CN1679786A - Chinese medicine preparation for treating bleeding, preparation and quality control thereof - Google Patents
Chinese medicine preparation for treating bleeding, preparation and quality control thereof Download PDFInfo
- Publication number
- CN1679786A CN1679786A CN 200510031253 CN200510031253A CN1679786A CN 1679786 A CN1679786 A CN 1679786A CN 200510031253 CN200510031253 CN 200510031253 CN 200510031253 A CN200510031253 A CN 200510031253A CN 1679786 A CN1679786 A CN 1679786A
- Authority
- CN
- China
- Prior art keywords
- preparation
- adjuvant
- add
- medicine
- methanol
- 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
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A Chinese medicine in the form of capsule, softgel, or dispersing tablet for treating hemorrhage is proportionally prepared from notoginseng and Japanese creeper through pulverizing notoginseng, decocting Japanese creeper twice, filtering and cnocentrating decoction, adding notoginseng powder and additive, and preparing capsule, softgel, or dispersing tablet. Its quality control method is also disclosed.
Description
Technical field:
The present invention relates to a kind of Chinese medicine preparation and preparation method thereof and method of quality control, relate in particular to a kind of hemorrhage Chinese medicine preparation and preparation method thereof and method of quality control for the treatment of.
Background technology:
Capsule in the Chinese medicine preparation or soft capsule or drop pill or dispersible tablet, change dosage form and manage as new drug research according to the relevant laws and regulations of China's drug control as a kind of pharmaceutical dosage form.The existing dosage form of this product is a tablet, has listed the national drug ministry standard in.
The technology features of the Chinese medicine preparation SANQI ZHIXUE PIAN that existing treatment is hemorrhage is that Radix Notoginseng powder is broken into fine powder, and Herba Euphorbiae Humifusae decocts with water secondary, 2 hours for the first time, 1 hour for the second time, collecting decoction filters, and filtrate is condensed into cream, add the Radix Notoginseng fine powder, after adding suitable adjuvant, mixing is made granule, dry below 60 ℃, tabletting.Shortcomings such as there is easy moisture absorption in the hemorrhage Chinese medicine preparation SANQI ZHIXUE PIAN of existing treatment, and dose is big, takes inconvenience, and inherent quality is wayward.
Summary of the invention:
The purpose of this invention is to provide a kind of hemorrhage Chinese medicine preparation and preparation method thereof and method of quality control for the treatment of, overcome the above-mentioned drawback of prior art, improve the quality and the curative effect of product, bioavailability and controllability and stability satisfy medical needs better.
The objective of the invention is to be achieved through the following technical solutions.
Treat hemorrhage Chinese medicine preparation, it is that main component is a Herba Euphorbiae Humifusae, capsule of Radix Notoginseng or soft capsule or drop pill or dispersible tablet.
Its preparation method is:
(1) medicine constituent and percentage by weight consumption thereof are got the raw materials ready as follows:
Herba Euphorbiae Humifusae 47.6-99.9%, Radix Notoginseng 0.1-52.4%;
The optimum weight percentage ratio of medicine constituent is: Herba Euphorbiae Humifusae 95.3%, Radix Notoginseng 4.7%.
(2) get Radix Notoginseng powder and be broken into fine powder, sieving for standby; Herba Euphorbiae Humifusae decocts with water secondary, and the decocting that adds 14 times of amounts for the first time boiled 2 hours, and the decocting that adds 12 times of amounts for the second time boiled 1 hour, and collecting decoction filters, and filtrate is concentrated into thick paste (d=1.30,80 ℃ of surveys), adds the Radix Notoginseng fine powder, and drying gets hybrid medicine, and is standby;
(3) get (2) prepared hybrid medicine, do not add adjuvant or add adjuvant, adjuvant and medicament mixed are even; Granulate dry, granulate; The granule branch Capsules of packing into promptly gets capsule;
Adjuvant is one or more combinations of following material: lactose, starch, carboxymethyl starch sodium, pregelatinized Starch, sucrose, glucose, mannitol, sorbitol, syrup, microcrystalline Cellulose, methylcellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl emthylcellulose, low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, calcium sulfate, calcium hydrogen phosphate, calcium phosphate, calcium carbonate, light magnesium oxide, Pulvis Talci, micropowder silica gel, aluminium hydroxide, boric acid or sodium chloride, dextrin, magnesium stearate, hydrogenated vegetable oil, Polyethylene Glycol;
Get (2) prepared hybrid medicine, do not add adjuvant or add adjuvant, mix homogeneously is suppressed or is dripped and makes soft capsule;
One or more combinations of the following material of adjuvant: PEG400, vegetable oil, aromatic hydrocarbon esters, glycerol, isopropyl alcohol, tween;
With one or more of stearic acid or glyceryl monostearate or insect wax or Cera Flava or Polyethylene Glycol (PEG4000 or PEG6000) or sodium stearate or glycerin gelatine or polyoxyethylene monostearate (S-40) or Poloxamerl88, use with by arbitrary proportion, add (2) prepared hybrid medicine after being heated to whole fusions, be transferred in the liquid containing bottle rapidly after stirring, airtight and the insulation at 70-100 ℃, under heat-retaining condition, go in the liquid coolant (liquid paraffin or methyl-silicone oil or vegetable oil or water or ethanol) by dropping-pill machine, condensation cured becomes ball, with the drop pill drop of molding to the greatest extent and remove coolant, dry coationg promptly;
Get (2) prepared hybrid medicine, do not add adjuvant or add film-making adjuvant, principal agent and film-making adjuvant mix homogeneously; Behind granulation, drying, the granulate, add colloidality silicon dioxide again, one or more combinations in magnesium stearate, the Pulvis Talci, mix homogeneously is pressed into dispersible tablet;
The drug quality control method that makes is: get this medicine 1-4g, put in the conical flask, add chloroform 10-50ml, supersound process 10-60 minute, filter filtrate low temperature evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution, other gets Herba Euphorbiae Humifusae control medicinal material 1-3g, shines medical material solution in pairs with legal system, according to thin layer chromatography (" an appendix VI of Chinese pharmacopoeia version in 2000 B) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol (7-9.5: 0.5-3) be developing solvent, launch, take out, dry, spray is with the 2-8% phosphomolybdic acid ethanol solution, it is clear to be heated to speckle colour developing at 105 ℃, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
According to high effective liquid chromatography for measuring, chromatographic condition and system suitability test are bulking agent with octadecylsilane chemically bonded silica; Acetonitrile-0.05% phosphoric acid (15-25: 75-85) be mobile phase; The detection wavelength is 150-250nm, and number of theoretical plate calculates by the ginsenoside Rg1 peak should be lower than 1500;
The preparation precision of reference substance solution takes by weighing ginsenoside Rg1's reference substance 2-8mg, puts in the 25ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, and promptly gets (containing ginsenoside Rg1 0.08-0.64mg among every 1ml);
This medicine porphyrize is got in the preparation of need testing solution, gets 1g, the accurate title, decide, place apparatus,Soxhlet's, it is an amount of to add methanol, reflux 2-10 hour, get methanol solution and put evaporate to dryness in the water-bath, residue adds water 10-60ml makes dissolving, is transferred in the separatory funnel, with water saturated n-butanol extraction 3-7 time, merge extractive liquid,, with the saturated water washing of n-butyl alcohol 1-3 time, each 25ml discards water washing liquor, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds methanol makes dissolving, is transferred in the 25ml measuring bottle, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy is drawn above-mentioned reference substance solution and each 5 μ l of need testing solution respectively, injects chromatograph of liquid, measures.
Specific embodiments:
The present invention further specifies as follows in conjunction with specific embodiments:
A kind ofly treat hemorrhage Chinese medicine preparation, it is that main component is a Herba Euphorbiae Humifusae, capsule of Radix Notoginseng or soft capsule or drop pill or dispersible tablet.
Chinese medicine preparation of the present invention is mainly used in treatment and spits blood, epistaxis, and the dysentery metrorrhagia, puerperal hemorrhage is more than, menorrhagia and traumatic hemorrhage.
The preparation method of Chinese medicine preparation of the present invention is:
(1) medicine constituent and weight consumption thereof are as follows:
Herba Euphorbiae Humifusae 1250g, Radix Notoginseng 62g;
(2) get Radix Notoginseng powder and be broken into fine powder, sieving for standby; Herba Euphorbiae Humifusae decocts with water secondary, and the decocting that adds 14 times of amounts for the first time boiled 2 hours, and the decocting that adds 12 times of amounts for the second time boiled 1 hour, and collecting decoction filters, and filtrate is concentrated into thick paste (d=1.30,80 ℃ of surveys), adds the Radix Notoginseng fine powder, and drying gets hybrid medicine, and is standby;
(3) the hemorrhage Chinese medicine preparation capsule of treatment is a hemostatic notoginseng capsuel, and its preparation method is a hybrid medicine of getting (2) gained, adds starch, dextrin is an amount of, mixing (the about altogether 10g of mixture), and granulation, drying is made about 1000; The granule branch is packed in the Capsules, promptly gets capsule.
