CN104548153A - Encapsulation and sterilization method of softly-bagged compound amino acid injection - Google Patents
Encapsulation and sterilization method of softly-bagged compound amino acid injection Download PDFInfo
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- CN104548153A CN104548153A CN201410811153.4A CN201410811153A CN104548153A CN 104548153 A CN104548153 A CN 104548153A CN 201410811153 A CN201410811153 A CN 201410811153A CN 104548153 A CN104548153 A CN 104548153A
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Abstract
The invention belongs to the field of preparation processes of compound amino acid injections, and in particular relates to an encapsulation and sterilization method of a softly-bagged compound amino acid injection. The encapsulation and sterilization method comprises the following steps: filling medicine liquid by using a bag-making and encapsulation integrated machine, and sterilizing by using a nitrogen-charging sterilization tank; and the steps from bag making to sealing specifically comprise the following processes: making bags, performing vacuum pumping on empty bags, charging nitrogen to the empty bags, injecting the medicine liquid into the bags, purging bag openings by using nitrogen, and welding a cover and sealing. By adopting the encapsulation and sterilization method disclosed by the invention, the possibility that the oxygen content of the medicine liquid with qualified dissolved oxygen content is increased again after the medicine liquid is encapsulated can be avoided to a greatest extent. By adopting the method, the softly-bagged compound amino acid injection can tolerate an over-killing process at 121 DEG C, an F0 value of the softly-bagged compound amino acid injection cannot be less than 12, a sterility assurance level (SAL) value of products is ensured to be less than 10<-6>, and the safety of clinical application of medicines can be ensured.
Description
Technical field
The invention belongs to Amino Acid Compound Injection preparation technology field, be specifically related to a kind of embedding and sterilizing methods of soft packed Amino Acid Compound Injection.
Background technology
Amino Acid Compound Injection is the transfusion of clinical conventional parenteral nutrition, for the important component part of parenteral nutrition administration, be mainly used in the patient that the aminoacid such as protein Deficiency of Intake, malabsorption can not meet organism metabolism needs, also for improving the nutriture of patients after surgery.Amino Acid Compound Injection product uses vial infusion bottle to pack usually, and because of the absolutely not permeability of glass material, at utmost decreasing preparation process Chinese medicine affects the oxidative degradation caused by extraneous oxygen.But determined by packaging material character, the Amino Acid Compound Injection of packed in flexible pouchy has more outstanding application advantage compared with glass bottle products in Clinical practice, first aid, transport, storage, safety etc.For this reason, the Amino Acid Compound Injection exploitation of packed in flexible pouchy is the study hotspot of pharmacy corporation always.
At present; for preventing in soft packed Amino Acid Compound Injection preparation and long term storage; drug degradation is made because soft bag breathability causes oxygen to enter; and then cause its colour changed into yellow, the light transmittance decline phenomenon of finished product; usual employing preparation, fill nitrogen filled protection technique; reduce the dissolved oxygen in medicinal liquid and the head space oxygen content after fill, carry out under nitrogen filled protection simultaneously or add the sterilization process of barrier outer bag protection.To barrier outer bag and the deoxidizer in addition of the product after sterilizing, to ensure the stability in product long storage periods.
Such as: the people such as Wu Qiang disclose a kind of anaerobic filling process for the soft bag infusion such as aminoacid, fat milk " gained injection is filtered and is filled in interior soft bag, is filled with nitrogen and jumps a queue after evacuation " in the preparation technology and product of (CN201010186184.7) a kind of soft bag injection.Yang little Mei adopts in " research of non-PVC-soft packaging amino acid (18AA-II) process for preparing injection liquid " " fill under nitrogen protection, in 115 DEG C of inflated with nitrogen sterilizing 30min, after product lamp inspection is qualified, vacuum packaging ".Ma Tao is at " the fat milk of packed with three-cavity bag, the composition and method of making the same of aminoacid and glucose injection " disclose a kind of filling process of nitrogen protection in (CN200710020197.5), " this filling machine is provided with evacuation-inflated with nitrogen system, medicine liquor metering system, heat-sealing system, complete evacuation-inflated with nitrogen to internal bag respectively, quality of liquid medicine metering and content, the functions such as inner bag sealing, regulate the fill volume of each medicinal liquid as required, ready made inner bag is loaded onto filling machine, fill also seals, pouring process carries out under nitrogen protection ", also disclose its sterilization process, inner bag good for embedding is loaded outer bag, adds oxygen absorbent between inside and outside bag, protect sterilizing to internal bag by the obstruct of outer bag and oxygen absorbent, ensure that medicine does not affect by sterilizing and produce degraded.
In sum, technical data disclosed in prior art, does not all describe processing step and technological parameter to its nitrogen filled protection filling process; To sterilization process, some employings 115 DEG C of inflated with nitrogen sterilizing 30min, also the concrete technology step of its sterilization process and parameter are not described, and the sterility assurance level of 115 DEG C of sterilizing 30min is lower, need the requirement strengthening control of microorganisms in process of production, add the aseptic underproof risk of product; Some employings add the method for outer bag and oxygen absorbent protection sterilizing; this kind of method can play a protective role to the inner bag of splendid attire medicine; but outer bag is sterilizing together with inner bag; when causing sterilizing, temperature penetrates difficulty; to the corresponding raising of requirement of sterilization time and temperature; and this kind of method is to barrier property, the heat resistance of outer bag, heat-resisting, the moisture resistance properties of deoxidizer have very high requirement, add production cost to a great extent.
Summary of the invention
The object of this invention is to provide a kind of embedding and sterilizing methods of soft packed Amino Acid Compound Injection, high-quality Amino Acid Compound Injection can be produced.
The embedding of soft packed Amino Acid Compound Injection of the present invention and sterilizing methods, comprise and use bag encapsulation all-in-one machine liquid drug and use to fill the sterilizing of nitrogen sterilizing cabinet, the step from bag to sealing is: bag → to empty bag evacuation → to empty bag fills in nitrogen → bag and injects medicinal liquid → nitrogen and purge bag mouth → welding cap sealing.
Wherein, preferred technical scheme is:
The described pumpdown time is 0.2 ~ 1.0s, and filling the nitrogen time is 0.2 ~ 0.4s, and filling nitrogen pressure is 0.2 ~ 0.5MPa.
To empty bag vacuum step, fill the operation of nitrogen step cycle to empty bag, cycling number of times is 1 ~ 3 time.When cycling number of times is 1 time, its step is as follows: to empty bag evacuation → fill nitrogen → to empty bag evacuation → fill nitrogen to empty bag to empty bag.
To empty bag vacuum step, to fill after the operation of nitrogen step cycle terminates to empty bag, in bag, inject medicinal liquid, the pressure injecting medicinal liquid is 0.1 ~ 0.3MPa.
Nitrogen purges in bag mouth step, and purge time is 0.2 ~ 0.6s.After the bag mouth step that purges nitrogen terminates, welding cap sealing immediately.
The sterilization steps of soft packed Amino Acid Compound Injection of the present invention is: fill nitrogen displacement → water filling → intensification → sterilizing → cooling → draining → aerofluxus.
Fill that nitrogen time swap is 5 ~ 15min, to fill nitrogen pressure be 0.5 ~ 1.5MPa.
Sterilising temp is 121 DEG C, and sterilization time is 12 ~ 15min.
Chilling temperature is 50 ~ 65 DEG C.
Detailed process of the present invention is as follows:
Medicinal liquid qualified for the dissolved oxygen content prepared is transported to bag encapsulation all-in-one machine, the empty bag made is carried out to evacuation, fills nitrogen, the air in emptying bag before liquid drug, for liquid drug creates oxygen-free environment; Then in bag, inject medicinal liquid under suitable pressure, avoid producing bubble; After injecting medicinal liquid, nitrogen purges bag mouth with the head space oxygen in emptying bag; Welding cap sealing rapidly again.Specific procedure is: bag → evacuation → fill nitrogen (evacuation, fill nitrogen cycle 1 ~ 3 time) → inject medicinal liquid → nitrogen to purge bag mouth → welding cap sealing.Medicinal fluid bag is put in sterilizing cabinet, fill nitrogen displacement, the lower 121 DEG C of sterilizing 12 ~ 15min of nitrogen atmosphere.
Amino Acid Compound Injection is oxidative degradation very easily; preparation, fill nitrogen filled protection technique must be adopted to this; and when using packed in flexible pouchy; the qualified medicinal liquid of dissolved oxygen through transport pump to bag-making loading all-in-one; often because fill time fluid pressure, cause medicinal liquid to inject in bag and namely form a large amount of bubble instantaneously, if do not adopt nitrogen filled protection filling process or nitrogen filled protection improper; all cause a bag inner liquid medicine dissolved oxygen content to raise again, and then affect the quality after medicated disinfecting.Concerning amino acid injection, because of the High Temperature High Pressure effect of sterilization process, in sterilization process, air penetrates in bag, and the degraded of aggravation oxidation of drug, causes the quality index such as product characteristics, light transmittance defective.To this, in sterilization process, adopt high pure nitrogen to replace air, the nitrogen atmosphere of inertia can be provided, play the effect preventing oxidation of drug from degrading.
Beneficial effect of the present invention is as follows:
Nitrogen filled protection encapsulating method of the present invention avoids the rising again of the qualified medicinal liquid of dissolved oxygen content oxygen content after fill to the full extent; sterilization process has played the protective effect of nitrogen atmosphere to the full extent; when having blocked on the one hand sterilizing, extraneous air enters in bag, the dissolved oxygen that before preventing sterilizing on the other hand, medicinal liquid itself contains and the destruction that head space oxygen produces.Adopt embedding of the present invention and sterilizing methods, make soft packed Amino Acid Compound Injection can tolerate 121 DEG C of overkill techniques, F0 value is not less than 12, ensure that the sterility assurance level SAL value of product is lower than 10
-6, ensured the safety that clinical drug is applied.
Detailed description of the invention
Below in conjunction with embodiment, the invention will be further described.
Embodiment 1
Qualified Amino Acid Compound Injection is prepared by formulation and technology, open bag encapsulation all-in-one machine, the empty bag made is carried out to evacuation, fills nitrogen, the pumpdown time is 0.6s, fill the nitrogen time be 0.3s, to fill nitrogen pressure be 0.3MPa, evacuation-fill nitrogen cycle to operate 2 times; In bag, inject medicinal liquid, the pressure injecting medicinal liquid is 0.2MPa; Use nitrogen to purge bag mouth, purge time is 0.4s; Welding cap is sealed.The medicinal fluid bag sterilizing of butt welding cap seal mouth, uses and fills nitrogen sterilizing cabinet, fills that nitrogen time swap is 10min, to fill nitrogen pressure be 1.0MPa in cabinet, and sterilization process parameter is 121 DEG C, 12min, F0 value is 12; Sterilizing chilling temperature is 55 DEG C.
Embodiment 2
Qualified Amino Acid Compound Injection is prepared by formulation and technology, open bag encapsulation all-in-one machine, the empty bag made is carried out to evacuation, fills nitrogen, the pumpdown time is 0.8s, fill the nitrogen time be 0.4s, to fill nitrogen pressure be 0.5MPa, evacuation-fill nitrogen cycle to operate 1 time; In bag, inject medicinal liquid, the pressure injecting medicinal liquid is 0.2MPa; Use nitrogen to purge bag mouth, purge time is 0.4s; Welding cap is sealed.The medicinal fluid bag sterilizing of butt welding cap seal mouth, uses and fills nitrogen sterilizing cabinet, fills that nitrogen time swap is 15min, to fill nitrogen pressure be 0.6MPa in cabinet, and sterilization process parameter is 121 DEG C, 15min, F0 value is 15; Sterilizing chilling temperature is 55 DEG C.
Embodiment 3
Qualified Amino Acid Compound Injection is prepared by formulation and technology, open bag encapsulation all-in-one machine, the empty bag made is carried out to evacuation, fills nitrogen, the pumpdown time is 0.2s, fill the nitrogen time be 0.2s, to fill nitrogen pressure be 0.2MPa, evacuation-fill nitrogen cycle to operate 3 times; In bag, inject medicinal liquid, the pressure injecting medicinal liquid is 0.3MPa; Use nitrogen to purge bag mouth, purge time is 0.6s; Welding cap is sealed.The medicinal fluid bag sterilizing of butt welding cap seal mouth, uses and fills nitrogen sterilizing cabinet, fills that nitrogen time swap is 5min, to fill nitrogen pressure be 1.0MPa in cabinet, and sterilization process parameter is 121 DEG C, 13min, F0 value is 13; Sterilizing chilling temperature is 55 DEG C.
Embodiment 4
Qualified Amino Acid Compound Injection is prepared by formulation and technology, open bag encapsulation all-in-one machine, the empty bag made is carried out to evacuation, fills nitrogen, the pumpdown time is 0.4s, fill the nitrogen time be 0.4s, to fill nitrogen pressure be 0.2MPa, evacuation-fill nitrogen cycle to operate 2 times; In bag, inject medicinal liquid, the pressure injecting medicinal liquid is 0.2MPa; Use nitrogen to purge bag mouth, purge time is 0.4s; Welding cap is sealed.The medicinal fluid bag sterilizing of butt welding cap seal mouth, uses and fills nitrogen sterilizing cabinet, fills that nitrogen time swap is 15min, to fill nitrogen pressure be 0.6MPa in cabinet, and sterilization process parameter is 121 DEG C, 12min, F0 value is 12; Sterilizing chilling temperature is 60 DEG C.
In above-described embodiment:
The encapsulating method of described soft packed Amino Acid Compound Injection, the step from bag to sealing is: bag → to empty bag evacuation → to empty bag fills in nitrogen → bag and injects medicinal liquid → nitrogen and purge bag mouth → welding cap sealing.
The sterilizing methods of described soft packed Amino Acid Compound Injection, step is: fill nitrogen displacement → water filling → intensification → sterilizing → cooling → draining → aerofluxus.
Claims (10)
1. the embedding of a soft packed Amino Acid Compound Injection and sterilizing methods, comprise and use bag encapsulation all-in-one machine liquid drug and use to fill the sterilizing of nitrogen sterilizing cabinet, it is characterized in that: the step from bag to sealing is: bag → to empty bag evacuation → to empty bag fills in nitrogen → bag and injects medicinal liquid → nitrogen and purge bag mouth → welding cap sealing.
2. the embedding of soft packed Amino Acid Compound Injection according to claim 1 and sterilizing methods, it is characterized in that: the pumpdown time is 0.2 ~ 1.0s, filling the nitrogen time is 0.2 ~ 0.4s, and filling nitrogen pressure is 0.2 ~ 0.5MPa.
3. the embedding of soft packed Amino Acid Compound Injection according to claim 1 and sterilizing methods, is characterized in that: to empty bag vacuum step, fill the operation of nitrogen step cycle to empty bag, cycling number of times is 1 ~ 3 time.
4. the embedding of soft packed Amino Acid Compound Injection according to claim 1 and sterilizing methods, it is characterized in that: to empty bag vacuum step, empty bag filled after the operation of nitrogen step cycle terminates, in bag, inject medicinal liquid, the pressure injecting medicinal liquid is 0.1 ~ 0.3MPa.
5. the embedding of soft packed Amino Acid Compound Injection according to claim 1 and sterilizing methods, is characterized in that: nitrogen purges in bag mouth step, and purge time is 0.2 ~ 0.6s.
6. the embedding of soft packed Amino Acid Compound Injection and sterilizing methods according to claim 1 or 5, is characterized in that: nitrogen purges after bag mouth step terminates, welding cap sealing immediately.
7. the embedding of soft packed Amino Acid Compound Injection according to claim 1 and sterilizing methods, is characterized in that: sterilization steps is: fill nitrogen displacement → water filling → intensification → sterilizing → cooling → draining → aerofluxus.
8. the embedding of soft packed Amino Acid Compound Injection according to claim 7 and sterilizing methods, is characterised in that: fill that nitrogen time swap is 5 ~ 15min, to fill nitrogen pressure be 0.5 ~ 1.5MPa.
9. the embedding of soft packed Amino Acid Compound Injection according to claim 7 and sterilizing methods, be characterised in that: sterilising temp is 121 DEG C, sterilization time is 12 ~ 15min.
10. the embedding of soft packed Amino Acid Compound Injection according to claim 7 and sterilizing methods, be characterised in that: chilling temperature is 50 ~ 65 DEG C.
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| CN201410811153.4A CN104548153A (en) | 2014-12-22 | 2014-12-22 | Encapsulation and sterilization method of softly-bagged compound amino acid injection |
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| CN201410811153.4A CN104548153A (en) | 2014-12-22 | 2014-12-22 | Encapsulation and sterilization method of softly-bagged compound amino acid injection |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109533449A (en) * | 2018-11-05 | 2019-03-29 | 广州柿宝生物科技有限公司 | Packaging process of powdery persimmon tannin |
| CN109533450A (en) * | 2018-11-05 | 2019-03-29 | 广州柿宝生物科技有限公司 | Packaging equipment and packaging process for powdery persimmon pectin |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109533449A (en) * | 2018-11-05 | 2019-03-29 | 广州柿宝生物科技有限公司 | Packaging process of powdery persimmon tannin |
| CN109533450A (en) * | 2018-11-05 | 2019-03-29 | 广州柿宝生物科技有限公司 | Packaging equipment and packaging process for powdery persimmon pectin |
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