CN110075063A - A kind of Maxamine injection and preparation method thereof - Google Patents
A kind of Maxamine injection and preparation method thereof Download PDFInfo
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- CN110075063A CN110075063A CN201910446110.3A CN201910446110A CN110075063A CN 110075063 A CN110075063 A CN 110075063A CN 201910446110 A CN201910446110 A CN 201910446110A CN 110075063 A CN110075063 A CN 110075063A
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- 238000002347 injection Methods 0.000 title claims abstract description 54
- 239000007924 injection Substances 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 42
- 239000000243 solution Substances 0.000 claims abstract description 42
- 238000007689 inspection Methods 0.000 claims abstract description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 238000012856 packing Methods 0.000 claims abstract description 25
- 230000001954 sterilising effect Effects 0.000 claims abstract description 25
- 239000008215 water for injection Substances 0.000 claims abstract description 24
- 239000012528 membrane Substances 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 13
- 239000002510 pyrogen Substances 0.000 claims abstract description 13
- 238000013329 compounding Methods 0.000 claims abstract description 11
- 238000010790 dilution Methods 0.000 claims abstract description 10
- 239000012895 dilution Substances 0.000 claims abstract description 10
- 238000001179 sorption measurement Methods 0.000 claims abstract description 10
- 238000013494 PH determination Methods 0.000 claims abstract description 9
- 239000012530 fluid Substances 0.000 claims abstract description 9
- 238000004806 packaging method and process Methods 0.000 claims abstract description 9
- 238000005261 decarburization Methods 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 10
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 claims description 8
- 238000010521 absorption reaction Methods 0.000 claims description 8
- 238000001514 detection method Methods 0.000 claims description 8
- 239000000835 fiber Substances 0.000 claims description 8
- 239000008236 heating water Substances 0.000 claims description 8
- 238000004659 sterilization and disinfection Methods 0.000 claims description 8
- 238000005303 weighing Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 2
- 229910017435 S2 In Inorganic materials 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 9
- 239000000126 substance Substances 0.000 abstract description 8
- 230000000087 stabilizing effect Effects 0.000 abstract description 3
- 238000004090 dissolution Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 7
- 238000010257 thawing Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 4
- 239000002075 main ingredient Substances 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000022120 Jeavons syndrome Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 238000011046 pyrogen test Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
Classifications
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/417—Imidazole-alkylamines, e.g. histamine, phentolamine
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of Maxamine injections, it is made of Maxamine, PH regulator, water for injection, a kind of preparation method of Maxamine injection includes: drug dissolution concentrated compounding, activated carbon adsorption pyrogen, medical fluid dilution and the determination of PH, filter membrane packing, sterilizing, lamp inspection, packaging.Character, pH value, clarity of solution and the color of the product that the present invention obtains, related substance, content etc. meet the quality standard regulation, and auxiliary material addition is few, greatly reduces security concern, at low cost, process stabilizing is feasible.
Description
Technical field
The invention belongs to field of orthopaedics more particularly to a kind of Maxamine injection and preparation method thereof.
Background technique
Maxamine injection is on October 7th, 2008 in Europe approval listing, trade name Ceplene, with IL-2
Combination is used for adult acute's myelogenous leukemia (AML) maintenance therapy.The specification of European drug surveilance office (EMEA) approval is
0.5ml:0.5mg, the administration route of approval are subcutaneous injection.
Domestic at present there has been no the approvals of Maxamine injection to list, according to " drug registration management method " attachment two
Regulation, this product belong to 3.1 class of chemical drugs, grind kind for non-original.
Maxamine is soluble easily in water, but its aqueous stability is bad, and placement for a long time is easy its shape and is easy to happen
Change, influence drug effect, there is research to add the auxiliary materials such as propylene glycol, sodium thiosulfate in its solution at present and its property is kept to stablize,
Addition auxiliary material not only increases production cost, while these auxiliary materials have very big safety issue, therefore also need to two hydrochloric acid
The preparation process of group amine injection improves.
Summary of the invention
It is an object of the invention to overcome problem above of the existing technology, provide a kind of Maxamine injection and
Preparation method, by character, pH value, clarity of solution and the face of the Maxamine injection that preparation method of the invention obtains
Color, related substance, content etc. meet the quality standard regulation, and auxiliary material addition is few, greatly reduces security concern, cost
Low, process stabilizing is feasible.
To realize above-mentioned technical purpose and the technique effect, the invention is realized by the following technical scheme:
A kind of Maxamine injection, injection are made of Maxamine, PH regulator, water for injection.
A kind of preparation method of Maxamine injection, includes the following steps:
S1, drug dissolve concentrated compounding: 0.5g Maxamine accurately weighed, 0.001g is accurate to, water for injection 50ml is added,
It is sufficiently stirred and makes it dissolve, obtain the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: Maxamine concentrated solution made from step S1 is heated to 60 DEG C, added by S2
The needle-use activated carbon of 0.1% (W/V), 60 DEG C of thermostatic absorption 25-30min filter decarburization；
S3, medical fluid dilution and the determination of PH: being added water for injection into the solution after step S2 decarburization and be diluted to 500ml,
PH is measured, adjusts PH to 4.3~4.7 using PH regulator as needed；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, is used after the completion of filtering
2ml cillin bottle carries out packing and rolls lid；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, in lamp inspection canopy
Under inspect sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product and rejected product point
It opens and is placed in terminal, spontaneously dry, lamp inspection qualified product is packed, warehousing finished products.
Further, the heating method in the step S2 is heating water bath
Further, the filtering decarburization in the step S2 was 0.22 μm of filter membrane decarburization.
Further, the PH regulator is 1mol/L sodium hydroxide or 1mol/L hydrochloric acid.
Further, the dispensed loading amount in the step S4 is every packing 0.7ml.
The beneficial effects of the present invention are:
The present invention cooperates two hydrochloric acid produced by concentrated compounding method, activated carbon adsorption pyrogen, concentrated solution dilution step jointly
Character, pH value, clarity of solution and the color of group amine injection, related substance, content etc. meet the quality standard regulation, and this
Maxamine injection is few relative to the addition of existing product auxiliary material, greatly reduces security concern, at low cost, process stabilizing
It is feasible, it is suitble to large-scale production.
Detailed description of the invention
The drawings described herein are used to provide a further understanding of the present invention, constitutes part of this application, this hair
Bright illustrative embodiments and their description are used to explain the present invention, and are not constituted improper limitations of the present invention.In the accompanying drawings:
Fig. 1 is preparation method flow chart of the invention.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts all other
Embodiment shall fall within the protection scope of the present invention.
Embodiment 1
A kind of Maxamine injection, it is made of Maxamine, PH regulator, water for injection.
A kind of preparation method of Maxamine injection as shown in Figure 1, includes the following steps:
S1, drug dissolve concentrated compounding: accurately weighing 0.505g Maxamine, water for injection 50ml is added, being sufficiently stirred makes
It is dissolved, and obtains the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: S2 Maxamine concentrated solution heating water bath made from step S1 is added to 60 DEG C
The needle-use activated carbon of 0.1% (W/V), 60 DEG C of thermostatic absorption 25min, filtered 0.22 μm of filter membrane decarburization；
S3, medical fluid dilution and the determination of PH: being added water for injection into the solution after step S2 decarburization and be diluted to 500ml,
PH to 4.3~4.7 is adjusted using 1mol/L sodium hydroxide；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, is used after the completion of filtering
2ml cillin bottle carries out packing and rolls lid, every packing 0.7ml；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, in lamp inspection canopy
Under inspect sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product and rejected product point
It opens and is placed in terminal, spontaneously dry, lamp inspection qualified product is packed, warehousing finished products.
Embodiment 2
A kind of Maxamine injection, it is made of Maxamine, PH regulator, water for injection.
A kind of preparation method of Maxamine injection as shown in Figure 1, includes the following steps:
S1, drug dissolve concentrated compounding: accurately weighing 0.501g Maxamine, water for injection 50ml is added, being sufficiently stirred makes
It is dissolved, and obtains the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: S2 Maxamine concentrated solution heating water bath made from step S1 is added to 60 DEG C
The needle-use activated carbon of 0.1% (W/V), 60 DEG C of thermostatic absorption 28min, filtered 0.22 μm of filter membrane decarburization；
S3, medical fluid dilution and the determination of PH: being added water for injection into the solution after step S2 decarburization and be diluted to 500ml,
PH to 4.3~4.7 is adjusted using 1mol/L sodium hydroxide；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, is used after the completion of filtering
2ml cillin bottle carries out packing and rolls lid, every packing 0.7ml；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, in lamp inspection canopy
Under inspect sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product and rejected product point
It opens and is placed in terminal, spontaneously dry, lamp inspection qualified product is packed, warehousing finished products.
Embodiment 3
A kind of Maxamine injection, it is made of Maxamine, PH regulator, water for injection.
A kind of preparation method of Maxamine injection as shown in Figure 1, includes the following steps:
S1, drug dissolve concentrated compounding: accurately weighing 0.504g Maxamine, water for injection 50ml is added, being sufficiently stirred makes
It is dissolved, and obtains the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: S2 Maxamine concentrated solution heating water bath made from step S1 is added to 60 DEG C
The needle-use activated carbon of 0.1% (W/V), 60 DEG C of thermostatic absorption 30min, filtered 0.22 μm of filter membrane decarburization；
S3, medical fluid dilution and the determination of PH: being added water for injection into the solution after step S2 decarburization and be diluted to 500ml,
PH to 4.3~4.7 is adjusted using 1mol/L hydrochloric acid；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, is used after the completion of filtering
2ml cillin bottle carries out packing and rolls lid, every packing 0.7ml；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, in lamp inspection canopy
Under inspect sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product and rejected product point
It opens and is placed in terminal, spontaneously dry, lamp inspection qualified product is packed, warehousing finished products.
Comparative example 1
A kind of Maxamine injection, it is made of Maxamine, PH regulator, water for injection.
A kind of preparation method of Maxamine injection, includes the following steps:
S1, drug dissolve concentrated compounding: accurately weighing 0.508g Maxamine, water for injection 50ml is added, being sufficiently stirred makes
It is dissolved, and obtains the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: S2 Maxamine concentrated solution heating water bath made from step S1 is added to 60 DEG C
The needle-use activated carbon of 0.0% (W/V), 60 DEG C of thermostatic absorption 30min, filtered 0.22 μm of filter membrane decarburization；
S3, medical fluid dilution and the determination of PH: being added water for injection into the solution after step S2 decarburization and be diluted to 500ml,
PH to 4.3~4.7 is adjusted using 1mol/L sodium hydroxide；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, is used after the completion of filtering
2ml cillin bottle carries out packing and rolls lid, every packing 0.7ml；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, in lamp inspection canopy
Under inspect sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product and rejected product point
It opens and is placed in terminal, spontaneously dry, lamp inspection qualified product is packed, warehousing finished products.
Comparative example 2
A kind of Maxamine injection, it is made of Maxamine, PH regulator, water for injection.
A kind of preparation method of Maxamine injection, includes the following steps:
S1, drug dissolve concentrated compounding: accurately weighing 0.501g Maxamine, water for injection 50ml is added, being sufficiently stirred makes
It is dissolved, and obtains the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: S2 Maxamine concentrated solution heating water bath made from step S1 is added to 60 DEG C
The needle-use activated carbon of 0.05% (W/V), 60 DEG C of thermostatic absorption 30min, filtered 0.22 μm of filter membrane decarburization；
S3, medical fluid dilution and the determination of PH: being added water for injection into the solution after step S2 decarburization and be diluted to 500ml,
PH to 4.3~4.7 is adjusted using 1mol/L sodium hydroxide；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, is used after the completion of filtering
2ml cillin bottle carries out packing and rolls lid, every packing 0.7ml；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, in lamp inspection canopy
Under inspect sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product and rejected product point
It opens and is placed in terminal, spontaneously dry, lamp inspection qualified product is packed, warehousing finished products.
Comparative example 3
A kind of Maxamine injection, it is made of Maxamine, PH regulator, water for injection.
A kind of preparation method of Maxamine injection, includes the following steps:
S1, drug dissolve concentrated compounding: accurately weighing 0.505g Maxamine, water for injection 50ml is added, being sufficiently stirred makes
It is dissolved, and obtains the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: S2 Maxamine concentrated solution heating water bath made from step S1 is added to 60 DEG C
The needle-use activated carbon of 0.2% (W/V), 60 DEG C of thermostatic absorption 30min, filtered 0.22 μm of filter membrane decarburization；
S3, medical fluid dilution and the determination of PH: being added water for injection into the solution after step S2 decarburization and be diluted to 500ml,
PH to 4.3~4.7 is adjusted using 1mol/L hydrochloric acid；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, is used after the completion of filtering
2ml cillin bottle carries out packing and rolls lid, every packing 0.7ml；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, in lamp inspection canopy
Under inspect sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product and rejected product point
It opens and is placed in terminal, spontaneously dry, lamp inspection qualified product is packed, warehousing finished products.
To embodiment 1,2,3 and comparative example 1,2,3 according to ultraviolet spectrophotometer method measuring method detect drug content and
Pyrogen, testing result is shown in Table 1, and carries out exposure experiments to light, hot test, freezing-thawing test respectively to embodiment 1,2,3.
Exposure experiments to light method are as follows: take this product appropriate, set in light cupboard (YB-2 type clarity detecting apparatus, day at room temperature
The manufacture of saliva university precision instrument factory), illumination about 4500Lx is placed 10 days, and sampling carries out every inspection when the 5th day and 10 days
It looks into, the results are shown in Table 2；
Hot test method are as follows: placed 10 days under the conditions of test specimen is placed in 60 DEG C of high temperature, and when the 5th day and 10 days
Sampling carries out every inspection, the results are shown in Table 3；
Freezing-thawing test method are as follows: take sample to do and recycle three times according to the requirement of " freezing-thawing test ", recycle sample every time -10
~-20 DEG C are investigated two days, are then investigated two days under 40 DEG C of acceleration environments, be the results are shown in Table 4.
The influence that pyrogen and main ingredient are adsorbed of 1 different activities charcoal dosage of table
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Comparative example 1 | Comparative example 2 | Comparative example 3 | |
| Activated carbon dosage | 0.10% | 0.10% | 0.10% | 0.00% | 0.05% | 0.02% |
| Concentration (mg/ml) after decarburization | 9.84 | 9.88 | 9.85 | 10.1 | 9.92 | 9.48 |
| Pyrogen test | It is qualified | It is qualified | It is qualified | It is unqualified | It is unqualified | It is qualified |
As can be seen from Table 1, active carbon is slight to the suction-operated of main ingredient, and the active carbon of 0.1% or more liquid volume is added
It can achieve the purpose that nonpyrogenic, and the loss of main ingredient is only 2.57% or so at this time, it was demonstrated that use concentrated compounding method
Preparating liquid can be removed pyrogen using the needle-use activated carbon of medicine liquid volume amount 0.1%, and main ingredient loss is less.
2 Maxamine injection exposure experiments to light of table investigates result
As can be seen from Table 2, for the sample of three embodiments after exposure experiments to light, character, pH value, visible foreign matters, solution are clear
Clear degree has no significant change compared with 0 day with color, and related substance slightly rises, and in experimental error, content is without obvious
Variation.
Result is investigated in 3 Maxamine injection hot test of table
As can be seen from Table 3, for the sample of three embodiments after hot test, character, pH value, visible foreign matters, solution are clear
Clear degree has no significant change compared with 0 day with color, and related substance slightly rises, and in experimental error, content is without obvious
Variation.
4 Maxamine injection freezing-thawing test of table investigates result
As can be seen from Table 4, for the sample of three embodiments after freezing-thawing test, character, pH value, visible foreign matters, solution are clear
Clear degree has no significant change compared with 0 day with color, in relation to substance, and in experimental error, content is without significant change.
By testing character, pH value, clarity of solution and color, the related it can be concluded that product obtained by this method above
Substance, content etc. meet the quality standard regulation, and auxiliary material addition is few, greatly reduces security concern, at low cost, technique is steady
It is fixed feasible.
In the description of this specification, the description of reference term " one embodiment ", " example ", " specific example " etc. means
Particular features, structures, materials, or characteristics described in conjunction with this embodiment or example are contained at least one implementation of the invention
In example or example.In the present specification, schematic expression of the above terms may not refer to the same embodiment or example.
Moreover, particular features, structures, materials, or characteristics described can be in any one or more of the embodiments or examples to close
Suitable mode combines.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.
Claims (6)
1. a kind of Maxamine injection, it is characterised in that: the injection is by Maxamine, PH regulator, injection
Water composition.
2. a kind of preparation method of Maxamine injection, which comprises the steps of:
S1, drug dissolve concentrated compounding: accurately weighing 0.5g Maxamine, are accurate to 0.001g, water for injection 50ml are added, sufficiently
It stirs to dissolve, obtains the Maxamine concentrated solution that concentration is about 10mg/ml；
Activated carbon adsorption pyrogen: Maxamine concentrated solution made from step S1 is heated to 60 DEG C, adds 0.1% (W/ by S2
V needle-use activated carbon), 60 DEG C of thermostatic absorption 25-30min filter decarburization；
S3, medical fluid dilution and the determination of PH: water for injection is added into the solution after step S2 decarburization and is diluted to 500ml, measures
PH adjusts PH to 4.3~4.7 using PH regulator as needed；
S4, filter membrane packing: solution made from step S3 is filtered with 0.22 μm of miillpore filter, and 2ml is used after the completion of filtering
Cillin bottle carries out packing and rolls lid；
S5, sterilizing: the product that step S4 is dispensed carries out 121 DEG C of high pressure steam sterilization 20min；
S6, lamp inspection, packaging: after sterilizing, injection color water is hunted leak, and injection bottle outer wall is rinsed after leak detection, is examined under lamp inspection canopy
Depending on sample, choosing has fiber, white point, the foreign matters such as white piece and the exceeded sample of white point, lamp inspection qualified product separately to put with rejected product
It sets in terminal, spontaneously dries, lamp inspection qualified product is packed, warehousing finished products.
3. a kind of preparation method of Maxamine injection according to claim 2, it is characterised in that: the step S2
In heating method be heating water bath.
4. a kind of preparation method of Maxamine injection according to claim 2, it is characterised in that: the step S2
In filtering decarburization be 0.22 μm of filter membrane decarburization.
5. a kind of preparation method of Maxamine injection according to claim 2, it is characterised in that: the PH is adjusted
Agent is 1mol/L sodium hydroxide or 1mol/L hydrochloric acid.
6. a kind of preparation method of Maxamine injection according to claim 2, it is characterised in that: the step S4
In dispensed loading amount be every packing 0.7ml.
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