CN1903184A - Effervesce tablets for treating liver diseases - Google Patents
Effervesce tablets for treating liver diseases Download PDFInfo
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Abstract
An effervescent tablet for treating hepatism is proportionally prepared from primary medicine, acid source, alkali source, filler, lubricant, sweetening agent and flavouring.
Description
Technical field
The invention belongs to the pharmaceutical technology field, be specifically related to a kind of effervescent tablet for the treatment of liver disease drug.
Technical background
Hepatopathy is a kind of commonly encountered diseases and frequently-occurring disease, and according to incompletely statistics, China's hepatitis and virus carrier account for 10% of total population, wherein based on viral hepatitis.
In the medicine of treatment hepatopathy, glycyrrhizic acid and salt thereof (single ammonium, diammonium) are being waved important role.Application number is that the patent documentation of CN02129437.2 discloses a kind of diammonium glycyrrhizanate transfusion preparation; Application number is that the patent documentation of CN200510074472.2 discloses diammonium glycyrrhizinate powder injection formulation and preparation method thereof.Also included in the national drug standards: diammonium glycyrrhizinate injection and infusion preparation thereof." new drug become a full member standard " 46 included diammonium glycyrrhizinate capsule.But the therapeutic effect of glycyrrhizic acid and salt thereof (single ammonium, diammonium) and enoxolone is still limited.
In order to heighten the effect of a treatment, people have developed compound preparation.Application number is that the patent documentation of CN03157562.5 discloses a kind of pharmaceutical composition for the treatment of hepatopathy and preparation method thereof and purposes.This pharmaceutical composition is combined according to special ratios by monoammonium glycyrrhizinate and L-cysteine hydrochloride; Application number is the patent documentation of CN200510076798.9 composition of medicine of disclosing a kind of diammonium glycyrrhizinate and preparation method thereof, and this pharmaceutical composition is that in diammonium glycyrrhizinate and cysteine, glycine, methionine and the vitamin B1 one or more are formed compound medicines; Compound glycyrrhizin injection (trade name: the compound medicine of forming by monoammonium glycyrrhizinate, glycine, cysteine hydrochloride U.S. energy).Also included in the national drug standards: compound ammonium glycyrrhizinato injection and compound monoammonium glycyrrhizinate injection.
Above-mentioned medicine nearly all is the mode administration with injection.Come for the hepatitis that needs medication for a long time, drug administration by injection not only brings misery to them, and treatment is inconvenient, and has increased the expense of treatment, has increased the weight of patient's burden.Though it is oral formulations that diammonium glycyrrhizinate capsule is arranged, this preparation is a single preparations of ephedrine, and therapeutic effect is limited; The low shortcoming that exists that waits of capsule bioavailability itself makes diammonium glycyrrhizinate capsule not demonstrate due therapeutic effect in clinical practice in addition, does not reach the therapeutic purposes of expection.
Therefore still there is demand in the patient for the oral formulations of good, the eutherapeutic treatment liver disease drug of compliance.
Effervescent tablet is a kind of novel tablet of external in recent years Application and Development, it contains gas-producing disintegrant, after effervescent tablet is put into drinking-water, under the effect of gas-producing disintegrant, at once produce a large amount of bubbles (carbon dioxide), make rapid disintegrate of tablet and thawing, the bubble that disintegrate sometimes produces also can make tablet roll up and down in water, quickens its disintegrate and thawing.Effervescent tablet has following advantage: 1, be convenient to preserve and carry; 2, disintegrate fast, taking convenience, onset be rapid.3, bioavailability height can improve clinical efficacy.4, be specially adapted to child, old people and the patient of pill difficulty that swallows; 5, through the effervescent tablet after the seasoning, taste is better, and good medicine is no longer bitter to the taste, and patient is more taken like a shot; 6, because a large amount of foams that disintegrate produces have increased medicine contacts with the direct of diseased region, bring into play its curative effect effect better, so effervescent tablet also is used for the control medication of oral disease etc.
In data-searching, find no any report about the effervescent tablet of treatment liver disease drug.
Summary of the invention
Based on above the deficiencies in the prior art, research worker of the present invention is developed a kind of effervescent tablet for the treatment of liver disease drug through a large amount of experiments, and it is that acid source, alkali source, filler and other adjuvants that principal agent preferably obtains with research worker of the present invention are prepared from.Clinical experiment is the result show, effervescent tablet of the present invention is than the better efficacy of existing peroral dosage form, and effervescent tablet of the present invention is convenient compared with the ejection preparation use, patient's compliance is better, is easier to be accepted by the patient.
An object of the present invention is to disclose a kind of effervescent tablet for the treatment of hepatitis medicament.
Another object of the present invention is the preparation method that discloses above-mentioned effervescent tablet.
Effervescent tablet of the present invention comprises principal agent and pharmaceutic adjuvant.
Above-mentioned pharmaceutic adjuvant comprises: acid source, alkali source, filler, lubricant, sweeting agent and correctives.
Above-mentioned principal agent and each pharmaceutic adjuvant consist of: principal agent 6-10 weight portion, acid source 2-4 weight portion, alkali source 3-6.5 weight portion, filler 11-14 weight portion, lubricant 0.5-1 weight portion, sweeting agent 1-1.5 weight portion, correctives 0.5-1 weight portion.
Above-mentioned principal agent comprises: glycyrrhizic acid and salt thereof.
In particular, above-mentioned principal agent comprises: glycyrrhizic acid, monoammonium glycyrrhizinate, diammonium glycyrrhizinate.
Preferably, above-mentioned principal agent also comprises: one or more in cysteine hydrochloride or cysteine, methionine, the glycine.
Above-mentioned acid source is a kind of in citric acid, tartaric acid, the succinic acid.
Above-mentioned alkali source is the sodium bicarbonate of coating agent parcel.
Above-mentioned coating agent is selected from Macrogol 4000.
The weight portion consumption of above-mentioned acid source and alkali source is 1: 1.5-1.6.
Above-mentioned alkali source: the weight part ratio of coating agent is 1: 0.45-0.50.
Above-mentioned filler is a mannitol.
Above-mentioned lubricant is selected from sodium lauryl sulphate or Stepanol MG.
Above-mentioned sweeting agent is selected from a kind of in cyclamate, stevioside, aspartame, protein sugar or the sucrose or several mixture.
Above-mentioned correctives is selected from a kind of in orange essence, flavoring orange essence, Herba Menthae essence or the Fructus Citri Limoniae essence.
Glycyrrhizic acid and salt thereof are that extraction separation obtains from Radix Glycyrrhizae, or obtain through derivatization, all have a good antihepatitic activity.
Cysteine or cysteine hydrochloride can be exchanged into methionine in vivo.Methionine has another name called methionine, is the aminoacid of unique sulfur-bearing, and is closely related with the metabolism of various sulfur-containing compounds in the organism.Methionine can utilize its with methyl, Toxic or medicine are methylated and play the antidotal effect.Therefore, methionine can be used for preventing and treating chronic or hepatic disease such as acute hepatitis, liver cirrhosis.
Glycine has another name called glycine, is the necessary aminoacid of human body.The activity that glycine can be regulated Kupffer Cell by the corresponding receptor that activates on the Kupffer Cell, the hepatic injury that multiple reason is caused has significant protective effect.
Research worker of the present invention is found, the different in kind of principal agent is also different to the selectivity of some pharmaceutic adjuvant in the effervescent tablet.Only select the pharmaceutic adjuvant that is fit to principal agent character, indexs such as the outward appearance of prepared effervescent tablet, stability, disintegration just can meet quality standard, and the effervescent tablet of preparing is only qualified effervescent tablet.For this reason, research worker of the present invention has been done a large amount of experiments, and having optionally to the principal agent in the effervescent tablet of the present invention, pharmaceutic adjuvant has carried out preferably.
Research worker of the present invention finds can obviously reduce with the filler with disintegration the disintegration time of effervescent tablet of the present invention, so be index with the disintegration time, the filler of using always is selected.
The mensuration of disintegration time, according to " two (appendix X A) inspection techniques disintegration of Chinese pharmacopoeia version in 2005 are carried out, be specially: get 1 of effervescent tablet, put in the 250ml beaker, fill 200ml water in the beaker, water temperature is 15-25 ℃, have numerous air-bubble to emit, when the gas around tablet or the fragment stopped to overflow, tablet melted or is dispersed in the water, it is left not have accumulative granule, and the record time at this moment is disintegration time.
