CN110638831A - Sodium bicarbonate ringer's injection and preparation process thereof - Google Patents
Sodium bicarbonate ringer's injection and preparation process thereof Download PDFInfo
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Abstract
The invention provides a ringer's injection of sodium bicarbonate and its preparation process, the ringer's injection of sodium bicarbonate is prepared by mixing water for injection with sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium bicarbonate, dihydrate of sodium citrate and citric acid monohydrate. The preparation method comprises sequentially adding the above medicinal materials into water for injection according to the prescription, stirring for dissolving, adding activated carbon, stirring for adsorbing, removing carbon, adding the medicinal liquid into diluting tank, adding sodium bicarbonate, adding water for injection to full volume, filtering, and measuring pH; filling CO2, bottling, sterilizing, and packaging. The invention provides a new proportioning component of sodium bicarbonate ringer's injection and proportioning proportion. The invention provides a new production and preparation process of a sodium bicarbonate ringer's injection. The production and preparation process has better sterilization effect.
Description
Technical Field
The present invention relates to an injection and its preparation process. Belongs to the field of injection medicine production.
Background
The ringer's injection of sodium bicarbonate is compound electrolyte injection, is used as supplement regulator of extracellular fluid to correct metabolic acidosis when the circulating blood volume and interstitial fluid are reduced (such as perioperative period). The ringer's injection of sodium bicarbonate can improve metabolic acidosis quickly and effectively, and has obvious effect on maintaining acid-base balance and electrolyte balance. The preparation proportion of the sodium bicarbonate ringer injection has no better proportion all the time, so that the prior sodium bicarbonate ringer injection has low drug effect and the treatment effect needs to be further improved.
In the production process of injection, aseptic production is always the key of injection production, and multiple times of sterilization are carried out in the process of producing injection so as to control the total number of bacteria within the qualified number.
The same applies to the production of ringer's bicarbonate injection, which must be controlled for the total bacterial count. The existing control method mainly comprises the steps of carrying out once activated carbon adsorption, degerming and impurity removal in a thick preparation tank after the preparation pharmaceutical industry is finished in a high-cleanness production environment area. Then filtering and decarburizing to finish sterilization. Depending on the mode, to achieve better sterilization, a sufficient amount of activated carbon must be added, and the activated carbon must be stirred and mixed in the concentration tank for a sufficient time to achieve better bacteria adsorption.
Therefore, when the quantity of the active carbon in the concentrated preparation tank is excessive and the adsorption time is too long, the active ingredients in the pharmaceutical industry in the concentrated preparation tank can be adsorbed, so that the active ingredient quantity of the final finished product is reduced, and if the quantity of the active carbon is excessive, new pollution is caused to the liquid medicine, and the procedure and cost for later-stage decarburization are increased. Therefore, in the production process of the existing sodium bicarbonate ringer injection, the consumption of the activated carbon needs to be controlled, the balance between the sterilization effect and the consumption of the activated carbon is taken, the sterilization requirement is properly reduced, the bacteria quantity can reach the standard within the specified control quantity, and the bacteria quantity is not further controlled.
For the ringer's injection of sodium bicarbonate, the lower the number of bacteria contained therein, the safer it is theoretically, and the faster the bacteria grow, and the unknown kind of bacteria can grow in various complicated environments, so if the number of bacteria packaged in the liquid medicine at the early stage is lower, the number of bacteria growing in the liquid medicine at a later stage in a certain period of time in stock is certainly lower. In the production period of the liquid medicine, it is very important to effectively sterilize the liquid.
Therefore, in the existing production mode of the sodium bicarbonate injection, the aim of better controlling the bacterial quantity, the attention is paid to losing the drug effect, the filtration cost is increased, and the problem contradiction which is difficult to solve is achieved.
Disclosure of Invention
In order to solve the problems, the invention provides a sodium bicarbonate ringer injection and a preparation process thereof.
The invention relates to a sodium bicarbonate ringer's injection, which comprises the following components in percentage by weight:
sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium bicarbonate, sodium citrate dihydrate and citric acid monohydrate are added into the water for injection.
The injection comprises the following components in parts by weight: 500 parts of water for injection, 2.92 parts of sodium chloride, 0.15 part of potassium chloride, 0.11 part of calcium chloride hydrate, 0.10 part of magnesium chloride, 1.175 part of sodium bicarbonate, 0.10 part of sodium citrate dihydrate and 0.0685 part of citric acid monohydrate.
The preparation process of the sodium bicarbonate ringer's injection of the invention is completed by the following steps,
(1) adding water for injection into a thick preparation tank, sequentially adding sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate according to the formula amount, stirring and dissolving, adding activated carbon, stirring and adsorbing to obtain a liquid medicine;
(2) starting circulation decarbonization;
(3) injecting water for injection into the diluting preparation tank; adding the medicinal liquid into diluting tank, repeatedly washing the concentrating tank with water for injection, adding into diluting tank, adding sodium bicarbonate, adding water for injection to full volume, filtering, and measuring pH;
(4) filling CO2, circularly making the liquid medicine uniform, taking the intermediate to monitor the pH value of the liquid medicine;
(5) filtering with 0.22 μm microporous filter until the visible foreign matter is qualified, sampling, and measuring pH;
(6) filling, sterilizing and packaging.
The invention relates to a preparation process of a sodium bicarbonate ringer's injection, which comprises the following steps:
(1) the injection water injected into the concentrated preparation tank is specifically that the injection water amount is 30% of the total volume after diluted preparation;
(2) 580g of active carbon is added, which accounts for 0.01 percent of the diluted amount of the liquid medicine, and the active carbon is stirred and adsorbed for 15 minutes after the active carbon is added;
(3) starting circulating decarburization, specifically, circulating decarburization for 20 minutes;
(4) the filtration is carried out by utilizing 3um titanium and then carrying out fine filtration by 0.45 um;
(5) and (3) sterilizing: sterilizing with superheated water bath at 121 deg.C for 12 min;
(6) and the packaging: packaging about 2 hours after sterilization, filling CO2 and adding an outer bag.
The invention relates to a preparation process of a sodium bicarbonate ringer's injection, which comprises the following steps:
adding sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate, stirring and dissolving, specifically, (1) preparing the ingredients: sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate; (2) carrying out ultrasonic sterilization: adding injection water with more than 5 times volume of the ingredients into an ultrasonic tank, putting the ingredients into the ultrasonic tank, performing ultrasonic oscillation for 8-10 minutes to perform first sterilization, and dissolving the ingredients into the injection water at the same time.
The invention relates to a preparation process of a sodium bicarbonate ringer's injection, which comprises the following steps:
the ultrasonic oscillation parameters are as follows: the sound intensity is 1-5W/cm2The frequency is 30-40KHz, and the bottom of the ultrasonic tank generates 10.5 mu m amplitude; the ultrasonic output power is 45-55w, the ultrasonic wave is pulse wave, and the pulse width is 8-12 ms.
The invention relates to a preparation process of a sodium bicarbonate ringer's injection, which comprises the following steps: after the injection water is supplemented to the full amount, the reflux water shearing sterilization is carried out in the diluting preparation tank; the reflux water shearing sterilization is specifically that the liquid in the blending tank is stirred and repeatedly rotated for 20-25 minutes.
The invention relates to a preparation process of a sodium bicarbonate ringer's injection, which comprises the following steps:
the stirring liquid in the diluting and blending tank rotates repeatedly, specifically, the stirring liquid in the diluting and blending tank rotates clockwise for 1-3 minutes, then the stirring liquid in the diluting and blending tank rotates anticlockwise for 1-3 minutes, the stirring liquid rotates repeatedly in the same way, and the rotation direction is changed every 1-3 minutes to generate high shearing force;
the stirring method for stirring the liquid in the diluting preparation tank to rotate repeatedly comprises the following steps: the water outlets of a plurality of first group of reflux pumps are arranged on the outer wall of the diluting preparation tank in a clockwise direction and from the tangential direction of the inner circle of the diluting preparation tank, the water inlets of the first group of reflux pumps are arranged at the bottom of the diluting preparation tank, and the arranged first group of reflux pumps complete the stirring of the clockwise rotation in the diluting preparation tank;
the water outlets of a plurality of second groups of reflux pumps are arranged on the outer wall of the diluting preparation tank in the anticlockwise direction and from the tangential direction of the inner circle of the diluting preparation tank, the water inlets of the second groups of reflux pumps are arranged at the bottom of the diluting preparation tank, and the arranged second groups of reflux pumps complete the stirring of the anticlockwise rotation in the diluting preparation tank;
the first group of reflux pumps and the second group of reflux pumps are repeatedly and alternately started to enable the liquid in the diluting preparation tank to repeatedly rotate to generate high shearing force;
the invention relates to a preparation process of a sodium bicarbonate ringer's injection, which comprises the following steps:
the water outlet parameters of the water outlet are as follows: the flow rate is more than 50L/min, and the flow speed is 2-3.5 m/s.
The invention relates to a preparation process of a sodium bicarbonate ringer's injection, which comprises the following steps:
in the filling process, the liquid in the diluting preparation tank is continuously and repeatedly rotated and stirred; stirring the liquid in the diluting and blending tank for 1-3 minutes, then stirring the liquid in the diluting and blending tank for 1-3 minutes from the reverse direction, repeatedly rotating in the way, and converting the rotating direction every 1-3 minutes to generate high shearing force;
until the liquid medicine in the diluting preparation tank is canned
Has the advantages that:
the invention provides a new proportioning component of sodium bicarbonate ringer's injection and proportioning proportion. The sodium bicarbonate ringer's injection has better treatment effect.
The invention provides a new production and preparation process of a sodium bicarbonate ringer's injection.
The production and preparation process has better sterilization effect.
Under the condition of not adding more active carbon for adsorption sterilization, ultrasonic sterilization, sterilization by the shearing force of boiling water in the concentrated preparation tank, sterilization by the shearing force of reflux water in the diluted preparation tank and multiple sterilization steps are facilitated, so that the total amount of bacteria in the liquid medicine is better reduced. Or under the condition of keeping the total amount of bacteria in the existing liquid medicine unchanged and qualified products, the invention can reduce the dosage of the active carbon and reduce the adsorption time of the active carbon so as to keep the effective components of the liquid medicine.
Detailed Description
The invention is firstly dissolved, then concentrated, diluted and finally canned.
The invention carries out ultrasonic sterilization during dissolution, then carries out concentrated preparation boiling sterilization, then carries out water flow sterilization in a diluting preparation tank, and finally carries out canning, and simultaneously carries out water flow sterilization.
The first embodiment is as follows:
a500 ml infusion bag of ringer's bicarbonate injection was prepared. 5800L medicinal liquid is prepared.
The mixture ratio is as follows:
example two:
a1000 ml infusion bag of ringer's bicarbonate injection was prepared. 7500L medicinal liquid is prepared.
The mixture ratio is as follows:
example three:
prepare 500 ml/bag of sodium bicarbonate ringer's injection.
1. Adding about 1.8 tons of water for injection (the amount of the water for injection is 30 percent of the total volume after diluted preparation) into a concentration preparation tank, and adding sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate according to the prescription amount in turn, stirring and dissolving. 580g of active carbon (0.01 percent of the diluted liquid medicine) is added, and the mixture is stirred and adsorbed for 15 minutes to obtain the liquid medicine.
2. And starting circulation to decarburize for 20 minutes.
3. 3 tons of water for injection are added into the diluting preparation tank in advance.
4. Adding the medicinal liquid into diluting tank, repeatedly washing the concentrating tank with about 300kg of water for injection, adding sodium bicarbonate, adding water for injection to full volume, filtering with 3 μm titanium, filtering with 0.45 μm, and measuring pH.
5. Filling CO2 about 22.0kg, circulating to make the liquid medicine uniform for 20 minutes, taking the intermediate (monitoring the pH of the liquid medicine first),
6. filtering the liquid medicine through a 0.22 mu m microporous filter until the visible foreign matters are qualified, sampling, measuring the PH value, opening a filling related valve and discharging for 10 seconds. Adjusting the total reflux valve to ensure that the pressure of the water for injection from the terminal filter is between 0.3 and 0.35Mpa, and simultaneously sending a filling signal.
7. And (6) filling.
8. And (3) sterilization: sterilizing in water bath at 121 deg.C with superheated water for 12 min.
9. Packaging: the outer bag was added about 2 hours after sterilization and CO2 was filled in the sandwich between the outer bag and the inner package.
Example four:
prepare 500 ml/bag of sodium bicarbonate ringer's injection.
1. About 1.8 tons of water for injection is added into the concentration tank (the water for injection is 30% of the total volume of the liquid medicine in the dilution tank after dilution).
Preparing ingredients: sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate;
carrying out ultrasonic sterilization: adding 100L of water for injection into an ultrasonic tank, and putting half of the ingredients into the ultrasonic tank, wherein ultrasonic oscillation is generated in the ultrasonic tank, and the ultrasonic oscillation parameters are as follows: sound intensity 1-5W/cm2The frequency is 30-40KHz, and the bottom of the ultrasonic tank generates 10.5 mu m amplitude; the ultrasonic output power is 45-55w, the ultrasonic wave is pulse wave, and the pulse width is 8-12 ms.
Performing primary sterilization by ultrasonic oscillation for 8-10 min, and dissolving the ingredients in water for injection. The liquid medicine which is sterilized for the first time in the ultrasonic tank and dissolved at the same time is put into the thick preparation tank.
Adding 100L of water for injection into the ultrasonic tank, adding the other half of the materials into the ultrasonic tank, sterilizing the ultrasonic tank for the second time, and adding the dissolved medicinal liquid into the concentration tank.
580g of activated carbon (0.01% of the diluted amount of the chemical solution) is put into the concentration tank, and the mixture is stirred and adsorbed for 15 minutes.
2. And starting circulation to decarburize for 20 minutes.
3. 3 tons of water for injection are added into the diluting preparation tank in advance.
4. The liquid medicine is pumped into a diluting preparation tank, about 300kg of injection water is used for repeatedly flushing the concentrating preparation tank and is also pumped into the diluting preparation tank, sodium bicarbonate is added, the injection water is supplemented to the full amount, the liquid in the diluting preparation tank is firstly stirred for 1-3 minutes, then the liquid in the diluting preparation tank is stirred again in the reverse direction for 1-3 minutes, the rotation is repeatedly carried out, the rotation direction is changed every 1-3 minutes, and high shear force sterilization is generated.
5. Then, the mixture was filtered through 3um titanium, fine filtered through 0.45um, and the pH was measured.
5. Filling CO2 about 22.0kg, circulating to make the liquid medicine uniform for 20 minutes, taking the intermediate (monitoring the pH of the liquid medicine first),
6. filtering the liquid medicine through a 0.22 mu m microporous filter until the visible foreign matters are qualified, sampling, measuring the PH value, opening a filling related valve and discharging for 10 seconds. Adjusting the total reflux valve to ensure that the pressure of the water for injection from the terminal filter is between 0.3 and 0.35Mpa, and simultaneously sending a filling signal.
7. And (6) filling. In the filling process, the liquid in the diluting preparation tank is continuously and repeatedly rotated and stirred; the liquid in the diluting and blending tank is stirred for 1-3 minutes, then the liquid in the diluting and blending tank is stirred for 1-3 minutes from the reverse direction, the rotation is repeated, the rotation direction is changed every 1-3 minutes, and high shearing force is generated until the liquid medicine in the diluting and blending tank is filled.
8. And (3) sterilization: sterilizing in water bath at 121 deg.C with superheated water for 12 min.
9. Packaging: the outer bag was added about 2 hours after sterilization and CO2 was filled in the sandwich between the outer bag and the inner package.
The stirring device for stirring the liquid in the diluting preparation tank to rotate repeatedly is as follows: set up two sets of backwash pumps on the tank is joined in marriage to the rare, and first set of backwash pump is used for stirring the interior liquid clockwise rotation of tank is joined in marriage to the rare, and the second set of backwash pump is used for stirring the interior liquid anticlockwise rotation of tank is joined in marriage to the rare.
The delivery port of first set of backwash pump sets up on the tank outer wall of rare matching with clockwise and from the circle tangential direction in the rare matching jar, for example, first set of backwash pump sets up 5 delivery ports, evenly from the top down distributes on the tank outer wall of rare matching. When the 5 water outlets spray liquid into the diluting preparation tank at a high speed along the tangential direction, the liquid medicine in the diluting preparation tank is stirred to rotate clockwise.
The water inlet of the first set of reflux pump is arranged at the bottom of the diluting preparation tank, and the liquid medicine is sucked from the bottom of the diluting preparation tank. Therefore, the liquid medicine is circulated by the first group of reflux pumps.
The water outlet of the second group of reflux pumps is arranged on the outer wall of the diluting preparation tank in the anticlockwise direction and in the tangential direction of the inner circle of the diluting preparation tank, and the first group of reflux pumps is referred to by other structures. The second group of reflux pumps agitates the liquid medicine in the diluting preparation tank to rotate anticlockwise. The water outlet parameters of the water outlet are as follows: the flow rate is more than 50L/min, and the flow speed is 2-3.5 m/s.
The first set of reflux pump and the second set of reflux pump are alternately started repeatedly to make the liquid in the diluting preparation tank rotate repeatedly to generate high shearing force.
Example five:
1000ml of the linger sodium bicarbonate injection with the specification per bag is prepared.
1. Adding about 2.5 tons of water for injection into a concentration preparation tank (the amount of the water for injection is 30 percent of the total volume of the liquid medicine in the concentration preparation tank after dilution preparation), and sequentially adding sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate according to the amount of the prescription, stirring and dissolving. 750g of activated carbon (0.01% of the diluted chemical solution) is added, and the mixture is stirred and adsorbed for 15 minutes.
And starting circulation to decarburize for 20 minutes.
4 tons of water for injection is added into the diluting preparation tank in advance.
Adding the medicinal liquid into diluting tank, repeatedly washing the concentrating tank with about 300kg of water for injection, adding sodium bicarbonate, adding water for injection to full volume, filtering with 3 μm titanium, filtering with 0.45 μm, and measuring pH.
Filling CO2 about 28.0kg, circulating to make the liquid medicine uniform for 20 minutes, taking the intermediate (monitoring the pH of the liquid medicine first),
filtering the liquid medicine through a 0.22 mu m microporous filter until the visible foreign matters are qualified, sampling, measuring the PH value, opening a filling related valve and discharging for 10 seconds. Adjusting the total reflux valve to ensure that the pressure of the water for injection from the terminal filter is between 0.3 and 0.35Mpa, and simultaneously sending a filling signal.
And (6) filling.
And (3) sterilization: sterilized at 121 ℃ for 12 minutes.
Packaging: packaging about 2 hours after sterilization, filling CO2 and adding an outer bag.
Example six:
1000ml of the linger sodium bicarbonate injection with the specification per bag is prepared.
About 2.5 tons of water for injection is added into the concentration tank (the water for injection accounts for 30 percent of the total volume of the liquid medicine in the dilution tank after dilution).
Preparing ingredients: sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate;
carrying out ultrasonic sterilization: adding 100L of water for injection into an ultrasonic tank, and putting half of the ingredients into the ultrasonic tank, wherein ultrasonic oscillation is generated in the ultrasonic tank, and the ultrasonic oscillation parameters are as follows: sound intensity 1-5W/cm2The frequency is 30-40KHz, and the bottom of the ultrasonic tank generates 10.5 mu m amplitude; the ultrasonic output power is 45-55w, the ultrasonic wave is pulse wave, the pulse width is 8-12ms, so as to sterilize for the first time and dissolve the ingredients in the water for injection. The liquid medicine which is sterilized for the first time in the ultrasonic tank and dissolved at the same time is put into the thick preparation tank.
Adding 100L of water for injection into the ultrasonic tank, adding the other half of the materials into the ultrasonic tank, sterilizing the ultrasonic tank for the first time, and adding the dissolved medicinal liquid into the concentration tank.
750g of activated carbon (0.01% of the diluted amount of the chemical liquid) was put into the thickening tank, and the mixture was stirred and adsorbed for 15 minutes.
2. And starting circulation to decarburize for 20 minutes.
3. 4 tons of water for injection is added into the diluting preparation tank in advance.
4. The liquid medicine is pumped into a diluting preparation tank, and about 300kg of water for injection is used for repeatedly flushing the concentrating preparation tank and is also pumped into the diluting preparation tank. Adding sodium bicarbonate, adding water for injection to full volume, stirring the liquid in the diluting tank to rotate clockwise for 1-3 min, then stirring the liquid in the diluting tank again from the reverse direction to rotate for 1-3 min, repeating the rotation, and converting the rotation direction once every 1-3 min to generate high shear force for sterilization.
5. Then filtering the liquid medicine with 3um titanium, finely filtering with 0.45um, and measuring the PH.
5. About 28kg of CO2 was charged, and after cycling the solution to homogeneity for 20 minutes, the intermediate was removed (first monitoring the pH of the solution).
6. Filtering the liquid medicine through a 0.22 mu m microporous filter until the visible foreign matters are qualified, sampling, measuring the PH value, opening a filling related valve and discharging for 10 seconds. Adjusting the total reflux valve to ensure that the pressure of the water for injection from the terminal filter is between 0.3 and 0.35Mpa, and simultaneously sending a filling signal.
7. And (6) filling. In the filling process, the liquid in the diluting preparation tank is continuously and repeatedly rotated and stirred; specifically, the liquid in the stirring diluting preparation tank rotates clockwise for 1-3 minutes, then the liquid in the stirring diluting preparation tank rotates anticlockwise for 1-3 minutes, the rotation is repeated in this way, and the rotation direction is changed every 1-3 minutes to generate high shearing force until the liquid medicine in the diluting preparation tank is filled.
8. And (3) sterilization: sterilizing in water bath at 121 deg.C with superheated water for 12 min.
9. Packaging: the outer bag was added about 2 hours after sterilization and CO2 was filled in the sandwich between the outer bag and the inner package.
The stirring device for stirring the liquid in the diluting preparation tank to rotate repeatedly is as follows: set up two sets of backwash pumps on the tank is joined in marriage to the rare, and first set of backwash pump is used for stirring the interior liquid clockwise rotation of tank is joined in marriage to the rare, and the second set of backwash pump is used for stirring the interior liquid anticlockwise rotation of tank is joined in marriage to the rare.
The delivery port of first set of backwash pump sets up on the tank outer wall of rare matching with clockwise and from the circle tangential direction in the rare matching jar, for example, first set of backwash pump sets up 5 delivery ports, evenly from the top down distributes on the tank outer wall of rare matching. When the 5 water outlets spray liquid into the diluting preparation tank at a high speed along the tangential direction, the liquid medicine in the diluting preparation tank is stirred to rotate clockwise.
The water inlet of the first set of reflux pump is arranged at the bottom of the diluting preparation tank, and the liquid medicine is sucked from the bottom of the diluting preparation tank. Therefore, the liquid medicine is circulated by the first group of reflux pumps.
The water outlet of the second group of reflux pumps is arranged on the outer wall of the diluting preparation tank in the anticlockwise direction and in the tangential direction of the inner circle of the diluting preparation tank, and the first group of reflux pumps is referred to by other structures. The second group of reflux pumps agitates the liquid medicine in the diluting preparation tank to rotate anticlockwise.
The water outlet parameters of the water outlet are as follows: the flow rate is more than 50L/min, and the flow speed is 2-3.5 m/s. The first set of reflux pump and the second set of reflux pump are alternately started repeatedly to make the liquid in the diluting preparation tank rotate repeatedly to generate high shearing force.
In the embodiment of the invention, various ingredients are firstly put into the ultrasonic tank for dissolution, and then ultrasonic sterilization is carried out. The ultrasonic wave is composed of a series of longitudinal waves with alternate density and is transmitted to the periphery through a liquid medium. When the sound energy is high enough, the attractive force among liquid phase molecules is broken in a loose half period to form a cavitation nucleus, the service life of the cavitation nucleus is about 0.1 mu S, the cavitation nucleus can generate local high-temperature and high-pressure environments of about 4000K and 100MPa at the moment of explosion, and generates microjet with strong impact at the speed of about 110m/S, the action of the microjet can form strong mechanical stirring effect among interfaces, and the effect can break through the limit of laminar boundary, so that the chemical reaction process and the transfer process among the interfaces are strengthened.
Ultrasonic waves are sound waves with a frequency greater than 20kHz and are mechanical vibrations that propagate in a medium. Due to the high frequency and short wavelength, the ultrasonic wave can cause cavitation and a series of special effects such as mechanical effect, thermal effect, chemical effect and biological effect besides the characteristics of good directivity, high power, strong penetrating power and the like. The sterilization effect of the ultrasonic wave is mainly due to the cavitation effect generated by the ultrasonic wave, so that the contents of the microbial cells are strongly vibrated, and the destruction effect on the microbes is achieved. The cavitation is a cavitation phenomenon that when ultrasonic waves act in a medium and the intensity of the ultrasonic waves exceeds a certain air threshold value, tiny bubble nuclei in liquid are activated under the action of the ultrasonic waves and show a series of dynamic processes such as oscillation, growth, shrinkage and collapse of the bubble nuclei. At the moment of adiabatic shrinkage and collapse, the air bubbles have a high temperature of 5000 ℃ or higher and a temperature change rate of 109K/s, and generate strong shock waves of 108N/m 2. The ultrasonic cavitation effect is utilized to generate local instantaneous high temperature, temperature alternation change, local instantaneous high pressure and pressure change in the liquid, so that certain bacteria in the liquid are killed, viruses are inactivated, and even cell walls of a few microorganisms with small volume are damaged.
In this example, the ultrasonic sterilization effect is as follows:
| duration of sterilization | Output power | Frequency of ultrasonic waves | Sterilizing effect |
| 1 minute | 50w | 30KHz | 8％ |
| 3 minutes | 50w | 30KHz | 14％ |
| 5 minutes | 50w | 30KHz | 17％ |
| 7 minutes | 50w | 30KHz | 21.5％ |
| 9 minutes | 50w | 30KHz | 22.5％ |
| 10 minutes | 50w | 30KHz | 23.3％ |
| 13 minutes | 50w | 30KHz | 24.0％ |
| 15 minutes | 50w | 30KHz | 24.4％ |
In the ultrasonic sterilization test, the sterilization time affects the final sterilization effect, and a longer sterilization time brings a better sterilization effect, and when the sterilization time is 5 minutes or more, the sterilization effect is greatly increased, but when the sterilization time exceeds a certain time, the sterilization effect is not increased in proportion to 13 minutes or more, so that the sterilization time within 5 to 10 minutes is considered to be most significant. The invention takes 5-10 minutes of ultrasonic sterilization time in the implementation, and balances the use cost and time of ultrasonic sound and sterilization.
The diluting preparation tank adopts a rotary injection water sterilization mode.
The volume of the ultrasonic tank is 100L, so that ultrasonic oscillation can be utilized, but the volumes of the concentration tank and the diluting tank are too large, and the cost is too high due to the adoption of ultrasonic oscillation.
Because the high-speed circulating water flow for injection prevents bacteria from adhering to the wall surface of the container, and the circulating water flow for injection has uncertain turbulence, molecules of water for injection are squeezed to each other to generate shearing force, and the shearing force has destructive effect on cells. Thereby achieving a certain effect.
But the shearing force sterilization of the injection water flow which is beneficial to high-speed circulation is not suitable for too long time, and the canning is completed within 16 hours because the canning time of the liquid medicine prepared by the liquid medicine person of the invention is not suitable for too long time. Therefore, the time of each step of the process must be strictly controlled, secondly, the shearing force sterilization effect of the injection water is limited, and when the circulation time exceeds 30 minutes, the sterilization effect is reduced, and the extension time becomes meaningless. Therefore, the water shearing force sterilization cycle time for injection is 20-25 minutes.
In the canning process, the liquid in the diluting preparation tank is continuously and repeatedly rotated and stirred until the liquid medicine in the diluting preparation tank is canned. Further inhibiting bacterial growth during this period.
The foregoing is illustrative of the present invention and does not represent the scope of the invention.
Claims (10)
1. The sodium bicarbonate ringer's injection is characterized by comprising the following components in percentage by weight:
sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium bicarbonate, sodium citrate dihydrate and citric acid monohydrate are added into the water for injection.
2. The ringer sodium bicarbonate injection according to claim 1, wherein the formulation comprises, by weight: 500 parts of water for injection, 2.92 parts of sodium chloride, 0.15 part of potassium chloride, 0.11 part of calcium chloride hydrate, 0.10 part of magnesium chloride, 1.175 part of sodium bicarbonate, 0.10 part of sodium citrate dihydrate and 0.0685 part of citric acid monohydrate.
3. A preparation process of a sodium bicarbonate ringer's injection is characterized by comprising the following steps,
(1) adding water for injection into a thick preparation tank, sequentially adding sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate according to the formula amount, stirring and dissolving, adding activated carbon, stirring and adsorbing to obtain a liquid medicine;
(2) starting circulation decarbonization;
(3) injecting water for injection into the diluting preparation tank; adding the medicinal liquid into diluting tank, repeatedly washing the concentrating tank with water for injection, adding into diluting tank, adding sodium bicarbonate, adding water for injection to full volume, filtering, and measuring pH;
(4) filling CO2, circularly making the liquid medicine uniform, taking the intermediate to monitor the pH value of the liquid medicine;
(5) filtering with 0.22 μm microporous filter until the visible foreign matter is qualified, sampling, and measuring pH;
(6) filling, sterilizing and packaging.
4. The preparation process of the ringer sodium bicarbonate injection according to claim 3, which comprises:
(1) the injection water injected into the concentrated preparation tank is specifically that the injection water amount is 30% of the total volume after diluted preparation;
(2) 580g of active carbon is added, which accounts for 0.01 percent of the diluted amount of the liquid medicine, and the active carbon is stirred and adsorbed for 15 minutes after the active carbon is added;
(3) starting circulating decarburization, specifically, circulating decarburization for 20 minutes;
(4) the filtration is carried out by utilizing 3um titanium and then carrying out fine filtration by 0.45 um;
(5) and (3) sterilizing: sterilizing with superheated water bath at 121 deg.C for 12 min;
(6) and the packaging: packaging about 2 hours after sterilization, filling CO2 and adding an outer bag.
5. The preparation process of the ringer's bicarbonate injection according to claim 3, wherein the sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate are added and stirred to dissolve, and specifically, (1) the ingredients are prepared: sodium chloride, potassium chloride, calcium chloride hydrate, magnesium chloride, sodium citrate dihydrate and citric acid monohydrate; (2) carrying out ultrasonic sterilization: adding injection water with more than 5 times volume of the ingredients into an ultrasonic tank, putting the ingredients into the ultrasonic tank, performing ultrasonic oscillation for 8-10 minutes to perform first sterilization, and dissolving the ingredients into the injection water at the same time.
6. The preparation process of the ringer sodium bicarbonate injection according to claim 5, wherein the ultrasonic oscillation parameters are: the sound intensity is 1-5W/cm2The frequency is 30-40KHz, and the bottom of the ultrasonic tank generates 10.5 mu m amplitude; the ultrasonic output power is 45-55w, the ultrasonic wave is pulse wave, and the pulse width is 8-12 ms.
7. The preparation process of the ringer's sodium bicarbonate injection as claimed in claim 3, wherein the dilution tank is cut and sterilized with reflux water after the water for injection is replenished to the full amount; the reflux water shearing sterilization is specifically that the liquid in the blending tank is stirred and repeatedly rotated for 20-25 minutes.
8. The preparation process of the ringer's bicarbonate injection as claimed in claim 7, wherein the stirring tank is configured to rotate the liquid repeatedly, specifically, the stirring tank is configured to rotate the liquid clockwise for 1-3 minutes, the stirring tank is configured to rotate the liquid counterclockwise for 1-3 minutes, and the rotation direction is changed every 1-3 minutes to generate high shear force;
the stirring method for stirring the liquid in the diluting preparation tank to rotate repeatedly comprises the following steps: the water outlets of a plurality of first group of reflux pumps are arranged on the outer wall of the diluting preparation tank in a clockwise direction and from the tangential direction of the inner circle of the diluting preparation tank, the water inlets of the first group of reflux pumps are arranged at the bottom of the diluting preparation tank, and the arranged first group of reflux pumps complete the stirring of the clockwise rotation in the diluting preparation tank;
the water outlets of a plurality of second groups of reflux pumps are arranged on the outer wall of the diluting preparation tank in the anticlockwise direction and from the tangential direction of the inner circle of the diluting preparation tank, the water inlets of the second groups of reflux pumps are arranged at the bottom of the diluting preparation tank, and the arranged second groups of reflux pumps complete the stirring of the anticlockwise rotation in the diluting preparation tank;
the first set of reflux pump and the second set of reflux pump are alternately started repeatedly to make the liquid in the diluting preparation tank rotate repeatedly to generate high shearing force.
9. The preparation process of the ringer's bicarbonate injection as claimed in claim 8, wherein the water outlet parameters of the water outlet are: the flow rate is more than 50L/min, and the flow speed is 2-3.5 m/s.
10. The process for preparing ringer's bicarbonate injection according to claim 3, wherein the repeated rotary agitation of the liquid in the dilution tank is continued during the filling process; stirring the liquid in the diluting and blending tank for 1-3 minutes, then stirring the liquid in the diluting and blending tank for 1-3 minutes from the reverse direction, repeatedly rotating in the way, and converting the rotating direction every 1-3 minutes to generate high shearing force;
until the liquid medicine in the diluting preparation tank is canned.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US11925703B1 (en) | 2022-07-29 | 2024-03-12 | Xellia Pharmaceuticals Aps | Liquid composition comprising glucose |
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