Sterile nano-bubble irrigation solution for cleaning silicone oil filled in eyeballs

Abstract

The embodiment of the invention provides a sterile nanobubble lavage fluid for cleaning silicone oil filled in eyeballs, and is characterized in that the sterile nanobubble-containing lavage fluid comprises nanobubbles with the size range of 100-500nm; the concentration of the nanobubbles is not lower than 2.0 * 10 < 7 > / mL. According to the sterile nano-bubble-containing lavage fluid, no chemical agent is used in the process of preparing the nano-bubble-containing lavage fluid and using the nano-bubble-containing lavage fluid to clean silicone oil in eyes, the risk of silicone oil removal operation is greatly reduced, residual silicone oil in the eyes can be safely and effectively removed, the existence time of nano-bubbles is longer, the nano-bubbles are easy to store, the silicone oil removal rate is higher, and the application range of the nano-bubble-containing lavage fluid is widened. The nano-bubble perfusate does not need to be prepared on site, can be prepared into the perfusate firstly, is stored under proper conditions and can be transported for a long distance, so that the risk of bacterial contamination caused by on-site preparation is avoided.

Description

Technical Field

[0001] The present application relates to the field of nanobubble technology, and in particular to a sterile nanobubble irrigation solution for cleaning silicone oil filled in an eyeball. Background Art

[0002] The vitreous body, as one of the important refractive media of the human eye, is located between the lens and the retina. It has a capacity of about 4 mL, occupies about 80% of the eye's volume, contains about 99% water, and is closely attached to the macula, optic disc, and the anterior limiting membrane of the peripheral retina.

[0003] Vitreous-retina (VR) lesions are a large class of treatable ophthalmic diseases, including inflammatory diseases of the retina, vitreous hemorrhage, etc., which can cause varying degrees of vitreous opacity, liquefaction or physical collapse. If not treated correctly, it will seriously affect vision and even cause blindness. Vitreous substitutes are key accessories for VR surgery to treat retinal diseases. Currently, the vitreous substitutes used in clinical practice include gases, such as SF6, C3F8, C2F6, and air; liquids, such as silicone oils (SO), balanced salt solutions, perfluorocarbon liquids, and semifluoroalkanes. Silicone oil is one of the most commonly used vitreous substitutes in clinical practice.

[0004] At present, the silicone oil used in clinical practice is polydimethylsiloxane (PDMS) polymer, with a chemical formula of (-Si(CH3)2O-)n. It has been used for more than 60 years in complex VR surgery, especially complex retinal detachment surgery, and has irreplaceable advantages. Although it brings many beneficial surgical effects, long-term silicone oil retention will cause silicone oil-related complications, among which silicone oil emulsification (SOE) is one of the most important reasons. Therefore, thorough silicone oil removal in the early postoperative period is crucial.

[0005] Previous studies have found that cleaning with perfusion fluid containing micro-nano bubbles can improve the removal rate of silicone oil. However, micron bubbles only stay in water for a short time, only a few minutes. Therefore, perfusion fluid containing micro-nano bubbles must be used immediately after preparation at the surgical site, and the equipment that produces micro-nano bubbles must be disinfected before surgery to avoid contaminating the perfusion fluid. The device for preparing bubbles is difficult to match with existing ophthalmic surgical instruments. These difficulties have hindered the promotion and application of micro-nano bubble cleaning technology in surgery.

[0006] In summary, the commonly used gas-liquid exchange cleaning method cannot clean emulsified silicone oil, the risk of chemical-enhanced removal technology is high, and there is still a lack of safe, thorough and effective methods for removing intraocular silicone oil. The pain point of silicone oil residue still exists and needs to be solved urgently. Summary of the invention

[0007] In view of the fact that existing silicone oil removal methods still lack safety, the commonly used gas-liquid exchange cleaning cannot clean emulsified silicone oil, and the high risk of chemical agent enhanced removal technology, the present application provides a sterile nanobubble irrigation fluid for cleaning silicone oil filled in the eyeball, aiming to use nanobubble technology to clean silicone oil and develop a safe, effective and practical intraocular silicone oil cleaning technology.

