CN104800188A - Preparation method of medical hydroxypropyl starch-based capsule - Google Patents
Preparation method of medical hydroxypropyl starch-based capsule Download PDFInfo
- Publication number
- CN104800188A CN104800188A CN201510241733.9A CN201510241733A CN104800188A CN 104800188 A CN104800188 A CN 104800188A CN 201510241733 A CN201510241733 A CN 201510241733A CN 104800188 A CN104800188 A CN 104800188A
- Authority
- CN
- China
- Prior art keywords
- starch
- glue
- capsule
- preparation
- froth breaking
- 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
- Jellies, Jams, And Syrups (AREA)
- General Preparation And Processing Of Foods (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention belongs to the technical field of medicine preparation, and relates to a preparation method for production of a starch-based capsule. The preparation method specifically comprises the following steps of starch etherifying, glue digestion, defoaming, impurity removal, glue dipping and forming, and the like. The prepared hydroxypropyl starch-based capsule has the advantages that the surface is smooth, the transparency is high, the disintegration time is short, the production technology is simplified, the production cost is reduced, and the hydroxypropyl starch-based capsule is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of starch base capsule, more particularly by starch etherificate, change glue, froth breaking, remove impurity, dip in the method that gum forming produces starch capsule.
Background technology
Capsule has in medicine, health product and functional food industry to be applied very widely.The many utilizations of conventional capsules are hydrolyzed obtained gelatin as capsule shell material by the skin of animal, ossein, inevitably have animal proteinum and remain, easily with the content medicine generation crosslinked action of band aldehyde radical class, thus the bad result such as cause medicine rotten.In addition, the gelatin of animal origin is unacceptable for vegetarian and religions belief personage.Therefore, also limit application and the popularization of gelatin glue capsule to a great extent, looking for plant capsule replaces gelatine capsule to be the task of top priority.
Starch is as a kind of renewable plant resources of wide material sources, there is stable in properties, biodegradable superperformance, starch is utilized to make capsule, both immunogenicity can not be there is, also without the need to worrying the problem of heavy metals exceeding standard, have simultaneously with low cost, without cross-linking reaction and the extensive advantage such as adaptability, be worthy of popularization.Starch through modification can obtain better gelling ability and mechanical strength, makes it close to the character of gelatin.
Patent CN1297601C discloses a kind of film-forming composition be made up of starch ether and coagulation system, and wherein said starch ether is hydroxypropyl starch or hydroxyethyl starch, and wherein coagulation system is by the mixture of hydrocolloid or hydrocolloid and cation
Composition, wherein said hydrocolloid is selected from polysaccharide.The content of hydroxypropyl starch ether is 88-98%, and the content of water is 2-12%, many
Sugar 0.01-10%, cation is 0.001-5%.
Patent CN1483393A discloses a kind of starch hollow capsule and production technology thereof, principal character is that this capsule is made up of components such as plant amylum or starch derivatives, plasticizer, water, and its proportioning is for being respectively 25%-4.9%, 0.1%-30%, 5%-20%.Be that starch or starch derivatives, water by mixing after proportioning and being heated to more than 60 DEG C, uniform stirring, and then are added plasticizer by proportioning, mix homogeneously during glue liquid, insulation leaves standstill, and pours insulation hopper into and after being stained with liquid, drying, make capsule again after removing bubble.
Patent CN 103937037 A discloses a kind of modified starch glue for the preparation of Capsules and starch matrix Capsules thereof, it is characterized in that: modified starch glue prepares by after hydroxypropyl starch or acid-treated hydroxypropyl starch and gellant mixing.The substitution value DS of described hydroxypropyl starch or acid-treated hydroxypropyl starch is in 0.1 ~ 0.93 scope, and gelatinization point is 25 ~ 60 DEG C of scopes.This modified starch glue after Heat Gelatinization gel, can be prepared starch matrix Capsules in water.
From above patent, usual starch capsule customary preparation methods is that first prepare modified starch by traditional method, then add other plasticizer etc., froth breaking after colloidal sol, finally dips in glue shaping forming.Because modified starch uses alkaline matter usually when using traditional handicraft to carry out etherificate process, easily produce by-product, simultaneously higher to equipment requirements, and storage easily absorbs water, and produces microorganism, makes capsule character poor.Leave standstill froth breaking, spended time is long, and weak effect, and vacuum defoaming or centrifugal froth breaking, though effect is better, operates more loaded down with trivial details, bring certain trouble to technique.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of medicinal hydroxypropyl starch capsule, to solve the above-mentioned various defects prepared plant capsule technology and exist, improve the performance of capsule, improve the quality of capsule simultaneously, simultaneously Simplified flowsheet.Specifically comprise the following steps: starch etherificate, change glue, froth breaking, remove impurity, dip in gum forming etc.It is characterized in that, use isopropyl alcohol is dispersant, Tetramethylammonium hydroxide, as catalyst, adds expoxy propane and prepares hydroxypropyl starch, adds ethanol and not only can remove the by-products such as unreacted expoxy propane and propylene glycol after colloidal sol, finally add ethanol and leave standstill froth breaking, the method defoaming effect is good, utilize the obtained capsule of this glue not only to have the advantages such as smooth surface, transparency is high, disintegration is short, and technique is simple, production cost is lower, is suitable for suitability for industrialized production.
Further, above-mentioned preparation method comprises the following steps:
(1) starch etherificate: by expoxy propane and catalyst blended after disperse medium, add food-grade starches, the volume of expoxy propane is (1.5 ~ 3) ml:1.0g with the ratio of starch quality, constantly stirs, and makes it fully react.
(2) starch slurry glue preparation: add water in glue pot, be warming up to 30 ~ 40 DEG C, adds the starch glue that step (1) is obtained, is warming up to 50 ~ 60 DEG C, adds reinforcing agent, stirs and obtains starch slurry glue;
(3) froth breaking, remove impurity: the washing with alcohol 3 ~ 5 times starch slurry glue being added 2 ~ 4 times of volumes, to remove the by-products such as unreacted expoxy propane and propylene glycol, finally adding ethanol leaves standstill a period of time, outwells to glue deaeration completely;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Further, above-mentioned steps (1), the source of described raw foods level starch is one or more in the starch such as Maninot esculenta crantz., sweet potato starch, corn starch, barley starch, preferred tapioca in the present invention.
Further, above-mentioned steps (2), described catalyst is sodium hydroxide, potassium hydroxide, Tetramethylammonium hydroxide, and be preferably the Tetramethylammonium hydroxide of 25%, the volume added is 1ml:15 ~ 45g with the ratio of starch quality.
Further, above-mentioned steps (2), described disperse medium is selected from methanol, ethanol, isopropyl alcohol, preferred isopropyl alcohol, and the volume added is 3 ~ 5 times of starch quality.
Further, above-mentioned steps (2), described reinforcing agent is one or more in sorbitol, carboxymethyl cellulose, sodium alginate.
Further, above-mentioned steps (1), described step (3), defoaming process adopts ethanol deaeration, and foam time is 2-8 hour, preferred 3.5-6.5 hour.
Further, the part by weight of starch glue according to claim 2, reinforcing agent, water is respectively: 20-70 part: 10-20 part: 20-45 part.
beneficial effect
The present invention compared with prior art, has significant progressive and following advantage:
(1) before colloidal sol, etherificate process is carried out to ative starch, avoid hydroxypropyl starch moisture absorption in storage, produce the quality that microorganism etc. affects capsule, etherification procedure uses isopropyl alcohol to be dispersant simultaneously, Tetramethylammonium hydroxide is as catalyst, and byproduct of reaction is few, and etherification reaction is complete.
(2) ethanol is added after colloidal sol, not only can remove the by-products such as unreacted expoxy propane and propylene glycol, add ethanol simultaneously, foam time is short, froth breaking is complete, utilizes the obtained capsule of this glue not only to have the advantages such as smooth surface, transparency is high, disintegration is short, also simplify production technology, save production cost, be suitable for suitability for industrialized production.
Detailed description of the invention
Embodiment 1
(1) starch etherificate: by expoxy propane and catalyst blended after disperse medium, add food-grade starches, the volume of expoxy propane is 1.5ml:1.0g with the ratio of starch quality, constantly stirs, and makes it fully react.
(2) starch slurry glue preparation: add water in glue pot, be warming up to 30 DEG C, adds the starch glue that step (1) is obtained, is warming up to 50 DEG C, adds reinforcing agent, stirs and obtains starch slurry glue;
(3) froth breaking, remove impurity: the washing with alcohol 3 times starch slurry glue being added 2 times of volumes, to remove the by-products such as unreacted expoxy propane and propylene glycol, finally adding ethanol leaves standstill a period of time, outwells to glue deaeration completely;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Embodiment 2
(1) starch etherificate: by expoxy propane and catalyst blended after disperse medium, add food-grade starches, the volume of expoxy propane is 2ml:1.0g with the ratio of starch quality, constantly stirs, and makes it fully react.
(2) starch slurry glue preparation: add water in glue pot, be warming up to 35 DEG C, adds the starch glue that step (1) is obtained, is warming up to 55 DEG C, adds reinforcing agent, stirs and obtains starch slurry glue;
(3) froth breaking, remove impurity: the washing with alcohol 4 times starch slurry glue being added 3 times of volumes, to remove the by-products such as unreacted expoxy propane and propylene glycol, finally adding ethanol leaves standstill a period of time, outwells to glue deaeration completely;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Embodiment 3
(1) starch etherificate: by expoxy propane and catalyst blended after disperse medium, add food-grade starches, the volume of expoxy propane is 2.5ml:1.0g with the ratio of starch quality, constantly stirs, and makes it fully react.
(2) starch slurry glue preparation: add water in glue pot, be warming up to 40 DEG C, adds the starch glue that step (1) is obtained, is warming up to 50 DEG C, adds reinforcing agent, stirs and obtains starch slurry glue;
(3) froth breaking, remove impurity: the washing with alcohol 5 times starch slurry glue being added 3 times of volumes, to remove the by-products such as unreacted expoxy propane and propylene glycol, finally adding ethanol leaves standstill a period of time, outwells to glue deaeration completely;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Embodiment 4
(1) starch etherificate: by expoxy propane and catalyst blended after disperse medium, add food-grade starches, the volume of expoxy propane is 3ml:1.0g with the ratio of starch quality, constantly stirs, and makes it fully react.
(2) starch slurry glue preparation: add water in glue pot, be warming up to 40 DEG C, adds the starch glue that step (1) is obtained, is warming up to 50 DEG C, adds reinforcing agent, stirs and obtains starch slurry glue;
(3) froth breaking, remove impurity: the washing with alcohol 5 times starch slurry glue being added 3 times of volumes, to remove the by-products such as unreacted expoxy propane and propylene glycol, finally adding ethanol leaves standstill a period of time, outwells to glue deaeration completely;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Embodiment 5
(1) starch etherificate: by expoxy propane and catalyst blended after disperse medium, add food-grade starches, the volume of expoxy propane is 2.5ml:1.0g with the ratio of starch quality, constantly stirs, and makes it fully react.
(2) starch slurry glue preparation: add water in glue pot, be warming up to 40 DEG C, adds the starch glue that step (1) is obtained, is warming up to 60 DEG C, adds reinforcing agent, stirs and obtains starch slurry glue;
(3) froth breaking, remove impurity: the washing with alcohol 3 times starch slurry glue being added 2 times of volumes, to remove the by-products such as unreacted expoxy propane and propylene glycol, finally adding ethanol leaves standstill a period of time, outwells to glue deaeration completely;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Comparative example
(2) starch slurry glue preparation: add water in glue pot, be warming up to 40 DEG C, add hydroxypropyl starch glue, be warming up to 60 DEG C, add reinforcing agent, stirs and obtains starch slurry glue;
(2) froth breaking: starch slurry glue is left standstill 3h, carries out froth breaking;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Respectively get capsule prepared by above-mentioned embodiment, and to the breakage of capsule and detect disintegration, the results are shown in Table 1.
Friability detects: get this product 50, put in surface plate, put into the exsiccator filling magnesium nitrate saturated solution, put 25 DEG C ± 1 DEG C constant temperature 24 hours, take out, put into by grain respectively immediately and stand upright in glass tubing on plank (thickness 2cm) (internal diameter is 24mm, and long is 200mm), by cylindrical counterweight, (material is politef, diameter is 22mm, heavy 20g ± 0.1g) freely fall from the glass mouth of pipe, whether break depending on capsule, if any breaking, must not more than 5.
Disintegration is detected: get prepared capsule 6, be placed in the screen cloth of disintegration time tester, add a cover baffle plate, opens instrument and the time of recording required for its disintegrate, is greater than 20min and is considered as defective.(method is shown in " Chinese Pharmacopoeia 2010 version two " annex inspection technique disintegration).
The different preparation method of table 1 obtains the investigation result of capsule
Claims (7)
1. a preparation method for medicinal hydroxypropyl starch capsule, concrete steps comprise starch etherificate, colloidal sol, froth breaking, remove impurity, dip in gum forming, it is characterized in that, add washing with alcohol remove impurity after colloidal sol, and leave standstill froth breaking.
2. method according to claim 1, is characterized in that comprising the following steps:
(1) starch etherificate: by expoxy propane and catalyst blended after disperse medium, add food-grade starches, the volume of expoxy propane is (1.5 ~ 3) ml:1.0g with the ratio of starch quality, constantly stirs, and makes it fully react;
(2) starch slurry glue preparation: add water in glue pot, be warming up to 30 ~ 40 DEG C, adds the starch glue that step (1) is obtained, is warming up to 50 ~ 60 DEG C, adds reinforcing agent, stirs and obtains starch slurry glue;
(3) froth breaking, remove impurity: the washing with alcohol 3 ~ 5 times starch slurry glue being added 2 ~ 4 times of volumes, to remove unreacted expoxy propane and propanediol by product, finally adds ethanol and leave standstill a period of time, outwells to glue deaeration completely;
(4) capsule preparation: the starch slurry glue after the froth breaking in above-mentioned steps (3) is obtained starch hollow capsule with conventional mode dunking method;
Method according to claim 2, is characterized in that, step (1), and the source of raw foods level starch is one or more in the starch such as Maninot esculenta crantz., sweet potato starch, corn starch, barley starch, preferred tapioca.
3. method according to claim 2, is characterized in that, step (2), and catalyst is sodium hydroxide, potassium hydroxide, Tetramethylammonium hydroxide, and be preferably the Tetramethylammonium hydroxide of 25%, the volume added is 1ml:15 ~ 45g with the ratio of starch quality.
4. method according to claim 2, is characterized in that, step (2) disperse medium is selected from methanol, ethanol, isopropyl alcohol, preferred isopropyl alcohol, and the volume added is 3 ~ 5 times of starch quality.
5. method according to claim 2, is characterized in that, step (2), and described reinforcing agent is one or more in sorbitol, carboxymethyl cellulose, sodium alginate.
6. method according to claim 2, is characterized in that, step (3), and defoaming process adopts ethanol deaeration, and foam time is 2-8 hour, preferred 3.5-6.5 hour.
7. method according to claim 2, is characterized in that, the part by weight of described starch glue, reinforcing agent, water is respectively: 20-70 part: 10-20 part: 20-45 part.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510241733.9A CN104800188B (en) | 2015-05-13 | 2015-05-13 | A kind of preparation method of medicinal hydroxypropul starch capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510241733.9A CN104800188B (en) | 2015-05-13 | 2015-05-13 | A kind of preparation method of medicinal hydroxypropul starch capsule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104800188A true CN104800188A (en) | 2015-07-29 |
| CN104800188B CN104800188B (en) | 2017-08-29 |
Family
ID=53685688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510241733.9A Active CN104800188B (en) | 2015-05-13 | 2015-05-13 | A kind of preparation method of medicinal hydroxypropul starch capsule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104800188B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055364A (en) * | 2015-07-31 | 2015-11-18 | 刘百平 | Preparation technology of oxidized hydroxypropyl starch hollow capsule |
| CN105778160A (en) * | 2016-03-22 | 2016-07-20 | 浙江中同科技有限公司 | Preparation method of hydroxypropyl starch capsules |
| CN105853389A (en) * | 2016-04-28 | 2016-08-17 | 湖南尔康湘药制药有限公司 | Sulfadiazine starch capsules and preparation method thereof |
| CN107126424A (en) * | 2017-04-21 | 2017-09-05 | 陈建峰 | A kind of preparation method of enteric solubility Capsules |
| CN108210476A (en) * | 2016-12-19 | 2018-06-29 | 湖南尔康制药股份有限公司 | Chloramphenicol starch capsule of gastric retention floating and preparation method thereof |
| CN108245492A (en) * | 2016-12-29 | 2018-07-06 | 湖南尔康制药股份有限公司 | A kind of preparation method of ranitidine hydrochloride capsules |
| CN108498478A (en) * | 2018-04-03 | 2018-09-07 | 华南农业大学 | A kind of preparation method of starch base hard capsule |
| CN108721244A (en) * | 2018-08-22 | 2018-11-02 | 张勇 | A kind of butylphenyl phthaleine hard capsule and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4026986A (en) * | 1975-05-22 | 1977-05-31 | The Dow Chemical Company | Capsule shell |
| CN103877586A (en) * | 2014-03-25 | 2014-06-25 | 暨南大学 | Medical hard capsule shell material with eucheuma gelatinae polysaccharide and preparation method thereof |
| CN103893772A (en) * | 2014-04-21 | 2014-07-02 | 湖南同泰胶囊有限公司 | Hydroxypropyl starch empty capsules and preparation process thereof |
