CN107412153A - A kind of Glycopyrronium bromide injection and preparation method thereof - Google Patents
A kind of Glycopyrronium bromide injection and preparation method thereof Download PDFInfo
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- CN107412153A CN107412153A CN201710248445.5A CN201710248445A CN107412153A CN 107412153 A CN107412153 A CN 107412153A CN 201710248445 A CN201710248445 A CN 201710248445A CN 107412153 A CN107412153 A CN 107412153A
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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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 a kind of Glycopyrronium bromide injection and preparation method thereof, it is prepared by following steps：Sterile nitrogen bubbling is passed through into water for injection；Add phenmethylol to mix, pH value is adjusted to 2.5 ~ 3.0 with pH adjusting agent；Glycopyrronium bromide is continuously added, mixed dissolution, pH value is adjusted to 2.1 ~ 2.3 with pH adjusting agent；Add water for injection to be settled to and carry out aseptic filtration with liquid measure, decoction；Decoction after filtering carries out filling；Canned parenteral solution is put into sterilizing cabinet and carries out 4.0 ~ 6.5min of terminal sterilization in 124~126 DEG C, obtains Glycopyrronium bromide injection finished product.This method technique is simple, easily operated, and obtained product quality is controllable, safe, suitable for industrialized production.
Description
Technical field
The present invention relates to pharmaceutical preparations technology field, and in particular to a kind of Glycopyrronium bromide injection and its preparation technology, especially
It is directed to the sterilization process of Glycopyrronium bromide injection.
Background technology
Glycopyrronium bromide, chemical name are bromination 3- hydroxyl -1,1- alkyl dimethyl pyrroles-α-cyclopenta mandelate, point
Minor is C19H28BrNO3, molecular weight 398.34.Structural formula is
Glycopyrronium bromide (Glycopyrronium Bromide) is quaternary ammonium salt anticholinergic agent, have gastric acid secretion inhibiting and
Gastrointestinal peristalsis effect is adjusted, similar to other anticholinergic agents, this product also has the anti-salivary secretion effect more stronger than atropine.
Glycopyrronium bromide injection lists in 2 months 1975 6 Nikkei FDA approval in the U.S., and it existed after September in 2007 7 days
Britain lists, and only has tablet listing at home at present.Glycopyrronium bromide injection is different from the applicable crowd of its tablet, it is preferred that emphasis is
Preoperative reduction saliva, trachea-bronchial epithelial cell and pharyngeal secretion thing, reduce gastric acid secretion, the heart are prevented before anesthesia induction and trachea cannula
The inhibitory action of dirty vagus reflex；In art, with operation or drug-induced or vagus reflex the correlation heart of contending with
Restrain not normal.Can antagonism choline influence (for example, bradycardia and excessive secretion thing), such as resist neostigmine and pyridine this, i.e.,
For reversing due to the medicine of the neuromuscular blockade of non depolarization muscle relaxant.Using in adult's complementary therapy treatment digestion
During property ulcer, quick cholinolytic effect, when not being resistant to for oral drugs.It is domestic at present that there has been no in Glycopyrronium bromide injection
The report in city.
Glycopyrronium bromide injection trade name ROBINUL, specification have 0.2mg/1mL, 0.4mg/2mL, 1mg/5mL, 4mg/
20mL, wherein 0.2mg/1mL, 0.4mg/2mL are unit dose package；1mg/5mL and 4mg/20mL is multiple-unit container.FDA is said
The composition and specification of the product are given on bright book；Domestic existing numerous patents report the preparation of Glycopyrronium bromide injection
Method：Publication number CN103690479A patent adds the infiltration of sodium chloride regulating liquid medicine on the basis of with reference to FDA prescriptions
Pressure, then 8~30min of steam sterilizing at a temperature of 115~121 DEG C, the experiment proved that under the sterilising conditions, the benzene in prescription
Methanol is oxidized to benzaldehyde or benzoic acid, or even other unknown impurities, causes decoction impurity content exceeding index；Publication number
The Glycopyrronium bromide injection mentioned in two patents of CN105362218A and CN104274392A does not contain preservative phenmethylol,
And terminal sterilization technique is used, but the administering mode of Glycopyrronium bromide injection is intravenous injection and intramuscular injection, vein
The sterility requirements of the injection with small volume of administration in itself are very high, although employing terminal sterilization technique decoction can be ensured firm
Sterile when having produced can meet requirement, but decoction it is whole during use (>=2 years), microorganism still can be with
Grown and bred, including bacterium, saccharomycete, fungi, staphylococcus and Escherichia coli etc., it is difficult in such decoction practical application
To reach long-term sterile requirement；0.9% sodium chloride is added in publication number CN104274392A prescriptions, was both added
Supplementary product kind, production craft step is added again, add the production risk of product.Bulk drug is dense in Glycopyrronium bromide injection
Spend for 0.2mg/mL, and the content of sodium chloride is 45 times of bulk drug, the additions of a large amount of sodium chloride brings high thin to parenteral solution
The endotoxic risk of bacterium, so as to have impact on the quality of liquid medicine of parenteral solution.
To sum up, the Glycopyrronium bromide injection that each prior art is recorded is degraded in order to avoid preservative (such as phenmethylol) to be generated
Other impurities, and do not use preservative in formula, but in the injections for being free of preservative in whole (>=2 years) during use of decoction
Liquid is difficult to the growth for suppressing microorganism in follow-up decoction, it is ensured that the sterile requirement of decoction.In some parenteral solutions use with
A large amount of sodium chloride are added in side, and the addition of a large amount of sodium chloride brings the risk of high bacterial endotoxin to parenteral solution, so as to shadow
The quality of liquid medicine of parenteral solution is rung.
The content of the invention
The invention provides a kind of Glycopyrronium bromide injection and its preparation technology.This method technique is simple, easily operated, and
It is safe and obtained product quality is controllable.
The purpose of the present invention can be reached by following measures：
A kind of Glycopyrronium bromide injection, it is prepared by following steps：
1) sterile nitrogen bubbling is passed through into water for injection；
2) add phenmethylol to mix, pH value is adjusted to 2.5~3.0 with pH adjusting agent；
3) glycopyrronium bromide is continuously added, mixed dissolution, pH value is adjusted to 2.1~2.3 with pH adjusting agent；
4) plus water for injection is settled to and carries out aseptic filtration with liquid measure, decoction；
5) decoction after filtering carries out filling；
6) canned parenteral solution is put into sterilizing cabinet and carries out 4.0~6.5min of terminal sterilization in 124~126 DEG C, obtained
Glycopyrronium bromide injection finished product.
The invention also discloses a kind of preparation method of above-mentioned Glycopyrronium bromide injection, this method equally include it is above-mentioned 1)~
6) step.
In above-mentioned steps (1) and (4), it can be carried out with liquid in Agitation Tank.The water added in advance into Agitation Tank includes pure
Change water, ultra-pure water and water for injection etc..In step 1), the water for injection is passed through sterile nitrogen drum under normal gentle agitation
Bubble.The water of step 1) addition total water consumption 60%~80%, preferably 70%~80%, water temperature is in 20~30 DEG C, preferably 20~25
DEG C, it is passed through sterile nitrogen time >=15min, stirring at least more than 30min (300 ± 10rpm of rotating speed), it is ensured that oxygen in the aqueous solution
Content is in below 10ppm
In a kind of preferred scheme, in step 2), 3), 4) or 5) during, decoction using nitrogen protection or side
Operation side is filled with nitrogen into decoction system, it is ensured that oxygen content is less than 10ppm in decoction system.In step 1)~6) with liquid,
Filtering with pouring process, it is necessary to be carried out under conditions of lucifuge.
In above-mentioned steps (2), the phenmethylol added is pharmaceutical grade auxiliary material, can meet ChP or USP standards.The step
Suddenly the pH adjusting agent in) is preferably selected from hydrochloric acid.It is medicinal grade hydrochloric acid for the hydrochloric acid of regulating liquid medicine system pH, can meets
ChP or USP standards, for being first diluted before adjusting pH value to hydrochloric acid as 0.5M~1.8M, preferably 0.8M~1.2M,
Excellent 0.8M~1.0M again, it is same in this step to keep the state for leading to nitrogen to maintain oxygen content in decoction system to be less than 10ppm.
In step (2), the quality dosage of phenmethylol is 40~50 times of glycopyrronium bromide quality, preferably 44~46 times, more excellent
Select 44.5~45.5 times.In a kind of preferred scheme, the content of Glycopyrronium bromide injection is 0.2mg/mL, contains 0.9% simultaneously
Wt phenmethylol, the pH value of whole decoction is 2.0~3.0.
In above-mentioned steps (3), the glycopyrronium bromide of recipe quantity is added, the addition of glycopyrronium bromide can be adjusted as needed
It is whole, more than 15min is stirred, is completely dissolved to material, pH value is adjusted to 2.1~2.3 with hydrochloric acid and/or sodium hydrate aqueous solution,
For being first diluted before adjusting pH value to hydrochloric acid as 0.2M~0.8M, preferably 0.2M~0.4M, for adjusting pH value
Sodium hydrate aqueous solution is first prepared before, and sodium hydrate aqueous solution concentration is 0.05M~0.15M, preferably 0.05M~0.1M；With
It can continue to be passed through more than sterile nitrogen 15min after pH adjusting agent regulation pH value.
In above-mentioned steps (4), above-mentioned decoction is preferably wrapped by sterilizing filter press filtration to fluid reservoir, sterilizing filter
0.45 μm of prefilter and two 0.22 μm of sterilizing filters are included, the prefilter and two sterilizing filters are in series
It is attached.A kind of scheme is：Decoction after constant volume passes through prefilter and two sterilizing filter press filtrations to fluid reservoir.At this
During record filtering beginning and end time, maintain the rate of filtration in 1.5~2.0L/min, filter pressure control 42~
48psi.A kind of preferred scheme is that decoction carries out decoction press filtration to fluid reservoir by prefilter and two sterilizing filter series connection.
In step (5), it is filling that decoction can use automatic filling machine to carry out, and further rolls lid, loading quantity inspection.A kind of excellent
Select in scheme, the target filling amount of automatic filling machine setting is respectively 1.2mL, 2.2mL, 5.3mL, 20.4mL, in pouring process
In, every 0.5~1.0h, extract 10 XiLin bottle liquid medicines and detect its loading amount, it is ensured that loading amount meets the minimum fill every specification
It is required that.
In above-mentioned steps (6), Glycopyrronium bromide injection subject to sterilization is put into ASMPE-2.5 type water-bath sterilization cabinets, gone out
Bacterium temperature is preferably set to 125 DEG C, preferably 4.0~6.5min of sterilization time, 4.5~6.0min, further preferably 4.5~5.5min.
Existing popular parenteral solution sterilising conditions are 121 DEG C, 5min, 10min, 15min, 30min etc., by early stage in the big of laboratory
Amount experiment, which is investigated, finds 121 DEG C, the F of 5min, 10min decoction0Value is less than 8, does not reach the sterilizing requirement of parenteral solution, 121 DEG C go out
Phenmethylol in bacterium 15min above prescriptions is oxidized to benzaldehyde or benzoic acid etc. and produces some other row unknown impuritie, gives
The relevant material detection of decoction brings bigger difficulty, can not establish suitable quality standard, and because phenmethylol is broken
The bad effect that antiseptic and inhibiting bacteria function can not be provided for follow-up parenteral solution.Various sterilising conditions have equally been attempted in the lab, to sample
Moral character shape, pH value, content, about material, visible foreign matters and F0Value carries out comprehensive consideration, finally found that only at 125 DEG C, 4.0
Under~6.5min sterilising conditions and the cooperation of other conditions, F after Glycopyrronium bromide injection sterilizing both can ensure that0Value >=12,
And can ensures that phenmethylol is not destroyed in prescription.The grand bromine of qualified lattice is obtained after terminal sterilization lamp inspection, sample detection are let pass
Ammonium parenteral solution finished product.
Instant invention overcomes the limitation for adding phenmethylol in Glycopyrronium bromide injection to avoid degraded from being difficult to, there is provided
One kind contains the Glycopyrronium bromide injection preparation technology of preservative phenmethylol, not sodium chloride-containing, and there is the technique prescription simply to close
Reason, preparation technology operation are easy, and have lucifuge and nitrogen filled protection with liquid, filtering and pouring process, are effectively reduced this product
With illumination and the contact of oxygen, the degraded of this product is delayed to a certain extent.The invention provides specific sterilizing parameter, and
Under the cooperation of other conditions (such as reducing dissolved oxygen and accurate control ph etc.), it is small to ensure that final decoction finished product had both met
Sterility requirements (the F of capacity decoction intravenous injection0Value >=12), the benzyl alcohol content in prescription compared to inventory still >=97%,
Phenmethylol is under the hot conditions of certain time without destroyed, there is provided the finished product decoction of better quality requirement so that finished product
Establishing for quality standard is simple and easy, also causes phenmethylol to play due antiseptic and inhibiting bacteria function in the life cycle of finished product decoction
Effect.Preparation is simple by the present invention, is suitable for industrialized production.
Embodiment
Embodiment one：
40L water for injection is added into 50L Agitation Tanks, water temperature is controlled at 20~30 DEG C, unlatching stirring (rotating speed 300 ±
10 rpm), sterile nitrogen bubbling 35min is passed through, the oxygen content measured in water is 8ppm, weighs 450g phenmethylols and is slowly added to match somebody with somebody
In flow container, its pH to 2.5 is adjusted with 0.5M hydrochloric acid；9.96g glycopyrronium bromides are added, stir 18min, material is completely dissolved, and is used
The pH value of 0.2M hydrochloric acid and 0.05M sodium hydrate aqueous solution regulating liquid medicine systems adds water to be settled to 50L to 2.1；By above-mentioned decoction
By 0.45 μm of prefilter of series connection and two 0.22 μm of sterilizing filters, it is 1.5L/min to control aseptic filtration speed, pressure
Power is 42psi, and filtrate is pressed onto in fluid reservoir, and automatic filling machine difference sets target filling amount is that 1.2mL and 2.2mL carrys out filling dress
Sample amount is 1mL and 2mL Glycopyrronium bromide injection, rolls lid.Canned XiLin bottle liquid medicine subject to sterilization is put into ASMPE-2.5 types
Water-bath sterilization cabinet, 125 DEG C of sterilizing 4.0min are set, take out sample and carry out lamp inspection, the sampling censorship of lamp inspection qualified samples：
0.2mg/1mL decoctions are colourless clear liquid, and content 98.5%, impurity C is 0.8%, and impurity L is not detected,
RRT0.28 impurity is 0.6%, unknown impuritie 0.4%, and always miscellaneous is 1.2%, and pH value 2.3, benzoic acid does not detect, benzene first
Alcohol content is 97.0%, and benzaldehyde content is 0.010%, bacterial endotoxin ＜ 268.0USP EU/mg, sterile；
0.4mg/2mL decoctions are colourless clear liquid, and content 98.7%, impurity C is 1.0%, and impurity L is not detected,
RRT0.28 impurity is 0.5%, unknown impuritie 0.3%, and always miscellaneous is 1.2%, and pH value 2.3, benzoic acid does not detect, benzene first
Alcohol content is 97.5%, and benzaldehyde content is 0.016%, bacterial endotoxin ＜ 277.8USP EU/mg, sterile.
Embodiment two：
42L water for injection is added into 70L Agitation Tanks, water temperature is controlled at 20~30 DEG C, unlatching stirring (rotating speed 300 ±
10 rpm), sterile nitrogen bubbling 35min is passed through, the oxygen content measured in water is 9ppm, weighs 630.1g phenmethylols and is slowly added to
In Agitation Tank, 1.8M hydrochloric acid adjusts its pH to 3.0；14.10g glycopyrronium bromides are added, stir 18min, material is completely dissolved, and is used
The pH value of 0.8M hydrochloric acid and 0.15M sodium hydrate aqueous solution regulating liquid medicine systems adds water to be settled to 70L to 2.3；By above-mentioned decoction
By 0.45 μm of prefilter of series connection and two 0.22 μm of sterilizing filters, it is 2.0L/min to control aseptic filtration speed, pressure
Power is 48psi, and filtrate is pressed onto in fluid reservoir, and sets target filling amount is that the next filling sample-loading amounts of 5.3mL are to automatic filling machine respectively
5mL Glycopyrronium bromide injection, roll lid.Canned XiLin bottle liquid medicine subject to sterilization is put into ASMPE-2.5 type water-bath sterilization cabinets,
125 DEG C of sterilizing 6.5min of setting, take out sample and carry out lamp inspection, the sampling censorship of lamp inspection qualified samples.
1mg/5mL decoctions are colourless clear liquid, and content 98.5%, impurity C is 0.24%, and impurity L is not detected,
RRT0.28 impurity is 0.2%, unknown impuritie 0.2%, and always miscellaneous is 0.8%, and pH value 2.3, benzoic acid does not detect, benzene first
Alcohol content is 97.3%, and benzaldehyde content is 0.022%, bacterial endotoxin ＜ 260.7USP EU/mg, sterile.
Embodiment three：
42L water for injection is added into 60L Agitation Tanks, water temperature is controlled at 20~30 DEG C, unlatching stirring (rotating speed 300 ±
10 rpm), sterile nitrogen bubbling 35min is passed through, the oxygen content measured in water is 8ppm, weighs 540.1g phenmethylols and is slowly added to
In Agitation Tank, its pH to 2.7 is adjusted with 1.0M hydrochloric acid；12.08g glycopyrronium bromides are added, stir 18min, material is completely dissolved, and is used
The pH value of 0.6M hydrochloric acid and 0.10M sodium hydrate aqueous solution regulating liquid medicine systems adds water to be settled to 60L to 2.2；By above-mentioned decoction
By 0.45 μm of prefilter of series connection and two 0.22 μm of sterilizing filters, it is 1.8L/min to control aseptic filtration speed, pressure
Power is 45psi, and filtrate is pressed onto in fluid reservoir, and sets target filling amount is that the next filling sample-loading amounts of 20.4mL are to automatic filling machine respectively
20mL Glycopyrronium bromide injection, roll lid.Canned XiLin bottle liquid medicine subject to sterilization is put into ASMPE-2.5 type water-bath sterilizations
Cabinet, 125 DEG C of sterilizing 5.5min are set, take out sample and carry out lamp inspection, the sampling censorship of lamp inspection qualified samples.
4mg/20mL decoctions are colourless clear liquid, and content 99.2%, impurity C is 0.7%, and impurity L is not detected,
RRT0.28 impurity is 0.3%, unknown impuritie 0.2%, and always miscellaneous is 1.1%, and pH value 2.2, benzoic acid does not detect, benzene first
Alcohol content is 99.5%, and benzaldehyde content is 0.009%, bacterial endotoxin ＜ 289.3USP EU/mg, sterile.
Claims (10)
1. a kind of Glycopyrronium bromide injection, it is characterised in that it is prepared by following steps：
（1）Sterile nitrogen bubbling is passed through into water for injection；
（2）Add phenmethylol to mix, pH value is adjusted to 2.5 ~ 3.0 with pH adjusting agent；
（3）Glycopyrronium bromide is continuously added, mixed dissolution, pH value is adjusted to 2.1 ~ 2.3 with pH adjusting agent；
（4）Add water for injection to be settled to and carry out aseptic filtration with liquid measure, decoction；
（5）Decoction after filtering carries out filling；
（6）Canned parenteral solution is put into sterilizing cabinet and carries out 4.0 ~ 6.5min of terminal sterilization in 124~126 DEG C, obtains Ge Long
Bromine ammonium parenteral solution finished product.
2. Glycopyrronium bromide injection according to claim 1, it is characterised in that in step 1）In, the use of the water for injection
Amount accounts for the 60~85% of total water consumption；The water for injection is passed through sterile nitrogen bubbling at 20~30 DEG C of temperature and stirring, is passed through
The min of sterile nitrogen time >=15；Mixing speed is 300 ± 10 rpm.
3. Glycopyrronium bromide injection according to claim 2, it is characterised in that in step 1）In, the use of the water for injection
Amount accounts for the 70% ~ 80% of total water consumption；The water for injection is passed through sterile nitrogen bubbling at 20 DEG C ~ 25 DEG C of temperature and stirring, really
Oxygen content is in below 10ppm in guarantor's water for injection.
4. Glycopyrronium bromide injection according to claim 1, it is characterised in that in step 2）、3）、4）Or 5）During,
Decoction is protected using nitrogen.
5. Glycopyrronium bromide injection according to claim 1, it is characterised in that in step 2）In, the quality dosage of phenmethylol
For 40~50 times of glycopyrronium bromide quality, preferably 44~46 times.
6. Glycopyrronium bromide injection according to claim 1, it is characterised in that in step 2）In, the pH adjusting agent is selected from
The concentration of hydrochloric acid, wherein hydrochloric acid is 0.5M ~ 1.8M, preferably 0.8M ~ 1.2M, more preferably 0.8M ~ 1.0M；Logical nitrogen is kept in the step
Oxygen content in decoction is maintained to be less than 10ppm.
7. Glycopyrronium bromide injection according to claim 1, it is characterised in that in step 3）In, the pH adjusting agent is selected from
Hydrochloric acid or sodium hydrate aqueous solution；Wherein the concentration of hydrochloric acid is 0.2M ~ 0.8M, preferably 0.2M ~ 0.4M；Sodium hydrate aqueous solution is dense
Spend for 0.05M ~ 0.15M, preferably 0.05M ~ 0.1M；More than the min of sterile nitrogen 15 is passed through after adjusting pH value with pH adjusting agent.
8. Glycopyrronium bromide injection according to claim 1, it is characterised in that in step 4）In, the decoction after constant volume passes through
Prefilter and two sterilizing filter press filtrations to fluid reservoir, the rate of filtration in 1.5 ~ 2.0L/min, filter pressure control 42 ~
48psi；Wherein prefilter is 0.45 μm, and two sterilizing filters are 0.22 μm.
9. Glycopyrronium bromide injection according to claim 1, it is characterised in that in step 6）In, parenteral solution is put into sterilizing cabinet
4.0 ~ 6.5min of terminal sterilization is carried out in 125 DEG C.
10. the preparation method of the Glycopyrronium bromide injection described in a kind of claim 1, it is characterised in that comprise the following steps：
（1）Sterile nitrogen bubbling is passed through into water for injection；
（2）Add phenmethylol to mix, pH value is adjusted to 2.5 ~ 3.0 with pH adjusting agent；
（3）Glycopyrronium bromide is continuously added, mixed dissolution, pH value is adjusted to 2.1 ~ 2.3 with pH adjusting agent；
（4）Add water for injection to be settled to and carry out aseptic filtration with liquid measure, decoction；
（5）Decoction after filtering carries out filling；
（6）Canned parenteral solution is put into sterilizing cabinet and carries out 3.5 ~ 7.0min of terminal sterilization in 124~126 DEG C, obtains Ge Long
Bromine ammonium parenteral solution finished product.
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| CN201710248445.5A CN107412153A (en) | 2017-04-17 | 2017-04-17 | A kind of Glycopyrronium bromide injection and preparation method thereof |
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| CN201710248445.5A CN107412153A (en) | 2017-04-17 | 2017-04-17 | A kind of Glycopyrronium bromide injection and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111166715A (en) * | 2018-11-11 | 2020-05-19 | 北京凯因科技股份有限公司 | Glycopyrronium bromide injection and preparation method thereof |
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| CN102988285A (en) * | 2012-12-13 | 2013-03-27 | 哈药集团技术中心 | Docetaxel injection composition 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 |
| CN105362218A (en) * | 2015-12-17 | 2016-03-02 | 浙江华海药业股份有限公司 | Glycopyrronium bromide injection and preparation method thereof |
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2017
- 2017-04-17 CN CN201710248445.5A patent/CN107412153A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102988285A (en) * | 2012-12-13 | 2013-03-27 | 哈药集团技术中心 | Docetaxel injection composition 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 |
| CN105362218A (en) * | 2015-12-17 | 2016-03-02 | 浙江华海药业股份有限公司 | Glycopyrronium bromide injection and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111166715A (en) * | 2018-11-11 | 2020-05-19 | 北京凯因科技股份有限公司 | Glycopyrronium bromide injection and preparation method thereof |
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Application publication date: 20171201 |
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| RJ01 | Rejection of invention patent application after publication |