CN115869247A - Atropine sulfate injection and preparation method thereof - Google Patents
Atropine sulfate injection and preparation method thereof Download PDFInfo
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- CN115869247A CN115869247A CN202111126322.7A CN202111126322A CN115869247A CN 115869247 A CN115869247 A CN 115869247A CN 202111126322 A CN202111126322 A CN 202111126322A CN 115869247 A CN115869247 A CN 115869247A
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- injection
- atropine sulfate
- sodium chloride
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- solution
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- 238000002347 injection Methods 0.000 title claims abstract description 87
- 239000007924 injection Substances 0.000 title claims abstract description 87
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 title claims abstract description 77
- 229960002028 atropine sulfate Drugs 0.000 title claims abstract description 77
- 238000002360 preparation method Methods 0.000 title claims abstract description 71
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 92
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 70
- 239000011780 sodium chloride Substances 0.000 claims abstract description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 34
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000001301 oxygen Substances 0.000 claims abstract description 19
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 19
- 238000005429 filling process Methods 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims description 56
- 239000000243 solution Substances 0.000 claims description 55
- 239000003814 drug Substances 0.000 claims description 53
- 239000007788 liquid Substances 0.000 claims description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 30
- 230000001954 sterilising effect Effects 0.000 claims description 29
- 238000004659 sterilization and disinfection Methods 0.000 claims description 20
- 238000001816 cooling Methods 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000005538 encapsulation Methods 0.000 claims description 5
- 239000008215 water for injection Substances 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000007789 sealing Methods 0.000 claims description 2
- 239000012299 nitrogen atmosphere Substances 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 13
- 229940079593 drug Drugs 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 5
- 230000003204 osmotic effect Effects 0.000 description 4
- 238000010525 oxidative degradation reaction Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- 206010008428 Chemical poisoning Diseases 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 230000000703 anti-shock Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of pharmacy, in particular to atropine sulfate injection and a preparation method thereof. The atropine sulfate injection consists of atropine sulfate, sodium chloride and water, and features that in each 10000ml of injection, atropine sulfate is contained in 5g and sodium chloride content is 80-105g, and in the preparation process, nitrogen filling process is added to make the dissolved oxygen content in the injection less than or equal to 2.0mg/L. The invention aims to provide a novel atropine sulfate injection and a preparation method thereof, which control related substances of the atropine sulfate injection by using accurate data, improve the clinical curative effect and safety, simplify the process procedures and are more suitable for industrial production.
Description
The technical field is as follows:
the invention relates to the technical field of pharmacy, in particular to atropine sulfate injection and a preparation method thereof.
Background art:
the atropine sulfate injection is an anticholinergic drug, and can relieve smooth muscle spasm, inhibit gland secretion, and dilate pupil. Clinically, atropine sulfate belongs to a common injection medicament, can relieve pain of internal organs of patients, can also be used for treating phospholipid pesticide poisoning, and has an antishock effect; this drug is also commonly used before anaesthetizing patients, can be used to treat chronic arrhythmias and has a good therapeutic effect.
Atropine sulfate injection produced by my company is firstly approved in 1981 (approval document: national drug standard H12020382), and the prescription only contains atropine sulfate and water for injection.
The safety of atropine sulfate injection in the prior art is challenged in many ways, one is that the injection does not contain an osmotic pressure regulator, the osmotic pressure is an important index which needs to be paid attention to by people, the safety of patients is affected when large dose is used without limit or the infusion speed is not adjusted according to the osmotic pressure value, and higher medication risk is brought to actual clinical use; secondly, atropine sulfate is easy to hydrolyze, and in the process of preparing the liquid medicine in the prior art, the related substances of a sample prepared by adding the raw material medicines for dissolving and then adjusting the pH value of the liquid medicine are higher, and the related substances are also key indexes influencing the safety of the medicine; thirdly, the liquid medicine preparation and encapsulation are carried out without nitrogen filling, so that the risk of product instability is increased; finally, the sterilization time of 30 minutes at 100-105 ℃ is not scientific, the sterilization time is too long, the energy consumption is increased, an over-killing process is not adopted, the F0 is less than 8, and finally, the reliable sterilization effect cannot be achieved.
In recent years, the national medicine management is more and more strict, and in order to improve the product safety and ensure the product quality stability, the consistency evaluation work of the curative effect and the quality is further required, so that how to provide a safer and more effective atropine sulfate injection becomes a challenge to be accomplished urgently.
The invention content is as follows:
in order to solve the problems, research personnel carry out a large number of experiments to finally determine that the osmotic pressure regulator sodium chloride is added into the prescription, so that the medication safety of patients is guaranteed; secondly, a nitrogen filling process is added in the process of preparing and encapsulating the liquid medicine, so that the dissolved oxygen is less than or equal to 2.0mg/L, and the risk of oxidative degradation of the product is reduced; meanwhile, the sequence of dissolving the raw material medicines and adjusting the pH value of the liquid medicine is adjusted, namely the pH value of the solution is adjusted to be acidic, and then the raw material medicines are added for dissolving, so that the generation of related substances is effectively controlled; the sterilization condition is set as 121 ℃, the sterilization time is controlled to be 8-15 min, and an overkill sterilization process is adopted, so that F0 is ensured to be more than 8, and the sterility guarantee level of the product is improved.
In summary, the invention aims to provide a novel atropine sulfate injection and a preparation method thereof, the method controls the generation of related substances from a production source by innovating a prescription process, greatly improves the quality of products, and ensures the requirements of clinical safe medication, and the specific technical scheme is as follows:
an atropine sulfate injection is composed of atropine sulfate, sodium chloride and water, and is characterized in that the atropine sulfate is contained in 10000ml of injection, the content of sodium chloride is 80-105g, and in the preparation method, a nitrogen charging process is added in the preparation and encapsulation processes of the traditional Chinese medicine liquid, so that the dissolved oxygen in the injection is less than or equal to 2.0mg/L.
Preferably, the injection comprises per 10000 ml: 5g of atropine sulfate and 80g of sodium chloride.
Preferably, the injection comprises per 10000 ml: 5g of atropine sulfate and 90g of sodium chloride.
Preferably, the injection comprises per 10000 ml: 5g of atropine sulfate and 100g of sodium chloride.
Preferably, the injection comprises per 10000 ml: 5g of atropine sulfate and 105g of sodium chloride.
Meanwhile, the invention also provides a preparation method of the atropine sulfate injection, which is characterized by comprising the following steps:
1) Adding 90% of batch injection water into a liquid preparation container, introducing nitrogen, and cooling;
2) Adding the sodium chloride with the prescription amount into a solution preparation container, stirring until the sodium chloride is fully dissolved, and adjusting the pH value of the solution to be acidic;
3) Adding the atropine sulfate with the prescription amount into a solution preparation container, continuously stirring until the atropine sulfate is completely dissolved, and adjusting the pH value of the solution;
4) Adding water for injection to full dose, filtering, sealing, and sterilizing.
Preferably, in the preparation method, the temperature is reduced to 25-40 ℃ after nitrogen is introduced in the step 1).
Preferably, in the preparation method, the pH value in the step 2) and the step 3) is 3.5-4.1.
Preferably, in the preparation method, the pH regulator is 0.1mol/L hydrochloric acid solution or 0.1mol/L sodium hydroxide solution.
Preferably, in the preparation method, a nitrogen environment is maintained in the whole preparation process.
Preferably, in the preparation method, the dissolved oxygen amount in the injection is less than or equal to 2.0mg/L after nitrogen is introduced.
Preferably, in the preparation method, the sterilization temperature after encapsulation is 121 ℃, and the sterilization time range is as follows: the sterilization time is more than or equal to 8min after 15 min.
Detailed Description
The present invention will be described in detail by the following examples, which are only preferred embodiments of the present invention and are not intended to limit the present invention, and equivalents and modifications of the technical features of the present invention are included in the scope of the present invention.
The prescription is as follows:
TABLE 1
Example 1
Prepared according to the prescription in the table 1, the specific method is as follows:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 25 ℃, starting stirring until the dissolved oxygen content is 2.0mg/L, adding 80g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to 3.5 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and keeping the liquid medicine for 12 minutes for sterilization at 121 ℃ to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Example 2
The preparation method comprises the following steps of:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 34 ℃, starting stirring until the dissolved oxygen content is 1.7mg/L, adding 90g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to 3.7 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, stirring uniformly, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and sterilizing at 121 ℃ for 8 minutes to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Example 3
The preparation method comprises the following steps of:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 40 ℃, starting stirring until the dissolved oxygen content is 1.6mg/L, adding 100g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to 3.9 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and keeping the liquid medicine for 15 minutes for sterilization at 121 ℃ to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Example 4
Prepared according to the prescription in the table 1, the specific method is as follows:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 30 ℃, starting stirring until the dissolved oxygen content is 1.3mg/L, adding 105g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH value to 4.1 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and sterilizing at 121 ℃ for 10 minutes to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Comparative experiment of material addition sequence:
comparative examples 1 to 1
The preparation method comprises the following steps of:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 25 ℃, starting stirring until the dissolved oxygen content is 2.0mg/L, adding 80g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adjusting the pH to 3.5 by using 0.1mol/L hydrochloric acid solution, adding injection water to full dose, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and sterilizing at 121 ℃ for 12 minutes to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Comparative examples 1 to 2
The preparation method comprises the following steps of:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 34 ℃, starting stirring until the dissolved oxygen content is 1.7mg/L, adding 90g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adjusting the pH to 3.7 by using 0.1mol/L hydrochloric acid solution, adding injection water to full dose, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and sterilizing at 121 ℃ for 8 minutes to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Comparative examples 1 to 3
The preparation method comprises the following steps of:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 40 ℃, starting stirring until the dissolved oxygen content is 1.6mg/L, adding 100g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adjusting the pH to 3.9 by using 0.1mol/L hydrochloric acid solution, adding injection water to full dose, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and sterilizing at 121 ℃ for 15 minutes to obtain the atropine sulfate injection.
The liquid medicine keeps the nitrogen protection state in the whole process.
Comparative examples 1 to 4
Prepared according to the prescription in the table 1, the specific method is as follows:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 30 ℃, starting stirring until the dissolved oxygen content is 1.3mg/L, adding 105g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adjusting the pH to 4.1 by using 0.1mol/L hydrochloric acid solution, adding injection water to full dose, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, keeping the liquid medicine for 10 minutes at 121 ℃ for sterilization, and obtaining the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
The results of the experiment were as follows (60 ℃ C. At high temperature):
as can be seen from the above table, the generation of related substances can be effectively controlled by adjusting the order of dissolving the raw material drugs and adjusting the pH value of the liquid medicine, i.e. firstly adjusting the pH value of the solution to acidity, and then adding the raw material drugs for dissolution.
Dissolved oxygen content comparative experiment:
the prescription of example 1 in table 1 is selected, namely 10000ml of injection contains: 5g of atropine sulfate, 80g of sodium chloride and the balance of water for injection.
Comparative example 2-1
Adding 90% of batch injection water into a solution preparation container, cooling to 25 ℃, measuring the dissolved oxygen content of the solution to be 4.7mg/L, starting stirring, adding 80g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to be 3.5 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to full dose, stirring uniformly, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, keeping the liquid medicine for 12 minutes for sterilization at 121 ℃ to obtain the atropine sulfate injection.
Comparative examples 2 to 2
Adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 25 ℃, starting stirring until the dissolved oxygen content is 2.3mg/L, adding 80g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to 3.5 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and keeping the liquid medicine for 12 minutes for sterilization at 121 ℃ to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Comparative examples 2 to 3
Adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 25 ℃, starting stirring until the dissolved oxygen content is 3.0mg/L, adding 80g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to 3.5 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, uniformly stirring, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and keeping the liquid medicine for 12 minutes for sterilization at 121 ℃ to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
The experimental results are as follows (high temperature 60 ℃):
from the above experiments, if the nitrogen-filling oxygen-reducing operation is not performed, the risk of oxidative degradation of the product is increased, and finally, the content of the product is reduced and the total impurities are increased.
The sterilization process influence experiment:
the prescription of example 1 in table 1 is selected, namely 10000ml of injection contains: 5g of atropine sulfate, 80g of sodium chloride and the balance of water for injection.
Comparative example 3-1:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 25 ℃, starting stirring until the dissolved oxygen content is 2.0mg/L, adding 80g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to 3.5 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, stirring uniformly, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and sterilizing at 115 ℃ for 32 minutes to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
Comparative example 3-2:
adding 90% of batch injection water into a solution preparation container, introducing nitrogen, cooling to 25 ℃, starting stirring until the dissolved oxygen content is 2.0mg/L, adding 80g of sodium chloride into the solution preparation container, stirring until the sodium chloride is fully dissolved, adjusting the pH to 3.5 by using 0.1mol/L hydrochloric acid solution, adding 5g of atropine sulfate into a preparation tank, continuously stirring until the atropine sulfate is fully dissolved, adding injection water to the full amount, stirring uniformly, filtering and encapsulating the liquid medicine by two 0.22 mu m filter cores, and sterilizing at 121 ℃ for 18 minutes to obtain the atropine sulfate injection.
The liquid medicine keeps a nitrogen protection state in the whole process.
As can be seen from the comparative experiments, the sterilization conditions can more effectively control the relevant substances of the injection.
As known, related substances are key indexes influencing the safety of medicines, and the injection has higher requirements on the related substances due to the administration route of the injection, the comparative experiment data show that the injection obtained in the patent application can greatly control the generation of the related substances while improving the content of the product, and the product quality and the clinical safety are more favorably guaranteed.
In conclusion, the applicant innovates a product prescription and a process through a large amount of researches, controls related substances of the atropine sulfate injection by using accurate data, simplifies process procedures while improving clinical curative effect and safety, and is more suitable for industrial production.
Claims (10)
1. An atropine sulfate injection is composed of atropine sulfate, sodium chloride and water, and is characterized in that atropine sulfate 5 (+ -0.1) g and sodium chloride 80-105g are contained in per 10000ml of injection, and in the preparation method, a nitrogen filling process is added in the preparation and encapsulation processes of the liquid medicine, so that the dissolved oxygen in the injection is less than or equal to 2.0mg/L.
2. The injection according to claim 1, wherein per 10000ml of the injection, the injection comprises: atropine sulfate 5 (+ -0.1) g and sodium chloride 80g.
3. The injection according to claim 1, wherein per 10000ml of the injection, the injection comprises: atropine sulfate 5 (+ -0.1) g and sodium chloride 90g.
4. The injection of claim 1, comprising per 10000ml of injection: atropine sulfate 5 (+ -0.1) g and sodium chloride 100g.
5. The process for preparing an injection according to claim 1, characterized in that:
1) Adding 90% of batch injection water into a liquid preparation container, introducing nitrogen, and cooling;
2) Adding the sodium chloride with the prescription amount into a solution preparation container, stirring until the sodium chloride is fully dissolved, and adjusting the pH value of the solution to be acidic;
3) Adding the atropine sulfate with the prescription amount into a solution preparation container, continuously stirring until the atropine sulfate is completely dissolved, and adjusting the pH value of the solution;
4) Adding water for injection to full dose, filtering, sealing, and sterilizing.
6. The method of claim 5, wherein the temperature of the solution in step 1) is reduced to 25-40 ℃ after the introduction of nitrogen.
7. The process for preparing an injection according to claim 5, wherein the pH in step 2) and step 3) is 3.5 to 4.1.
8. The method for preparing an injection according to claim 5, wherein the pH adjusting agent is a 0.1mol/L hydrochloric acid solution or a 0.1mol/L sodium hydroxide solution.
9. The method of claim 5, wherein the nitrogen atmosphere is maintained throughout the preparation.
10. The method of claim 5, wherein the post-encapsulation sterilization temperature is 121 ℃ and the sterilization time ranges are: the sterilization time is more than or equal to 8min within 15 min.
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| CN202111126322.7A CN115869247A (en) | 2021-09-26 | 2021-09-26 | Atropine sulfate injection and preparation method thereof |
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| CN202111126322.7A CN115869247A (en) | 2021-09-26 | 2021-09-26 | Atropine sulfate injection and preparation method thereof |
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