Sterilized directly-prepared blowing-filling-sealing bottle-throwing eye washing liquid and preparation technology of sterile directly-prepared blowing-filling-sealing bottle-throwing eye washing liquid

Abstract

The invention relates to the technical field of intelligent manufacturing, in particular to sterile directly-prepared blowing-filling-sealing-time-throwing-bottle eye washing liquid and a preparation process thereof. The process comprises the following steps: S1, preparing materials; s2, concentrated preparation; s3, diluting and preparing; s4, sterilizing and filtering; and S5, through a BFS sterile filling process, injecting the to-be-filled eyedrops in the liquid storage tank while performing blow molding on the secondary throwing bottle by using sterilized sterile air, and sealing to obtain the secondary throwing bottle eyedrops. The eye washing liquid in the secondary throwing bottle is prepared from directly prepared eye washing liquid materials in a sterile manner; a multi-stage filtration sterilization and storage time threshold early warning discarding process is adopted in the preparation process, so that the sterile condition in the preparation process is ensured; and meanwhile, a BFS sterile filling process is adopted, so that blowing, filling and sealing are integrated, and sterility is realized.

Description

Technical Field

[0001] The present invention relates to the field of intelligent manufacturing technology, and in particular to a sterile direct-mix blow-fill-seal disposable bottle eyewash and a preparation process thereof. Background Art

[0002] To ensure sterility during the production of eyewash solutions, BFS technology is required. BFS (Blow-Fill-Seal) technology involves blow molding (suitable plastic particles are melted at high temperatures to form a tube embryo, which is then extruded into a container mold and blown into shape), filling, and sealing all within the same station on the same equipment. This technology effectively prevents contamination through the equipment's enclosed BFS system and airflow control system.

[0003] However, in the typical eyewash preparation process, although the BFS process can achieve aseptic filling, the eyewash preparation process before filling and the waiting period for filling only require a sterilization filtration of the liquid to be filled after the preparation is completed. Currently, it is difficult to ensure the sterility of the eyewash to be filled. If the filled eyewash cannot meet sterile conditions, the shelf life and sanitary conditions of the eyewash after filling cannot be guaranteed. The filling process often requires a certain waiting time, and during the filling process, the liquid in the liquid storage tank needs to be sucked out. At this time, the liquid storage tank is connected to the suction device, which may introduce bacteria into the liquid storage tank and easily breed bacteria in the liquid storage tank. Therefore, the common practice is to add auxiliary antibacterial ingredients such as preservatives to the eyewash to achieve the effect of bacterial inhibition. Summary of the Invention

[0004] The main purpose of the present invention is to provide a sterile direct-mix blow-fill-seal disposable bottle eyewash and its preparation process to solve the above technical problems.

[0005] To achieve the above-mentioned object, the present invention provides a preparation process for a sterile, directly formulated, blow-fill-seal disposable bottle eyewash solution, comprising the following steps: S1, material preparation: taking the volume Q of the dilution tank as the total liquid volume, prepare the water for injection and eyewash materials according to the preset ratio; S2, concentrated preparation: inject freshly prepared water for injection into the cleaned concentrated preparation tank, put the eyewash material into the concentrated preparation tank, and stir to obtain concentrated preparation solution; S3, dilution: The concentrated solution is filtered through a first hydrophilic PES membrane filter installed on a first water pipe between the concentrated solution tank and the dilution solution tank, and then directly injected into the cleaned dilution solution tank. Freshly prepared water for injection is then added to the dilution solution tank until the volume is full, and the solution is stirred to obtain the diluted solution. S4, sterilizing filtration: S41, filtering the diluted solution prepared in step S3 through a sterilizing filter assembly installed between the dilution tank and the liquid storage tank of the filling process, and then transferring the filtered solution to the liquid storage tank, wherein the temperature of the liquid storage tank is controlled at 50-60°C, and the sterilizing filter assembly includes at least two stages of second hydrophilic PES membrane filters; S42, obtaining the storage time of the liquid in the liquid storage tank. When the storage time is greater than a preset threshold time, discarding the diluted liquid in the liquid storage tank, flushing the liquid storage tank with the diluted liquid in step S3, and then refilling the diluted liquid; S43, when the preset time interval is reached, flushing the liquid storage tank and re-injecting the diluted liquid; S5, Blow Fill Seal: Through the BFS aseptic filling process, sterile air is used to blow the disposable bottle, and at the same time, the eye drops to be filled in the liquid storage tank are injected, and the disposable bottle of eye wash is obtained after sealing.

