Totally enclosed high barrier aseptic multi-dose delivery system

Abstract

The present application relates to the field of medical packaging, in particular to a full-closed high-barrier sterile multi-dose delivery system, comprising a bottle body, a valve body, a dropper, a flexible diaphragm valve and a dispenser; the bottle body is a multi-layer composite structure; a liquid inlet hole, a backflow groove, a backflow hole and an isolation bin are arranged on the valve body; a bacteria-resistant filter membrane is integrally packaged in the valve body; a one-way valve is in conical surface sealing with the valve body; the flexible diaphragm valve blocks the gas collection groove and leaves a limited pressure deformation gap with the valve body; a reset spring is sleeved between the valve body and the flexible diaphragm valve; the dropper forms a liquid inlet gap with the flexible diaphragm valve, and a droplet hole is arranged on the dropper; the droplet hole comprises a small-diameter straight section and a tapered section, and the flexible diaphragm valve blocks the small-diameter straight section; a flow guide ring gap is left between the dispenser and the valve body, a flow guide ring gap is formed between the dispenser and the dropper, a flow guide block is arranged in the flow guide ring gap, and a flow guide groove is arranged on the dispenser. It can not only reduce the volatilization of the liquid medicine, but also prevent the backflow of the residual liquid due to gravity.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical packaging, and more particularly to a fully enclosed, high-barrier, sterile, multi-dose delivery system. Background Technology

[0002] In daily life, dropper bottles are needed for precise medication administration, the most common being eye dropper bottles. Currently, dropper bottles on the market have issues such as medication contamination from the air flowing back into the bottle after the medication is dispensed, and medication residue remaining on the dropper head.

[0003] To address this issue, a new type of sterile drip bottle with an air-blocking mechanism (authorization number CN118415813B) has emerged on the market. After dripping, the conical valve core on the flexible diaphragm valve, under the action of a return spring, seals the conical drip orifice in the nozzle, preventing external air and residual medication from entering and contaminating the orifice. Furthermore, during the backflow of residual medication, the drainage channel is directly connected to the outside air, ensuring good return performance of the bottle. However, in actual use, it has been found that the drip head of the sterile drip bottle, sealed in plains areas, leaks during high-altitude areas and air transport.

[0004] To address this issue, a new aseptic delivery system for ophthalmic drugs, with publication number CN121606437A, has emerged on the market. This system features a conical plug on the bottle cap that continuously seals the drip hole. Even when the medication inside the bottle is under high pressure, pushing against the flexible diaphragm valve and preventing the valve core from blocking the drip hole, the medication cannot leak out once it enters the drip hole, achieving a good sealing effect. A pressure-limiting deformation gap is maintained between the valve core of the flexible diaphragm valve and the hollow spring column, ensuring that no matter how much force is applied... The pressure bottle can only dispense a fixed amount of liquid, ensuring that the liquid drips out as droplets rather than spraying out. A guide block in the drainage hole, resting against the drip column, diffuses small droplets into larger ones, reducing the impact on the eyes and minimizing user discomfort. A large gap between the nozzle and the dispenser improves the return flow of residual liquid and external air, as well as the airflow between the isolation tank and the external environment, allowing residual liquid in the isolation tank to evaporate more quickly. Although the leakage problem has been solved, the following issues still exist in actual use: 1. Most bottles have a single-layer structure. When the liquid medicine in the bottle contains volatile drugs such as borneol, the volatile drugs will not only permeate outward through the bottle but also evaporate through the antibacterial filter membrane and the return air channel; 2. When the liquid medicine in the bottle has low viscosity and is used frequently in a short period of time, the residual amount of liquid medicine will be too large to evaporate in time. If the bottle is inverted, due to gravity, the residual liquid medicine can easily flow back from the large gap between the nozzle and the dispenser onto the drip column, contaminating the liquid medicine dripping from the drip hole; 3. The drip hole in the existing technology has an inverted conical structure, which, together with the pressure-limiting deformation gap between the valve core and the hollow spring column, achieves drop-by-drop dispensing. However, the formation of a single drop volume is highly dependent on the surface tension and viscosity of the liquid medicine itself, as well as the user's extrusion angle. 4. The lack of geometrically mandated specifications for the degree and rate of dispensing leads to extremely poor accuracy in the amount of liquid dispensed; 5. When the antibacterial filter membrane is assembled in the valve body, a gap will form between the antibacterial filter membrane and the valve body when a pressure difference occurs inside and outside the bottle, resulting in poor sealing; 6. Some drug solutions contain viscous water-soluble polymers such as polyethylene glycol or polyvinyl alcohol, resulting in high viscosity and poor fluidity. The highly viscous drug solution flows back into the isolation tank for evaporation. After the water evaporates, the viscous water-soluble polymers will form a film in the isolation tank. When using the five-row series isolation tank structure in the gas-barrier sterile drip bottle with residual liquid external treatment (authorization announcement number: CN118415813B), the vertical width of the top four rows of isolation tanks is relatively small. When a film forms in the isolation tank, it can easily cause blockage in the small space of the isolation tank.

[0005] In existing technologies, integrating the antibacterial filter membrane with the valve body solves the problem of assembly gaps between the membrane and the valve body. A one-way diaphragm on the valve body seals the membrane, preventing contact between the medication and the membrane, thus protecting the membrane without hindering gas return. The one-way diaphragm also blocks the gas return channel, preventing drug evaporation. However, when the one-way diaphragm is fitted to the valve body, the two are planar and highly susceptible to temperature and manufacturing precision issues. In practical use, the small size of the diaphragm leads to poor manufacturing and assembly quality with the valve body, making sealing failure common and severely limiting overall product quality. Furthermore, this valve body fails to address issues such as drug evaporation and residual liquid backflow contaminating the medication after passing through the bottle. Summary of the Invention

[0006] The purpose of this invention is to provide a fully enclosed, high-barrier, sterile, multi-dose delivery system that can reduce the volatilization of volatile components in the drug solution, prevent residual drug solution from backflowing and contaminating the freshly dropped solution due to inversion, and improve the droplet accuracy and sealing effect between the one-way valve and the valve body.

[0007] To achieve the above objectives, the technical solution adopted by this invention is: a fully enclosed, high-barrier, sterile, multi-dose delivery system, comprising: a bottle body, a valve body, a dropper, a flexible diaphragm valve, and a dispenser; the bottle body is a multi-layer composite structure with a barrier layer; the valve body extends into the bottle body and is sealed to fit the bottle body, and is provided with an inlet hole and a connected reflux groove, a vent hole, and an isolation chamber on the valve body, and has rounded corners between the top wall and the outer wall of the valve body; a hollow spring column is integrally formed with the valve body and integrally encapsulated with a barrier layer. The system includes: a bacteriostatic filter membrane with a cavity; a one-way valve comprising an integrally formed positioning ring, elastic connecting wires, and a conical plug sleeve, wherein the elastic connecting wires are evenly distributed circumferentially between the positioning ring and the conical plug sleeve; the positioning ring being sealed and fixed in the valve body; and the inner conical hole of the conical plug sleeve forming a conical surface seal with the hollow spring column; a flexible diaphragm valve, sealed and fixed on the valve body, with a valve core having a conical seal extending from the flexible diaphragm valve, and a pressure-limiting deformation gap between the valve core and the hollow spring column; and a return spring, coaxially fitted onto the hollow spring column and the valve body. The valve core is mounted on the valve body; the nozzle is sealed and fixed to the valve body, and forms an inlet gap with the flexible diaphragm valve that communicates with the inlet hole. Several positioning blocks are evenly distributed circumferentially on the outer wall of the nozzle, and a dripping hole is provided in the dripping column of the nozzle. The dripping hole includes: an inlet groove, a small-diameter straight section, and a conical section connected axially in sequence. A sealing ring protrudes from the wall of the inlet groove, and the conical seal of the valve core extends into the inlet groove and abuts against the sealing ring, sealing the small-diameter straight section. The distributor, along with the valve body and the nozzle, positions... The bottle mouth of the block and the bottle body are sealed together. A flow guide ring gap is left between the rounded corners of the distributor and the valve body. A flow guide hole with several flow guide blocks is set in the flow guide column of the distributor. The drip column is located in the flow guide hole and forms a flow guide ring gap between the flow guide hole and the flow guide hole. The flow guide block abuts against the drip column. The distributor is sealed against the nozzle. Several flow guide grooves connected to the flow guide ring gap and the flow guide ring gap are arranged circumferentially on the distributor. Each flow guide block is located at the inlet end of a flow guide groove. The width of the flow guide block is smaller than the width of the flow guide groove.

[0008] Furthermore, in the aforementioned fully enclosed high-barrier sterile multi-dose delivery system, the bottle body is co-extruded from three layers: an inner layer, a barrier layer, and an outer layer. The thickness of the bottle body is 0.3–0.4 mm. The inner layer is made of any one of LDPE, HDPE, PP, COC, and COP. The barrier layer is made of any one of PA, EVOH, COC, and COP. The outer layer is made of any one of HDPE, PP, and PET.

[0009] Furthermore, in the aforementioned fully enclosed high-barrier sterile multi-dose delivery system, the diameter of the small-diameter straight section in the dropper hole is 0.2±0.02mm, and the length of the small-diameter straight section is 0.2~2mm. When the length of the small-diameter straight section is <1mm, a large-diameter straight section is extended on the large-diameter end of the conical section.

[0010] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, three drainage grooves are evenly distributed around the circumference of the dispenser, with a width of 0.8±0.02mm. Three drainage blocks are evenly distributed around the circumference of the drainage holes, with the end wall width of the drainage block abutting against the drip column being 0.28±0.02mm. The centerline of the drainage block is aligned with the centerline of the corresponding drainage groove. An annular groove communicating with the drainage grooves is provided on the inner wall of the dispenser.

[0011] Furthermore, in the aforementioned fully enclosed high-barrier sterile multi-dose delivery system, the drainage block is an isosceles trapezoid, and the large bottom end of the drainage block is connected to the inlet end of the drainage channel by a smooth arc transition. An arc-shaped groove that fits the drip column is provided on the end wall of the drainage block.

[0012] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, the isolation chamber is composed of five rows of isolation slots arranged in series from top to bottom. A longitudinal barrier rib is provided on the valve body, blocking the beginning and end of all isolation slots. A reflux trough and a return air hole are both located on the barrier ribs. The beginning of the uppermost isolation slot is connected to the reflux trough, and the end of the lowermost isolation slot is connected to the return air hole. A barrier plate is provided between two adjacent isolation slots. A ventilation slot is provided on each barrier plate. The ventilation slot on the barrier plate connected to the uppermost isolation slot is located at the end, and the ventilation slot on the barrier plate connected to the lowermost isolation slot is located at the beginning. The ventilation slots on adjacent barrier plates are staggered.

[0013] Furthermore, in the aforementioned fully enclosed high-barrier sterile multi-dose delivery system, several supporting ribs are arranged circumferentially in each isolation tank, and an air passage groove is provided on the side wall of the supporting ribs.

[0014] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, except for the bottommost isolation slot, the vertical widths of the other isolation slots are the same, with the bottommost isolation slot having a greater vertical width than the other isolation slots.

[0015] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, the isolation chamber consists of twelve isolation slots connected in series in three rows and four columns. Barrier plates are installed between adjacent rows of isolation slots, and barrier ribs are installed between adjacent columns of isolation slots. Return channels and vent holes are respectively located on two symmetrical barrier ribs. The isolation slots in the first row of the first column are directly connected to the return channels, and the isolation slots in the second row of the third column are directly connected to the vent holes. Ventilation slots are provided on both barrier plates in the first column. The barrier ribs between the first and second columns are connected to the isolation slots in the third row of the first column and the third row of the second column. The second column has ventilation slots on both baffle plates. Ventilation slots are also provided on the baffle ribs with return air holes, connecting to the isolation slots of the first row of the second and third columns. Ventilation slots are also provided on the baffle ribs between the third and fourth columns, connecting to the isolation slots of the first row of the third and fourth columns. Ventilation slots are also provided on both baffle plates in the fourth column. Ventilation slots are also provided on the baffle ribs between the third and fourth columns, connecting to the isolation slots of the third row of the fourth column. Ventilation slots are also provided on the baffle plate located between the second and third rows of isolation slots in the third column.

[0016] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, the ventilation slots on the two barrier plates in the same column are staggered.

[0017] Furthermore, in the aforementioned fully enclosed high-barrier sterile multi-dose delivery system, a gas collection groove and an installation groove are provided on the valve body, which are connected to the reflux groove and the reflux port. A hollow spring column is arranged in the gas collection groove, and the lower end of the hollow spring column extends downward into the installation groove. The outer wall of the hollow spring column extending into the installation groove is an inverted conical wall. The height of the lower end of the hollow spring column extending into the installation groove is greater than the height of the inner conical hole of the conical plug sleeve. The slope of the conical surface of the inverted conical wall is the same as the slope of the conical surface of the inner conical hole. The diameter of the small diameter end of the lower end of the hollow spring column is greater than the diameter of the small diameter end of the inner conical hole and smaller than the diameter of the large diameter end of the inner conical hole.

[0018] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, the elastic connecting wire is arc-shaped, with its two ends respectively disposed on the inner side wall of the positioning ring and the outer side wall of the conical plug sleeve, and the center of the elastic connecting wire being concentric with the center of the conical plug sleeve and the positioning ring.

[0019] Furthermore, in the aforementioned fully enclosed high-barrier sterile multi-dose delivery system, a stop ring is protruding from the outer wall of the positioning ring, an annular retaining ring with an outer diameter larger than the positioning ring is integrally formed at the lower end of the positioning ring, an annular inner groove is provided on the inner wall of the mounting groove, the positioning ring abuts against the top inner wall of the mounting groove, the stop ring is inserted into the annular inner groove and is interference-fitted with the annular inner groove, and the annular retaining ring abuts against the opening edge of the mounting groove.

[0020] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, a conical sealing hole is coaxially arranged on the droplet column. When the length of the small-diameter straight section is <1mm, the conical sealing hole is connected to the large-diameter straight section. When the length of the small-diameter straight section is 1-2mm, the conical sealing hole is connected to the conical section. The cone angle of the conical sealing hole is 36°, and the diameter of the large-diameter end of the conical sealing hole is 0.76±0.02mm. A bottle cap is fitted onto the dispenser. Several perforated holes are evenly distributed around the top wall of the bottle cap. A conical plug is provided at the center of the bottle cap, which can be inserted into the conical sealing hole to form a conical surface seal with the conical sealing hole.

[0021] Furthermore, in the aforementioned fully enclosed, high-barrier, sterile, multi-dose delivery system, the bottle cap includes: an integrally formed cap body, a tear ring, and a limiting ring. Hollow holes and conical plugs are provided on the cap body. Tear marks are provided between the cap body, the tear ring, and the limiting ring. A retaining ring that engages with the bottom of the dispenser is provided at the bottom of the limiting ring. A shoulder is provided on the outer wall of the dispenser. An outer protruding ring is provided on the outer wall of the shoulder. The outer protruding ring and the outer wall of the shoulder are smoothly connected by an arc-shaped guide surface. An annular connecting groove that abuts against the shoulder is provided on the inner wall of the cap body. An inner protruding ring that engages with the outer protruding ring is provided on the inner wall of the annular connecting groove.

[0022] The advantages of this invention are as follows: 1. The bottle body is formed by co-extrusion of an inner layer, a barrier layer and an outer layer to form a multi-layer composite structure, thereby reducing the volatilization of volatile components in the liquid medicine. In addition, a one-way valve is set at the bottom of the valve body to seal and block the cavity of the hollow spring column, so that the volatile components in the liquid medicine cannot volatilize out through the return channel of the recovered air and the residual liquid medicine. The two barrier schemes work together to greatly reduce the volatilization of volatile components in the liquid medicine, thereby effectively protecting the effective ingredients in the liquid medicine.

[0023] 2. The inner conical hole of the conical plug sleeve in the one-way valve abuts against the lower end of the hollow spring column and fits against the inverted conical wall to form a conical seal. Compared with the planar seal structure formed by the one-way diaphragm and the hollow spring column in the prior art, it has automatic centering and self-locking performance, and the overall sealing performance is better. This greatly reduces the defect rate and improves the yield and assembly efficiency during the assembly process. Moreover, because the conical seal structure between the one-way valve and the hollow spring column has good sealing performance, it can prevent drug leakage. Therefore, the antibacterial filter membrane is no longer limited to hydrophobicity, and hydrophilic or amphiphilic antibacterial filter membranes can also be used, making the application scope of the fully enclosed high-barrier sterile multi-dose delivery system of the present invention wider.

[0024] 3. The lengths of the small-diameter straight section and the conical section in the dripping orifice are controlled according to the different kinematic viscosities of the liquid medicine. This controls the throttling resistance, pressure diffusion, and speed reduction when the liquid medicine flows out. Then, in conjunction with the pressure-limiting deformation gap between the valve core and the hollow spring column on the flexible diaphragm valve, the liquid medicine is dripped drop by drop and the dripping accuracy of each drop is precisely controlled.

[0025] 4. By evenly distributing several positioning blocks around the circumference of the dropper to divide and reduce the space of the flow guide ring gap (corresponding to the annular gap between the dispenser and the dropper in a sterile delivery system for ophthalmic drugs that can resist pressure difference and prevent leakage, as disclosed in CN121606437A), the space of the flow guide ring gap is reduced, and the amount of residual drug solution that can be stored is reduced. With the reduction of the amount of residual drug solution remaining in the flow guide ring gap, the residual drug solution is less likely to backflow under its own tension and viscosity. Even if some residual drug solution happens to backflow through the drainage channel, the residual drug solution will adhere to the drainage channel when flowing through the drainage channel to form a liquid film, reducing the backflow rate. Moreover, the drainage block at the inlet end of the drainage channel also plays a blocking role, further preventing the residual drug solution from backflowing into the drainage ring gap and affecting the droplet column.

[0026] 5. Select valve bodies with different isolation chamber structures based on whether the liquid contains viscous, water-soluble polymers such as polyethylene glycol or polyvinyl alcohol. When the liquid does not contain highly viscous, water-soluble polymers, use an isolation chamber consisting of five rows of isolation channels. The large number of isolation channels reduces the liquid film thickness and increases the evaporation rate of the residual liquid. When the liquid contains highly viscous, water-soluble polymers, use an isolation chamber consisting of twelve isolation channels in three rows and four columns. By reducing the number of isolation channels, the vertical width of each isolation channel is increased to avoid blockage of the isolation channels due to film formation and ensure the return efficiency of the residual liquid. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the structure of the fully enclosed, high-barrier, sterile, multi-dose delivery system described in this invention.

[0028] Figure 2 yes Figure 1 A cross-sectional structural diagram.

[0029] Figure 3 yes Figure 2 A schematic diagram of the structure after removing the bottle body and cap.

[0030] Figure 4 yes Figure 1 A cross-sectional view of the bottle cap.

[0031] Figure 5 This is a schematic diagram of the valve body from one side, showing an isolation chamber consisting of five rows of upper and lower isolation slots.

[0032] Figure 6 yes Figure 5 A schematic diagram of the structure on the other side.

[0033] Figure 7 yes Figure 5 and Figure 6 The diagram shows a cross-sectional view of the valve body.

[0034] Figure 8 yes Figure 5 and Figure 6 The diagram shows the structure of the valve body after it has been unfolded.

[0035] Figure 9 This is a schematic diagram of the valve body from one side, showing an isolation chamber consisting of twelve isolation slots arranged in three rows and four columns.

[0036] Figure 10 yes Figure 9 A schematic diagram of the structure on the other side.

[0037] Figure 11 yes Figure 9 and Figure 10 The diagram shows the structure of the valve body after it has been unfolded.

[0038] Figure 12 Figure 2 A schematic diagram of the structure of a one-way valve.

[0039] Figure 13 yes Figure 12 A schematic diagram of the structure from a top-down view.

[0040] Figure 14 yes Figure 12 A cross-sectional structural diagram.

[0041] Figure 15 yes Figure 2 A schematic diagram of the structure of a flexible diaphragm valve.

[0042] Figure 16 yes Figure 15 A cross-sectional structural diagram.

[0043] Figure 17 yes Figure 2 A schematic diagram of the structure of a dropper with a straight section of less than 1 mm in diameter.

[0044] Figure 18 yes Figure 17 A structural diagram viewed from below.

[0045] Figure 19 yes Figure 17 A cross-sectional structural diagram.

[0046] Figure 20 yes Figure 2 A schematic diagram of the structure of a dropper with a straight section of 1-2 mm in diameter.

[0047] Figure 21 yes Figure 2 A schematic diagram of the distributor.

[0048] Figure 22 yes Figure 21 A top-down structural diagram.

[0049] Figure 23 yes Figure 21 A structural diagram viewed from below.

[0050] Figure 24 yes Figure 21 A cross-sectional structural diagram.

[0051] Figure 25 This is a chromatogram obtained from the determination of borneol content using gas chromatography with internal standard method. Among them, Serial number A is SC260429 - Fully enclosed high-barrier sterile multi-dose delivery system 10ml - 0 days; Serial number B is SC260429 - Fully enclosed high-barrier sterile multi-dose delivery system - lay flat - accelerate for 1 month; Serial number C is SC260429 - Fully enclosed high-barrier sterile multi-dose delivery system - upright - accelerated 1 month; Serial number D is SC260429 - Fully enclosed high-barrier sterile multi-dose delivery system - inverted - accelerated 1 month; Serial number E is the new 10ml polypropylene antibacterial multi-dose pharmaceutical eye drop bottle - horizontal placement - accelerated 1 month; Serial number F is a 10ml polyethylene antibacterial multi-dose pharmaceutical eye drop bottle - placed horizontally - accelerated for 1 month; Serial number G is a 10ml polyethylene pump-type multi-dose pharmaceutical eye drop bottle - placed horizontally - accelerated for 1 month. Detailed Implementation

[0052] The technical solution of the present invention will be further described below with reference to the accompanying drawings and preferred embodiments.

[0053] like Figures 1-3 As shown, the fully enclosed high-barrier sterile multi-dose delivery system of the present invention includes: a bottle body 1, a valve body 2, a dropper 3, a flexible diaphragm valve 4, and a dispenser 5; the bottle body 1 is a multi-layer composite structure with a barrier layer, which is co-extruded from an inner layer, a barrier layer, and an outer layer. The inner layer is made of any one of LDPE, HDPE, PP, COC, and COP, and is in direct contact with the drug solution, with good chemical compatibility. The barrier layer is made of any one of PA, EVOH, COC, and COP, which prevents the penetration of volatile components in the drug solution and reduces the volatilization of volatile components in the drug solution. The outer layer is made of any one of HDPE, PP, and PET, which has high mechanical strength and good weather resistance, and is used to support the bottle body 1. The thickness of the bottle body 1 is 0.3-0.4 mm, which ensures strength while also having good elasticity, making it convenient to press and drip the solution.

[0054] like Figure 2 , Figure 3 , Figures 5 to 11 As shown, the valve body 2 extends into the bottle body 1 and seals tightly against it. The valve body 2 is provided with an inlet port 21 and connected to a return channel 22, a return air port 23, a gas collecting channel 24, and a mounting slot 25. A rounded corner 26 is provided between the top wall and the outer wall of the valve body 2. An isolation chamber connected to the return air port 23 and the return channel 22 is provided on the outer wall of the valve body 2. The isolation chamber is composed of several isolation channels 27 connected in series. A hollow spring column 28 is connected to the valve... The body 2 is integrally formed and set in the gas collection groove 24. The lower end of the hollow spring column 28 extends downward into the mounting groove 25. The outer wall of the hollow spring column 28 extending into the mounting groove 25 is an inverted conical wall. The antibacterial filter membrane 6 is integrally encapsulated in the hollow spring column 28 and blocks the cavity of the hollow spring column 28. The return groove 22, the return air hole 23, the gas collection groove 24, the cavity of the hollow spring column 28 and the isolation chamber constitute a return channel for recovering residual drug liquid and air.

[0055] like Figure 2 , Figure 3 , Figures 12-14As shown, the one-way valve 7 includes an integrally formed positioning ring 71, an elastic connecting wire 72, and a conical plug sleeve 73. The conical plug sleeve 73 is coaxially arranged with the positioning ring 71. The elastic connecting wire 72 is evenly distributed circumferentially between the positioning ring 71 and the conical plug sleeve 73. The elastic connecting wire 72 is arc-shaped, and its two ends are respectively located on the inner side wall of the positioning ring 71 and the outer side wall of the conical plug sleeve 73. The center of the elastic connecting wire 72 is aligned with the center of the conical plug sleeve 73. With concentric centers, the positioning ring 71 is fixedly sealed in the mounting groove 25. The conical plug sleeve 73 is fitted onto the lower end of the hollow spring column 28. The inner conical hole of the conical plug sleeve 73 abuts against the lower end of the hollow spring column 28 and fits against the inverted conical wall to form a conical surface seal. The conical surface seal between the one-way valve 7 and the hollow spring column 28 has a better sealing effect than the planar seal formed by the one-way diaphragm and the plane of the hollow spring column in the prior art. The planar seal has extremely high requirements for the coaxiality of the assembly. The high pressure and slight misalignment of the sealing surface can lead to one side being pressed tightly while the other side has a gap and leaks. The one-way diaphragm installed on the valve body 2 is small in size and is prone to defects during assembly. The conical seal used in this application can automatically center and lock when the two conical surfaces are pressed together, automatically correcting the deviation caused by assembly, ensuring that the sealing force is evenly distributed on the entire circumference, avoiding local leakage caused by uneven load, greatly reducing the defect rate, improving the yield rate and assembly efficiency, and also improving the sealing effect. The lower end of the hollow spring column 28 extending into the mounting groove 25 is higher than the height of the inner conical hole of the conical plug sleeve 73. The conical surface slope of the inverted conical wall is the same as the conical surface slope of the inner conical hole. The diameter of the small diameter end of the lower end of the hollow spring column 28 is greater than the diameter of the small diameter end of the inner conical hole and less than the diameter of the large diameter end of the inner conical hole, so as to ensure that the conical plug sleeve 73 has sufficient stroke to make conical surface fit with the lower end of the hollow spring column 28.

[0056] In this embodiment, a stop ring 711 protrudes from the outer wall of the positioning ring 71, and an annular retaining ring 712 with an outer diameter larger than that of the positioning ring 71 is integrally formed at the lower end of the positioning ring 71. An annular inner groove 251 is provided on the inner wall of the mounting groove 25. The positioning ring 71 abuts against the top inner wall of the mounting groove 25, the stop ring 711 is inserted into the annular inner groove 251 and is press-fitted with the annular inner groove 251, and the annular retaining ring 712 abuts against the opening edge of the mounting groove 25. The positioning ring 71 forms a double-layer sealing structure through the press-fit between the stop ring 711 and the annular inner groove 251 and the close fit between the annular retaining ring 712 and the mounting groove 25. Compared with the single-layer sealing structure in the prior art where the positioning ring in the anti-leakage valve body is stuck in the mounting groove and limited by the stop ring in the mounting groove, the double-layer sealing structure has higher connection stability and stronger sealing performance.

[0057] like Figure 2 , Figure 3 , Figure 15 , Figure 16 As shown, the flexible diaphragm valve 4 is sealed and fixed on the valve body 2 and blocked on the gas collection groove 24. A valve core 41 with a cone seal is extended on the flexible diaphragm valve 4. A pressure-limiting deformation gap H is left between the valve core 41 and the hollow spring column 28. The return spring 8 is coaxially fitted on the hollow spring column 28 and the valve core 41 of the flexible diaphragm valve 4, and provides a return force to the flexible diaphragm valve 4 through elasticity.

[0058] like Figure 2 , Figure 3 , Figures 17-20 As shown, the drip nozzle 3 is sealed and fixed on the valve body 2 and surrounds the outside of the liquid inlet 21. Several pressure blocks 31 are spaced at intervals around the bottom circumference of the drip nozzle 3, abutting against the flexible diaphragm valve 4 and the valve body 2. A liquid inlet gap communicating with the liquid inlet 21 is formed between the flexible diaphragm valve 4 and the drip nozzle 3. Several positioning blocks 32 are evenly distributed circumferentially on the outer wall of the drip nozzle 3. An inner cone 33 and a drip column 34 extend from the first top wall of the drip nozzle 3. A drip hole 35 is provided in the drip column 34. The drip hole 35 includes: sequentially axially connected... The system includes a liquid inlet trough 351, a small-diameter straight section 352, and a conical section 353. A sealing ring 3511 protrudes from the wall of the liquid inlet trough 351. The conical seal of the valve core 41 extends into the liquid inlet trough 351 and abuts against the sealing ring 3511, blocking the small-diameter straight section 352. The diameter of the small-diameter straight section 352 in the drip hole 35 is 0.2±0.02mm, and the length of the small-diameter straight section 352 is 0.2~2mm. When the length of the small-diameter straight section 352 is <1mm, a large-diameter straight section 354 extends from the large-diameter end of the conical section 353.

[0059] like Figure 2 , Figure 3 , Figures 21-24As shown, the dispenser 5 is sealed and pressed against the outer wall of the valve body 2 and the positioning block 32 of the nozzle 3, and is also sealed and snapped against the valve body 2 and the bottle mouth of the bottle body 1. The dispenser 5 fixes the valve body 2 to the bottle mouth of the bottle body 1. When assembling the dispenser 5, the positioning block 32 on the nozzle 3 guides the dispenser 5, and the cooperation between the dispenser 5 and the positioning block 32 improves the connection stability between the nozzle 3 and the dispenser 5. A return groove 2 is left between the fillet 26 of the dispenser 5 and the valve body 2. A flow guide ring gap 51 is connected to the nozzle 3. The positioning block 32 on the nozzle 3 is located above the flow guide ring gap 51. An outer cone 52 and a flow guide column 53 are extended on the second top wall of the dispenser 5. A flow guide hole 54 is provided in the flow guide column 53. The drip column 34 is located in the flow guide hole 54 and forms a flow guide ring gap with the flow guide hole 54. Three isosceles trapezoidal flow guide blocks 55 are evenly distributed around the circumference of the flow guide hole 54. The flow guide blocks 55 abut against the drip column 34. The end wall of the flow guide blocks 55 is provided with a... The drip column 34 fits into the arc-shaped groove. The second top wall and outer cone 52 of the distributor 5 are respectively sealed and abutted against the first top wall and inner cone 33 of the drip nozzle 3. Three drainage grooves 56 are evenly distributed around the circumference of the distributor 5. Each drainage groove 56 is located on the inner wall of the second top wall and outer cone 52 and is connected to the drainage annular gap. Each drainage block 55 is located at the inlet end of a drainage groove 56. The centerline of the drainage block 55 is aligned with the centerline of the corresponding drainage groove 56. The large bottom end of the drainage block 55 is aligned with the drainage groove 56. The inlet ends are connected by a smooth arc transition. The width of the guide block 55 is smaller than the width of the guide groove 56. The width of the end wall of the guide block 55 abutting against the droplet column 34 is 0.28±0.02mm. The width of the guide groove 56 is 0.8±0.02mm. An annular groove 57 connected to the guide groove 56 is provided on the inner wall of the second top wall. When the second top wall abuts against the first top wall of the dropper 3, the annular groove 57 is connected to the guide ring gap 51 through the gap between the positioning blocks 32.