(4) the hemorrhage Chinese medicine preparation soft capsule of treatment is a Radix Notoginseng hemostasis soft capsule, and its preparation method is to get (2) gained hybrid medicine, adds water and makes dissolving, and PEG400 is an amount of in adding, and mix homogeneously is suppressed or dripped and makes soft capsule.
(5) the hemorrhage Chinese medicine preparation drop pill of treatment is a Radix Notoginseng hemostasis drop pill, its preparation method is taking polyethylene glycol PEG6000 250g, stearic acid 50g, Poloxamerl88 25g, treat to add (2) gained hybrid medicine after Polyethylene Glycol PEG6000, stearic acid, Poloxamerl88 are heated to whole fusions, be transferred in the liquid containing bottle rapidly after stirring, airtight and the insulation at 80 ℃, under heat-retaining condition, go in the liquid paraffin by dropping-pill machine, be condensed into ball, with the drop pill drop of molding to the greatest extent and the erasing liquor paraffin body, cold drying promptly.
(6) the hemorrhage Chinese medicine preparation dispersible tablet of treatment is a Radix Notoginseng hemostasis dispersible tablet, its preparation method is a hybrid medicine of getting (2) gained, cross 100 mesh sieves with the swollen shallow lake P5000 800g of dimension, polyvinylpolypyrrolidone INF-10 600g, PEG6000 500g and PEG4000 500g, mix homogeneously is crossed 80 mesh sieve secondaries, colloidality silicon dioxide, magnesium stearate are crossed 100 mesh sieves respectively, with above-mentioned mixed powder mix homogeneously, cross 80 mesh sieve secondaries, tabletting, make about 2000, promptly.
The method of quality control that the present invention treats hemorrhage Chinese medicine preparation is: get this medicine 2.4g, put in the conical flask, add chloroform 30ml, supersound process 30 minutes filters, and filtrate low temperature evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution.Other gets Herba Euphorbiae Humifusae control medicinal material 2g, shines medical material solution in pairs with legal system.According to thin layer chromatography test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with chloroform-methanol (9: 1), launch, take out, dry, spray is with 5% phosphomolybdic acid ethanol solution, 105 ℃ be heated to speckle develop the color clear.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
According to high effective liquid chromatography for measuring, chromatographic condition and system suitability test are bulking agent with octadecylsilane chemically bonded silica; Acetonitrile-0.05% phosphoric acid (19: 81) is mobile phase; The detection wavelength is 203nm, and number of theoretical plate calculates by the ginsenoside Rg1 peak should be lower than 1500;
The preparation precision of reference substance solution takes by weighing ginsenoside Rg1's reference substance 5mg, puts in the 25ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, and promptly gets (containing ginsenoside Rg1 0.2mg among every 1ml);
This medicine porphyrize is got in the preparation of need testing solution, gets 1g, the accurate title, decide, place apparatus,Soxhlet's, it is an amount of to add methanol, reflux 6 hours, get methanol solution and put evaporate to dryness in the water-bath, residue adds water 30ml makes dissolving, is transferred in the separatory funnel, with water saturated n-butanol extraction 5 times (25ml, 20ml, 20ml, 10ml, 10ml), merge extractive liquid,, with the saturated water washing of n-butyl alcohol 2 times, each 25ml discards water washing liquor, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds methanol makes dissolving, is transferred in the 25ml measuring bottle, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy is drawn above-mentioned reference substance solution and each 5 μ l of need testing solution respectively, injects chromatograph of liquid, measures.
Advantage of the present invention is:
Carry, taking convenience, the bioavilability height, controllability and good stability are conducive to improve curative effect.
Claims (4)
1, a kind ofly treats hemorrhage Chinese medicine preparation, it is characterized in that it is that main component is a Herba Euphorbiae Humifusae, capsule of Radix Notoginseng or soft capsule or drop pill or dispersible tablet.
