CN105362218A - Glycopyrronium bromide injection and preparation method thereof - Google Patents
Glycopyrronium bromide injection and preparation method thereof Download PDFInfo
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- CN105362218A CN105362218A CN201510953030.9A CN201510953030A CN105362218A CN 105362218 A CN105362218 A CN 105362218A CN 201510953030 A CN201510953030 A CN 201510953030A CN 105362218 A CN105362218 A CN 105362218A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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Abstract
The invention discloses glycopyrronium bromide injection and a preparation method thereof. The glycopyrronium bromide injection comprises glycopyrronium bromide, a pH adjusting agent and water for injection, and no benzyl alcohol or sodium chloride is contained. The glycopyrronium bromide injection prepared through the preparation method is controllable in quality, good in stability and suitable for industrial production.
Description
Technical field
The invention belongs to medical art, relate to a kind of Glycopyrronium bromide injection and preparation method thereof.
Background technology
Glycopyrronium bromide, chemical name is bromination-3 hydroxyl-1,1-alkyl dimethyl pyrrole-α-cyclopenta mandelate.
Glycopyrronium bromide is quaternary amines anticholinergic agent, has gastric acid secretion inhibiting and regulates gastrointestinal peristalsis effect.This product also has the anti-salivation effect stronger than atropine, but does not have central cholinolytic active.Only there is tablet at home at present, have injection to go on the market in the U.S..
Glycopyrronium bromide injection, thereafter, is gone on the market in Britain in JIUYUE in 2007 in Nikkei FDA approval February 6 in 1975 in U.S.'s listing on the 7th.As the product of the new route of administration of glycopyrronium bromide, this product is different from the use crowd of oral formulations, and emphasis is applicable to premedicate, reduces saliva, trachea-bronchial epithelial cell and pharyngeal secretion thing, reduce gastric acid secretion, the inhibitory action stoping cardiac vagal to reflect before induction of anesthesia and tracheal intubation; In art, with operation or the dependency arrhythmia that is drug-induced or vagus reflex of contending with.
According to Glycopyrronium bromide injection commercially available product, (commodity are called
injection) description is known, and containing 0.9% benzyl alcohol in this product prescription, with hydrochloric acid or sodium hydroxide as pH adjusting agent, water for injection is solvent; PH value is 2.0 ~ 3.0, and specification is 1mL:0.2mg, 2mL:0.4mg, 5mL:1mg and 20mL:4mg, and wherein 5mL:1mg and 20mL:4mg two kinds of specifications are multiple dosing.Former grinding in Glycopyrronium bromide injection adds benzyl alcohol, but the interpolation of benzyl alcohol can cause side effect, even can cause the generation of death by accident, especially pediatric patients, syndrome of panting is there will be when neonate is greater than 99mg/kg/day or the light neonate of birth weight gives benzyl alcohol, wherein with central nervous system impression, metabolic acidosis, the symptoms such as asthmatic breathing are that main manifestations feature also there will be gradation neurasthenia simultaneously, epilepsy, intracranial is begun to learn, hematological abnormality, skin injury, liver and renal damage, hypotension, the symptom such as bradycardia or cardiovascular collapse.Early, more easily there is toxic reaction in the patient of a little, under-weight neonate and reception high dose benzyl alcohol.Therefore existing glycopyrronium bromide injection unstable properties, and drug risk is higher, is unsuitable for life-time service.
CN104274392A discloses a kind of Glycopyrronium bromide injection compositions, and every 1000 compositionss are composed of the following components: glycopyrronium bromide 0.1g ~ 0.4g, and sodium chloride 9g ~ 18g, 2mol/L hydrochloric acid solution is appropriate, and water for injection adds to 1000mL ~ 2000mL.Although not containing benzyl alcohol in said composition, containing sodium chloride in prescription, the concentration of sodium chloride is 22.5 to 180 times of glycopyrronium bromide concentration.
CN103690479A discloses a kind of Glycopyrronium bromide injection, be made up of glycopyrronium bromide, sodium chloride, pH adjusting agent and water for injection, the each component of this Glycopyrronium bromide injection is composed as follows: glycopyrronium bromide 0.1 ~ 0.5mg/mL, sodium chloride 7.0 ~ 10.0mg/mL, it is 1.0 ~ 4.0 that pH adjusting agent adds to injection pH value, and water for injection adds to 1000mL.Although not containing benzyl alcohol in same said composition, containing sodium chloride in prescription, the concentration of sodium chloride is 14 to 100 times of glycopyrronium bromide concentration.
For not removing endotoxic technique containing activated carbon adsorption, the endotoxin contained by sodium chloride itself will be brought in product, and as ensured, product endotoxin limit meets the requirements, and needs to carry out exception to glycopyrronium bromide and sodium chloride endotoxin and strictly controls.Sodium chloride grinds as former the component do not contained in product in addition, and for injection, new component is introduced may bring unnecessary safety problem.Therefore be still necessary to provide a kind of new solution to overcome above shortcoming at present, make Glycopyrronium bromide injection up-to-standard, there is good stability simultaneously, and cheap, be conducive to commercially producing.
Summary of the invention
Glycopyrronium bromide injection compositions of the present invention, said composition comprises glycopyrronium bromide, pH adjusting agent and water for injection composition, not containing benzyl alcohol and sodium chloride.
Glycopyrronium bromide injection compositions of the present invention, each component of said composition is composed as follows: glycopyrronium bromide 0.2-0.3mg/mL, pH adjusting agent regulate injection pH value to 2.0 ~ 3.0, water for injection.
To the present invention further provides optimal technical scheme be glycopyrronium bromide component is 0.2mg/mL.
Glycopyrronium bromide injection compositions of the present invention, in preferred per unit preparation, glycopyrronium bromide content is 1mL:0.2mg or 2mL:0.4mg.
Glycopyrronium bromide injection compositions of the present invention, compositions is not containing benzyl alcohol.Because benzyl alcohol can exist certain potential safety hazard when being directly used in intravenously administrable, and benzyl alcohol eremacausis can become benzaldehyde in atmosphere, causes related substance in Glycopyrronium bromide injection product to increase.Glycopyrronium bromide injection compositions of the present invention, not sodium chloride-containing in compositions.As increased sodium chloride in product, not only increasing supplementary product kind, adding production craft step simultaneously, for sterile preparation, increasing production craft step not only can affect production efficiency, can increase the production risk of product simultaneously.And for the injection of this low dose of Glycopyrronium bromide injection, the concentration of Glycopyrronium bromide injection is about 0.2mg/mL, and the concentration of sodium chloride tens times of Glycopyrronium bromide injection even hundred times often.Endotoxin step is not removed containing activated carbon adsorption in production process of the present invention, the bacterial endotoxin of prescription Raw and adjuvant is all brought in final products, as sodium chloride-containing in product, the bacterial endotoxin standard of glycopyrronium bromide crude drug than sodium chloride-containing is more not strict, thus causes being difficult to find qualified glycopyrronium bromide crude drug supplier.
Glycopyrronium bromide injection compositions of the present invention, technical scheme optimum in prescription directly adds concentrated hydrochloric acid to carry out pH value adjustment, and while guarantee product quality is high, directly adding easier also the avoiding of operation increases the probability that processing step brings pollution.
Present invention also offers a kind of preparation method of Glycopyrronium bromide injection in addition, more preferably technical scheme comprises the following steps:
A) glycopyrronium bromide (gram) of prescription weight is taken;
B) water for injection (mL) of less than 40 DEG C prescription volumes 95% is taken;
C) solution ph to 2.0 ~ 3.0 are regulated with concentrated hydrochloric acid;
D) added by glycopyrronium bromide a) obtaining prescription weight in above-mentioned c) solution, stirring and dissolving is also supplemented to prescription volume water for injection;
E) after improvement PVDF (Kynoar) membrane filtration of 0.22 μm, carry out fill sterilizing, obtain the Glycopyrronium bromide injection of every ml containing glycopyrronium bromide 0.2-0.3mg, preferably every ml is containing the Glycopyrronium bromide injection of glycopyrronium bromide 0.2mg.
The preparation method of Glycopyrronium bromide injection of the present invention, sterilizing is employing 121 DEG C damp and hot water-bath sterilization 12-15min terminal sterilization technique, preferred sterilizing 15min.
The preparation method of Glycopyrronium bromide injection of the present invention, does not remove bacterial endotoxin step containing activated carbon adsorption in preparation process.
From the mathematical model of microorganism killing, when initial contamination is identical, sterilizing F
0be worth larger, sterility assurance level is higher.Therefore, obviously for reducing the risk of product residue microorganism, select high F as far as possible
0value is natural.With reference to the decision tree that European Union's sterilization process is selected, because of first-selected F
0be greater than the sterilization process of 12.Ambroxol hydrochloride injection prepared in accordance with the present invention can tolerate the sterilization process of 121 degree of 15min, can meet the sterilization process condition that current existing regulation is the strictest.
F
0value as the parameter verifying sterilizing reliability, refer to certain sterilising temp (T), Z value for 10 DEG C of sterilization effects produced with 121 DEG C, Z value is 10 DEG C of identical suitable times (min) of the sterilization effect produced.
Glycopyrronium bromide injection compositions of the present invention, use the bacterial endotoxin of glycopyrronium bromide crude drug to be no more than 555.5Eu/mg, and concentrated hydrochloric acid is as strong acid, strong acid be it is generally acknowledged and can be destroyed bacterial endotoxin, therefore without the need to controlling concentrated hydrochloric acid endotoxin.
A kind of Glycopyrronium bromide injection compositions provided by the invention, wherein Glycopyrronium bromide injection bacterial endotoxin≤111.1Eu/mL.
The technique effect that the present invention is useful is: this Glycopyrronium bromide injection compositions is not containing benzyl alcohol and sodium chloride, and product quality is high simultaneously, and stability is stablized, and its preparation method production technology is simple, and cost is low, is applicable to commercially producing.
Detailed description of the invention
In order to more fully understand the present invention, spy provides following specific embodiment, but the present invention is not limited to following examples.
Comparative example 1:
| Composition | Consumption |
| Glycopyrronium bromide | 0.2g |
| Benzyl alcohol | 9.0g |
| Concentrated hydrochloric acid | In right amount |
| Water for injection | Be settled to 1000mL |
Preparation method is: the water for injection taking less than 40 DEG C is about 950mL, dissolves completely, regulate solution ph to 2.5 with concentrated hydrochloric acid after adding benzyl alcohol; The glycopyrronium bromide of recipe quantity is added in above-mentioned solution, is stirred to dissolve, mend and inject water to 1000mL; Fill after the improvement PVDF membrane filtration of 0.22 μm, 121 DEG C of 15min sterilizings, obtain the Glycopyrronium bromide injection of every mL containing glycopyrronium bromide 0.2mg.
Comparative example 2:
| Composition | Consumption |
| Glycopyrronium bromide | 0.2g |
| Concentrated hydrochloric acid | In right amount |
| Water for injection | Be settled to 1000mL |
Preparation method is: the water for injection taking less than 40 DEG C is about 950mL, regulates solution ph to 1.0 with concentrated hydrochloric acid; The glycopyrronium bromide of recipe quantity is added in above-mentioned solution, is stirred to dissolve, mend and inject water to 1000mL; Fill after the improvement PVDF membrane filtration of 0.22 μm, 121 DEG C of 15min sterilizings, obtain the Glycopyrronium bromide injection of every mL containing glycopyrronium bromide 0.2mg.
Comparative example 3:
| Composition | Consumption |
| Glycopyrronium bromide | 0.2g |
| Concentrated hydrochloric acid | In right amount |
| Water for injection | Be settled to 1000mL |
Preparation method is: the water for injection taking less than 40 DEG C is about 950mL, regulates solution ph to 4.0 with concentrated hydrochloric acid; The glycopyrronium bromide of recipe quantity is added in above-mentioned solution, is stirred to dissolve, mend and inject water to 1000mL; Fill after the improvement PVDF membrane filtration of 0.22 μm, 121 DEG C of 15min sterilizings, obtain the Glycopyrronium bromide injection of every ml containing glycopyrronium bromide 0.2mg.
Embodiment 1
| Composition | Consumption |
| Glycopyrronium bromide | 0.2g |
| Concentrated hydrochloric acid | In right amount |
| Water for injection | Be settled to 1000mL |
Preparation method is: the water for injection taking less than 40 DEG C is about 950mL, regulates solution ph to 2.5 with concentrated hydrochloric acid; The glycopyrronium bromide of recipe quantity is added in above-mentioned solution, is stirred to dissolve, mend and inject water to 1000mL; Fill after the improvement PVDF membrane filtration of 0.22 μm, 121 DEG C of 15min sterilizings, obtain the Glycopyrronium bromide injection of every mL containing glycopyrronium bromide 0.2mg, wherein record Glycopyrronium bromide injection bacterial endotoxin≤111.1Eu/mL.
Embodiment 2
| Composition | Consumption |
| Glycopyrronium bromide | 0.2g |
| Concentrated hydrochloric acid | In right amount |
| Water for injection | Be settled to 1000mL |
Preparation method is: the water for injection taking less than 40 DEG C is about 950mL, regulates solution ph to 2.0 with concentrated hydrochloric acid; The glycopyrronium bromide of recipe quantity is added in above-mentioned solution, is stirred to dissolve, mend and inject water to 1000mL; Fill after the improvement PVDF membrane filtration of 0.22 μm, 121 DEG C of 15min sterilizings, obtain the Glycopyrronium bromide injection of every 1mL containing glycopyrronium bromide 0.2mg, wherein record Glycopyrronium bromide injection bacterial endotoxin≤111.1Eu/mL.
Embodiment 3
| Composition | Consumption |
| Glycopyrronium bromide | 0.2g |
| Concentrated hydrochloric acid | In right amount |
| Water for injection | Be settled to 1000mL |
Preparation method is: the water for injection taking less than 40 DEG C is about 950mL, regulates solution ph to 3.0 with concentrated hydrochloric acid; The glycopyrronium bromide of recipe quantity is added in above-mentioned solution, is stirred to dissolve, mend and inject water to 1000mL; Fill after the improvement PVDF membrane filtration of 0.22 μm, 121 DEG C of 15min sterilizings, obtain the Glycopyrronium bromide injection of every mL containing glycopyrronium bromide 0.2mg, wherein record Glycopyrronium bromide injection bacterial endotoxin≤111.1Eu/mL.
Get comparative example 1, embodiment 1 sample, investigate steadiness under being placed on high temperature 60 DEG C (0 day, 10 days, 20 days) condition respectively, the results are shown in Table 1.
Visible according to table 1 result, containing benzyl alcohol with not containing the contrast of benzyl alcohol prescription, all to degrade generation benzaldehyde containing benzyl alcohol prescription, and not containing benzyl alcohol prescription total impurities and single unknown impuritie amount less, the Glycopyrronium bromide injection therefore not containing benzyl alcohol prescription is more stable.
Get comparative example 2, comparative example 3, embodiment 1, embodiment 2, embodiment 3 investigate steadiness under being placed on high temperature 60 DEG C (0 day, 10 days, 20 days) condition respectively, the results are shown in Table 2.
Visible according to table 2 result, when pH value is 1.0,60 DEG C of total impuritieses of 20 days of Glycopyrronium bromide injection are 8.86%.When pH value is 4.0,60 DEG C of total impuritieses of 20 days of Glycopyrronium bromide injection are 19.02%, and under same stability sky said conditions, its single impurity C is all than pH value 2.0, impurity content under 2.5 and 3.0 conditions exceeds a lot, wherein impurity C is the hydrolysis impurity of glycopyrronium bromide, and therefore show the less stable of Glycopyrronium bromide injection at this pH value, Glycopyrronium bromide injection is more stable at pH value 2.0-3.0.
Claims (10)
1. a Glycopyrronium bromide injection compositions, said composition comprises glycopyrronium bromide, pH adjusting agent and water for injection, not containing benzyl alcohol and sodium chloride.
2. Glycopyrronium bromide injection compositions according to claim 1, is characterized in that: each component of said composition is composed as follows: glycopyrronium bromide 0.2-0.3mg/mL, pH adjusting agent regulate injection pH value to 2.0 ~ 3.0 and water for injection.
3. Glycopyrronium bromide injection compositions according to claim 1, is characterized in that: glycopyrronium bromide component is 0.2mg/mL.
4. Glycopyrronium bromide injection compositions according to claim 1, is characterized in that: in per unit preparation, glycopyrronium bromide content is 1mL:0.2mg or 2mL:0.4mg.
5. according to the Glycopyrronium bromide injection compositions one of claim 1-4 Suo Shu, it is characterized in that: pH adjusting agent is selected from hydrochloric acid, preferred concentrated hydrochloric acid.
6. according to the Glycopyrronium bromide injection compositions one of claim 1-4 Suo Shu, it is characterized in that: use glycopyrronium bromide crude drug bacterial endotoxin≤555.5Eu/mg.
7. the Glycopyrronium bromide injection compositions as described in one of claim 1-4, this Glycopyrronium bromide injection bacterial endotoxin≤111.1Eu/mL.
8. prepare a method for Glycopyrronium bromide injection compositions as claimed in claim 1, comprise the following steps:
A) glycopyrronium bromide of prescription weight is taken;
B) water for injection of less than 40 DEG C 95% prescription volumes is taken;
C) solution ph to 2.0 ~ 3.0 are regulated with concentrated hydrochloric acid;
D) added by glycopyrronium bromide a) obtaining prescription weight in above-mentioned c) solution, stirring and dissolving is also supplemented to prescription volume water for injection;
E) after the improvement Kynoar membrane filtration of 0.22 μm, carry out fill sterilizing, obtain the Glycopyrronium bromide injection of every mL containing glycopyrronium bromide 0.2-0.3mg, preferably every ml is containing the Glycopyrronium bromide injection of glycopyrronium bromide 0.2mg.
9. preparation method according to claim 8, is characterized in that: sterilizing is employing 121 DEG C damp and hot water-bath sterilization 12-15min terminal sterilization technique, preferred sterilizing 15min.
10. preparation method according to claim 8 or claim 9, is characterized in that: in preparation process containing activated carbon adsorption except endotoxin step.
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| CN201510953030.9A CN105362218A (en) | 2015-12-17 | 2015-12-17 | Glycopyrronium bromide injection and preparation method thereof |
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| CN201510953030.9A CN105362218A (en) | 2015-12-17 | 2015-12-17 | Glycopyrronium bromide injection and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107412153A (en) * | 2017-04-17 | 2017-12-01 | 南京健友生化制药股份有限公司 | A kind of Glycopyrronium bromide injection and preparation method thereof |
| CN111437254A (en) * | 2020-05-28 | 2020-07-24 | 成都欣捷高新技术开发股份有限公司 | Glycopyrronium bromide injection and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103553996A (en) * | 2013-11-13 | 2014-02-05 | 李兴惠 | Anticholinergic pharmaceutical composition |
| CN103690479A (en) * | 2013-12-04 | 2014-04-02 | 广东嘉博制药有限公司 | Glycopyrronium bromide injection and preparation method thereof |
| CN104274392A (en) * | 2013-07-01 | 2015-01-14 | 成都苑东药业有限公司 | Glycopyrronium bromide injection liquid composition and preparation method thereof |
-
2015
- 2015-12-17 CN CN201510953030.9A patent/CN105362218A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274392A (en) * | 2013-07-01 | 2015-01-14 | 成都苑东药业有限公司 | Glycopyrronium bromide injection liquid composition and preparation method thereof |
| CN103553996A (en) * | 2013-11-13 | 2014-02-05 | 李兴惠 | Anticholinergic pharmaceutical composition |
| CN103690479A (en) * | 2013-12-04 | 2014-04-02 | 广东嘉博制药有限公司 | Glycopyrronium bromide injection and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 国家食品药品监督管理局药品审评中心: "《药品技术评价文集》", 31 October 2006 * |
| 孟胜男等: "《药剂学》", 30 September 2011 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107412153A (en) * | 2017-04-17 | 2017-12-01 | 南京健友生化制药股份有限公司 | A kind of Glycopyrronium bromide injection and preparation method thereof |
| CN111437254A (en) * | 2020-05-28 | 2020-07-24 | 成都欣捷高新技术开发股份有限公司 | Glycopyrronium bromide injection and preparation method thereof |
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Application publication date: 20160302 |