[0060] When in use, inverting or tilting bottle 1 causes the liquid medicine in bottle 1 to press against valve body 2 and check valve 7. After being pressurized by the liquid medicine, the conical seal between the conical stopper 73 and the hollow spring column 28 on check valve 7 is improved, preventing the liquid medicine from contacting the antibacterial filter membrane 6. Pressing bottle 1 further increases the force exerted by the liquid medicine on check valve 7, making the conical seal between the conical stopper 73 and the hollow spring column 28 even tighter through self-locking. The liquid medicine then enters the flexible diaphragm valve 4 through inlet hole 21. In the liquid inlet gap between the bottle body 1 and the dropper 3, the liquid in the liquid inlet gap will exert pressure on the flexible diaphragm valve 4 and the dropper 3. The flexible diaphragm valve 4 is elastic, and after being subjected to pressure, it will overcome its own elasticity and the elasticity of the return spring 8, causing the valve core 41 to deform towards the hollow spring column 28. The cone seal on the valve core 41 will separate from the sealing ring 3511 and will no longer block the small diameter straight section 352 in the drip hole 35. The liquid will then enter the drip hole 35 through the liquid inlet groove 351 and drip out. During dripping, because a one-way valve 7 is provided, and there is a cone-shaped sealing structure with good sealing performance between the one-way valve 7 and the hollow spring column 28, the liquid will be blocked by the one-way valve 7 and will not be able to contact the antibacterial filter membrane 6. Therefore, the antibacterial filter membrane 6 with hydrophobic, hydrophilic or amphiphilic properties can be selected according to actual needs.

[0061] In this embodiment, the diameter of the small-diameter straight section 352 in the dripping orifice 35 is 0.2 mm. The length of the small-diameter straight section 352 is controlled between 0.2 and 2 mm depending on the kinematic viscosity of the liquid. For example, when the liquid contains viscous water-soluble polymers such as polyethylene glycol or polyvinyl alcohol, the kinematic viscosity of the liquid is relatively high, increasing the flow resistance in the dripping orifice 35. In this case, the length of the small-diameter straight section 352 is controlled between 0.2 and 1 mm (inclusive of 0.2 mm but exclusive of 1 mm), and a large-diameter straight section 354 is extended from the large-diameter end of the tapered section 353. Figure 19As shown, during the dripping process, the pressure-limiting deformation gap H between the valve core 41 and the hollow spring column 28 on the flexible diaphragm valve 4 can strictly limit the opening between the valve core 41 and the dripping orifice 35. Combined with the 0.2mm orifice diameter, it controls the maximum amount of medicine squeezed into the dripping orifice 35. The small-diameter straight section 352 with a length of 0.2 to 1mm (inclusive of 0.2mm and exclusive of 1mm) in the dripping orifice 35 reduces the throttling resistance by shortening the flow path, ensuring the basic flow rate of medicine in the dripping orifice 35. The conical section 353 converts kinetic energy into pressure energy through the diffusion effect, eliminating jet and homogenizing pressure. The large-diameter end face of the large-diameter straight section 354 provides uniform contact line pinning, allowing the droplets to slowly accumulate under gravity and break neatly after overcoming viscous delay. This achieves drip-by-drop and precise control of the dripping accuracy of each drop of medicine. When the liquid does not contain viscous, water-soluble polymers, its kinematic viscosity is low, resulting in low flow resistance in the dripping orifice 35. In this case, the length of the small-diameter straight section 352 is controlled between 1 and 2 mm (inclusive). Extending the length of the small-diameter straight section 352 provides higher laminar flow damping, limiting the liquid flow rate to a constant level. Simultaneously, to provide sufficient distance for diffusion and deceleration of the low-kinematic-viscosity liquid, a longer conical section 353 is provided on the small-diameter straight section 352. This, combined with the existing pressure-limiting deformation gap H, allows the liquid to flow slowly and converge on the conical section 353, achieving precise droplet delivery. Since the total length of the dripping orifice 35 is fixed, after extending both the small-diameter straight section 352 and the conical section 353, the large-diameter straight section 354 is no longer provided. Figure 20 As shown.

[0062] The kinematic viscosity of the drug solution was obtained after preparation, while the length of the small-diameter straight section 352 was determined through multiple experiments. The kinematic viscosity of the drug solution was recorded after each preparation, and dripping tests were conducted using dripping orifices 35 with different lengths of small-diameter straight sections 352 until a dripping orifice 35 that could ensure both drop-by-drop and dripping accuracy was selected. Specifically, under normal temperature conditions of 25℃, when the viscosity of the drug solution is 43-50 mm² / s, the length of the small-diameter straight section 352 needs to be limited to 0.2 mm; when the viscosity of the drug solution is 0.9-1.2 mm² / s, the length of the small-diameter straight section 352 needs to be limited to 2.0 mm.

[0063] When the bottle body 1 is released, the flexible diaphragm valve 4, under its own elasticity and the elasticity of the return spring 8, drives the valve core 41 to re-seal the drip hole 35. The pressure in the bottle body 1 is less than the pressure of the air outside the bottle. Under the pressure difference, the conical plug sleeve 73 on the one-way valve 7 leaves the hollow spring column 28, and the cavity of the hollow spring column 28 is opened. When the bottle body 1 expands and resets, it generates a negative pressure. Under the negative pressure, outside air is drawn into the drainage ring gap. The residual medicine that has not dripped from the drip column 34 flows along the drainage block 55 into the drainage groove 56 after contacting any drainage block 55. When the air in the drainage ring gap enters the drainage groove 56 at the same time, it shears and entrains the residual medicine, so that the air and the residual medicine are evenly mixed. The air mixed with the atomized medicine quickly enters the annular groove 57 under the guidance of the drainage groove 56. The mixed gas enters from the drainage groove 56 of the small space. After entering the large annular groove 57, the flow rate decreases. Since the density of the residual liquid is greater than that of the gas, the gas's ability to carry the residual liquid is reduced after the speed decreases. Under gravity, some of the residual liquid separates from the gas. Then, the gas and residual liquid enter the guide annular gap 51 through the gap between the positioning blocks 32. Then, they enter the isolation grooves 27 connected in series in the isolation chamber through the guide annular gap 51 and the return groove 22. The residual liquid will form a thin and large liquid film in each isolation groove 27, which accelerates the evaporation of the residual liquid. The gas comes into contact with the antibacterial filter membrane 6 through the air return hole 23, the air collection groove 24, and the cavity of the hollow spring column 28. Finally, the filtered air flows back to the bottle 1. When the pressure in the bottle 1 is balanced with the external pressure, the conical plug sleeve 73 in the one-way valve 7 is reset under the elastic force of the elastic connecting wire 72 and abuts against the hollow spring column 28 to form a conical seal.

[0064] To prevent residual medication from flowing back and contaminating the newly dispensed medication in the drip column 34 when the bottle 1 is inverted, several positioning blocks 32 are evenly distributed around the circumference of the dropper 3 to divide and reduce the space of the guide ring gap 51 (corresponding to the annular gap 71 between the dispenser and the dropper in a sterile delivery system for ophthalmic drugs that can withstand pressure difference and prevent leakage, as disclosed in CN121606437A). After the space of the guide ring gap 51 is reduced, the amount of residual medication that can be stored is reduced. With the reduced amount of residual medication remaining in the guide ring gap 51, the residual medication is less likely to flow back due to its own tension and viscosity. Even if some residual medication happens to flow back through the drainage channel 56, the residual medication will adhere to the drainage channel 56 and form a liquid film to reduce the backflow. In addition, the drainage block 55 at the inlet end of the drainage channel 56 also plays a blocking role, further preventing the residual medication from flowing back into the drainage ring gap and affecting the drip column 34.

[0065] When refluxing residual drug solution, different isolation chamber structures are required depending on the viscosity of the solution. When the solution does not contain viscous, water-soluble polymers, its viscosity is low, its flowability is good, and no film residue will form after evaporation. The isolation chamber used consists of five rows of isolation tanks 27 connected in series from top to bottom. Figures 5-8 As shown, except for the bottommost isolation groove 27, the vertical widths of the other isolation grooves 27 are all the same. The vertical width of the bottommost isolation groove 27 is greater than that of the other isolation grooves 27. By increasing the vertical width of the bottommost row of isolation grooves 27, the vertical widths of the other four rows of isolation grooves 27 are compressed, reducing the flow cross-sectional area of ​​the other four rows of isolation grooves 27. This causes a narrowing effect when the residual medicine and air flow in the other four rows of isolation grooves 27, increasing the flow velocity. A baffle rib 271 is longitudinally arranged on the valve body 2, blocking the beginning and end of all isolation grooves 27. The return groove 22 and the return air hole 23 are both arranged on the baffle rib 271. The beginning of the topmost isolation groove 27 is connected to the return groove 22, and the end of the bottommost isolation groove 27 is connected to the return air hole. The holes 23 are connected, and a baffle plate 272 is set between two adjacent isolation grooves 27. Each baffle plate 272 is provided with a ventilation groove 273. The ventilation groove 273 on the baffle plate 272 connected to the uppermost isolation groove 27 is located at the tail end, and the ventilation groove 273 on the baffle plate 272 connected to the lowermost isolation groove 27 is located at the head end. The ventilation grooves 273 on the adjacent baffle plates 272 are staggered. Several support ribs 274 are arranged circumferentially in each isolation groove 27. An air passage groove 275 is provided on the side wall of the support rib 274. The residual medicine and air flow back in a spiral manner in the five rows of interconnected isolation grooves 27. The residual medicine will form a liquid film on the baffle plate 272 and evaporate. The more isolation grooves 27 there are, the thinner the liquid film and the faster the evaporation.

[0066] When the liquid contains viscous, water-soluble polymers such as polyethylene glycol or polyvinyl alcohol, the liquid has high viscosity and poor flowability. The highly viscous liquid flows back to the isolation tank 27 for evaporation. After the water evaporates, the viscous, water-soluble polymers form a film in the isolation tank 27. However, when using the aforementioned five-row series-connected isolation tank 27, the top four rows of tanks have a relatively small vertical width. When a film forms in the isolation tank 27, it easily causes blockage in the small space. Therefore, when using highly viscous liquids, the isolation chamber with the above structure is prone to blockage due to film formation, making it impossible to recover the residual liquid. To solve this problem, for liquids containing viscous, water-soluble polymers such as polyethylene glycol or polyvinyl alcohol, the isolation chamber used consists of twelve isolation tanks 27' connected in series in three rows and four columns. Figures 9-11 As shown, Figure 11 The order of the first to fourth columns is based on Figure 9Arranged clockwise, the first column refers to the column containing the isolation grooves 27' connected to the return trough 22. A baffle plate 272' is installed between two adjacent rows of isolation grooves 27', and a baffle rib 271' is installed between two adjacent rows of isolation grooves. The return trough 22 and the return air hole 23 are respectively located on two symmetrical baffle ribs 271'. The isolation grooves 27' in the first row of the first column are directly connected to the return trough 22, and the isolation grooves 27' in the second row of the third column are directly connected to the return air hole 23. Both baffle plates 272' in the first column are provided with ventilation grooves 273'. The baffle ribs 271' between the first and second columns are provided with ventilation grooves 274' that connect to the isolation grooves 27' in the third row of the first column and the third row of the second column. Both baffle plates 272' in the second column are provided with ventilation grooves 274'. 73', an air passage 274' is provided on the barrier rib 271' with the return air hole 23, which is connected to the isolation groove 27' of the first row of the second column and the isolation groove 27' of the first row of the third column. An air passage 274' is provided on the barrier rib 271' between the third column and the fourth column, which is connected to the isolation groove 27' of the first row of the third column and the isolation groove 27' of the first row of the fourth column. An air passage 273' is provided on both barrier plates 272' in the fourth column. An air passage 274' is provided on the barrier rib 271' between the third column and the fourth column, which is connected to the isolation groove 27' of the third row of the fourth column and the isolation groove 27' of the third row of the third column. An air passage 273' is provided on the barrier plate 272' located between the second and third rows of the isolation groove 27' in the third column. The air passages 273' on the two barrier plates 272' in the same column are staggered. The mixed gas containing air and highly viscous liquid flows through the ventilation channel 273' and the air passage channel 274' to achieve isolation. By reducing the number of isolation channels 27', the vertical width of each isolation channel 27' is increased, avoiding blockage of the isolation channels 27' due to film formation, and ensuring the return efficiency of residual liquid.

[0067] like Figure 1 , Figure 2 , Figure 4 , Figure 19 , Figure 20As shown, a conical sealing hole 341 is coaxially arranged on the drip column 34. When the length of the small-diameter straight section 352 is <1mm, the conical sealing hole 341 is connected to the large-diameter straight section 354. When the length of the small-diameter straight section 352 is 1-2mm, the conical sealing hole 341 is connected to the conical section 353. The cone angle of the conical sealing hole 341 is 36°, and the diameter of the large-diameter end of the conical sealing hole 341 is 0.76±0.02mm. A bottle cap 9 is fitted onto the dispenser 5. Several perforated holes 91 are evenly distributed around the top wall of the bottle cap 9. A conical plug 92 is provided at the center of the bottle cap 9, which can be inserted into the conical sealing hole 341 to form a conical surface seal with the conical sealing hole 341. The bottle cap 9 includes: an integrally formed The cover 93, tear ring 94, and limiting ring 95, as well as the hollow hole 91 and cone plug 92, are all provided on the cover 93. Tear marks are provided between the cover 93, tear ring 94, and limiting ring 95. A retaining ring 951 that is engaged with the bottom of the distributor 5 is provided at the bottom of the limiting ring 95. A shoulder 58 is provided on the outer wall of the distributor 5. An outer protruding ring 581 is provided on the outer wall of the shoulder 58. The outer protruding ring 581 and the outer wall of the shoulder 58 are smoothly connected by an arc-shaped guide surface. An annular connecting groove 931 that can abut against the shoulder 58 is provided on the inner wall of the cover 93. An inner protruding ring 932 that can be misaligned and engaged with the outer protruding ring 581 is provided on the inner wall of the annular connecting groove 931. Regardless of how the structure of the drip hole 35 changes, the cone angle and the diameter of the large-diameter end of the conical sealing hole 341 remain unchanged. Only one type of bottle cap 9 is needed to seal the drip holes 35 with different structures. In use, the tear ring 94 is torn open through the tear marks, and the cap body 93 on the bottle cap 9 can be opened. The inner convex ring 932 on the cap body 93 and the outer convex ring 581 on the dispenser 5 are misaligned and engaged, which not only makes it easy to close and fix the bottle cap 9 on the dispenser 5, but also does not affect the subsequent opening of the cap.

[0068] The barrier properties of the fully enclosed, high-barrier, sterile, multi-dose delivery system described in this invention were verified using Pearl Brightening Eye Drops containing borneol. Pearl Brightening Eye Drops were filled into eye drop bottles with different structures. Each eye drop bottle containing Pearl Brightening Eye Drops was then placed in an accelerated stability test chamber for 30 days before being taken out for testing. The Pearl Brightening Eye Drops in each eye drop bottle had the same dilution concentration. The ambient temperature of the accelerated stability test chamber was set to 40℃±2℃ and the humidity to 25%±5%.

[0069] The testing methods are as follows (refer to Guideline 9001 of Part IV of the Chinese Pharmacopoeia 2025: Guidelines for Stability Testing of Active Pharmaceutical Ingredients and Preparations):

[0070] S1. Chromatographic conditions and system suitability test: Using a capillary column (30m length, 0.25mm inner diameter, 0.25μm film thickness) with polyethylene glycol 20000 (PEG-20M) as the stationary phase, the temperature program is as follows: initial temperature 70℃, hold for 1 minute; increase to 220℃ at a rate of 15℃ per minute, hold for 6 minutes; injection port temperature 210℃; detector temperature 230℃; split injection, split ratio 5:1; theoretical plate number calculated based on borneol peak should not be less than 20000; the resolution of borneol, isoborneol peaks and n-octadecane peak should meet the requirements (>1.5); ensure that borneol, isoborneol and n-octadecane do not interfere with each other;

[0071] S2. Preparation of internal standard solution: Take 400 mg of n-octadecane, dilute with ethyl acetate to 1000 ml, and the solution is ready (shelf life 3 months); it can be used as a reference for quantification.

[0072] S3. Preparation of blank matrix solution: Transfer 5 ml of internal standard solution using a high-precision measuring instrument, place this 5 ml internal standard solution into a glass test tube with a stopper, then accurately add 5 ml of purified water using a high-precision measuring instrument, shake to extract, let stand to separate the layers, and take the supernatant to obtain the sample matrix; this simulates the sample matrix and is used to prove that, apart from borneol and isoborneol, other substances will not produce interfering peaks on the chromatogram (excluding false positives).

[0073] S4. Preparation of reference solution: Accurately weigh 10 mg each of borneol reference standard and isoborneol reference standard, place them in a 50 ml volumetric flask, add internal standard solution to dissolve and dilute to the mark, shake well, and the reference solution is obtained (the shelf life of the reference solution is 1 month); it is used to establish the mathematical relationship between the "peak area ratio" and the "true concentration" (calculate the correction factor F).

[0074] S5. Preparation of the test solution: Accurately measure 5 ml of Pearl Brightening Eye Drops, place it in a stoppered test tube, accurately add 5 ml of internal standard solution, shake to extract, let stand to separate the layers, and take the supernatant. The borneol must be transferred from the drug solution to the organic phase (supernatant) before it can be injected into the chromatograph.

[0075] S6. Determination method: Inject 1 μL each of the blank solution, control solution, and test solution into the gas chromatograph and record the chromatogram, such as... Figure 25 As shown, the total amount of borneol and isoborneol in the sample was calculated using the internal standard method based on the chromatogram; the acceptable range for the sample is: the total amount of borneol (calculated as the total amount of borneol (C10H18O) and isoborneol (C10H18O)) in each 1 ml of eye drops should be 0.02% to 0.08%.

[0076] The formula for calculating the internal standard method involved in S6 is as follows:

[0077] Internal standard concentration = Internal standard sample volume × Internal standard purity / Dilution factor (1000);

[0078] Correction factor F = (internal standard peak area / internal standard concentration) / (control peak area / control concentration);

[0079] Content = Correction factor F × Peak area in test solution / (Peak area of ​​internal standard in test solution / Concentration of internal standard in test solution) / Sample concentration (5 / 10);

[0080] Borneol content = Borneol content + Isoboron content;

[0081] Control concentration = Sample weight of control standard × Purity of control standard / Dilution factor (50).

[0082] The measured chromatogram is as follows Figure 25 As shown, the vertical axis represents the peak area, and the horizontal axis represents the elution time. The elution order is as follows: borneol (6.905 min), isoborneol (7.180 min), and n-octadecane peak (8.046 min). The following experimental data were obtained through the peak chart and the internal standard method calculation formula:

[0083]

[0084] Note: ① The delivery systems mentioned in this table are all eye drop bottles mentioned in the experiment.

[0085] ② In this table, '0 days' refers to the immediate state of the Pearl Brightening Eye Drops immediately after they are filled into the eye drop bottle and sealed, before being placed in the accelerated stability test environment (40℃±2℃, RH25%±5%). The borneol content, physicochemical parameters, etc., measured at this time are considered as initial baseline values, used to characterize the initial barrier performance of the eye drop bottle and the initial quality state of the product under no accelerated stress. The test data at each subsequent sampling time point are normalized and compared with this initial baseline value (denoted as 100%) to evaluate the change law of the barrier effect of the eye drop bottle on volatile components (borneol) over time. Samples in each eye drop bottle are considered qualified as long as the content of volatile components (borneol) in the '0 days' state is between 0.02% and 0.08%.

[0086] ③ The chromatogram corresponding to sample A (SC260429-fully enclosed high-barrier sterile multi-dose delivery system 10ml-0 days) in the chromatogram represents the peak time and peak area of ​​borneol in the SC260429-fully enclosed high-barrier sterile multi-dose delivery system (flat, upright, inverted) at 0 days in this table.

[0087] The chromatograms and experimental data show that the fully enclosed, high-barrier, sterile, multi-dose delivery system of this invention exhibits the best camphor barrier performance among all tested packaging materials: throughout the entire accelerated testing period, this packaging group showed the smallest decrease in camphor content and the highest retention rate, significantly better than other groups, and the camphor content at each time point met the quality standard requirements. This indicates that the multi-layered composite structure of the bottle 1 with a barrier layer and the one-way valve 7 forming a conical seal with the hollow spring column 28 can effectively inhibit the volatilization and loss of volatile components such as camphor through the bottle wall and reflux channel, reducing the permeability of volatile components such as camphor.

[0088] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the specific implementation of the present invention. Any modifications or equivalent substitutions that do not depart from the spirit and scope of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. A fully enclosed, high-barrier, sterile, multi-dose delivery system, comprising: Bottle body, valve body, dropper, flexible diaphragm valve and dispenser; characterized in that, The bottle body is a multi-layered composite structure with a barrier layer; The valve body extends into the bottle body and seals against the bottle body. The valve body is provided with a liquid inlet hole and a connected reflux groove, vent hole and isolation chamber. The valve body has rounded corners between the top wall and the outer wall. The hollow spring column is integrally formed with the valve body and is encapsulated with an antibacterial filter membrane that blocks its cavity. A one-way valve includes an integrally formed positioning ring, an elastic connecting wire, and a conical plug sleeve. The elastic connecting wire is evenly distributed circumferentially between the positioning ring and the conical plug sleeve. The positioning ring is sealed and fixed in the valve body. The inner conical hole of the conical plug sleeve and the hollow spring column form a conical surface seal. The flexible diaphragm valve is sealed and fixed on the valve body. A valve core with a cone seal is extended on the flexible diaphragm valve, and a pressure-limiting deformation gap is left between the valve core and the hollow spring column. The return spring is coaxially mounted on the hollow spring column and valve core. The drip nozzle is sealed and fixed on the valve body, and has an inlet gap that is connected to the inlet hole and is surrounded by the flexible diaphragm valve. Several positioning blocks are evenly distributed around the outer wall of the drip nozzle, and a drip hole is provided in the drip column of the drip nozzle. The drip hole includes: an inlet groove, a small-diameter straight section and a conical section connected axially in sequence. A sealing ring is provided protruding on the wall of the inlet groove. The conical seal of the valve core extends into the inlet groove and abuts against the sealing ring. The valve core blocks the small-diameter straight section. The dispenser is sealed to the valve body, the positioning block of the nozzle, and the bottle mouth. A flow guide ring gap is left between the rounded corners of the dispenser and the valve body. A flow guide hole with several flow guide blocks is provided in the flow guide column of the dispenser. The drip column is located in the flow guide hole and forms a flow guide ring gap with the flow guide hole. The flow guide block abuts against the drip column. The dispenser is sealed against the nozzle. Several flow guide grooves connected to the flow guide ring gap and the flow guide ring gap are arranged circumferentially on the dispenser. Each flow guide block is located at the inlet end of a flow guide groove. The width of the flow guide block is smaller than the width of the flow guide groove.

2. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 1, characterized in that, The bottle body is co-extruded from three layers: an inner layer, a barrier layer, and an outer layer. The thickness of the bottle body is 0.3-0.4 mm. The inner layer is made of any one of LDPE, HDPE, PP, COC, and COP. The barrier layer is made of any one of PA, EVOH, COC, and COP. The outer layer is made of any one of HDPE, PP, and PET.

3. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 1, characterized in that, The diameter of the small-diameter straight section in the drip hole is 0.2±0.02mm, and the length of the small-diameter straight section is 0.2~2mm. When the length of the small-diameter straight section is <1mm, a large-diameter straight section is extended on the large-diameter end of the conical section.

4. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 1, characterized in that, The distributor has three drainage grooves evenly distributed around its circumference, with a width of 0.8±0.02mm. There are three drainage blocks evenly distributed around the circumference of the drainage holes. The width of the end wall of the drainage block that abuts against the droplet column is 0.28±0.02mm. The center line of the drainage block is aligned with the center line of the corresponding drainage groove. An annular groove connected to the drainage groove is provided on the inner wall of the distributor.

5. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 4, characterized in that, The drainage block is an isosceles trapezoid, and the large bottom end of the drainage block is connected to the inlet end of the drainage channel by a smooth arc transition. An arc-shaped groove that fits the drip column is provided on the end wall of the drainage block.

6. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 1, characterized in that, The isolation chamber consists of five rows of isolation slots arranged at intervals from top to bottom. A longitudinal baffle rib is installed on the valve body, blocking the beginning and end of all the isolation slots. A return channel and a return air hole are both located on the baffle rib. The beginning of the uppermost isolation slot is connected to the return channel, and the end of the lowermost isolation slot is connected to the return air hole. A baffle plate is installed between two adjacent isolation slots. Each baffle plate has a venting slot. The venting slot on the baffle plate connected to the uppermost isolation slot is located at the end, and the venting slot on the baffle plate connected to the lowermost isolation slot is located at the beginning. The venting slots on adjacent baffle plates are staggered.

7. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 1, characterized in that, Several supporting ribs are arranged circumferentially in each isolation groove, and an air passage groove is provided on the side wall of the supporting ribs.

8. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 6, characterized in that, Except for the bottommost isolation groove, all other isolation grooves have the same vertical width, with the bottommost isolation groove having a wider vertical width than the others.

9. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 1, characterized in that, The isolation chamber consists of twelve isolation slots connected in series in three rows and four columns. A baffle plate is installed between two adjacent rows of isolation slots, and a baffle rib is installed between two adjacent columns of isolation slots. Return channels and return air holes are respectively located on two symmetrical baffle ribs. The isolation slots in the first row of the first column are directly connected to the return channels, and the isolation slots in the second row of the third column are directly connected to the return air holes. Both baffle plates in the first column have ventilation slots. The baffle ribs between the first and second columns have ventilation slots that connect to the isolation slots in the third row of the first column and the third row of the second column. The two baffle plates in the second column... Each plate is equipped with a ventilation slot. On the baffle rib with return air holes, there is a ventilation slot that connects to the isolation slot of the first row of the second column and the isolation slot of the first row of the third column. On the baffle rib between the third and fourth columns, there is a ventilation slot that connects to the isolation slot of the first row of the third column and the isolation slot of the first row of the fourth column. Both baffle plates in the fourth column are equipped with ventilation slots. On the baffle rib between the third and fourth columns, there is a ventilation slot that connects to the isolation slot of the third row of the fourth column and the isolation slot of the third row of the third column. On the baffle plate located between the second and third rows of isolation slots in the third column, there is a ventilation slot.

10. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 9, characterized in that, The ventilation slots on the two barrier plates in the same column are staggered.

11. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 1, characterized in that, The valve body is provided with a gas collecting groove and a mounting groove that are connected to the return groove and the return air hole. The hollow spring column is arranged in the gas collecting groove, and the lower end of the hollow spring column extends downward into the mounting groove. The outer wall of the hollow spring column extending into the mounting groove is an inverted conical wall. The height of the lower end of the hollow spring column extending into the mounting groove is greater than the height of the inner conical hole of the conical plug sleeve. The slope of the conical surface of the inverted conical wall is the same as the slope of the conical surface of the inner conical hole. The diameter of the small diameter end of the lower end of the hollow spring column is greater than the diameter of the small diameter end of the inner conical hole and smaller than the diameter of the large diameter end of the inner conical hole.

12. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 11, characterized in that, The elastic connecting wire is arc-shaped, with its two ends respectively located on the inner wall of the positioning ring and the outer wall of the conical plug sleeve. The center of the elastic connecting wire is concentric with the center of the conical plug sleeve and the positioning ring.

13. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 12, characterized in that, A stop ring is protruding from the outer wall of the positioning ring. An annular retaining ring with an outer diameter larger than the positioning ring is integrally formed at the lower end of the positioning ring. An annular inner groove is provided on the inner wall of the mounting groove. The positioning ring abuts against the top inner wall of the mounting groove. The stop ring is inserted into the annular inner groove and is interference-fitted with the annular inner groove. The annular retaining ring abuts against the edge of the opening of the mounting groove.

14. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 3, characterized in that, A conical sealing hole is coaxially arranged on the droplet column. When the length of the small-diameter straight section is <1mm, the conical sealing hole is connected to the large-diameter straight section. When the length of the small-diameter straight section is 1-2mm, the conical sealing hole is connected to the conical section. The cone angle of the conical sealing hole is 36°, and the diameter of the large-diameter end of the conical sealing hole is 0.76±0.02mm. A bottle cap is fitted on the dispenser. Several perforated holes are evenly distributed around the top wall of the bottle cap. A conical plug is set in the center of the bottle cap, which can be inserted into the conical sealing hole to form a conical surface seal with the conical sealing hole.

15. The fully enclosed, high-barrier, sterile, multi-dose delivery system according to claim 14, characterized in that, The bottle cap includes: an integrally formed cap body, a tear ring, and a limiting ring. Hollow holes and conical plugs are provided on the cap body. Tear marks are provided between the cap body, the tear ring, and the limiting ring. A retaining ring that engages with the bottom of the dispenser is provided at the bottom of the limiting ring. A shoulder is provided on the outer wall of the dispenser. An outer convex ring is provided on the outer wall of the shoulder. The outer convex ring and the outer wall of the shoulder are smoothly connected by an arc-shaped guide surface. An annular connecting groove that can abut against the shoulder is provided on the inner wall of the cap body. An inner convex ring that can be misaligned and engaged with the outer convex ring is provided on the inner wall of the annular connecting groove.

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