present invention relates to technical field of functional sugar, the xylitol grains and its preparation of specifically a kind of directly compressible
Method.
Background technique
Xylitol is a kind of natural edible health sugar alcohol, is the normal glycometabolism intermediate of the mankind.Its chemical molecular
Formula is C5H12O5, white crystals or crystalline powder, is highly soluble in water.Xylitol is with function such as its sugar-free, moisturizing, sweet taste, health cares
Energy characteristic, is applied to food, medical material.Since xylitol is for taking care of one's teeth, oral care, prevention otitis, fresh breath
Have fine effect, in order to make its in the oral cavity the effect of play more preferable, xylitol has been made into diversified forms at present
Lozenge.However xylitol has stronger hygroscopicity, therefore poor fluidity, is not easy direct tablet compressing, so wanting to xylitol
Tabletting just must overcome above-mentioned unfavorable conditions.Currently, existing correlation can be used for the patent report of the xylitol of tabletting both at home and abroad.
The country mostly uses the wet granulation technique of addition adhesive, such as patent CN200410070541.8 " directly compressible
Xylitol grains and its manufacturing method ", CN201110453099.7 " a kind of xylitol of directly compressible and its preparation side
Method ", " one kind can by CN200810238544.6 " a kind of DC grade xylitol wet granulation preparation process " and CN200510068255.2
Xylitol grains of direct tablet compressing and preparation method thereof " in the technical method mentioned.The technical method is more original, operating procedure
It is cumbersome, and adhesive needs a large amount of water or other solvents to be configured to solution compared with indissoluble solution, and viscous stifled sieve is easy to appear in granulation process
Net phenomenon, further need exist for increase drying equipment dried, be also added into the formula of the above patent other polyalcohols or its
His sweetener, reduces xylitol purity.
Patent CN200810238544.6 " xylitol grains of directly compressible and preparation method thereof " is used more first
Into fluidized granulating method, but a part of adhesive is also required to then be sprayed with hot water wiring solution-forming in spraying mode in technique
Onto material, adhesive process for preparation is comparatively laborious also to be needed to filter out the bulky grain not dissolved, and needs to use while hot.
The amount of binder that the particle that this method is made for the benefit of forms tabletting, raising tabletting hardness is added is bigger, and in tabletting
Magnesium stearate is also added in journey, this not only improves the cost of granulation and tabletting, and also reduces wooden in particle and tabletting
Sugar alcohol purity
Summary of the invention
Technical assignment of the invention is to provide a kind of xylitol grains and preparation method thereof of directly compressible.
Technical assignment of the invention is realized in the following manner:
A kind of xylitol grains of directly compressible, the mass percent ingredient of the xylitol grains are as follows: Determination of Xylitol 98
~99%, binder content is 1~2%.
The adhesive is sodium carboxymethylcellulose.
A kind of the step of preparation method of the xylitol grains of directly compressible, this method, is as follows:
Step 1) is pulverized and mixed feeding: xylosic alcohol powder being broken into 100 mesh powder below, addition binder powders mixing will mix
It closes uniform powder and is packed into boiling granulator hopper and prepare granulation；
Step 2 prepares wetting agent: it is spare that wetting agent being added into Liquid spray reservoir；
Step 3) is granulated: opening the boiling granulator is set as material, in fluidized state, by prilling temperature in equipment
It 40~60 DEG C, by wetting agent in spraying form, is constantly sprayed between material particles, required profit has been sprayed in 1~2 hour
Humectant；After having sprayed, hot wind is opened to 70~90 DEG C, dry 0~40min, then open cold wind and drop to room temperature, then screened out with sieve
Grain；
Step 4) tabletting: gained particle is directly pressed into tablet with tablet press machine, obtains high rigidity, high-purity xylitol tablet.
Purity >=99.5% of xylitol in the step 1).
In the step 1) adhesive be sodium carboxymethylcellulose, the adhesive viscosities range be 800~
1600mPa.S, the adhesive adding proportion are the 1~1.5% of xylitol quality.