[0006] Preferably, the eyewash materials include: sodium hyaluronate: 0.01-0.05 g / L, vitamin B12: 0.0001-0.0008% g / L, sodium chloride: 0.1-1.0% g / L, boric acid or borax: 0.001-5.0% g / L, menthol: 0.001-0.005% g / L, propylene glycol 0.01-0.02% g / L, and taurine 0.1-0.2% g / L.

[0007] Preferably, the sterilizing filtration component has multiple second hydrophilic PES membrane filters; wherein, the filter membrane of the second hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane, and the filter membrane pore size of different second hydrophilic PES membrane filters is different. The filter membrane pore size of the second hydrophilic PES membrane filter located in front of the water flow is larger than the filter membrane pore size of the second hydrophilic PES membrane filter located at the rear, and the filter membrane pore size of the last second hydrophilic PES membrane filter is 0.18-0.25μm.

[0008] Preferably, the pore size of the filter membranes of the first hydrophilic PES membrane filter and the last second hydrophilic PES membrane filter is 0.22 μm.

[0009] Preferably, the volume q of the concentrated formulation tank is 25% of the volume Q of the diluted formulation tank.

[0010] Preferably, before step S1, the process further includes preparing water for injection by means of purified water multi-effect distillation.

[0011] Preferably, step S3 includes: S31, filtering the concentrated solution from step S2 through a first hydrophilic PES membrane filter installed on a first water delivery pipe between the concentrated solution tank and the diluted solution tank, and then directly injecting the filtered solution into the cleaned diluted solution tank; wherein the filter membrane of the first hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane with a pore size of 0.18-0.25 μm; S32, injecting freshly prepared injection water into the concentrated preparation tank at least three times to rinse the concentrated preparation tank and the first water delivery pipe, and the rinse water is filtered through the first hydrophilic PES membrane filter and then injected into the dilute preparation tank; S33, injecting freshly prepared water for injection into the dilution tank to the full amount, controlling the temperature to 50-60° C., and stirring for 20-40 minutes by non-contact magnetic stirring; S34, sampling and inspecting the diluted solution prepared in step S33; if the sampling and inspection meets the conditions, proceed to step S4; if not, discard the diluted solution.

[0012] Preferably, the step S5 further includes a light inspection step S6: placing the disposable eyewash bottle on a light inspection table and letting it stand, and then picking out unqualified products.

[0013] Preferably, step S6 further includes the step of packaging and labeling.

[0014] Preferably, the sampling inspection in step S34 includes detecting the osmotic pressure of the diluted solution, detecting the pH value of the diluted solution, and detecting whether the appearance and shape of the diluted solution meet the requirements.

[0015] The present invention also provides a disposable bottle eyewash solution, which is prepared using the preparation process of the aseptic direct-mixed blow-fill-seal disposable bottle eyewash solution as described in any of the above items.

[0016] The present invention has at least the following beneficial effects: (1) In the process of converting concentrated preparation to diluted preparation, sterilization is usually not performed in the prior art. In the present invention, the concentrated preparation tank and the first water pipe are flushed by injecting freshly prepared injection water into the concentrated preparation tank at least three times, and the flushing water is filtered through the hydrophilic PES membrane filter and then injected into the diluted preparation tank. In particular, the contamination that may be generated during the feeding stage is filtered out to prevent the growth of bacteria in the diluted preparation tank. (2) By installing a sterilizing filter assembly between the dilution tank and the liquid storage tank of the filling process, the dilution liquid is filtered through the sterilizing filter assembly and then transported to the liquid storage tank; a multi-stage sterilizing filter assembly is used to ensure the sterility of the eyewash solution in the liquid storage tank before filling; (3) When the storage time of the liquid in the liquid storage tank is greater than the preset threshold time, the diluted liquid in the liquid storage tank is discarded, and the diluted liquid in step S33 is used to flush the liquid storage tank, and then the diluted liquid is re-injected; since the BFS aseptic filling process may be discontinuous and the injection needs to be carried out continuously, usually enough liquid needs to be stored in the liquid storage tank before filling, resulting in the liquid in the liquid storage tank being stored for a long time, bacteria may breed; due to the connection of the liquid pipette, bacteria may also be brought in; by setting a threshold, the risk of bacterial growth is reduced; in addition, when the preset time interval is reached, the liquid storage tank is flushed and the diluted liquid is re-injected; double protection is provided to ensure the sterility of the diluted liquid in the liquid storage tank; (4) The sterilization filtration component comprises multiple second hydrophilic PES membrane filters; wherein the filter membrane of the second hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane, and the filter membrane pore sizes of different second hydrophilic PES membrane filters are different. The filter membrane pore size of the second hydrophilic PES membrane filter located in front of the water flow is larger than the filter membrane pore size of the second hydrophilic PES membrane filter located at the rear, and the filter membrane pore size of the last second hydrophilic PES membrane filter is 0.18-0.25 μm; multi-stage filtration enhances the sterilization effect; (5) The formula of the eyewash is: sodium hyaluronate: 0.01-0.05 g / L, vitamin B12: 0.0001-0.0008% g / L, sodium chloride: 0.1-1.0% g / L, boric acid or borax: 0.001-5.0% g / L, menthol: 0.001-0.005% g / L, propylene glycol 0.01-0.02% g / L, taurine 0.1-0.2% g / L; it has a dual repair mechanism, sodium hyaluronate repairs micro-damage to the corneal surface, and vitamin B12 improves the conduction function of the optic nerve; for long-lasting comfort, the osmotic pressure of the eyewash formula is adjusted to 260-340mOsm / kg, and the pH value of the eyewash formula is 6.5-7.8 to reduce irritation; antioxidant synergy, sodium hyaluronate scavenges free radicals, and vitamin B12 inhibits oxidative stress; No preservatives. The antibacterial properties of sodium hyaluronate and the stability of vitamin B12 avoid the need for preservatives. Sterilization conditions in the process are strictly controlled to minimize the possibility of bacterial growth. (6) BFS aseptic filling: Blow-fill-seal (blowing-filling-sealing) technology is completed within 12-14 seconds, and multiple processes are completed simultaneously, effectively ensuring the safety of product use; final product testing shows that it meets sterility requirements after 14 days of incubation; (7) Convenient and anti-pollution: The disposable eyewash bottle adopts an independent small packaging design, which is small and portable. Each bottle is independently sealed to avoid secondary contamination. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings are part of the present invention and are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention, but do not constitute an undue limitation of the present invention. Obviously, the drawings described below are only some embodiments. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without inventive effort. In the accompanying drawings: Figure 1 The present invention is a flowchart of a process for preparing a sterile, directly formulated, blow-fill-seal disposable bottle eyewash solution according to an embodiment of the present invention.

[0018] Figure 2 for Figure 1 Sub-flowchart of step S3 in .

[0019] Figure 3 for Figure 1 Sub-flowchart of step S4 in . DETAILED DESCRIPTION

[0020] The following is a clear and complete description of the technical problems solved by the embodiments of the present invention, the technical solutions adopted, and the technical effects achieved, in conjunction with the accompanying drawings and specific embodiments. Obviously, the embodiments described are only part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other equivalent or obviously modified embodiments obtained by ordinary technicians in this field without paying creative work fall within the scope of protection of the present invention. The embodiments of the present invention can be concretized in a variety of different ways as defined and covered in the claims.

[0021] It should be noted that in the following description, many specific details are given for ease of understanding, but it is obvious that the present invention can be implemented without these specific details.

[0022] It should be noted that, in the absence of clear limitations or conflicts, the various embodiments of the present invention and the technical features therein can be combined with each other to form a technical solution.

[0023] Please combine Figures 1 to 3 The present invention provides a preparation process for a sterile direct-mix blow-fill-seal disposable bottle eyewash solution, comprising steps S1 to S7.

[0024] Specifically, the process includes the following steps: S1, material preparation; S2, concentrated mixing; S3, diluted mixing; S4, sterilization and filtration; S5, blow-fill-seal; S6, light inspection; and S7, packaging and labeling.

[0025] The above preparation process is described in detail below in steps.

[0026] S1, prepare materials: take the volume Q of the dilution tank as the total liquid volume, and prepare water for injection and eyewash materials according to the preset ratio.

[0027] Preferably, the eyewash materials include: sodium hyaluronate: 0.01-0.05 g / L, vitamin B12: 0.0001-0.0008% g / L, sodium chloride: 0.1-1.0% g / L, boric acid or borax: 0.001-5.0% g / L, menthol: 0.001-0.005% g / L, propylene glycol 0.01-0.02% g / L, and taurine 0.1-0.2% g / L.

[0028] The above formula has the following advantages: a dual repair mechanism, with sodium hyaluronate repairing micro-damage to the corneal surface and vitamin B12 improving optic nerve conduction function; long-lasting comfort, with the osmotic pressure of the eyewash formula adjusted to 260-340mOsm / kg and the pH value of the eyewash formula at 6.5-7.8 to reduce irritation; antioxidant synergy, with sodium hyaluronate scavenging free radicals and vitamin B12 inhibiting oxidative stress; and no preservatives, eliminating the need for preservatives through the antibacterial properties of sodium hyaluronate and the stability of vitamin B12.

[0029] S2, concentrated preparation: inject freshly prepared injection water into the cleaned concentrated preparation tank, put the eyewash solution material into the concentrated preparation tank, and stir to obtain a concentrated solution; specifically, in a cleaned concentrated preparation tank with a volume of q, the temperature is controlled at 50-60°C, inject no more than the volume q of freshly prepared injection water, put the eyewash solution material in step S1 into the concentrated preparation tank, and stir for 20-40 minutes by contactless magnetic stirring under heat preservation conditions.

[0030] Preferably, the volume q of the concentrated formulation tank is 25% of the volume Q of the diluted formulation tank.

[0031] Preferably, before step S1, the process also includes preparing the water for injection by means of purified water multi-effect distillation. The process for preparing water for injection can be selected as needed. For example, in a specific example, the equipment of Ningbo Feichuang Pharmaceutical Equipment Co., Ltd., model: 3T-2RO, is used to prepare water for injection; specifically, the process water uses tap water as the water source, and is purified through multi-media filtration, activated carbon filtration, and reverse osmosis to prepare purified water for pretreatment of containers, pipes, pumps and other equipment that come into contact with eyewash solution; the water for injection is prepared by a multi-effect distillation machine and used for the final treatment of polyethylene plastic pipes, preparation of eyewash solution and articles, equipment and pipes; the purified water delivery pipeline is made of 304 stainless steel, and the injection water storage tank and delivery pipeline are both made of 316L stainless steel; the water quality of the process water is regularly monitored and can only be used after passing the inspection; the storage tank pipeline should be regularly cleaned (cleaning is required after a batch of production is completed) and disinfected.

[0032] Specifically, the standard for freshly prepared water for injection is that the storage time of water for injection should not exceed 2 hours. In the water for injection production workshop, if the water in the water for injection storage tank is not used for more than 2 hours, it should be discarded, and the storage tank and pipelines should be cleaned and disinfected before re-making water.

[0033] In this embodiment, the concentration tank is equipped with a magnetic stirrer, and the stirring paddle is driven by non-contact magnetic force to avoid the risk of contamination caused by mechanical seals.

[0034] S3, dilution, includes: filtering the concentrated solution through a first hydrophilic PES membrane filter installed on a first water pipe between the concentrated solution tank and the dilution solution tank, and then directly injecting it into the cleaned dilution solution tank. Then, freshly prepared water for injection is injected into the dilution solution tank to the full volume, and stirring is performed to obtain the dilution solution. Specifically, it may include: S31, filtering the concentrated solution from step S2 through a first hydrophilic PES membrane filter installed on a first water delivery pipe between the concentrated solution tank and the diluted solution tank, and then directly injecting the filtered solution into the cleaned diluted solution tank; wherein the filter membrane of the first hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane with a pore size of 0.18-0.25 μm; S32, injecting freshly prepared injection water into the concentrated preparation tank at least three times to rinse the concentrated preparation tank and the first water delivery pipe, and the rinse water is filtered through the first hydrophilic PES membrane filter and then injected into the dilute preparation tank; S33, injecting freshly prepared water for injection into the dilution tank to the full amount, controlling the temperature to 50-60° C., and stirring for 20-40 minutes by non-contact magnetic stirring; S34, sampling and inspecting the diluted solution prepared in step S33; if the sampling inspection conditions are met, the process proceeds to step S4; if not, the diluted solution is discarded. Specifically, the sampling inspection includes testing the osmotic pressure of the diluted solution, testing the pH value of the diluted solution, and testing the appearance of the diluted solution to see if it meets the conditions.

[0035] In a specific example, the first hydrophilic PES membrane filter adopts an SPSHR series pharmaceutical grade hydrophilic PES membrane filter, using a PES (hydrophilic polyethersulfone) filter membrane with a pore size of 0.22 μm.

[0036] In this embodiment, the dilution tank is equipped with a magnetic stirrer, and the stirring paddle is driven by non-contact magnetic force to avoid the risk of contamination caused by mechanical seals.

[0037] S4, sterilizing filtration: S41, filtering the diluted solution prepared in step S3 through a sterilizing filter assembly installed between the dilution tank and the liquid storage tank of the filling process, and then transferring the filtered solution to the liquid storage tank, wherein the temperature of the liquid storage tank is controlled at 50-60°C, and the sterilizing filter assembly includes at least two stages of second hydrophilic PES membrane filters; S42, obtaining the storage time of the liquid in the liquid storage tank. When the storage time is greater than a preset threshold time (which can be set according to actual conditions, such as temperature, production requirements, etc.), discard the diluted liquid in the liquid storage tank, and use the diluted liquid in step S3 to flush the liquid storage tank, and then re-inject the diluted liquid.

[0038] In this application, the diluted eyewash solution cannot be blown and filled directly. It needs to be sterilized in step S4 before it can be stored in the liquid storage tank for use. The liquid storage tank has a storage time limit. Liquid that exceeds the storage time threshold must be discarded and cannot be used for filling.

[0039] The step S4 further includes: S43, when a preset time interval (which can be set according to actual conditions, such as temperature, production requirements, etc.) is reached, the liquid storage tank is flushed and the diluted liquid is re-injected.

[0040] The liquid storage tank is cleaned at intervals of time, the liquid in the original liquid storage tank is discarded, and the diluted liquid is re-injected.

[0041] Preferably, the sterilizing filtration component has multiple second hydrophilic PES membrane filters; wherein, the filter membrane of the second hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane, and the filter membrane pore size of different second hydrophilic PES membrane filters is different. The filter membrane pore size of the second hydrophilic PES membrane filter located in front of the water flow is larger than the filter membrane pore size of the second hydrophilic PES membrane filter located at the rear, and the filter membrane pore size of the last second hydrophilic PES membrane filter is 0.18-0.25μm.

[0042] Preferably, the pore size of the filter membranes of the first hydrophilic PES membrane filter and the last second hydrophilic PES membrane filter is 0.22 μm.

[0043] S5, Blow Fill Seal: Through the BFS aseptic filling process, sterile air is used to blow the disposable bottle, and the eye drops to be filled in the liquid storage tank are injected, and the disposable bottle of eye wash is obtained after sealing.

[0044] Specifically, in one embodiment, the blow-fill-seal process includes: Collect materials and check the manufacturer, batch number, and quantity of polyethylene granules (LDPE Basel 3020D: highly transparent medical-grade polyethylene plastic raw material granules). Clean and disinfect the polyethylene granules as required when entering the clean area. Transport the polyethylene granules to the extruder screw through the automatic vacuum feeding system and set the temperature to the appropriate temperature for the current material being used. The extrusion screw heating temperature is 170-185°C, the holding time is 65 minutes, the pressure is 400.0-402.0 bar, and the speed is 85 rpm (in order to allow the material in the extrusion screw to fully melt, the heating zone needs to be kept warm for a certain period of time before the extruder can be started).

[0045] Make appropriate adjustments based on production specifications and room temperature factors, and wait for the material temperature to reach the set temperature for a period of time before starting the next step; adjust the extrusion motor to set speed 90.0rpm, extrusion pressure 398.0bar, hydraulic axis temperature 35.9℃, hydraulic pressure 116.4bar, quickly inject into the mold, cool the mold with 13-30℃ chilled water (2.8-4.8L / min), demould, and form a tube embryo (tube embryo inflation: sterilized, filtered, compressed air is blown out from the inside of the tube embryo, and the size of the blow is controlled by a proportional valve to keep the tube embryo full). During the tube embryo production process, observe the formed tube embryo, which should have no flash, uniform injection, uniform tube mouth thickness, and weigh. The average weight of each tube embryo should be 0.2-0.3g.

[0046] The filling module drives the filling needle down into the bottle, and the eyewash solution is injected into the bottle through the insulated infusion pipe (the pipe is covered with an insulation layer to reduce temperature fluctuations). If the temperature of the bottle mold exceeds the set value, the control module automatically increases the coolant flow or lowers the temperature until it reaches the set value, and then performs filling (quantitative filling of 10-18mL). After sealing, the bottle head mold remains closed, and the first cooling channel (bottle head mold) further reduces the bottle mouth temperature to prevent damage to the properties of the eyewash solution. Waste removal: The punching mechanism removes waste from vertically placed bottles to prevent the eyewash solution from flowing into the high-temperature bottle mouth area due to horizontal placement; waste is discharged through the blanking channel, and the baffle controls the blanking rhythm to prevent blockage; Vertical conveying: Finished bottles are delivered vertically by the conveyor belt, with bottle guards on both sides ensuring the stability of the bottles and reducing the risk of tipping.

[0047] Preferably, after step S5, the step S6 of light inspection is further included: the disposable eyewash bottles are placed on a light inspection table for a period of time, and unqualified products are sorted out. Specifically, in one embodiment, the light inspector removes the inspected products, places them on the light inspection table for a period of time, sorts out products that do not meet the appearance requirements, and finally places the qualified products on a conveyor belt to be sent to the packaging workshop for labeling and packaging.

[0048] Preferably, step S6 is followed by a packaging and labeling step. After the labeling is completed and the qualified cartons (batch number, date, expiration date) are labeled, the qualified cartons with the batch number printed on them are folded into a shape, sealed with tape, and neatly stacked for packing.

[0049] The present invention also provides a disposable bottle eyewash solution, which is prepared using the preparation process of the aseptic direct-mixed blow-fill-seal disposable bottle eyewash solution as described in any of the above items.

[0050] The present invention has at least the following beneficial effects: (1) In the process of converting concentrated preparation to diluted preparation, sterilization is usually not performed in the prior art. In the present invention, the concentrated preparation tank and the first water pipe are flushed by injecting freshly prepared injection water into the concentrated preparation tank at least three times, and the flushing water is filtered through the hydrophilic PES membrane filter and then injected into the diluted preparation tank. In particular, the contamination that may be generated during the feeding stage is filtered out to prevent the growth of bacteria in the diluted preparation tank. (2) By installing a sterilizing filter assembly between the dilution tank and the liquid storage tank of the filling process, the dilution liquid is filtered through the sterilizing filter assembly and then transported to the liquid storage tank; a multi-stage sterilizing filter assembly is used to ensure the sterility of the eyewash solution in the liquid storage tank before filling; (3) When the storage time of the liquid in the liquid storage tank is greater than the preset threshold time, the diluted liquid in the liquid storage tank is discarded, and the diluted liquid in step S33 is used to flush the liquid storage tank, and then the diluted liquid is re-injected; since the BFS aseptic filling process may be discontinuous and the injection needs to be carried out continuously, usually enough liquid needs to be stored in the liquid storage tank before filling. If the liquid in the liquid storage tank is stored for a long time, bacteria may grow. By setting a threshold, the risk of bacterial growth is reduced; in addition, when the preset time interval is reached, the liquid storage tank is flushed and the diluted liquid is re-injected; double protection is provided to ensure the sterility of the diluted liquid in the liquid storage tank; (4) The sterilization filtration component comprises multiple second hydrophilic PES membrane filters; wherein the filter membrane of the second hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane, and the filter membrane pore sizes of different second hydrophilic PES membrane filters are different. The filter membrane pore size of the second hydrophilic PES membrane filter located in front of the water flow is larger than the filter membrane pore size of the second hydrophilic PES membrane filter located at the rear, and the filter membrane pore size of the last second hydrophilic PES membrane filter is 0.18-0.25 μm; multi-stage filtration enhances the sterilization effect; (5) The formula of the eyewash is: sodium hyaluronate: 0.01-0.05 g / L, vitamin B12: 0.0001-0.0008% g / L, sodium chloride: 0.1-1.0% g / L, boric acid or borax: 0.001-5.0% g / L, menthol: 0.001-0.005% g / L, propylene glycol 0.01-0.02% g / L, taurine 0.1-0.2% g / L; it has a dual repair mechanism, sodium hyaluronate repairs micro-damage to the corneal surface, and vitamin B12 improves the conduction function of the optic nerve; for long-lasting comfort, the osmotic pressure of the eyewash formula is adjusted to 260-340mOsm / kg, and the pH value of the eyewash formula is 6.5-7.8 to reduce irritation; antioxidant synergy, sodium hyaluronate scavenges free radicals, and vitamin B12 inhibits oxidative stress; No preservatives. The antibacterial properties of sodium hyaluronate and the stability of vitamin B12 avoid the need for preservatives. Sterilization conditions in the process are strictly controlled to minimize the possibility of bacterial growth. (6) BFS aseptic filling: Blow-fill-seal (blowing-filling-sealing) technology is completed within 12-14 seconds, and multiple processes are completed simultaneously, effectively ensuring the safety of product use; the eyewash produced by the technical solution of the present invention is subjected to sterility testing, and the sterility test results of the eyewash meet the sterility requirements; (7) Convenient and anti-pollution: The disposable eyewash bottle adopts an independent small packaging design, which is small and portable. Each bottle is independently sealed to avoid secondary contamination.

[0051] The embodiments described above are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention, and should all be included in the scope of protection of the present invention.

Claims

1. A process for preparing a sterile, direct-mix blow-fill-seal disposable bottle eyewash solution, characterized in that: Including steps: S1, material preparation: taking the volume Q of the dilution tank as the total liquid volume, prepare the water for injection and eyewash materials according to the preset ratio; S2, concentrated preparation: In the cleaned concentrated preparation tank, inject freshly prepared injection water, put the eyewash material into the concentrated preparation tank, and stir to obtain concentrated preparation liquid; S3, dilution: The concentrated solution is filtered through a first hydrophilic PES membrane filter installed on a first water pipe between the concentrated solution tank and the dilution solution tank, and then directly injected into the cleaned dilution solution tank. Freshly prepared water for injection is then added to the dilution solution tank until the volume is full, and the solution is stirred to obtain the diluted solution. S4, sterilizing filtration: S41, filtering the diluted solution prepared in step S3 through a sterilizing filter assembly installed between the dilution tank and the liquid storage tank of the filling process, and then transferring the filtered solution to the liquid storage tank. The temperature of the liquid storage tank is controlled at 50-60°C. The sterilizing filter assembly includes at least two stages of second hydrophilic PES membrane filters. S42, obtaining the storage time of the liquid in the liquid storage tank. When the storage time is greater than a preset threshold time, discarding the diluted liquid in the liquid storage tank, flushing the liquid storage tank with the diluted liquid in step S3, and then refilling the diluted liquid; S43, when the preset time interval is reached, flushing the liquid storage tank and re-injecting the diluted liquid; S5, Blow Fill Seal: Through the BFS aseptic filling process, sterile air is used to blow the disposable bottle, and at the same time, the eye drops to be filled in the liquid storage tank are injected, and the disposable bottle of eye wash is obtained after sealing.

2. The preparation process according to claim 1, characterized in that Eyewash ingredients include: sodium hyaluronate: 0.01-0.05 g / L, vitamin B12: 0.0001-0.0008% g / L, sodium chloride: 0.1-1.0% g / L, boric acid or borax: 0.001-5.0% g / L, menthol: 0.001-0.005% g / L, propylene glycol 0.01-0.02% g / L, taurine 0.1-0.2% g / L.

3. The preparation process according to claim 1, characterized in that The sterilizing filtration component comprises multiple second hydrophilic PES membrane filters; wherein, the filter membrane of the second hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane, and different second hydrophilic PES membrane filters have different filter membrane pore sizes. The filter membrane pore size of the second hydrophilic PES membrane filter located in front of the water flow is larger than the filter membrane pore size of the second hydrophilic PES membrane filter located at the rear, and the filter membrane pore size of the last second hydrophilic PES membrane filter is 0.18-0.25 μm.

4. The preparation process according to claim 3, characterized in that The pore size of the first hydrophilic PES membrane filter and the last second hydrophilic PES membrane filter is 0.22 μm.

5. The preparation process according to claim 1, characterized in that: The volume q of the concentrated preparation tank is 25% of the volume Q of the diluted preparation tank.

6. The preparation process according to claim 1, characterized in that Before step S1, the method further includes preparing water for injection by means of purified water multi-effect distillation.

7. The preparation process according to claim 1, characterized in that The step S3 comprises: S31, filtering the concentrated solution from step S2 through a first hydrophilic PES membrane filter installed on a first water delivery pipe between the concentrated solution tank and the diluted solution tank, and then directly injecting the filtered solution into the cleaned diluted solution tank; wherein the filter membrane of the first hydrophilic PES membrane filter is a hydrophilic polyethersulfone filter membrane with a pore size of 0.18-0.25 μm; S32, injecting freshly prepared injection water into the concentrated preparation tank at least three times to rinse the concentrated preparation tank and the first water delivery pipe, and the rinse water is filtered through the first hydrophilic PES membrane filter and then injected into the dilute preparation tank; S33, injecting freshly prepared water for injection into the dilution tank to the full amount, controlling the temperature to 50-60° C., and stirring for 20-40 minutes by non-contact magnetic stirring; S34, sampling and inspecting the diluted solution prepared in step S33; if the sampling and inspection meets the conditions, proceed to step S4; if not, discard the diluted solution.

8. The preparation process according to claim 1, characterized in that After step S5, the step S6 of light inspection is also included: the disposable eyewash bottle is placed on a light inspection table for a while, and unqualified products are selected; after step S6, the step S6 also includes the step of packaging and labeling.

9. The preparation process according to claim 7, characterized in that: The sampling inspection in step S34 includes detecting the osmotic pressure of the diluted solution, detecting the pH value of the diluted solution, and detecting whether the appearance of the diluted solution meets the requirements.

10. A disposable bottle eyewash, characterized in that: The eyewash is prepared by the preparation process of the sterile direct-prepared blow-fill-seal disposable bottle according to any one of claims 1 to 9.

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