2, a kind of preparation method for the treatment of hemorrhage Chinese medicine preparation is characterized in that:
(1) medicine constituent and percentage by weight consumption thereof are as follows:
Herba Euphorbiae Humifusae 47.6-99.9%, Radix Notoginseng 0.1-52.4%;
(2) get Radix Notoginseng powder and be broken into fine powder, sieving for standby; Herba Euphorbiae Humifusae decocts with water secondary, and the decocting that adds 14 times of amounts for the first time boiled 2 hours, and the decocting that adds 12 times of amounts for the second time boiled 1 hour, and collecting decoction filters, and filtrate is concentrated into thick paste (d=1.30,80 ℃ of surveys), adds the Radix Notoginseng fine powder, and drying gets hybrid medicine, and is standby;
(3) get (2) obtained hybrid medicine, add suitable adjuvant after, make capsule or soft capsule or drop pill or dispersible tablet;
Its capsular preparation method is: get (2) prepared hybrid medicine, do not add adjuvant or add adjuvant, adjuvant and medicament mixed are even; Granulate dry, granulate; The granule branch Capsules of packing into promptly gets capsule;
Adjuvant is one or more combinations of following material: lactose, starch, carboxymethyl starch sodium, pregelatinized Starch, sucrose, glucose, mannitol, sorbitol, syrup, microcrystalline Cellulose, methylcellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl emthylcellulose, low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, calcium sulfate, calcium hydrogen phosphate, calcium phosphate, calcium carbonate, light magnesium oxide, Pulvis Talci, micropowder silica gel, aluminium hydroxide, boric acid or sodium chloride, dextrin, magnesium stearate, hydrogenated vegetable oil, Polyethylene Glycol;
The preparation method of its soft capsule is: get (2) prepared hybrid medicine, do not add adjuvant or add adjuvant, mix homogeneously is suppressed or is dripped and makes soft capsule;
Adjuvant is one or more combinations of following material: PEG400, vegetable oil, aromatic hydrocarbon esters, glycerol, isopropyl alcohol, tween;
The preparation method of drop pill is: with one or more of stearic acid or glyceryl monostearate or insect wax or Cera Flava or Polyethylene Glycol (PEG4000 or PEG6000) or sodium stearate or glycerin gelatine or polyoxyethylene monostearate (S-40) or Poloxamerl88, use with by arbitrary proportion, add (2) prepared hybrid medicine after being heated to whole fusions, be transferred in the liquid containing bottle rapidly after stirring, airtight and the insulation at 70-100 ℃, under heat-retaining condition, go in the liquid coolant (liquid paraffin or methyl-silicone oil or vegetable oil or water or ethanol) by dropping-pill machine, condensation cured becomes ball, with the drop pill drop of molding to the greatest extent and remove coolant, dry coationg promptly;
The preparation method of dispersible tablet is: get (2) prepared hybrid medicine, do not add adjuvant or add film-making adjuvant, medicine and film-making adjuvant mix homogeneously; Behind granulation, drying, the granulate, add colloidality silicon dioxide again, one or more combinations in magnesium stearate, the Pulvis Talci, mix homogeneously is pressed into dispersible tablet;
Adjuvant is one or more combinations of following material: low-substituted hydroxypropyl cellulose, the swollen shallow lake 5000 of dimension, polyvinylpolypyrrolidone 1NF-10, polyethylene glycols, polyvinylpyrrolidone class, methylcellulose, ethyl cellulose, hydroxypropyl emthylcellulose, cellulose acetate-phthalate, hydroxypropyl methylcellulose phthalate, hydroxymethyl ethyl cellulose, microcrystalline Cellulose, citric acid, cholic acid or fumaric acid, succinic acid, tartaric acid.
3, a kind of method of quality control for the treatment of hemorrhage Chinese medicine preparation is characterized in that
Get this medicine 1-4g, put in the conical flask, add chloroform 10-50ml, supersound process 10-60 minute, filter filtrate low temperature evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution, other gets Herba Euphorbiae Humifusae control medicinal material 1-3g, shines medical material solution in pairs with legal system, according to thin layer chromatography (" an appendix VI of Chinese pharmacopoeia version in 2000 B) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol (7-9.5: 0.5-3) be developing solvent, launch, take out, dry, spray is with the 2-8% phosphomolybdic acid ethanol solution, it is clear to be heated to speckle colour developing at 105 ℃, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
According to high effective liquid chromatography for measuring, chromatographic condition and system suitability test are bulking agent with octadecylsilane chemically bonded silica; Acetonitrile-0.05% phosphoric acid (15-25: 75-85) be mobile phase; The detection wavelength is 150-250nm, and number of theoretical plate calculates by the ginsenoside Rg1 peak should be lower than 1500;
The preparation precision of reference substance solution takes by weighing ginsenoside Rg1's reference substance 2-8mg, puts in the 25ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, and promptly gets (containing ginsenoside Rg1 0.08-0.64mg among every 1ml);
This medicine porphyrize is got in the preparation of need testing solution, gets 0.5-2g, the accurate title, decide, place apparatus,Soxhlet's, it is an amount of to add methanol, reflux 2-10 hour, get methanol solution and put evaporate to dryness in the water-bath, residue adds water 10-60ml makes dissolving, is transferred in the separatory funnel, with water saturated n-butanol extraction 3-7 time, merge extractive liquid,, with the saturated water washing of n-butyl alcohol 1-3 time, each 25ml discards water washing liquor, n-butyl alcohol liquid is put evaporate to dryness in the water-bath, residue adds methanol makes dissolving, is transferred in the 25ml measuring bottle, adds methanol and is diluted to scale, shake up, promptly;
Algoscopy is drawn above-mentioned reference substance solution and each 5 μ l of need testing solution respectively, injects chromatograph of liquid, measures.