The wetting agent is pure water, and the dosage of the pure water is the 0.5~1.50% of xylitol quality.
The partial size of the particle screened out in the step 3) with sieve is 20~80 mesh.
The mass content of water is 0.15~0.3% in the particle, and the mass content of xylitol is 98~99%, adhesive
Mass content be 1~2%.
Compared to the prior art xylitol grains of a kind of directly compressible of the invention and preparation method thereof, pass through production
Adjust in the process binder dosage, wetting agent type and dosage, prilling temperature and time, drying temperature and time, granule size,
The indexs such as water content produce the big particle of direct tablet compressing hardness.Adhesive dry powder directly and material mixing, without still further into
Row dissolution, and material is mixed, is pelletized, drying carries out in the same device, production process simple operations are convenient.Granulation bonding used
Dosage is few, and hardness of the xylitol grains in tableting processes for raising tabletting can add magnesium stearate etc. and be used as glidant at present,
And the mobility of particle and compressibility of this method production are high, can directly carry out the made tabletting hardness >=150N of tabletting, in tabletting
Xylitol purity >=98%, the purity of xylitol in tabletting can be improved again by not adding other auxiliary substances in blocks in tableting processes
Tabletting cost can be reduced.
Specific embodiment
Embodiment 1:
1) it is pulverized and mixed feeding: the xylosic alcohol powder of purity 99.7% being broken into 100 mesh powder below, is added after weighing 100kg powder
The sodium carboxymethylcellulose powder 1kg added is uniformly mixed, and the powder mixed is packed into and prepares to pelletize in boiling granulator hopper.
2) prepare wetting agent: it is spare into Liquid spray reservoir to weigh pure water 0.5kg.
3) be granulated: opening boiling granulator makes material in equipment in fluidized state, and prilling temperature is set as 40 DEG C, will
Water as wetting agent is sprayed between powder particles in spraying form, continuous to spray into, and the hydrojet time 1 hour；After having sprayed
Continue out hot wind to 70 DEG C of drying 0min, then opens cold wind and drop to room temperature；Partial size particle between 20~80 mesh is screened out with sieve,
Measure water content be 0.17%, xylitol purity 98.4%, binder content 1.21%.
4) tabletting: being directly pressed into tablet with tablet press machine for gained particle, and obtaining hardness is 169.3N, 98.4% xylose of purity
Alcohol tablet.
Embodiment 2:
1) it is pulverized and mixed feeding: the xylosic alcohol powder of purity 99.7% being broken into 100 mesh powder below, is added after weighing 100kg powder
The sodium carboxymethylcellulose powder 1.2kg added is uniformly mixed, and the powder mixed is packed into and prepares to make in boiling granulator hopper
Grain.
2) prepare wetting agent: it is spare into Liquid spray reservoir to weigh pure water 1kg.
3) be granulated: opening boiling granulator makes material in equipment in fluidized state, and prilling temperature is set as 50 DEG C, will
Water as wetting agent is sprayed between powder particles in spraying form, continuous to spray into, and the hydrojet time 1.5 hours；It has sprayed
After continue out hot wind to 80 DEG C of drying 20min, then open cold wind and drop to room temperature；Partial size is screened out between 30~60 mesh with sieve
Grain, measurement water content be 0.23%, xylitol purity 98.37%, binder content 1.41%.
4) tabletting: being directly pressed into tablet with tablet press machine for gained particle, and obtaining hardness is 152.1N, 98.37% xylose of purity
Alcohol tablet.
Embodiment 3:
1) it is pulverized and mixed feeding: the xylosic alcohol powder of purity 99.7% being broken into 100 mesh powder below, is added after weighing 100kg powder
The sodium carboxymethylcellulose powder 1.5kg added is uniformly mixed, and the powder mixed is packed into and prepares to make in boiling granulator hopper
Grain.
2) prepare wetting agent: it is spare into Liquid spray reservoir to weigh pure water 1.5kg.
3) be granulated: opening boiling granulator makes material in equipment in fluidized state, and prilling temperature is set as 60 DEG C, will
Water as wetting agent is sprayed between powder particles in spraying form, continuous to spray into, hydrojet time 2 h；After having sprayed
Continue out hot wind to 90 DEG C of drying 40min, then opens cold wind and drop to room temperature；Partial size is screened out between 40~70 mesh with sieve
Grain, measurement water content be 0.16%, xylitol purity 98.29%, binder content 1.49%.
4) tabletting: being directly pressed into tablet with tablet press machine for gained particle, and obtaining hardness is 178.9N, 98.29% xylose of purity
Alcohol tablet.
The technical personnel in the technical field can readily realize the present invention with the above specific embodiments,.But it answers
Work as understanding, the present invention is not limited to above-mentioned several specific embodiments.On the basis of the disclosed embodiments, the technology
The technical staff in field can arbitrarily combine different technical features, to realize different technical solutions.
Claims (8)
1. a kind of xylitol grains of directly compressible, which is characterized in that the mass percent ingredient of the xylitol grains are as follows: wood
Content of sugar alcohol is 98~99%, and binder content is 1~2%.
2. xylitol grains according to claim 1, which is characterized in that the adhesive is sodium carboxymethylcellulose.
3. a kind of preparation method of the xylitol grains of directly compressible, which is characterized in that the step of this method is as follows:
Step 1) is pulverized and mixed feeding: xylosic alcohol powder being broken into 100 mesh powder below, addition binder powders mixing will mix
It closes uniform powder and is packed into boiling granulator hopper and prepare granulation；
Step 2 prepares wetting agent: it is spare that wetting agent being added into Liquid spray reservoir；
Step 3) is granulated: opening the boiling granulator is set as material, in fluidized state, by prilling temperature in equipment
It 40~60 DEG C, by wetting agent in spraying form, is constantly sprayed between material particles, required profit has been sprayed in 1~2 hour
Humectant；After having sprayed, hot wind is opened to 70~90 DEG C, dry 0~40min, then open cold wind and drop to room temperature, then screened out with sieve
Grain；
Step 4) tabletting: gained particle is directly pressed into tablet with tablet press machine, obtains high rigidity, high-purity xylitol tablet.
4. the preparation method of xylitol grains according to claim 3, which is characterized in that xylitol in the step 1)
Purity >=99.5%.
5. the preparation method of xylitol grains according to claim 3, which is characterized in that adhesive in the step 1)
For sodium carboxymethylcellulose, the adhesive viscosities range is 800~1600mPa.S, and the adhesive adding proportion is
The 1~1.5% of xylitol quality.
6. the preparation method of xylitol grains according to claim 3, which is characterized in that the wetting agent is pure water,
The dosage of the pure water is the 0.5~1.50% of xylitol quality.
7. the preparation method of xylitol grains according to claim 3, which is characterized in that use sieve in the step 3)
The partial size of the particle screened out is 20~80 mesh.
8. the preparation method of xylitol grains according to claim 7, which is characterized in that the quality of water in the particle
Content is 0.15~0.3%, and the mass content of xylitol is 98~99%, and the mass content of adhesive is 1~2%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811366053.XA CN109172533A (en) | 2018-11-16 | 2018-11-16 | A kind of xylitol grains of directly compressible and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811366053.XA CN109172533A (en) | 2018-11-16 | 2018-11-16 | A kind of xylitol grains of directly compressible and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109172533A true CN109172533A (en) | 2019-01-11 |
Family
ID=64940186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811366053.XA Pending CN109172533A (en) | 2018-11-16 | 2018-11-16 | A kind of xylitol grains of directly compressible and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109172533A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109770365A (en) * | 2019-03-29 | 2019-05-21 | 汤臣倍健股份有限公司 | One kind of multiple chewable vitamin tablets and preparation method thereof |
| CN112137097A (en) * | 2020-10-10 | 2020-12-29 | 广东青云山药业有限公司 | Oral instant granules and preparation method thereof |
| CN112603893A (en) * | 2020-12-29 | 2021-04-06 | 山东福田药业有限公司 | Xylitol particles capable of being directly tabletted and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992010168A1 (en) * | 1990-12-12 | 1992-06-25 | Xyrofin Oy | Directly compressible xylitol and method |
| CN101869236A (en) * | 2010-06-09 | 2010-10-27 | 山东福田药业有限公司 | Xylitol particles capable of being directly pressed into tablets and preparation method thereof |
| CN102429885A (en) * | 2011-12-30 | 2012-05-02 | 山东力诺科峰制药有限公司 | DC-xylitol and preparation method thereof |
-
2018
- 2018-11-16 CN CN201811366053.XA patent/CN109172533A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992010168A1 (en) * | 1990-12-12 | 1992-06-25 | Xyrofin Oy | Directly compressible xylitol and method |
| CN101869236A (en) * | 2010-06-09 | 2010-10-27 | 山东福田药业有限公司 | Xylitol particles capable of being directly pressed into tablets and preparation method thereof |
| CN102429885A (en) * | 2011-12-30 | 2012-05-02 | 山东力诺科峰制药有限公司 | DC-xylitol and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 张光杰: "《药物辅料应用技术》", 31 December 1991, 中国医药科技出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109770365A (en) * | 2019-03-29 | 2019-05-21 | 汤臣倍健股份有限公司 | One kind of multiple chewable vitamin tablets and preparation method thereof |
| CN112137097A (en) * | 2020-10-10 | 2020-12-29 | 广东青云山药业有限公司 | Oral instant granules and preparation method thereof |
| CN112603893A (en) * | 2020-12-29 | 2021-04-06 | 山东福田药业有限公司 | Xylitol particles capable of being directly tabletted and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6165511A (en) | Polyol composition | |
| CN109172533A (en) | A kind of xylitol grains of directly compressible and preparation method thereof | |
| CA2058959C (en) | A fructose-based granulated product and a process for the production th ereof | |
| DE69928110T2 (en) | SUPPORT MATERIAL HELP | |
| JP2011231129A (en) | Process for preparing solidified maltitol and its use in food and pharma products | |
| EP2334202A1 (en) | Tabletting of ervthritol | |
| CN110200931A (en) | A kind of calcium vitamin D chewable tablets | |
| DE19943496C1 (en) | Directly compressible raw material for compressed air | |
| CN101869236A (en) | Xylitol particles capable of being directly pressed into tablets and preparation method thereof | |
| WO2006119697A1 (en) | Xylitol granules capable of directly being pressed into tablets and preparation process thereof | |
| KR101557162B1 (en) | Granulated maltitol for direct squeezing and a method for producing the same | |
| CN108926524B (en) | Instant gelatin product block and preparation method thereof | |
| CN102480998B (en) | The compressing tablet of erythrite and isomalt | |
| JP5090345B2 (en) | Method for producing powder containing xylitol crystal particles and other polyol | |
| KR20170030524A (en) | Sugar compositions for tableting by direct compression | |
| CN1852862B (en) | A kind of hydroxyapatite calcium phosphate particle, its preparation method and its application | |
| JP5110810B2 (en) | Sugar alcohol powder composition for tableting | |
| JPH1059842A (en) | Composition for tablet and making tablet | |
| EP2293774B1 (en) | Directly extrudable polyol combination | |
| CN106265725B (en) | Calcium carbonate taste-masking granules and preparation method thereof | |
| CN102429885B (en) | DC (Directly compressible)-xylitol and preparation method thereof | |
| DE2129646B2 (en) | METHOD FOR MANUFACTURING TABLETS OF UNIFORM SHAPE AND SIZE | |
| JP2006335686A (en) | Method for producing erythritol-sorbitol mixed granule for direct tableting | |
| CN112603893A (en) | Xylitol particles capable of being directly tabletted and preparation method thereof | |
| RU2205630C1 (en) | Methods for tabletting biologically active substances (variants) |
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 |
Application publication date: 20190111 |
|
| RJ01 | Rejection of invention patent application after publication |