Experimental design: principal agent is carried out proportioning with different filleies by identical amount, and the amount of other components remains unchanged in the prescription, is pressed into effervescent tablet with identical pressure, carries out the mensuration of disintegration time.Experimental result sees Table 1.
The selection of table 1 filler
| Form (g: g) | Disintegration time (s) |
| Main ingredient: lactose main ingredient: starch main ingredient: sweet mellow wine main ingredient: dextrin main ingredient: sucrose main ingredient: glucose main ingredient: microcrystalline cellulose | 137 188 114 180 152 166 126 |
By above-mentioned experimental result as can be seen, when filler used mannitol, the disintegration time of effervescent tablet of the present invention is short, and was effective.
Alkali source commonly used has sodium carbonate and sodium bicarbonate, and sodium bicarbonate consumption wherein is little, and gas production is big, so the selection sodium bicarbonate is an alkali source.Acid source commonly used is a kind of in citric acid, tartaric acid, the succinic acid.Research worker of the present invention finds that the acid source in the effervescent tablet of the present invention and the consumption of alkali source have tangible influence for the disintegration time of effervescent tablet.So be index with the disintegration time consumption of acid source and alkali source has been carried out preferably.
Experimental design: proportioning is carried out in the design of acid source and alkali source according to the form below, and the amount of other components remains unchanged in the prescription, is pressed into effervescent tablet with identical pressure.Experimental result sees Table 2.
The selection of table 2 soda acid ratio
| Acid source: alkali source (g: g) | Disintegration time (s) |
| 1∶1.2 1∶1.3 1∶1.4 1∶1.5 1∶1.6 1∶1.7 1∶1.8 1∶1.7 | 115 107 95 86 89 97 104 112 |
By above-mentioned result of the test as can be seen, when the consumption of acid source and alkali source is 1: during 1.5-1.6, disintegration time the best of effervescent tablet.
Macrogol 4000 and polyethylene glycol 6000 are the coating agent of alkali source in the effervescent tablet commonly used, and research worker of the present invention is index with the disintegration time, and coating agent Macrogol 4000 and polyethylene glycol 6000 are selected.
Experimental design: alkali source is carried out proportioning with different coating agents by identical amount, and the amount of other components remains unchanged in the prescription, is pressed into effervescent tablet with identical pressure, carries out the mensuration of disintegration time.Experimental result sees Table 3.
The selection of table 3 coating agent
| Form (g: g) | Disintegration time (s) |
| The Macrogol 4000 polyethylene glycol 6000 | Short long |
By above-mentioned experimental result as can be seen, when coating agent used Macrogol 4000, the disintegration time of effervescent tablet of the present invention is short, and was effective.
With Macrogol 4000 the alkali source sodium bicarbonate is wrapped up, can increase the stability of effervescent tablet, but amount can impact disintegration greatly again.So with stability with to the influence of disintegration time is index, the reasonable volume of Macrogol 4000 has been carried out preferably.Experimental design and the results are shown in Table 4 and table 5.
The selection of table 4 Macrogol 4000 consumption
| Sodium bicarbonate: Macrogol 4000 (g: g) | Stability |
| 1∶0.20 1∶0.25 1∶0.30 1∶0.35 1∶0.40 1∶0.45 1∶0.50 1∶0.55 1∶0.60 | Difference difference difference slightly poor slightly poor carefully |
By above-mentioned experimental result as can be seen, when sodium bicarbonate: the consumption of Macrogol 4000 is during greater than 1: 0.45, the good stability of effervescent tablet of the present invention.
The selection of table 5 Macrogol 4000 consumption
| Sodium bicarbonate: Macrogol 4000 (g: g) | Influence to disintegration time |
| 1∶0.45 1∶0.50 1∶0.55 1∶0.60 1∶0.65 1∶0.70 | Slight greatly very big very big |
By above-mentioned experimental result as can be seen, when sodium bicarbonate: the consumption of Macrogol 4000 is 1: during 0.45-0.50, the disintegration time of effervescent tablet is not almost had influence.
Lubricant in the effervescent tablet of the present invention is selected from sodium lauryl sulphate or Stepanol MG.
Sweeting agent in the effervescent tablet of the present invention is selected from a kind of in cyclamate, stevioside, aspartame, protein sugar or the sucrose or several mixture.
Correctives in the effervescent tablet of the present invention is selected from a kind of in orange essence, flavoring orange essence, Herba Menthae essence or the Fructus Citri Limoniae essence.
Specific embodiment
Following specific embodiment is intended to further specify the present invention, rather than restriction the present invention.
Embodiment 1
(1) principal agent: monoammonium glycyrrhizinate 60g, L-cysteine hydrochloride 30g
(2) preparation prescription is:
Principal agent 90g
Citric acid 20g
Sodium bicarbonate 30g
Mannitol 140g
Stepanol MG 5g
Cyclamate 10g
Orange essence 5g
(3) get the acid source drying for standby; Get the alkali source drying, with alkali source: the coating agent weight part ratio is 1: 0.45 coating agent fusion, adds alkali source dry powder, abundant mix homogeneously, and behind the parcel, 80 mesh sieves were pulverized in cooling; Above-mentioned each component is mixed, with conventional pharmaceutical technology technology granulation, drying, granulate, tabletting, check, pack, obtain effervescent tablet of the present invention.
Embodiment 2
(1) principal agent: diammonium glycyrrhizinate 50g
(2) preparation prescription is:
Principal agent 50g
Tartaric acid 40g
Sodium bicarbonate 65g
Mannitol 110g
Sodium lauryl sulphate 10g
Stevioside 15g
Flavoring orange essence 10g
(3) get the acid source drying for standby; Get the alkali source drying, with alkali source: the coating agent weight part ratio is 1: 0.50 coating agent fusion, adds alkali source dry powder, abundant mix homogeneously, and behind the parcel, 80 mesh sieves were pulverized in cooling; Above-mentioned each component is mixed, with conventional pharmaceutical technology technology granulation, drying, granulate, tabletting, check, pack, obtain effervescent tablet of the present invention.
Embodiment 3
(1) principal agent: monoammonium glycyrrhizinate 6g, cysteine hydrochloride 4.5g, glycine 60g
(2) preparation prescription is:
Principal agent 70.5g
Succinic acid 35g
Sodium bicarbonate 50g
Mannitol 120g
Stepanol MG 5g
Aspartame 14.5g
Herba Menthae essence 5g
(3) get the acid source drying for standby; Get the alkali source drying, with alkali source: the coating agent weight part ratio is 1: 0.48 coating agent fusion, adds alkali source dry powder, abundant mix homogeneously, and behind the parcel, 80 mesh sieves were pulverized in cooling; Above-mentioned each component is mixed, with conventional pharmaceutical technology technology granulation, drying, granulate, tabletting, check, pack, obtain effervescent tablet of the present invention.
Embodiment 4
(1) principal agent: monoammonium glycyrrhizinate 35g, glycine 25g, methionine 25g
(2) preparation prescription is:
Principal agent 85g
Citric acid 30g
Sodium bicarbonate 45g
Mannitol 115g
Sodium lauryl sulphate 8g
Protein sugar 10g
Fructus Citri Limoniae essence 7g
(3) get the acid source drying for standby; Get the alkali source drying, with alkali source: the coating agent weight part ratio is 1: 0.46 coating agent fusion, adds alkali source dry powder, abundant mix homogeneously, and behind the parcel, 80 mesh sieves were pulverized in cooling; Above-mentioned each component is mixed, with conventional pharmaceutical technology technology granulation, drying, granulate, tabletting, check, pack, obtain effervescent tablet of the present invention.
Effervescent tablet any surface finish of the present invention, exquisiteness.A slice effervescent tablet input is filled in the 250ml beaker of 20 ℃ of drinking waters of 200ml, at the bottom of it is sunken to glass very soon, and emit a large amount of bubbles immediately, tablet is dissolving rapidly thereupon, forms clear solution in 2 minutes.
Research worker of the present invention is a curative with the effervescent tablet of the present invention among the embodiment 2, serves as the contrast medicine with commercially available diammonium glycyrrhizinate capsule, has carried out following clinical experiment.
Case is selected inclusion criteria: chronic hepatitis B patient.The diagnosis of chronic hepatitis B meets the viral hepatitis diagnostic criteria that the Xi'an meeting is formulated in 2000.ALT is greater than 1.5 times of normal value upper limits; The pregnant feminine gender of being excused from an examination to test is urinated in women of child-bearing age patient's medication in preceding 3 days.
Exclusion standard: acute hepatitis, chronic hepatitis severe or chronic severe hepatitis, decompensated cirrhosis, with hepatocarcinoma and other malignant tumor persons, gestation or preparation gravid woman, women breast-feeding their children, treat and used the affect the treatment medicine of observation of the medicine that falls enzyme and antiviral drugs and immunoregulation medicament etc. in preceding 1 month, the serious heart, lung, brain, renal insufficiency and systemic immune system disease can not be observed test requirements document person.
Selection meets 80 routine patients of people's set condition, male's 58 examples wherein, women's 22 examples.Age, 20-50 year accounted for 78% in 20-60 year.Be divided into test group (diammonium glycyrrhizinate effervescent tablet group of the present invention) 40 example and matched group (diammonium glycyrrhizinate capsule group) 40 examples at random, every group of men and women's example number equity.
Therapeutic Method: adopt at random, the method for blind method, parallel control the oral diammonium glycyrrhizinate effervescent tablet of the present invention of test group (50mg/ grain, self-control), the oral diammonium glycyrrhizinate capsule of matched group (50mg/ grain, Jiangsu Zhengda Tianqing Drug Industry Co., Ltd).Two groups of dosage are 1-10 week 150mg/d, 3 times on the one; The 11st all 300mg/d, 3 times on the one; The 12nd all 150mg/d, 3 times on the one; Be for 12 weeks the course of treatment, followed up a case by regular visits to for 4 weeks after the drug withdrawal.Do not use other the liver protecting and ALT lowering medicine, antiviral agents and immunoregulation medicament in the therapeutic process.
Observation index: before the treatment, observe clinical symptoms (weak, nauseating, poor appetite, abdominal distention, hepatalgia) after treatment 4,8,12 weeks and the drug withdrawal 4 weeks respectively; Blood biochemistry index.
Curative effect is judged: the clinical symptoms orders of severity such as weak, nauseating, poor appetite, abdominal distention, hepatalgia are all with the 0-3 minute mark.Weak: 0 be divided into asymptomatic; 1 is divided into slightly, and movable back occurs; 2 fens moderates, bed can be alleviated; 3 are divided into severe, and bed is not alleviated.Feel sick: did nothing 0 fen; Having but not having vomiting is 1 minute; It is 2 minutes that idol has vomiting; Vomiting frequently is 3 minutes.Poor appetite: nothing was reduced to 0 fen; Less than former appetite is 1 minute; Less than 1/2 former appetite is 2 minutes; Less than 1/3 former appetite is 3 minutes; Abdominal distention: did nothing 0 fen; Feel is 1 minute; The influence feed is 2 minutes; It is 3 minutes that tympanitic resonance is arranged.Hepatalgia: did nothing 0 fen; It is 1 minute that idol has (1-3 time weekly); Often (weekly more than 3 times) are 2 minutes; The influence sleep is 3 minutes.
Clinical efficacy is with produce effects, effective and invalid assessment: produce effects serves as that treatment back symptom total points descends 〉=75%; Effectively be treatment back symptom total points decline 〉=50%, but≤75%; Invalid for treating back symptom total points decline≤50%.
Biochemical curative effect is with produce effects, effective and invalid assessment: produce effects serve as that treatment back ALT recovers normally; Effectively be treatment back ALT decline 〉=50%, but recover normal; Invalid for not reaching above-mentioned standard after the treatment.
General curative effect is with produce effects, effective and invalid assessment: produce effects is treated back ALT and is recovered normal, and the clinical symptoms total points descends 〉=75%; Effectively for the ALT recovery of treatment back is normal, the clinical symptoms total points descends 〉=50%, but≤75%, or treatment back ALT decline 〉=50%, but recover normal, and the clinical symptoms total points descends 〉=75%; Invalid for not reaching above-mentioned standard.Total effective rate is with produce effects+effectively calculating.
The result:
Evaluation of clinical curative effect: test group produce effects 18 examples, effective 11 examples, invalid 11 examples, total effective rate is 72.5%; Matched group produce effects 12 examples, effective 9 examples, invalid 19 examples, total effective rate is 52.5%; Two groups relatively there were significant differences (P＜0.05).
Biochemical curative effect compares: test group produce effects 15 examples, and effective 11 examples, invalid 14 examples, total effective rate is 65.0%; Matched group produce effects 11 examples, effective 7 examples, invalid 22 examples, total effective rate is 45.0%; Two groups relatively there were significant differences (P＜0.05).
General curative effect is estimated: test group is totally treated produce effects 14 examples, effective 8 examples, invalid 18 examples, total effective rate 55.0%; Matched group produce effects 10 examples, effective 6 examples, invalid 24 examples, total effective rate 40.0%; There were significant differences (P＜0.05) for two groups of total effective rates.
By above-mentioned clinical experiment result as can be seen: diammonium glycyrrhizinate effervescent tablet of the present invention has better therapeutic effect than existing preparation diammonium glycyrrhizinate capsule.
Claims (10)
1, the effervescent tablet of treatment liver disease drug, it is that principal agent and pharmaceutic adjuvant are prepared from, it is characterized in that each ingredients weight parts consists of: principal agent 6-10 weight portion, acid source 2-4 weight portion, alkali source 3-6.5 weight portion, filler 11-14 weight portion, lubricant 0.5-1 weight portion, sweeting agent 1-1.5 weight portion, correctives 0.5-1 weight portion.
2, effervescent tablet according to claim 1 is characterized in that, described principal agent comprises glycyrrhizic acid, monoammonium glycyrrhizinate or diammonium glycyrrhizinate.
3, effervescent tablet according to claim 1 and 2 is characterized in that, described principal agent also comprises one or more in cysteine hydrochloride, cysteine, methionine, the glycine.
4, effervescent tablet according to claim 1 is characterized in that, described acid source is a kind of in citric acid, tartaric acid, the succinic acid.
5, effervescent tablet according to claim 1 is characterized in that, described alkali source is the sodium bicarbonate of coating agent parcel.
6, effervescent tablet according to claim 1 is characterized in that, described coating agent is a Macrogol 4000.
7, effervescent tablet according to claim 1 is characterized in that, the weight portion consumption of described acid source and alkali source is 1: 1.5-1.6.
8, effervescent tablet according to claim 1 is characterized in that, described alkali source: the weight part ratio of coating agent is 1: 0.45-0.50.
9, effervescent tablet according to claim 1 is characterized in that, described filler is a mannitol.
10, effervescent tablet according to claim 1 is characterized in that, described lubricant is selected from sodium lauryl sulphate or Stepanol MG; Described sweeting agent is selected from a kind of in cyclamate, stevioside, aspartame, protein sugar or the sucrose or several mixture; Described correctives is selected from a kind of in orange essence, flavoring orange essence, Herba Menthae essence or the Fructus Citri Limoniae essence.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610109286 CN1903184A (en) | 2006-08-08 | 2006-08-08 | Effervesce tablets for treating liver diseases |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610109286 CN1903184A (en) | 2006-08-08 | 2006-08-08 | Effervesce tablets for treating liver diseases |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101947211A (en) * | 2010-08-28 | 2011-01-19 | 浙江金华康恩贝生物制药有限公司 | Method for preparing acetylcysteine effervescent tablet |
| CN103330684A (en) * | 2013-07-01 | 2013-10-02 | 杭州市西溪医院 | Preparation method of diammonium glycyrrhizinate lipid compound effervescent granule |
-
2006
- 2006-08-08 CN CN 200610109286 patent/CN1903184A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101947211A (en) * | 2010-08-28 | 2011-01-19 | 浙江金华康恩贝生物制药有限公司 | Method for preparing acetylcysteine effervescent tablet |
| CN103330684A (en) * | 2013-07-01 | 2013-10-02 | 杭州市西溪医院 | Preparation method of diammonium glycyrrhizinate lipid compound effervescent granule |
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Effective date of registration: 20081031 Address after: No. 66, Xiangjiang Road, Meihekou, Jilin Applicant after: Duprofit Pharmacy Company Limited Address before: Eastern Ring Road, Meihekou economic and Trade Development Zone, Jilin Applicant before: Aerbeila Medicine Holding(Tonghua) Co., Ltd. |
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Application publication date: 20070131 |