4, a kind of preparation method for the treatment of hemorrhage Chinese medicine preparation according to claim 2 is characterized in that the optimum weight percentage ratio of its main constituent is:
Herba Euphorbiae Humifusae 95.3%, Radix Notoginseng 4.7%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510031253 CN1679786A (en) | 2005-02-05 | 2005-02-05 | Chinese medicine preparation for treating bleeding, preparation and quality control thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510031253 CN1679786A (en) | 2005-02-05 | 2005-02-05 | Chinese medicine preparation for treating bleeding, preparation and quality control thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1679786A true CN1679786A (en) | 2005-10-12 |
Family
ID=35066792
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510031253 Pending CN1679786A (en) | 2005-02-05 | 2005-02-05 | Chinese medicine preparation for treating bleeding, preparation and quality control thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1679786A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100506219C (en) * | 2006-03-02 | 2009-07-01 | 四川泰华堂制药有限公司 | Notoginseng hemostatic and its preparing method |
-
2005
- 2005-02-05 CN CN 200510031253 patent/CN1679786A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100506219C (en) * | 2006-03-02 | 2009-07-01 | 四川泰华堂制药有限公司 | Notoginseng hemostatic and its preparing method |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1739612A (en) | Wind dispelling and pain relieving Chinese medicine prepn and its prepn process and quality control method | |
| CN102012405B (en) | Detection method for flavonoids compounds in cotton rose general flavone | |
| CN103432099A (en) | Tacrolimus slow-releasing capsule and preparation method thereof | |
| CN1733266A (en) | Chinese traditional medicine preparation for relieving food retention, resolving stagnation and harmonizing stomach, process for preparing the same and quality controlling method thereof | |
| CN117064939B (en) | Pudi blue anti-inflammatory capsule and preparation method thereof | |
| WO2012027968A1 (en) | Panaxatriol saponins enteric pellet, capsule comprising same and method for preparing same | |
| CN101653491A (en) | Preparation technology and quality control method of preparation containing cassia twig and tuckahoe | |
| CN1739739A (en) | Chinese medicine prepn for treating ulcer and its prepn process and quality control method | |
| CN1679900A (en) | Chinese medicine preparation for treating rheumatosis and arthralgia syndrome making method and quality control thereof | |
| CN1679786A (en) | Chinese medicine preparation for treating bleeding, preparation and quality control thereof | |
| CN1679780A (en) | Chinese medicine preparation for treating gynecopathy, preparation and quality control thereof | |
| CN1772084A (en) | Tongshu oral cavity refreshing tablet and its prepn | |
| CN1679787A (en) | Chinese medicine preparation for treating angiopathy, preparation and quality control thereof | |
| WO2013044570A1 (en) | Detection method of medicine for curing mastitis and hyperplasia of mammary glands | |
| CN1709370A (en) | Chinese medicine formulation for treating digestive tract disease, and its preparation method and quality control method | |
| CN1813953A (en) | Chinese medicine formulation for promoting blood circulation to arrest pain, and its preparing method and quality control method | |
| CN101011495A (en) | Kidney tonifying pill preparation made of fish air bladder and its preparation | |
| CN1723946A (en) | Oral preparation of 'Guipixin', method for preparing same and quality control | |
| CN1739751A (en) | Chinese medicine prepn for invigorating spleen and benefiting vital energy and its prepn process and quality control method | |
| CN1679785A (en) | Chinese medicine preparation for treating inflammation preparation and quality control thereof | |
| CN1709360A (en) | Chinese medicine formulation for expelling toxin by cooling, and its preparing method and quality control method | |
| CN103385863B (en) | Sodium azulene sulfonate sustained-release preparation | |
| CN1679782A (en) | Chinese medicine preparation for treating pain, preparation and quality control thereof | |
| CN1762373A (en) | 'Xueshuantong' soft capsule and its preparation | |
| CN105377280B (en) | A kind of drug and preparation method thereof for enriching blood |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |