CN1830434A - Preparation method of troxerutin injection - Google Patents

Preparation method of troxerutin injection Download PDF

Info

Publication number
CN1830434A
CN1830434A CN 200510051480 CN200510051480A CN1830434A CN 1830434 A CN1830434 A CN 1830434A CN 200510051480 CN200510051480 CN 200510051480 CN 200510051480 A CN200510051480 A CN 200510051480A CN 1830434 A CN1830434 A CN 1830434A
Authority
CN
China
Prior art keywords
troxerutin
medicinal liquid
injection
preparation
exchange resin
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
Application number
CN 200510051480
Other languages
Chinese (zh)
Inventor
郭智华
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LOKIS PHARMACEUTICAL (JILIN) GROUP CO Ltd
Original Assignee
LOKIS PHARMACEUTICAL (JILIN) GROUP CO Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by LOKIS PHARMACEUTICAL (JILIN) GROUP CO Ltd filed Critical LOKIS PHARMACEUTICAL (JILIN) GROUP CO Ltd
Priority to CN 200510051480 priority Critical patent/CN1830434A/en
Publication of CN1830434A publication Critical patent/CN1830434A/en
Pending legal-status Critical Current

Links

Abstract

An injection of troxerutin for treating obliterative syndrome, thrombophlebitis, capillary hemorrhage is prepared through ion exchange of troxerutin, mixing with the water for injection, pouring in containers, sterilizing, and lamp examining.

Description

A kind of preparation method of troxerutin injection
Technical field
The invention discloses a kind of preparation method of troxerutin injection, contain troxerutin and water for injection that rutin obtains through hydroxyethylation.Handle through ion exchange technique in the preparation, obtain the troxerutin medicinal liquid, prepare jointly with water for injection, fill after sterilization, lamp inspection, packing, is made finished product.This technical process is handled through ion exchange technique, has guaranteed that metal ion is removed more than 99.99% fully, guarantees that metal ion is checked up to specification in the preparation; Simultaneously, other hydroxyethyl rutin derivant is removed major part too, has guaranteed that the inspection of preparation hydroxyethyl rutin derivant is up to specification, and has made little, the stable curative effect of making of better stability of preparation, zest, has improved clarity.Be used for inaccessible comprehensive card, thrombophlebitis, capillary hemorrhage etc.
Background technology
The cardiovascular and cerebrovascular disease sickness rate is high always, and is the trend of rising, and this has become a worldwide problem.
Troxerutin is the Flavonoid substances rutin of extracting in the leguminous plant Flos Sophorae, obtains troxerutin through hydroxyethylation.Troxerutin this product can suppress hematoblastic gathering, prevents thrombotic effect.Simultaneously the blood vessel injury that can cause medmain, Kallidin I increases capillary resistance, reduces capillary permeability, can prevent the edema that vascular permeability raises and causes.
The troxerutin injection Chinese medicine poor stability of present listing, and other hydroxyethyl rutin derivant of pair invalid element phenomenon hypersensitive is arranged.
The troxerutin injection formulation good stability of explained hereafter of the present invention, other hydroxyethyl rutin derivative content can be controlled in 5%, and little, the stable curative effect of zest has improved clarity.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of troxerutin injection.
Preparation method of the present invention comprises: troxerutin is handled through ion exchange technique in the troxerutin injection, obtains the troxerutin medicinal liquid, prepares jointly with water for injection, and fill after sterilization, lamp inspection, packing, is made finished product preparation.
Preparation method detailed process of the present invention is as follows:
A) get the fresh water for injection of 20%~80%80~90 ℃ of amount of preparation, be cooled to 20~40 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 5.5~7.0,, collect troxerutin stream medicinal liquid respectively by cation exchange resin and anion exchange resin.
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.02%~0.5% 15~30 minutes is with 40~50 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
C) with the medicinal liquid standardize solution, regulate pH5.5~7.0, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
Above-mentioned preparation method is preferably:
A) get the fresh water for injection of 30%85~90 ℃ of amount of preparation, be cooled to 25~30 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 5.8~6.0,, collect the troxerutin medicinal liquid respectively by cation exchange resin and anion exchange resin.
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.3% 25~30 minutes is with 40~50 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
C) with the medicinal liquid standardize solution, regulate pH5.8~6.0, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
Through the troxerutin injection that said method is made, character is the clear liquid of yellow or sundown, and specification can be 1ml, 2ml, 4ml, 5ml, 10ml, 15ml, 20ml, and most preferred specification is 2ml, 10ml, and every ml contains troxerutin 30mg or 50mg.
Troxerutin injection of the present invention clinical practice, intramuscular injection, a 60~150mg, 2 times on the one; 20 was 1 course of treatment, available 1~3 course of treatment, 3~7 days at interval per course of treatment.Or follow the doctor's advice.Intravenous drip, a 320~500mg, 1 time on the one; Instil with 5~10% glucose injections or low molecular dextran injection dilution back.Or follow the doctor's advice.
Troxerutin injection of the present invention is used for inaccessible comprehensive card, thrombophlebitis, capillary hemorrhage etc.
Troxerutin is the Flavonoid substances rutin of extracting in the leguminous plant Flos Sophorae, obtains troxerutin through hydroxyethylation.Troxerutin this product can suppress hematoblastic gathering, prevents thrombotic effect.Simultaneously the blood vessel injury that can cause medmain, Kallidin I increases capillary resistance, reduces capillary permeability, can prevent the edema that vascular permeability raises and causes.
The troxerutin injection Chinese medicine poor stability of present listing, and other hydroxyethyl rutin derivant of pair invalid components phenomenon hypersensitive is arranged.
The troxerutin injection formulation good stability of explained hereafter of the present invention, other hydroxyethyl rutin derivative content can be controlled in 5%, and little, the stable curative effect of zest has improved clarity.
The specific embodiment
Following embodiment further describes the present invention, but described embodiment only is used to illustrate the present invention rather than restriction the present invention.
Embodiment 1
A) get the fresh water for injection of 20%80 ℃ of amount of preparation, be cooled to 20 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 5.8,, collect troxerutin stream medicinal liquid respectively by cation exchange resin and anion exchange resin.
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.02% 30 minutes is with 45 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
C) with the medicinal liquid standardize solution, regulate pH5.8, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
Embodiment 2
A) get the fresh water for injection of 30%85 ℃ of amount of preparation, be cooled to 25 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 6.0,, collect troxerutin stream medicinal liquid respectively by cation exchange resin and anion exchange resin.
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.3% 20 minutes is with 48 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
C) with the medicinal liquid standardize solution, regulate pH6.0, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
Embodiment 3
A) get the fresh water for injection of 40%86 ℃ of amount of preparation, be cooled to 30 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 6.5,, collect troxerutin stream medicinal liquid respectively by cation exchange resin and anion exchange resin.
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.08% 27 minutes is with 46 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
C) with the medicinal liquid standardize solution, regulate pH6.5, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
Embodiment 4
A) get the fresh water for injection of 40%90 ℃ of amount of preparation, be cooled to 40 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 7.0,, collect the troxerutin medicinal liquid respectively by cation exchange resin and anion exchange resin.
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.5% 15 minutes is with 50 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
C) with the medicinal liquid standardize solution, regulate pH7.0, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
Embodiment 5
A) get the fresh water for injection of 70%80 ℃ of amount of preparation, be cooled to 35 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 5.5,, collect troxerutin stream medicinal liquid respectively by cation exchange resin and anion exchange resin.
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.02% 30 minutes is with 42 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
C) with the medicinal liquid standardize solution, regulate pH5.5, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
Experimental example 1
This experimental example is the most preferably detection of relevant every gainer under specification 2ml, 10ml outward appearance, pH value, the injection item of injection of the present invention.
Character: injection of the present invention is the clear liquid of yellow or sundown.
PH value: measure according to two appendix VI of Chinese Pharmacopoeia version in 2000 H, this injection pH value is 5.5~7.0, meets quality standard.
Pyrogen: get this product, check (two appendix XI of Chinese Pharmacopoeia version in 2000 D) dosage in accordance with the law by the every kg injection of rabbit body weight 2ml, up to specification.
Aseptic: get this product, check (two appendix XI of Chinese Pharmacopoeia version in 2000 H mensuration) in accordance with the law, this product is up to specification.
Clarity: get this product, check that according to " clarity test detailed rules and regulations and criterion " this product is up to specification.
Experimental example 2
This experimental example is the most preferably qualitative determination of composition among specification 2ml, the 10ml of injection of the present invention.
(1) get the about 20mg of this product, it is a small amount of to add water 20ml, hydrochloric acid 1ml and zinc powder, puts in the water-bath and heats, and shows the redness that continues.
(2) get the about 20mg of this product, it is a small amount of to add water 20ml and aluminum chloride, and solution shows glassy yellow.
(3) get this product, add water and make the solution that contains 20 μ g among every 1ml, measure, absorption maximum is arranged, minimal absorption is arranged at the wavelength place of 283nm at the wavelength place of 254nm and 347nm according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A).
Injection of the present invention is all up to specification with the inspection of beginning a project.
Experimental example 3
Experimental example is the injection of the present invention mensuration of other hydroxyethyl rutin derivants among specification 2ml, the 10ml most preferably.
It is fixed to get the accurate title of this product (being equivalent to troxerutin 15mg), puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, as need testing solution; Precision is measured in right amount, adds mobile phase and makes the solution that contains troxerutin 0.12mg among every 1ml, as prerun solution.According to the method test under the troxerutin assay item, get prerun solution 10 μ l and inject chromatograph of liquid, regulate detection sensitivity, make main constituent chromatograph peak height be 40%~60% of full amount; Get need testing solution 10 μ l again, inject chromatograph of liquid, the record chromatogram is to 2 times of main constituent peak retention time.Calculate by area normalization method, other material peak area sums must not be greater than 20% (injection) of total peak area
The preparation precision of need testing solution takes by weighing this product an amount of (being equivalent to troxerutin 15mg approximately) and puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shakes up, promptly.
Algoscopy is got need testing solution 10 μ l, according to the chromatographic condition under the assay item, injects chromatograph of liquid, and the record chromatograph is to 2 times of the main peak retention time, and except that main peak, other material peak area sum must not be greater than 20% (injection) of total peak area.
Injection of the present invention is through three batches mensuration, and other hydroxyethyl rutin derivant projects are up to specification.
Experimental example 4
Experimental example is the most preferably quantitative assay of troxerutin among specification 2ml, the 10ml of injection of the present invention.
Precision is measured this product 2ml and is put in the 25ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, and precision is measured 2ml, puts in the 25ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, according to troxerutin item method mensuration down.
Chromatographic condition and system suitability test are filler with octadecane bonding glue silicon; With 0.1% citric acid soln acetonitrile-oxolane (85: 9: 6) is mobile phase; The detection wavelength is 254nm.Number of theoretical plate calculates by the troxerutin peak should be not less than 2000, and the separating degree at troxerutin peak and other material peak should meet the requirements.
It is an amount of that algoscopy is got this product, accurate claims surely, add mobile phase dissolving and dilution and make every 1ml, in contain the solution of troxerutin 0.20mg, precision is measured 10 μ l and is injected chromatograph of liquid, the record chromatogram; It is an amount of that precision takes by weighing the troxerutin reference substance in addition, measures with method, presses external standard method with calculated by peak area, promptly.
Injection variable concentrations 10ml of the present invention: 500mg, 10ml: the 300mg specification each through three batches assay, result's following (seeing Table 1):
Table 1: troxerutin assay result
Specification Lot number Account for labelled amount %
10ml∶500mg 20040501 98.7
20040502 100.4
20040503 99.1
10∶300mg 20040501 99.6
20040502 98.5
20040503 100.1
Experimental example 5
This experimental example is the toxicity test of injection of the present invention.
The undue toxicity: press two appendix XI of Chinese Pharmacopoeia version in 2000 C undue toxicity's inspection method inspection, press the administration of intravenously administrable method, this product is up to specification.
Comparative example 1
Troxerutin clarity of injection, other hydroxyethyl rutin derivative content limit that the explanation of this comparative example is produced with process using ion-exchange treatment of the present invention is better than producing with conventional compound method.
Table 2: the comparison of technology of the present invention and common process troxerutin clarity of injection, other hydroxyethyl rutin derivative content limits
One technology of the present invention Two common process
Method for making A) get the fresh water for injection of 30%85 ℃ of amount of preparation, be cooled to 25 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 6.0, by cation exchange resin and anion exchange resin, collect the troxerutin medicinal liquid respectively.B) get above-mentioned troxerutin medicinal liquid, adding 0.3% A) get the fresh water for injection of 20 ℃ of amount of preparation, add troxerutin, fully stir and make dissolving fully, regulate pH value 6.0, the active carbon heated and boiled of adding 0.3% 25 minutes, with 40 ℃ of medicinal liquid circulation coolings, decarbonization filtering.
Active carbon heated and boiled 25 minutes is with 40 ℃ of medicinal liquid circulation coolings, decarbonization filtering.C) with the medicinal liquid standardize solution, regulate pH6.0, with medicinal liquid through the end-filtration fill in ampoule, 115 ℃ of sterilizations in 25 minutes, lamp inspection, packing, preparation gets product. B) with the medicinal liquid standardize solution, regulate pH6.0, with medicinal liquid through the end-filtration fill in ampoule, 115 ℃ of sterilizations in 25 minutes, lamp inspection, packing, preparation gets product.
Clarity 200 are not all had white point, white piece, precipitation etc. In 200 180 qualified, phenomenons such as other 20 equal white points, white piece.
Other hydroxyethyl rutin derivants 4% 15%
Comparative example 2
Because of troxerutin belongs to Flavonoid substances, the report of untoward reaction was arranged clinically.Zest was little when the explanation of this comparative example was used clinically with troxerutin injection of the present invention, and untoward reaction is few.
Table 3: technology of the present invention and the comparison clinically of common process troxerutin injection
Nomenclature of drug Troxerutin injection of the present invention Common process troxerutin injection
Usage and dosage Intramuscular injection, a 60~150mg, 2 times on the one; 20 was 1 course of treatment, available 1~3 course of treatment, 3~7 days at interval per course of treatment.Or follow the doctor's advice.Intravenous drip, a 320~500mg, 1 time on the one; Instil with 5~10% glucose injections or low molecular dextran injection dilution back.Or follow the doctor's advice.
Clinical use Treat 82 routine patients with coronary heart disease Treat 90 routine patients with coronary heart disease
Untoward reaction is observed Phenomenons such as no itch all over, uncomfortable in chest, weak, erythra, cardiopalmus. The 1 example phenomenon of itching is arranged
Zest is observed 3 examples have the mild pain phenomenon 10 examples have the pain phenomenon, and there is constriction 3 routine injection sites.
Comparative example 3
This comparative example explanation troxerutin injection of the present invention and common process troxerutin injection compare by the stability of acceleration in 6 months.
Table 4: technology of the present invention and common process troxerutin injection accelerated stability are relatively
Troxerutin injection of the present invention Common process troxerutin injection
Standard code Troxerutin content 90.0%~110.0% clarity: other hydroxyethyl rutin derivant up to specification: less than 20% pH value: 5.5~7.0
0 month Troxerutin content 99.8% clarity: other hydroxyethyl rutin derivant up to specification: 4% pH value: 6.0 Troxerutin content 98.9% clarity: other hydroxyethyl rutin derivant up to specification: 15% pH value: 6.0
1 month Troxerutin content 99.8% clarity: other hydroxyethyl rutin derivant up to specification: 4% pH value: 6.0 Troxerutin content 98.9% clarity: other hydroxyethyl rutin derivant up to specification: 16% pH value: 6.2
2 months Troxerutin content 99.8% clarity: other hydroxyethyl rutin derivant up to specification: 4% pH value: 6.0 Troxerutin content 98.4% clarity: other hydroxyethyl rutin derivant up to specification: 17% pH value: 6.2
3 months Troxerutin content 99.8% clarity: other hydroxyethyl rutin derivant up to specification: 4% pH value: 6.0 Troxerutin content 98.0% clarity: other hydroxyethyl rutin derivant up to specification: 17% pH value: 6.2
6 months Troxerutin content 99.8% clarity: other hydroxyethyl rutin derivant up to specification: 4% pH value: 6.0 Troxerutin content 97.8% clarity: other hydroxyethyl rutin derivant up to specification: 17% pH value: 6.3
Show that by above data the quality stability of troxerutin injection of the present invention is better than common process troxerutin injection.

Claims (6)

1. the preparation method of a troxerutin injection, described preparation method detailed process is as follows:
A) get the fresh water for injection of 20%~80%80~90 ℃ of amount of preparation, be cooled to 20~40 ℃, add the troxerutin in the prescription, fully stir and make dissolving fully, regulate pH value 5.5~7.0,, collect the troxerutin medicinal liquid respectively by cation exchange resin and anion exchange resin;
B) get above-mentioned troxerutin medicinal liquid, the active carbon heated and boiled of adding 0.02%~0.5% 15~30 minutes is with 40~50 ℃ of medicinal liquid circulation coolings, decarbonization filtering;
C) with the medicinal liquid standardize solution, regulate pH5.5~7.0, with medicinal liquid through the end-filtration fill in ampoule, sterilization, lamp inspection, packing, preparation gets product.
2. troxerutin weight according to claim 1 is characterized in that 1~40% (W/V) for total dose volume.
3. the cation exchange resin according to the described use of claim 1 is 732 types, and anion exchange resin is 701 types.
4. decarbonization filtering filter membrane according to claim 1 is 0.45 μ m filter membrane, and the end-filtration filter membrane is 0.22 μ m filter membrane.
5. pH value regulator according to claim 1 is 1~20% hydrochloric acid solution or 1~20% sodium hydroxide solution.
6. sterilising conditions according to claim 1 is 100~121 ℃, and 15~30 minutes, institute used equipment to be water-bath sterilize cabinet, vacuum sterilizer.
CN 200510051480 2005-03-08 2005-03-08 Preparation method of troxerutin injection Pending CN1830434A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 200510051480 CN1830434A (en) 2005-03-08 2005-03-08 Preparation method of troxerutin injection

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN 200510051480 CN1830434A (en) 2005-03-08 2005-03-08 Preparation method of troxerutin injection

Publications (1)

Publication Number Publication Date
CN1830434A true CN1830434A (en) 2006-09-13

Family

ID=36993036

Family Applications (1)

Application Number Title Priority Date Filing Date
CN 200510051480 Pending CN1830434A (en) 2005-03-08 2005-03-08 Preparation method of troxerutin injection

Country Status (1)

Country Link
CN (1) CN1830434A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101953783A (en) * 2010-09-15 2011-01-26 河南辅仁怀庆堂制药有限公司 Preparation process of troxerutin injection
CN110066300A (en) * 2019-05-08 2019-07-30 丁朝霞 Spent ion exchange resin refines the preparation method of Troxerutin and Troxerutin
CN114569550A (en) * 2022-03-08 2022-06-03 石家庄四药有限公司 Troxerutin injection and preparation method thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101953783A (en) * 2010-09-15 2011-01-26 河南辅仁怀庆堂制药有限公司 Preparation process of troxerutin injection
CN110066300A (en) * 2019-05-08 2019-07-30 丁朝霞 Spent ion exchange resin refines the preparation method of Troxerutin and Troxerutin
CN114569550A (en) * 2022-03-08 2022-06-03 石家庄四药有限公司 Troxerutin injection and preparation method thereof

Similar Documents

Publication Publication Date Title
CN101066244A (en) Small volume vincamine injection and its prepn process
CN1799605A (en) 'Shengmai' infusion and its preparation process
CN1923197A (en) Freeze-dried temzolomide powder for injection and its preparing process
CN1830434A (en) Preparation method of troxerutin injection
CN1830440A (en) Metronidazule injection and its preparation method and use
CN105663035A (en) Lidocaine hydrochloride injection and preparation method thereof
CN102038680B (en) Medical composition
CN1830451B (en) Preparation method of erigeron breviscapus glucese injection
CN1830443A (en) Preparation method of sophora flavescens freeze dried powder injection
CN1939357A (en) Preparation of Ginkgo Damo injection
CN1732936A (en) Nimodipine emulsion injection liquid and method for preparing the same
CN1751691A (en) Small volume intravenous injection of gastrodine and its prepn. method
CN1264522C (en) Medicinal composition, its preparation method and its use
CN102302495A (en) Tropisetron hydrochloride medicament composition for injection
CN100490824C (en) Medicinal composition for treating blood vessel kind disease, its preparation process and its use
CN1830426A (en) New houttuynine sodium bisulfite injection and its preparation method and use
CN1634091A (en) Injectio of gastrodine, its preparing process and usage
CN1241555C (en) Elemene fatty emulsion injection and preparing method thereof
CN1830452A (en) Preparation method of clindamycin hydrochloride freeze dried powder injection
CN111249227A (en) Preparation method of fondaparinux sodium injection
CN101721359A (en) Potassium dehydroandrogrpholide succinate injection and preparation method thereof
CN1824295A (en) Preparation technology of poly gelatin peptide injection liquid
CN114306219B (en) Stable R-ketamine pharmaceutical composition
CN1555788A (en) Thio pronine transfursion liquid and its preparation method
CN107115290B (en) (S) -4-hydroxy-2-oxo-1-pyrrolidine acetamide injection with good clarity and preparation method thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C57 Notification of unclear or unknown address
DD01 Delivery of document by public notice

Addressee: Xu Wenjie

Document name: Notification of the application for patent for invention to go through the substantive examination procedure

C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication