Preparation and encapsulation method of higenamine hydrochloride injection

Abstract

The invention provides a preparation method and a filling and sealing method of a higenamine hydrochloride injection, due to the fact that higenamine hydrochloride is difficult to completely dissolve in water and can be degraded to generate impurities under the conditions of high temperature, oxygen, metal ions and the like, the higenamine hydrochloride is not easy to dissolve in water, and the higenamine hydrochloride is not easy to dissolve in water. The liquid preparation and potting method sequentially comprises a liquid preparation step, an ultrafiltration sterilization step and a potting step, liquid preparation is carried out under the nitrogen condition, the problem of solubility of higenamine hydrochloride can be effectively solved by adopting the liquid preparation mode, the generated medicine impurities are few, the potting effect is good, the reject ratio is low, and the production cost is low. The medicine quality of the higenamine hydrochloride injection is favorably guaranteed.

Description

TECHNICAL FIELD

[0001] The application relates to the field of medicine production, in particular to a preparation and sealing method of norlaudanosine hydrochloride injection. BACKGROUND

[0002] The injection is a sterile preparation of a solution, emulsion or suspension for injection into the human body, or a powder or concentrated solution for preparing or diluting into a solution or suspension before use. The norlaudanosine hydrochloride injection is a solution type injection, which is a liquid preparation containing norlaudanosine hydrochloride as a main drug. The solvent of the injection is water. The quality requirements of the injection generally include the pH value, osmotic pressure, stability, safety, sterility and pyrogen of the injection; the pH value of the injection is generally controlled in the range of 4-9, the osmotic pressure of the injection is equal to or close to the osmotic pressure of the plasma, the injection should have good physical and chemical stability to maintain safety and effectiveness during the storage period, the injection should be safe, that is, non-toxic and non-irritating to the body, and the injection should not contain any living microorganisms and pyrogen.

[0003] Since norlaudanosine hydrochloride is difficult to completely dissolve in water, and norlaudanosine hydrochloride will degrade to produce impurities under the conditions of high temperature, oxygen and metal ions, therefore, a suitable preparation and sealing method should be adopted in the preparation process of the norlaudanosine hydrochloride injection, so as to avoid the preparation of poor norlaudanosine hydrochloride injection. At present, there is no literature report on the preparation and sealing method of the norlaudanosine hydrochloride injection. SUMMARY

[0004] The application provides a preparation and sealing method of norlaudanosine hydrochloride injection, which can effectively solve the solubility problem of norlaudanosine hydrochloride, has less drug impurities, good sealing effect, less adverse rate, and is beneficial to guarantee the medicine quality of the norlaudanosine hydrochloride injection.

[0005] The application provides a preparation and sealing method of norlaudanosine hydrochloride injection, which sequentially comprises a preparation step, an ultrafiltration sterilization step and a sealing step, the preparation step comprises a pre-nitrogen treatment step, and then each component of the injection is sequentially added in a preparation unit, the ultrafiltration step is that the preparation is passed through an ultrafiltration unit, and the sealing step is that the preparation and the solution after ultrafiltration are filled and sealed through a sealing device.

[0006] The application provides a preparation and sealing method of norlaudanosine hydrochloride injection, the preparation step uses a preparation device, the preparation device comprises an aeration module, a heat preservation module, a feeding module and a preparation module, the preparation module comprises a preparation tank, the heat preservation module surrounds the preparation module, the feeding module comprises a feeder, the feeder is located above the preparation tank, materials can be directly added to the preparation tank through the feeder, and a stirring module is arranged at the bottom of the preparation tank.

[0007] The application provides a preparation and sealing method of norlaudanosine hydrochloride injection, the preparation method is that nitrogen is pre-charged into the preparation tank through the aeration module, five feeding storage chambers are arranged in the feeder, sodium bicarbonate, hydrochloric acid solution, EDTA-2Na, cysteine and norlaudanosine hydrochloride are respectively added into the feeding storage chambers, feeding ports are arranged below each feeding storage chamber, materials in the feeding storage chambers can be directly added into the preparation tank through the feeding ports, water is added into the preparation tank through a liquid conveying pipeline above the preparation tank under the condition of nitrogen, sodium bicarbonate is added into the preparation tank through the feeder, hydrochloric acid solution is added into the preparation tank through the feeder, a sampling port is arranged on the preparation tank body, after detecting that the pH value of the solution in the preparation tank is 4.5-5, EDTA-2Na, cysteine and norlaudanosine hydrochloride are respectively added into the preparation tank through the feeder, and hydrochloric acid solution is added into the preparation tank through the feeder until the pH value of the solution in the preparation tank is 2.5-3.5, the stirring modules are all in the starting state during the feeding process, so that the materials in the preparation tank are uniformly mixed, and the solution in the preparation tank is subjected to an ultrafiltration sterilization step.

[0008] The application provides a preparation and sealing method of norlaudanosine hydrochloride injection, the preparation device is ingenious and reasonable, and the norlaudanosine hydrochloride injection prepared by using the preparation device has low impurity content and high stability.

[0009] The application provides a preparation and sealing method of norlaudanosine hydrochloride injection, the solution after the preparation step and the ultrafiltration sterilization step is filled into an ampoule through a sealing device to obtain the norlaudanosine hydrochloride injection, the empty ampoule is conveyed to the filling mechanism through a bottle feeding gear wheel mechanism, the liquid filling is completed through the limiting stopper of the sealing mechanism, the ampoule filled with the solution is sealed through a wire drawing mechanism, and then the ampoule is taken out to obtain the norlaudanosine hydrochloride injection with the sealed liquid.

[0010] The application has the beneficial effect that the application provides a preparation and filling sealing method of norlaudanosine hydrochloride injection solution, since norlaudanosine hydrochloride is difficult to be completely dissolved in water, and norlaudanosine hydrochloride will be degraded to produce impurities under the conditions of high temperature, oxygen and metal ions, etc., the preparation and filling sealing method of the application sequentially comprises a preparation step, an ultrafiltration sterilization step and a filling sealing step, the preparation is carried out under the condition of nitrogen, and the norlaudanosine hydrochloride injection solution with less impurity content and high stability can be prepared. BRIEF DESCRIPTION OF DRAWINGS

[0011] Figure 1 The application is a preparation and filling sealing device.

[0012] 1-preparation module, 2-heat preservation module, 3-feeding module, 4-sampling port, 5-aeration module, 6-ultrafiltration module, 7-filling sealing device. DETAILED DESCRIPTION

[0013] The technical solutions of the application will be clearly and completely described below through the embodiments of the application and the drawings, obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor are within the protection scope of the application. EMBODIMENT

[0014] A preparation and filling sealing method of norlaudanosine hydrochloride injection solution Figure 1 A preparation and filling device of norlaudanosine hydrochloride injection solution is shown, the preparation and filling device comprises a preparation module 1, a heat preservation module 2, a feeding module 3 and an aeration module 5, the preparation module 1 comprises a preparation tank, the heat preservation module 2 surrounds the preparation module 1, a sampling port 4 is arranged on the surface of the preparation tank, the feeding module 3 comprises a feeder, the feeder is located above the preparation tank, material can be directly added to the preparation tank through the feeder, and a stirring module is arranged at the bottom of the preparation tank. The aeration module 5 is connected to the top of the preparation tank through a ventilation pipeline. The bottom of the preparation module 1 is sequentially connected to an ultrafiltration module 6 and a filling sealing device 7 through pipelines.

[0015] The method of the present application comprises a liquid preparation step, an ultrafiltration sterilization step and a filling and sealing step, the liquid preparation step comprises a pre-nitrogen treatment step, and then the components of the injection solution are sequentially added in a liquid preparation unit, the ultrafiltration step is to pass the prepared liquid through an ultrafiltration module, and the filling and sealing step is to pass the prepared liquid and the solution after ultrafiltration through a filling and sealing device for filling and sealing. The liquid preparation step uses a liquid preparation device, which comprises an aeration module 5, a heat preservation module 2, a feeding module 3 and a liquid preparation module 1, the liquid preparation module 1 comprises a liquid preparation tank, the heat preservation module 2 surrounds the liquid preparation module 1, the feeding module 3 comprises a feeder, the feeder is located above the liquid preparation tank, the material can be directly added to the liquid preparation tank through the feeder, and a stirring module is arranged at the bottom of the liquid preparation tank.

[0016] The liquid preparation method is to first pre-charge nitrogen into the liquid preparation tank through the aeration module, five feeding storage chambers are arranged in the feeder, sodium bicarbonate, hydrochloric acid solution, EDTA-2Na, cysteine and norlaudanosine hydrochloride are respectively added into the feeding storage chambers, and a feeding port is arranged below each feeding storage chamber to directly add the material in the feeding storage chamber into the liquid preparation tank. Under the condition of nitrogen, water is first added into the liquid preparation tank through a liquid conveying pipeline above the liquid preparation tank, then sodium bicarbonate is added into the liquid preparation tank through the feeder, then the hydrochloric acid solution is added into the liquid preparation tank through the feeder, a sampling port is arranged on the tank body of the liquid preparation tank, after detecting that the pH value of the solution in the liquid preparation tank is 4.5-5, EDTA-2Na, cysteine and norlaudanosine hydrochloride are respectively added into the liquid preparation tank through the feeder, and then the hydrochloric acid solution is added into the liquid preparation tank through the feeder until the pH value of the solution in the liquid preparation tank is 2.5-3.5. The stirring modules are all in the starting state during the feeding process, so that the materials in the liquid preparation tank are uniformly mixed, and then the solution in the liquid preparation tank is subjected to the ultrafiltration sterilization step.

[0017] Finally, the solution after the liquid preparation step and the ultrafiltration sterilization step is filled into ampoule bottles through the filling and sealing device to obtain norlaudanosine hydrochloride injection. First, the empty ampoule bottles are conveyed to the filling mechanism through the bottle feeding gear wheel mechanism, the liquid filling is completed through the filling and sealing mechanism limit stopper, then the ampoule bottles containing the solution are sealed through the wire drawing mechanism, and the norlaudanosine hydrochloride injection with the liquid sealed in the tank is obtained.

[0018] The above embodiments compare the technical solutions and beneficial effects of the present application, and it should be understood that the above embodiments are only specific embodiments of the present application and are not used to limit the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the present application.

Claims

1. A method for preparing and filling norlaudanosine hydrochloride injection, characterized in that, The method sequentially comprises a liquid preparation step, an ultrafiltration sterilization step and a filling and sealing step, the liquid preparation step comprises a pre-nitrogen treatment step, and then each component of the injection solution is sequentially added in a liquid preparation unit, the ultrafiltration step is that the liquid preparation is passed through an ultrafiltration unit, and the filling and sealing step is that the liquid preparation and the solution after ultrafiltration are filled and sealed through a filling and sealing device.

2. The method of claim 1, wherein, The liquid preparation step uses a liquid preparation device, the liquid preparation device comprises an aeration module, a heat preservation module, a feeding module and a liquid preparation module, the liquid preparation module comprises a liquid preparation tank, the heat preservation module surrounds the liquid preparation module, the feeding module comprises a feeder, the feeder is located above the liquid preparation tank, materials can be directly added to the liquid preparation tank through the feeder, and a stirring module is arranged at the bottom of the liquid preparation tank.

3. The method of claim 1 or 2, wherein the method further comprises: The liquid preparation method is that nitrogen is pre-charged into the liquid preparation tank through the aeration module, five feeding storage chambers are arranged in the feeder, sodium bicarbonate, hydrochloric acid solution, EDTA-2Na, cysteine and norlaudanosine hydrochloride are respectively added into the feeding storage chambers, each feeding storage chamber is provided with a feeding port below the feeding storage chamber, materials in the feeding storage chamber can be directly added into the liquid preparation tank, water is added into the liquid preparation tank through a liquid conveying pipeline above the liquid preparation tank under the condition of nitrogen, then sodium bicarbonate is added into the liquid preparation tank through the feeder, then the hydrochloric acid solution is added into the liquid preparation tank through the feeder, a sampling port is arranged on the tank body of the liquid preparation tank, after the pH value of the solution in the liquid preparation tank is detected to be 4.5-5, EDTA-2Na, cysteine and norlaudanosine hydrochloride are respectively added into the liquid preparation tank through the feeder, then the hydrochloric acid solution is added into the liquid preparation tank through the feeder until the pH value of the solution in the liquid preparation tank is detected to be 2.5-3.5, the stirring modules are in the starting state during the feeding process, so that the materials in the liquid preparation tank are uniformly mixed, and then the solution in the liquid preparation tank is subjected to the ultrafiltration sterilization step.

4. The method of claim 3, wherein the liquid is mixed and filled in the container. The liquid preparation device is ingenious and reasonable, and the norlaudanosine hydrochloride injection prepared by using the liquid preparation device has low impurity content and high stability.

5. The method of claim 4, wherein the liquid is mixed and filled in the container. The solution after the liquid preparation step and the ultrafiltration sterilization step is filled into ampoule bottles through a filling and sealing device to obtain norlaudanosine hydrochloride injection, first, empty ampoule bottles are conveyed to the filling mechanism through a bottle feeding gear wheel mechanism, liquid filling is completed through a filling and sealing mechanism stopper, then the ampoule bottles containing the solution are sealed through a wire drawing mechanism, and the norlaudanosine hydrochloride injection with the filled and sealed solution is obtained.

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