| CN104262493A (en) * | 2014-09-05 | 2015-01-07 | 湖南尔康制药股份有限公司 | Preparation method and use of medicinal pregelatinized hydroxypropyl starch |
-
2015
- 2015-05-13 CN CN201510241733.9A patent/CN104800188B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4026986A (en) * | 1975-05-22 | 1977-05-31 | The Dow Chemical Company | Capsule shell |
| CN103877586A (en) * | 2014-03-25 | 2014-06-25 | 暨南大学 | Medical hard capsule shell material with eucheuma gelatinae polysaccharide and preparation method thereof |
| CN103893772A (en) * | 2014-04-21 | 2014-07-02 | 湖南同泰胶囊有限公司 | Hydroxypropyl starch empty capsules and preparation process thereof |
| CN104262493A (en) * | 2014-09-05 | 2015-01-07 | 湖南尔康制药股份有限公司 | Preparation method and use of medicinal pregelatinized hydroxypropyl starch |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055364A (en) * | 2015-07-31 | 2015-11-18 | 刘百平 | Preparation technology of oxidized hydroxypropyl starch hollow capsule |
| CN105055364B (en) * | 2015-07-31 | 2018-02-27 | 陕西嘉元生物工程有限公司 | A kind of manufacture craft for aoxidizing hydroxypropul starch Capsules |
| CN105778160A (en) * | 2016-03-22 | 2016-07-20 | 浙江中同科技有限公司 | Preparation method of hydroxypropyl starch capsules |
| CN105853389A (en) * | 2016-04-28 | 2016-08-17 | 湖南尔康湘药制药有限公司 | Sulfadiazine starch capsules and preparation method thereof |
| CN108210476A (en) * | 2016-12-19 | 2018-06-29 | 湖南尔康制药股份有限公司 | Chloramphenicol starch capsule of gastric retention floating and preparation method thereof |
| CN108245492A (en) * | 2016-12-29 | 2018-07-06 | 湖南尔康制药股份有限公司 | A kind of preparation method of ranitidine hydrochloride capsules |
| CN107126424A (en) * | 2017-04-21 | 2017-09-05 | 陈建峰 | A kind of preparation method of enteric solubility Capsules |
| CN108498478A (en) * | 2018-04-03 | 2018-09-07 | 华南农业大学 | A kind of preparation method of starch base hard capsule |
| CN108498478B (en) * | 2018-04-03 | 2020-08-07 | 华南农业大学 | Preparation method of starch-based hard capsules |
| CN108721244A (en) * | 2018-08-22 | 2018-11-02 | 张勇 | A kind of butylphenyl phthaleine hard capsule and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104800188B (en) | 2017-08-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104800188A (en) | Preparation method of medical hydroxypropyl starch-based capsule | |
| JP5902697B2 (en) | Novel cellulose ethers and their use | |
| CN104324381B (en) | Starch capsule having moisturizing capability and preparation method thereof | |
| CN105733031B (en) | A kind of polysaccharide-based gel compound membrane and its preparation method and application | |
| TWI454484B (en) | Preparation of Alkalized Cellulose and Water - soluble Cellulose Ether | |
| CN101433526B (en) | Non-gelatine enteric hard capsule shell material and method for producing the same | |
| CN104721167A (en) | Starch soft capsules | |
| CN105985449B (en) | A kind of modified hydroxypropul starch and preparation method thereof, a kind of plant hollow capsule and preparation method thereof | |
| JPH038817B2 (en) | ||
| CN104873977B (en) | The preparation method of composite starch special glue and its Capsules | |
| CN103834066A (en) | Low-viscosity starch glue for preparing starch capsules as well as preparation method and application of low-viscosity starch glue | |
| JP2005513255A (en) | Hexoxylan film-forming composition for capsule production and product capsule | |
| CN110054703B (en) | Preparation method of enzyme-modified pregelatinized hydroxypropyl starch | |
| CN104784148B (en) | A kind of film-forming composition for preparing plant capsule and preparation method thereof | |
| CN104800189B (en) | A kind of starch plant Capsules | |
| CN106692104A (en) | Plant starch composition for hollow capsule | |
| CN104800186A (en) | Starch-based vacant capsule and preparation process thereof | |
| KR20130028010A (en) | Method for preparing nonionic water-soluble cellulose ether | |
| CN106729729A (en) | A kind of Capsules plant amylum composition | |
| CN104922089A (en) | Preparation method of high-performance starch capsule | |
| CN103525886A (en) | Clean type liquid guanidine gum and preparation method thereof | |
| CN108752645A (en) | A kind of edible packing membrane and preparation method thereof with high-barrier function | |
| CN104311682A (en) | Preparation method of medicinal carboxymethyl starch | |
| JP2005239845A (en) | Manufacturing method of cellulose derivative having improved solubility | |
| CN106729728A (en) | A kind of Capsules plant amylum composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |