Platelet storage bag and manufacturing method thereof

Abstract

The invention relates to the field of manufacturing of medical supplies, in particular to a platelet storage bag which comprises a bag body with the periphery fixedly connected to form a space in the center side for storing platelets, and a connecting pipe communicated with the interior of the bag body for circulation of the platelets. The bag body comprises two layers of isolating membranes which are in contact with blood platelets and only allow gas to pass through, oxygen generating layers and carbon dioxide absorbing layers which are compounded on the opposite surfaces of the two layers of isolating membranes in a one-to-one correspondence manner, calcium peroxide microcapsules are embedded in the oxygen generating layers, lithium hydroxide microcapsules are embedded in the carbon dioxide absorbing layers, and the oxygen generating layers and the carbon dioxide absorbing layers are compounded in a one-to-one correspondence manner. The oxygen generating layer can slowly release oxygen, the carbon dioxide absorbing layer can absorb carbon dioxide, oxygen filling and vacuumizing operation is not needed any more, platelets can be directly stored in the storage bag, use is convenient, and meanwhile the storage duration of the platelets can be guaranteed.

Description

Technical Field

[0001] This application relates to the field of medical device manufacturing, and in particular to a platelet preservation bag and a method for manufacturing the same. Background Technology

[0002] Platelet preservation bags are used to preserve platelets for transfusion in patients with thrombocytopenia and abnormal bleeding. Platelets undergo metabolism within the preservation bag; if oxygen levels decrease, the metabolism produces lactic acid, lowering the platelet's pH and causing damage. Therefore, preservation bags require high oxygen permeability to extend platelet storage time.

[0003] In addition to improving the oxygen permeability of the storage bag membrane through the material itself, existing platelet storage bags also have structural optimizations. For example, a platelet storage bag with publication number CN118948614A has an oxygen-filled bag and a vacuum bag on both sides of the platelet storage bag. The pressure difference between the oxygen-filled bag and the platelet storage bag ensures that oxygen can permeate into the platelet storage bag.

[0004] Regarding the aforementioned technologies, the storage bag requires multiple layers of film to be heat-sealed, and different pipelines need to be connected between different film layers for oxygen filling and vacuuming, making the use of the storage bag inconvenient. Summary of the Invention

[0005] In order to make the storage bag more convenient to use and to prevent the platelet storage time from being reduced, this application provides a platelet storage bag and a method for manufacturing the same.

[0006] Firstly, the platelet preservation bag provided in this application adopts the following technical solution.

[0007] A platelet storage bag includes a bag body fixedly connected to the periphery to form a space on the central side for storing platelets, and a connecting tube connected to the bag body for platelet circulation. The bag body includes two isolation membranes that contact the platelets and allow only gas to pass through, and an oxygen generating layer and a carbon dioxide absorbing layer that are correspondingly composited on opposite surfaces of the two isolation membranes. Calcium peroxide microcapsules are embedded in the oxygen generating layer, and lithium hydroxide microcapsules are embedded in the carbon dioxide absorbing layer.

[0008] By adopting the above technical solution, the calcium peroxide microcapsules in the oxygen generation layer can absorb moisture in the environment to produce oxygen and deliver it to the platelets between the two isolation membranes through the isolation membrane. The lithium hydroxide microcapsules in the carbon dioxide absorption layer can absorb carbon dioxide between the two isolation membranes, so that the platelets in the bag can always maintain a good state of aerobic respiration, prolong the platelet storage time, and are convenient to use without the need for vacuuming or oxygen filling.

[0009] Optionally, the separator is a PTFE / PE composite membrane.

[0010] By adopting the above technical solution, the isolation membrane can effectively block liquids while allowing oxygen and carbon dioxide to pass through.

[0011] Optionally, the oxygen generating layer is a PE film and the carbon dioxide absorbing layer is a PP film.

[0012] By adopting the above technical solutions, the PE film has good toughness, which helps to protect the calcium peroxide microcapsules, and the PP film is corrosion resistant and suitable for the alkaline environment of lithium hydroxide microcapsules, which helps to reduce the degradation of lithium hydroxide.

[0013] Optionally, the oxygen generating layer has a porous membrane on the surface away from the isolation membrane, and the porous membrane is a SiO2 / PVP composite membrane.

[0014] By adopting the above technical solution, silica forms nanopores to allow outside air to enter, and then PVP is hydrophilic so that the oxygen generation layer is less likely to come into contact with too much oxygen, thus better controlling the oxygen release rate and preventing premature deactivation of calcium peroxide.

[0015] Secondly, the platelet preservation bag manufacturing method provided in this application adopts the following technical solution.

[0016] A method for manufacturing a platelet preservation bag, comprising the following steps.

[0017] S1. