CN107224427A - A kind of Glycopyrronium bromide injection composition and preparation method thereof - Google Patents
A kind of Glycopyrronium bromide injection composition and preparation method thereof Download PDFInfo
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- CN107224427A CN107224427A CN201710281398.4A CN201710281398A CN107224427A CN 107224427 A CN107224427 A CN 107224427A CN 201710281398 A CN201710281398 A CN 201710281398A CN 107224427 A CN107224427 A CN 107224427A
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- glycopyrronium bromide
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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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- 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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Abstract
The invention provides a kind of formulation and technology is simple, it can ensure that Glycopyrronium bromide injection of product quality and preparation method thereof again simultaneously, sodium chloride in prescription is used as osmotic pressure regulator, parenteral solution can be avoided to occur hypotonic phenomenon in intramuscular injection and drip-feed, technique uses terminal sterilization, better meet sterility barrier requirement, nitrogen charging operation is carried out with liquid and filling process, effectively reduce contact of this product with oxygen, the degraded of this product is delayed to a certain extent, prescription amount of substance relevant with the Glycopyrronium bromide injection that technique is prepared using the present invention is relatively low, it is quality controllable, stability is good, more suitable for industrialized production.
Description
Technical field
The present invention relates to pharmaceutical technology field, more particularly 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 pyrroles-α-cyclopenta mandelate., point
Minor is C19H28BrNO3, molecular weight is 398.34, and structural formula is：
Glycopyrronium bromide is quaternary amines anticholinergic agent, with suppression gastric secretion and regulation gastrointestinal peristalsis effect；This product also has
The anti-salivary secretion effect more stronger than atropine, but without central cholinolytic activity.Only has tablet at home at present, abroad
Existing parenteral solution listing.
Glycopyrronium bromide injection in 2 months 1975 6 Nikkei FDA approval in U.S.'s listing, thereafter, in September in 2007 7 days
In Britain's listing.As the product of the new method of administration of glycopyrronium bromide, this product is different from the applicable crowd of oral formulations, and emphasis is fitted
For premedicate, saliva, trachea-bronchial epithelial cell and pharyngeal secretion thing are reduced, gastric acid secretion is reduced, in anesthesia induction and trachea cannula
The preceding inhibitory action for preventing cardiac vagal from reflecting；In art, with the operation or drug-induced or vagus reflex that contends with
Correlation arrhythmia cordis.Can antagonism choline influence (for example, bradycardia and excessive secretion thing), such as confrontation neostigmine and pyrrole
Pyridine this, i.e. the medicine for reversing the neuromuscular blockade due to non depolarization muscle relaxant.Using in adult's complementary therapy
When treating peptic ulcer, quick cholinolytic effect, when not being resistant to for oral drugs.It is domestic at present to only have glycopyrronium bromide mouthful
Oral dosage form is listed, and not yet has the production listing of glycopyrronium bromide injection.
It can be seen from U.S.'s Glycopyrronium bromide injection commercially available product (trade name ROBINUL Injection) specification, this
It is preservative to contain 0.9% phenmethylol in product prescription, and with hydrochloric acid and/or sodium hydroxide as pH adjusting agent, water for injection is molten
Agent；PH value is 2.0~3.0；Specification is 1ml:0.2mg、2ml:0.4mg、5ml:1mg and 20ml:4mg, wherein 5ml:1mg and
20ml:Two kinds of specifications of 4mg are multiple dosing.Phenmethylol can exist certain as a kind of preservative, when being directly used in intravenously administrable
Potential safety hazard, and phenmethylol can slowly be oxidized to benzaldehyde and benzoic acid in atmosphere, especially in multiple dosing, can not keep away
The meeting exempted from comes in contact with oxygen, causes the quality of product to be difficult to ensure that.
It was found from the structural analysis of glycopyrronium bromide, it can carry out partial hydrolysis and cause the generation of impurity, and after hydrolysis
Impurity may be oxidized.Unknown impuritie in the sample that can also find oxidized destruction is tested by Oxidative demage substantially to increase
Plus.The presence of this explanation oxygen can have certain influence to the quality of product, therefore avoid the contact with oxygen as far as possible in process of production
It is very important.
Therefore, this area needs a kind of formulation and technology simple in a hurry, while can ensure that the system of the parenteral solution of product quality again
Preparation Method, the present invention meets such demand.
The content of the invention
In view of the above-mentioned problems, the present invention provides a kind of new Glycopyrronium bromide injection composition and preparation method thereof, at this
Side and preparation process are easy, it is easy to operate, the product quality prepared is controllable.
The present invention provides a kind of Glycopyrronium bromide injection composition, and every 1000 compositions are composed of the following components：
Glycopyrronium bromide：0.1g~0.4g, sodium chloride：9g~18g, 2mol/L hydrochloric acid solution are appropriate, and water for injection is added to
1000ml~2000ml.
Wherein, glycopyrronium bromide content is 1ml in per unit preparation:0.1mg、1ml:0.2mg or 2ml:0.4mg.
Further, every 1000 compositions are composed of the following components：Glycopyrronium bromide：0.1g, sodium chloride：9g, 2mol/L
Appropriate hydrochloric acid solution, water for injection adds to 1000ml.
Or, every 1000 compositions are composed of the following components：Glycopyrronium bromide：0.2g, sodium chloride：9g, 2mol/L hydrochloric acid
Appropriate solution, water for injection adds to 1000ml.
Or, every 1000 compositions are composed of the following components：Glycopyrronium bromide：0.4g, sodium chloride：18g, 2mol/L hydrochloric acid
Appropriate solution, water for injection adds to 2000ml.
The invention also discloses the preparation method of Glycopyrronium bromide injection composition, this method comprises the following steps：
(1) liquid is matched somebody with somebody：The water for injection of recipe quantity is taken, the temperature control of water for injection adds prescription full dose below 40 DEG C
Sodium chloride, stirring be completely dissolved it, with 2mol/L hydrochloric acid solutions adjust pH to 2.3~2.7, under conditions of nitrogen charging add
The glycopyrronium bromide of prescription full dose, stirring is completely dissolved it, standby；
(2) aseptic filtration：By the above-mentioned decoction prepared with " 0.45 μm of+0.22 μm of poly (ether sulfone) film of+0.22 μm of polypropylene screen gathers
The sterilizing filter refined filtration of ether sulfone film " series connection；
(3) embedding：The decoction after aseptic filtration is no less than sign loading amount embedding in nothing by every under conditions of nitrogen charging
In the low borosilicate glass ampoule bottle of color；
(4) sterilize：Using 121 DEG C of 12~15min of wet-hot steams sterilizing.
It is preferred that, using 121 DEG C of wet-hot steam sterilizing 15min in step 4.
The Glycopyrronium bromide injection that the present invention is provided has advantages below：
(1) prescription is simple, the sodium chloride in prescription as osmotic pressure regulator, parenteral solution can be avoided in intramuscular injection and
Occurs hypotonic phenomenon during drip-feed；
(2) terminal sterilization is used, sterility barrier requirement is better met；
(3) nitrogen charging operation is carried out with liquid and filling process, effectively reduces contact of this product with oxygen, to a certain extent
Delayed the degraded of this product, using the present invention prescription amount of substance relevant with the Glycopyrronium bromide injection that technique is prepared compared with
Low, quality controllable, stability is good, more suitable for industrialized production.
Embodiment
Below in conjunction with test example and embodiment, the present invention is described in further detail, but the not limit to the present invention
System, the equivalent substitution of all any this areas made according to the disclosure of invention belongs to protection scope of the present invention.
With liquid temperature degree development test
8 100ml beaker is taken respectively and is numbered, 0.9g sodium chloride is added in each beaker, then is separately added into
Temperature is 20 DEG C, 40 DEG C, 60 DEG C, 80 DEG C of each 100ml of water for injection, is stirred to dissolve, separately takes glycopyrronium bromide to be placed in appearance in right amount
In device, each 4 parts of the glycopyrronium bromide solution that concentration is respectively 0.1mg/ml and 0.2mg/ml is made, 1.0mol/L hydrochloric acid is used respectively
Solution regulation pH value is about 2.5, is filtered with 0.22 μm of miillpore filter, and embedding damp and hot is gone out in 1ml ampoule bottles using 121 DEG C
Bacterium 15min.Testing program is shown in Table 1.Detect the pH value of solution, about material and content with sampling after sterilizing before sterilization respectively.
Result of the test is shown in Table 2.
Table 1 investigates testing program with liquid temperature degree
Table 2 investigates result with liquid temperature degree
From table 2 it can be seen that the decoction of two specifications, when being more than 60 DEG C with liquid temperature degree, the relevant material increase of decoction compared with
To be obvious, quality stability declines, therefore to ensure this product quality stability, with reference to produce reality, the present invention will match somebody with somebody liquid temperature degree
Control is at 20 DEG C~40 DEG C.
Nitrogen charging influences to test on the quality of finished product
4 100ml beaker is taken respectively and is numbered, 0.9g sodium chloride is added in each beaker, and adding temperature is
20 DEG C~40 DEG C of each 100ml of water for injection, is stirred to dissolve；The beaker that numbering is No. 2 and No. 4 is taken, under conditions of nitrogen charging
Appropriate glycopyrronium bromide is added, the glycopyrronium bromide solution that concentration is respectively 0.1mg/ml and 0.2mg/ml is made, it is No. 1 to take numbering
With the beaker of No. 3, not nitrogen charging be directly added into appropriate glycopyrronium bromide, the lattice that concentration is respectively 0.1mg/ml and 0.2mg/ml are made
Grand bromine ammonium salt solution；It is about 2.5 to adjust pH value with 1.0mol/L hydrochloric acid solutions respectively, is filtered with 0.22 μm of miillpore filter, wherein
Numbering is that embedding is in 1ml ampoule bottles under conditions of nitrogen charging for decoction in No. 2 and No. 4 beakers, and numbering is No. 1 and No. 3 beakers
In decoction not nitrogen charging, direct embedding is in 1ml ampoule bottles after filtering, using 121 DEG C of moist heat sterilization 15min.After sterilization
Sample the character for detecting solution, pH value, about material and content, result of the test is shown in Table 3.
The nitrogen charging of table 3 influences result to the quality of finished product
From table 3 it can be seen that under the conditions of non-nitrogen charging and nitrogen charging, character, pH value, the content of two specification decoctions all do not have
Generation notable difference, but relevant material changes substantially, and the relevant material of decoction is significantly lower than non-nitrogen charging under the conditions of nitrogen charging
Under the conditions of decoction relevant material, illustrate that nitrogen charging has a major impact to the control of the relevant material of this product.To ensure that this quality is steady
Qualitative, the present invention carries out nitrogen charging control in liquid and pouring process.
The selection of sterilization process condition
Injection sterilization process is the important process process for ensureing its quality and security.To ensure sterilizing validity and system
The sterility assurance level of agent, the preferred terminal sterilization technique of small liquid drugs injection, therefore sterilising conditions need to be selected and verified.Prepare dense
Degree is respectively 0.1mg/ml and 0.2mg/ml glycopyrronium bromide solution, nitrogen charging embedding after filtering, respectively with overkill method (F0
>=12) sterilized with probability of surviving method (8≤F0 ＜ 12), compare the change of this quality before and after sterilizing.Respectively at before sterilizing, 115
(8≤F0 ＜ 12) after (8≤F0 ＜ 12), 121 DEG C of wet-hot steams sterilizing 8min after DEG C wet-hot steam sterilizing 30min, 121 DEG C it is wet
The character of (F0 >=12) sampling detection sample after (F0 >=12), 121 DEG C of wet-hot steams sterilizing 15min after vapours sterilizing 12min,
PH value, about material and content.Result of the test is shown in Table 4.
The sterilization process condition Selection experiment result of table 4
From table 4, it can be seen that this product is under four kinds of sterilising conditions, character, pH value and the content of decoction are without bright before and after sterilizing
Show before the relevant material after change, but sterilizing relatively sterilizes and increased；Decoction has after 115 DEG C of wet-hot steam sterilizing 30min
Pass material is higher, and the relevant material difference of decoction is little during 121 DEG C of wet-hot steams sterilizing 8min~15min, and is slightly below
The relevant material of decoction after 115 DEG C of wet-hot steam sterilizing 30min.In order to preferably control this product sterile wind in process of production
Danger, meets sterility barrier requirement, and 121 DEG C of wet-hot steam sterilizing 12min~15min (F0 >=12) of selection are used as this product terminal sterilization
Condition, preferably 121 DEG C wet-hot steams sterilizing 15min.
Following embodiments can realize the effect of above-mentioned experiment.
Embodiment 1
1000ml water for injection is taken, the temperature control of water for injection adds 9g sodium chloride at 30 DEG C or so, and stirring makes it
It is completely dissolved, pH to 2.3 is adjusted with 2mol/L hydrochloric acid solutions, 0.1g glycopyrronium bromide is added under conditions of nitrogen charging, stirring makes
It is completely dissolved；The above-mentioned decoction prepared is gone here and there with " 0.45 μm of+0.22 μm of poly (ether sulfone) film of+0.22 μm of polypropylene screen poly (ether sulfone) film "
The sterilizing filter refined filtration of connection；The decoction after aseptic filtration is no less than 1ml embeddings in colourless by every under conditions of nitrogen charging
In low borosilicate glass ampoule bottle；Using 121 DEG C of wet-hot steams sterilizing 15min, lamp inspection obtains Glycopyrronium bromide injection.
Embodiment 2
1000ml water for injection is taken, the temperature control of water for injection adds 9g sodium chloride at 20 DEG C or so, and stirring makes it
It is completely dissolved, pH to 2.5 is adjusted with 2mol/L hydrochloric acid solutions, 0.2g glycopyrronium bromide is added under conditions of nitrogen charging, stirring makes
It is completely dissolved；The above-mentioned decoction prepared is gone here and there with " 0.45 μm of+0.22 μm of poly (ether sulfone) film of+0.22 μm of polypropylene screen poly (ether sulfone) film "
The sterilizing filter refined filtration of connection；The decoction after aseptic filtration is no less than 1ml embeddings in colourless by every under conditions of nitrogen charging
In low borosilicate glass ampoule bottle；Using 121 DEG C of wet-hot steams sterilizing 15min, lamp inspection obtains Glycopyrronium bromide injection.
Embodiment 3
2000ml water for injection is taken, the temperature control of water for injection adds 18g sodium chloride at 40 DEG C or so, and stirring makes
It is completely dissolved, and pH to 2.7 is adjusted with 2mol/L hydrochloric acid solutions, and 0.4g glycopyrronium bromide, stirring are added under conditions of nitrogen charging
It is completely dissolved it；The above-mentioned decoction prepared is used into " 0.45 μm of+0.22 μm of poly (ether sulfone) film of+0.22 μm of polypropylene screen poly (ether sulfone) film "
The sterilizing filter refined filtration of series connection；The decoction after aseptic filtration is no less than 2ml embeddings in nothing by every under conditions of nitrogen charging
In the low borosilicate glass ampoule bottle of color；Using 121 DEG C of wet-hot steams sterilizing 15min, lamp inspection obtains Glycopyrronium bromide injection.
Embodiment 4
1000ml water for injection is taken, the temperature control of water for injection adds 9g sodium chloride at 40 DEG C or so, and stirring makes it
It is completely dissolved, pH to 2.5 is adjusted with 2mol/L hydrochloric acid solutions, 0.1g glycopyrronium bromide is added under conditions of nitrogen charging, stirring makes
It is completely dissolved；The above-mentioned decoction prepared is gone here and there with " 0.45 μm of+0.22 μm of poly (ether sulfone) film of+0.22 μm of polypropylene screen poly (ether sulfone) film "
The sterilizing filter refined filtration of connection；The decoction after aseptic filtration is no less than 1ml embeddings in colourless by every under conditions of nitrogen charging
In low borosilicate glass ampoule bottle；Using 121 DEG C of wet-hot steams sterilizing 12min, lamp inspection obtains Glycopyrronium bromide injection.
Embodiment 5
1000ml water for injection is taken, the temperature control of water for injection adds 9g sodium chloride at 30 DEG C or so, and stirring makes it
It is completely dissolved, pH to 2.7 is adjusted with 2mol/L hydrochloric acid solutions, 0.2g glycopyrronium bromide is added under conditions of nitrogen charging, stirring makes
It is completely dissolved；The above-mentioned decoction prepared is gone here and there with " 0.45 μm of+0.22 μm of poly (ether sulfone) film of+0.22 μm of polypropylene screen poly (ether sulfone) film "
The sterilizing filter refined filtration of connection；The decoction after aseptic filtration is no less than 1ml embeddings in colourless by every under conditions of nitrogen charging
In low borosilicate glass ampoule bottle；Using 121 DEG C of wet-hot steams sterilizing 15min, lamp inspection obtains Glycopyrronium bromide injection.
Comparative example
Glycopyrronium bromide injection, manufacturer：Taro Pharmaceuticals (Ireland) Limited, specification：
1ml:0.2mg。
The influence factor of test example 1 is tested
(1) hot test
The Glycopyrronium bromide injection and comparative example that Example 1, embodiment 2, embodiment 3 are prepared are positioned over height
Under the conditions of 60 DEG C of temperature, detected respectively at sampling in the 5th day after setting-out and the 10th day.Result of the test see the table below 5.
The high temperature influence factor result of the test of table 5
As known from Table 5, sample of the embodiment of the present invention and comparative example were placed 10 days under the conditions of 60 DEG C of high temperature, with 0 day
Compare, character, pH value, visible foreign matters and content have no significant change in inspection target, relevant material increased.Comparative example
Sample relevant material at 0 day is placed 10 days under the same conditions apparently higher than sample of the embodiment of the present invention, and comparative example
Afterwards, relevant material increase trend also becomes apparent compared with the embodiment of the present invention.
(2) exposure experiments to light
The Glycopyrronium bromide injection and comparative example that Example 1, embodiment 2, embodiment 3 are prepared are positioned over by force
Under the conditions of light (4500lx ± 500lx), detected respectively at sampling in the 5th day after setting-out and the 10th day.Result of the test see the table below
6。
Table the last 6 shadow rings factorial experiments result
As known from Table 6, sample of the embodiment of the present invention was placed 10 days under the conditions of strong light 4500lx ± 500lx, with 0 day phase
Than, character in inspection target, pH value, visible foreign matters, have no significant change about material and content.Illustrate this product in illumination condition
Lower quality stability is preferable.Comparative example was placed after 10 days under the same conditions, compared with 0 day, and indices are also without substantially
Change, but relevant material is above the relevant material of sample of the embodiment of the present invention.
It can be seen from influence factor result of the test 10 are placed under the conditions of 60 DEG C of high temperature and strong light 4500lx ± 500lx
After it, the relevant material of sample of the embodiment of the present invention is below the relevant material of comparative example.
The accelerated test of test example 2
The embodiment of the present invention 1, embodiment 2, embodiment 3 and comparative example are taken, by commercially available back, respectively in 40 DEG C of temperature
± 2 DEG C, place 6 months under conditions of relative humidity 75% ± 5%.January, the 2nd month, March during experiment and
The sampling of 6th the end of month is detected.Result of the test is shown in Table 7.
The accelerated test result of table 7
As known from Table 7, the embodiment of the present invention 1,2,3 and comparative example press commercially available back, in 40 DEG C ± 2 DEG C of temperature, phase
After being placed 6 months under conditions of humidity 75% ± 5%, compared with 0 month, the character of this product, pH value, visible foreign matters and content are equal
Without significant change, relevant material is in increase trend.But the relevant material of comparative example is apparently higher than this hair under the same conditions
The relevant material of bright embodiment sample.
The long term test of test example 3
The embodiment of the present invention 1, embodiment 2, embodiment 3 and comparative example are taken, by commercially available back, respectively in 25 DEG C of temperature
± 2 DEG C, place 24 months under conditions of relative humidity 60% ± 10%.March, June, September during experiment,
December, the 18th month and the sampling of the 24th the end of month are detected.Result of the test is shown in Table 8.
The long term test comparing result of table 8
As known from Table 8, the embodiment of the present invention 1,2,3 and comparative example press commercially available back, in 25 DEG C ± 2 DEG C of temperature, phase
After being placed 24 months under conditions of humidity 60% ± 10%, compared with 0 month, the character, pH value, visible foreign matters and content of this product
Have no significant change, relevant material is increased slightly.But the relevant material of comparative example is real higher than the present invention under the same conditions
Apply the relevant material of a sample.
By the result of table 7 and table 8, comparative example and the sample of the embodiment of the present invention 1,2,3 are using identical commercially available
After being packaged under the conditions of accelerated test and place 6 months, being placed 24 months under the conditions of long term test, the character of sample, pH values,
Visible foreign matters and content have no significant change, and growth trend is presented in relevant material, and under the same conditions, using nitrogen charging technique
The relevant material of the sample of the embodiment of the present invention of preparation is far below comparative example.
The Glycopyrronium bromide injection prepared by above-mentioned results showed that using the prescription and technique of the present invention, prescription
Simply, nitrogen charging operation is being carried out with liquid and filling process, is effectively controlling relevant material in the degraded of this product, product relatively low；Adopt
With terminal sterilization, sterility barrier requirement is better met；The glycopyrronium bromide note prepared using the prescription and technique of the present invention
Penetrate liquid quality controllable, stability is good, had made marked progress compared with prior art tool, be more suitable for industrialized production.
Claims (7)
1. a kind of Glycopyrronium bromide injection composition, it is characterised in that every 1000 compositions are composed of the following components：
Glycopyrronium bromide 0.1g~0.4g, sodium chloride 9g~18g, 2mol/L hydrochloric acid solutions are appropriate, water for injection add to 1000ml~
2000ml。
2. Glycopyrronium bromide injection composition according to claim 1, it is characterised in that glycopyrronium bromide in per unit preparation
Content is 1ml:0.1mg、1ml:0.2mg or 2ml:0.4mg.
3. Glycopyrronium bromide injection composition according to claim 1 or 2, it is characterised in that every 1000 compositions by
Following components is constituted：Glycopyrronium bromide 0.1g, sodium chloride 9g, 2mol/L hydrochloric acid solution are appropriate, and water for injection adds to 1000ml.
4. Glycopyrronium bromide injection composition according to claim 1 or 2, it is characterised in that every 1000 compositions by
Following components is constituted：Glycopyrronium bromide 0.2g, sodium chloride 9g, 2mol/L hydrochloric acid solution are appropriate, and water for injection adds to 1000ml.
5. Glycopyrronium bromide injection composition according to claim 1 or 2, it is characterised in that every 1000 compositions by
Following components is constituted：Glycopyrronium bromide 0.4g, sodium chloride 18g, 2mol/L hydrochloric acid solution are appropriate, and water for injection adds to 2000ml.
6. the preparation method of the Glycopyrronium bromide injection composition according to any one of Claims 1 to 5, it is characterised in that
This method comprises the following steps：
(1) liquid is matched somebody with somebody：The water for injection of recipe quantity is taken, the temperature control of water for injection adds the chlorine of prescription full dose below 40 DEG C
Change sodium, stirring is completely dissolved it, adjusts pH to 2.3~2.7 with 2mol/L hydrochloric acid solutions, prescription is added under conditions of nitrogen charging
The glycopyrronium bromide of full dose, stirring is completely dissolved it, standby；
(2) aseptic filtration：By above-mentioned decoction " 0.45 μm of+0.22 μm of polypropylene screen+0.22 μm of the poly (ether sulfone) film polyether sulfone prepared
The sterilizing filter refined filtration of film " series connection；
(3) embedding：The decoction after aseptic filtration is no less than sign loading amount embedding in colourless low by every under conditions of nitrogen charging
In borosilicate glass ampoule bottle；
(4) sterilize：Using 121 DEG C of 12~15min of wet-hot steams sterilizing.
7. the preparation method of Glycopyrronium bromide injection composition according to claim 6, it is characterised in that adopted in step 4
With 121 DEG C of wet-hot steams sterilizing 15min.
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| 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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| 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 |
| 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 |
| 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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| US20020151598A1 (en) * | 2001-04-17 | 2002-10-17 | Banerjee Partha S. | Bronchodilating compositions and methods |
| EP1915129A2 (en) * | 2005-08-01 | 2008-04-30 | CHIESI FARMACEUTICI S.p.A. | Pharmaceutical formulations comprising a long-acting beta2-agonist for administration by nebulisation |
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| 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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| CN104274392A (en) | 2015-01-14 |
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