[0008] According to the first aspect of the present application, there is provided a sterile nanobubble irrigation solution for cleaning silicone oil filled in an eyeball, comprising:

[0009] Nanobubbles with a size range of 100-500nm;

[0010] The concentration is not less than 2.0*10 7 / mL of nanobubbles.

[0011] Furthermore, the preparation method of the sterile nanobubble-containing lavage fluid includes: a contact pressure dissolution preparation method and a non-contact pressure permeation preparation method.

[0012] Furthermore, the contact pressure dissolution preparation method comprises:

[0013] The pressurized dissolved gas technology is used to dissolve sterile gas in the lavage fluid;

[0014] Use a stirrer or ultrasonic probe to evenly disperse the sterile gas in the lavage fluid;

[0015] Through the decompression process, the sterile gas is prompted to form nanobubbles to obtain stable nanobubble water;

[0016] The nanobubble water is disinfected and sterilized to obtain a sterile nanobubble-containing irrigation fluid.

[0017] Furthermore, the non-contact pressure permeation preparation method comprises:

[0018] The sterile gas is pressurized to a certain pressure, so that the gas passes through the semipermeable membrane or microporous material into the lavage fluid;

[0019] Through the decompression process, the sterile gas is prompted to form nanobubbles to obtain stable nanobubble water;

[0020] The nanobubble water is disinfected and sterilized to obtain a sterile nanobubble-containing irrigation fluid.

[0021] Furthermore, the sterile gas is one of sterile air, sterile oxygen, sterile nitrogen and sterile hydrogen.

[0022] Furthermore, the matrix of the irrigation fluid is physiological saline, balanced salt solution or other liquids suitable for ophthalmic surgery.

[0023] Furthermore, during the decompression process, the size and distribution of the generated nanobubbles can be adjusted by controlling the speed and method of decompression.

[0024] Furthermore, the sterile nanobubble lavage fluid needs to be filtered using a filtration device to remove any undissolved particles to ensure transparency and purity.

[0025] Furthermore, the sterile nanobubble lavage solution is packaged in a sterile container and sealed and stored until use.

[0026] Furthermore, constant temperature needs to be controlled during the decompression process to produce more uniform nanobubbles.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] 1. The present application proposes a sterile nanobubble perfusion solution, in which nanobubbles have a higher concentration than microbubbles, and no chemical agents are used in the process of preparing the nanobubble perfusion solution and using it to clean the silicone oil in the eye, which greatly reduces the risk of silicone oil removal surgery and can safely and effectively remove residual silicone oil in the eye.

[0029] 2. Nanobubbles exist longer, are easy to preserve, and have a higher silicone oil removal rate. Nanobubble perfusion fluid does not need to be prepared immediately before use. It can be prepared into perfusion fluid first, stored under suitable conditions, and can be transported over long distances to avoid the risk of contamination caused by on-site preparation.

[0030] It should be understood that the contents described in the Summary of the Invention are not intended to limit the key or important features of the embodiments of the present application, nor are they intended to limit the scope of the present application. Other features of the present application will become easily understood through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The above and other features, advantages and aspects of the embodiments of the present application will become more apparent with reference to the following detailed description in conjunction with the accompanying drawings. The accompanying drawings are used to better understand the present solution and do not constitute a limitation of the present application. In the accompanying drawings, the same or similar reference numerals represent the same or similar elements, among which:

[0032] Figure 1 A flow chart showing the preparation of sterile nanobubble irrigation fluid by the contact pressure dissolution preparation method according to an embodiment of the present application is shown;

[0033] Figure 2 A flow chart of preparing sterile nanobubble irrigation fluid by a non-contact pressurized permeation preparation method according to an embodiment of the present application is shown. DETAILED DESCRIPTION

[0034] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0035] In addition, the term "and / or" in this article is only a description of the association relationship between the associated objects, indicating that there can be three relationships. For example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. In addition, the character " / " in this article generally indicates that the associated objects before and after are in an "or" relationship.

[0036] Embodiment 1

[0037] The present application proposes a sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball, wherein the sterile nanobubble lavage solution comprises:

[0038] Nanobubbles with a size range of 100-500nm;

[0039] The concentration is not less than 2.0*10 7 / mL of nanobubbles.

[0040] Preferably, the preparation method of the sterile nanobubble-containing lavage fluid includes: a contact pressure dissolution preparation method and a non-contact pressure permeation preparation method.

[0041] Specifically, Figure 1 As shown, the contact pressure dissolution preparation method includes steps S31-S34:

[0042] Step S31: using pressurized gas dissolution technology to dissolve sterile nitrogen in the lavage fluid;

[0043] Step S32: using a stirrer or an ultrasonic probe to evenly disperse the sterile nitrogen in the lavage fluid;

[0044] Step S33: Promoting the sterile nitrogen to form nanobubbles through a decompression process to obtain stable nanobubble water;

[0045] Step S34: Finally, the nanobubble water is disinfected and sterilized to obtain a sterile nanobubble-containing irrigation solution.

[0046] Among them, the sterile gas in this embodiment is preferably sterile nitrogen, because it has stable chemical properties, is not easy to react with other substances, and is harmless to the human body. Of course, it can also be replaced by other sterile gases, such as sterile air, sterile oxygen, and sterile hydrogen. The specific gas selected depends on the specific needs and purposes of the experiment. The matrix of the irrigating fluid is physiological saline, balanced salt solution or other liquids without chemical agents and suitable for ophthalmic surgery.

[0047] In the contact pressure dissolution preparation method of the above embodiment, preferably, in step S31, sterile nitrogen is pressurized to about 2-5MPa (20-50 atmospheres) to ensure that the gas is fully dissolved in the irrigating fluid; wherein the pressure dissolution time is about 10-30 minutes to ensure that the gas is fully dissolved. During the decompression process of step S33, the pressure is gradually reduced to normal pressure (about 0.1MPa) to promote the formation of nanobubbles. The decompression rate should be controlled to reduce 0.1-0.5MPa per minute to avoid the bubbles from quickly merging into large bubbles. The decompression process should last for about 15-60 minutes, depending on the decompression rate and the desired bubble size distribution. After the pressure dissolution in step S32, use a stirrer or ultrasonic probe for about 5-15 minutes to ensure that the gas is evenly dispersed in the irrigating fluid.

[0048] More specifically, the contact pressure dissolution preparation method of the above embodiment includes the following steps:

[0049] (1) Preparation stage: Ensure that all equipment (such as pressurized container, stirrer, ultrasonic probe, etc.) has been disinfected and is in a sterile state, and connect sterile nitrogen to the pressurized container.

[0050] (2) Dissolution under pressure: Pour the irrigating fluid (such as saline) into a pressurized container, seal it, and pressurize it to 2-5 MPa. Maintain the pressure for 10-30 minutes to allow the nitrogen to fully dissolve in the irrigating fluid.

[0051] (3) Stirring or ultrasonic treatment: Turn on the stirrer or ultrasonic probe and treat the pressurized lavage fluid for 5-15 minutes to ensure that the gas is evenly dispersed.

[0052] (4) Decompression to form bubbles: gradually reduce the pressure to normal pressure, and control the decompression rate to 0.1-0.5 MPa per minute for 15-60 minutes to promote the formation of nanobubbles.

[0053] (5) Disinfection and sterilization: The irrigation fluid containing nanobubbles is disinfected and sterilized, such as using a filtration device to remove undissolved particles, and then sterilized using high-pressure steam sterilization or chemical sterilants.

[0054] (6) Package and store: The sterile nanobubble lavage solution is packaged in a sterile container and sealed until use. Under appropriate conditions (such as a cool, dry, and light-proof place), the lavage solution can be stored for several months.

[0055] like Figure 2 As shown, the non-contact pressure permeation preparation method includes steps S41-S43:

[0056] S41: pressurizing sterile hydrogen gas to a certain pressure, so that the gas passes through a semipermeable membrane or microporous material into the lavage fluid;

[0057] S42: Promoting the sterile hydrogen to form nanobubbles through a decompression process to obtain stable hydrogen nanobubble water;

[0058] S43: Disinfecting and sterilizing the nanobubble water to obtain a sterile nanobubble-containing irrigation solution.

[0059] Among them, the preferred sterile gas in this embodiment is sterile hydrogen. Hydrogen has a very small molecular size and is easy to penetrate the cell membrane, which helps to improve the stability and dispersibility of nanobubbles in physiological saline. Moreover, hydrogen easily forms stable nanobubbles during decompression, and the bubble size is uniform, which is conducive to improving the cleaning efficiency of silicone oil. Of course, it can also be replaced by other sterile gases, such as sterile air, sterile oxygen, and sterile nitrogen. The specific choice of which gas depends on the specific needs and purposes of the experiment. The matrix of the irrigating fluid is physiological saline, balanced salt solution or other chemical-free liquids suitable for ophthalmic surgery.

[0060] Preferably, in the non-contact pressurized permeation preparation method of the present embodiment, in the pressurization stage of step S41, the sterile hydrogen is pressurized to about 2-5MPa (megapascals), and this pressure range can ensure that the gas effectively penetrates the semipermeable membrane without causing damage to the membrane material. A polytetrafluoroethylene (PTFE) membrane or similar material with a pore size of 0.2-0.5 microns is selected to allow hydrogen to pass through while preventing bacteria and other particles from entering. In the decompression stage of step S42, the pressure is slowly reduced to normal pressure, and the decompression rate is controlled to reduce by about 0.1-0.5MPa per second to ensure the uniform generation of nanobubbles. During the entire preparation process, the liquid temperature is maintained between 20-25°C to maintain the stability of the gas solubility.

[0061] More specifically, the non-contact pressure dissolution preparation method of the above embodiment includes the following steps:

[0062] (1) Preparation stage:

[0063] Ensure that all equipment (including pressurizing devices, semipermeable membrane devices, decompression devices and liquid storage containers) are strictly disinfected and in a sterile state.

[0064] Connect sterile hydrogen to the pressurizing device and set the initial pressure value (eg, 2 MPa).

[0065] Prepare the base for the lavage fluid, such as normal saline, ensuring it is sterile and placed in a sealed container.

[0066] (2) Pressurized dissolution:

[0067] Start the pressurizing device, pressurize the sterile hydrogen to the set value, and maintain it for a period of time (such as 10-15 minutes) to allow the hydrogen to fully dissolve in the physiological saline.

[0068] (3) Gas permeation:

[0069] The pressurized saline solution is introduced into a device equipped with a semipermeable membrane through a pipe to ensure that the saline solution does not come into direct contact with the hydrogen gas, but rather that gas exchange is carried out through the semipermeable membrane.

[0070] Maintain this state for a period of time (eg, 30 minutes) to allow hydrogen to pass through the semipermeable membrane into the physiological saline.

[0071] (4) Decompression to generate nanobubbles:

[0072] Slowly open the pressure reducing device and gradually reduce the system pressure to normal pressure at the preset pressure reducing rate (such as reducing 0.1MPa per second).

[0073] During the decompression process, the generation of nanobubbles was observed and recorded, and the size and distribution of the bubbles could be optimized by adjusting the decompression rate.

[0074] (5) Disinfection, sterilization and packaging:

[0075] The generated nanobubble water is disinfected and sterilized again to ensure a sterile state.

[0076] Use a sterile filter to filter out any possible undissolved particles to ensure the clarity and purity of the lavage fluid.

[0077] The sterile nanobubble lavage solution was packaged in a sterile container and sealed until use.

[0078] Preferably, during the decompression process, the size and distribution of the generated nanobubbles are adjusted by controlling the speed and manner of decompression. Specifically,

[0079] The speed of decompression includes rapid decompression and slow decompression. Rapid decompression causes the gas to precipitate rapidly from the supersaturated solution to form a large number of large-sized microbubbles. Slowly reducing the pressure allows the gas to precipitate gradually, which may form smaller-sized nanobubbles. In this application, slow decompression is generally used to obtain a large number of small-sized nanobubbles.

[0080] The decompression methods include step decompression, linear decompression and pulse decompression. Among them, step decompression gradually reduces the pressure, and each step is maintained for a period of time to control the growth and merging of bubbles. In the linear decompression method, the pressure decreases at a constant rate, which can provide a more uniform bubble size distribution. Pulse decompression can control the generation and stabilization of bubbles through periodic rapid decompression and pressure recovery.

[0081] Preferably, temperature affects the solubility of gas in liquid. Higher temperature usually reduces the solubility of gas, thereby promoting the generation of bubbles. Therefore, temperature control is also an important factor during the decompression process. Maintaining a constant temperature during the decompression process can ensure the consistency and repeatability of bubble generation.

[0082] Preferably, the sterile nanobubble irrigation solution is packaged in a sterile container and sealed until use. Compared with micro-nano bubbles, nanobubble irrigation solution does not need to be prepared immediately before use, but can be prepared into irrigation solution first, stored under suitable conditions, and can be transported over long distances, avoiding the risk of contamination caused by on-site preparation.

[0083] According to the embodiments of the present application, the following technical effects are achieved:

[0084] 1. The present application proposes a sterile nanobubble perfusion solution, in which nanobubbles have a higher concentration than microbubbles, and no chemical agents are used in the process of preparing the nanobubble perfusion solution and using it to clean the silicone oil in the eye, which greatly reduces the risk of silicone oil removal surgery and can safely and effectively remove residual silicone oil in the eye.

[0085] 2. Nanobubbles exist longer, are easy to preserve, and have a higher silicone oil removal rate. Nanobubble perfusion fluid does not need to be prepared immediately before use. It can be prepared into perfusion fluid first, stored under suitable conditions, and can be transported over long distances to avoid the risk of contamination caused by on-site preparation.

[0086] Embodiment 2

[0087] This example proves through specific experiments that the high-concentration nanobubble perfusion solution has a better effect on removing silicone oil in the eye. The test is shown in the following table

[0088] In vitro cleaning experiment: Fresh ex vivo pig eyeballs were selected for vitrectomy, and the prepared oil / water mixture (emulsified silicone oil) was injected into it and left for 1 hour to prepare a silicone oil residual eye model (N=16). The eyes were randomly divided into control group: balanced salt solution irrigation group (BSS); Group A: micro-nano bubble-balanced salt solution irrigation group; Group B-FY: low-concentration nanobubble-slow-release balanced salt solution irrigation, using nanobubble-balanced salt solution prepared by pressurization technology, and reducing the concentration of nanobubbles by negative pressure before use for vitreous irrigation; Group B-WFY: high-concentration nanobubble-slow-release balanced salt solution irrigation, using the prepared high-concentration nanobubble-balanced salt solution, without negative pressure suction, and releasing the nanobubbles in the solution by gravity for vitreous irrigation. The average particle size of the bubbles in Group A was 30-50 microns, and the concentration was 2*10 5 ~9*10 5 The average bubble size of the B-FY group was 150-200 nm, and the concentration was 0.5-1*10 7 / mL; the average bubble size of the B-WFY group was 200-300nm, and the concentration range was 2.0*10 7 ~5*10 8 Pieces / mL.

[0089] The above experiments all used 500ml of irrigating fluid for silicone oil cleaning experiments, dissected pig eyeballs, made retina, posterior lens capsule, and anterior vitreous flat films, and semi-quantitatively recorded the amount of residual silicone oil, as shown in Tables 1-3. Among the four groups of experimental data, the B-WFY group with high concentration of nanobubbles had the least amount of retinal silicone oil residue. In terms of the residual silicone oil in the posterior lens capsule, each group had a good cleaning effect, among which the B-WFY group had statistical differences in residual area and residual number compared with other groups, and the silicone oil cleaning effect was the best. In previous silicone oil cleaning operations, we observed that the anterior vitreous body usually had more residual silicone oil droplets, so the observation of the amount of residual silicone oil in the anterior vitreous body had better clinical significance in various data. The experiment found that the silicone oil cleaning rate of the B-WFY group was statistically different from that of the control group, and there was no statistical difference compared with the A group and the B-FY group, but the silicone oil cleaning rate of the B-WFY group was the highest, reaching 99.80%.

[0090] Table 1

[0091]

[0092] Table 2

[0093]

[0094] Table 3

[0095]

[0096] According to the embodiments of the present application, the following technical effects are achieved:

[0097] The present application proposes a sterile nanobubble perfusion solution, which does not use any chemical agents in the process of preparing the nanobubble perfusion solution and using it to clean the silicone oil in the eye, greatly reducing the risk of silicone oil removal surgery, and can safely and effectively remove residual silicone oil in the eye. In addition, a higher concentration of nanobubble perfusion solution has a better effect on removing silicone oil in the eye.

[0098] In the technical solution of this application, the acquisition, storage and application of user personal information involved are in compliance with the provisions of relevant laws and regulations and do not violate public order and good morals.

[0099] It should be understood that the various forms of processes shown above can be used to reorder, add or delete steps. For example, the steps recorded in this application can be executed in parallel, sequentially or in different orders, as long as the expected results of the technical solution disclosed in this application can be achieved, and this document is not limited here.

[0100] The above specific implementations do not constitute a limitation on the protection scope of this application. It should be understood by those skilled in the art that various modifications, combinations, sub-combinations and substitutions can be made according to design requirements and other factors. Any modifications, equivalent substitutions and improvements made within the spirit and principles of this application should be included in the protection scope of this application.

Claims

1. A sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball, characterized in that: The sterile nanobubble-containing lavage fluid comprises: Nanobubbles with a size range of 100-500nm; The concentration is not less than 2.0*10 7 Nanobubbles per mL.

2. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to claim 1, characterized in that: The preparation method of the sterile nanobubble-containing lavage solution includes: a contact pressure dissolution preparation method and a non-contact pressure permeation preparation method.

3. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to claim 2, characterized in that: The contact pressure dissolution preparation method comprises: The pressurized dissolved gas technology is used to dissolve sterile gas in the lavage fluid; Use a stirrer or ultrasonic probe to evenly disperse the sterile gas in the lavage fluid; Through the decompression process, the sterile gas is prompted to form nanobubbles to obtain stable nanobubble water; The nanobubble water is disinfected and sterilized to obtain a sterile nanobubble-containing irrigation fluid.

4. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to claim 2, characterized in that: The non-contact pressure permeation preparation method comprises: The sterile gas is pressurized to a certain pressure, so that the gas passes through the semipermeable membrane or microporous material into the lavage fluid; Through the decompression process, the sterile gas is prompted to form nanobubbles to obtain stable nanobubble water; The nanobubble water is disinfected and sterilized to obtain a sterile nanobubble-containing irrigation fluid.

5. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to any one of claims 3 and 4, characterized in that: The sterile gas is one of sterile air, sterile oxygen, sterile nitrogen and sterile hydrogen.

6. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to any one of claims 3 and 4, characterized in that: The matrix of the irrigating fluid is physiological saline, balanced salt solution or other liquids without chemical agents and suitable for ophthalmic surgery.

7. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to any one of claims 3 and 4, characterized in that: During the decompression process, the size and distribution of the generated nanobubbles can be adjusted by controlling the speed and method of decompression.

8. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to claim 1, characterized in that: The sterile nanobubble lavage fluid needs to be filtered using a filtration device to remove any undissolved particles to ensure transparency and purity.

9. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to claim 8, characterized in that: The sterile nanobubble lavage solution is packaged in a sterile container and sealed and stored until use.

10. The sterile nanobubble lavage solution for cleaning silicone oil filled in the eyeball according to claim 7, characterized in that: Constant temperature needs to be controlled during the decompression process to produce more uniform nanobubbles.

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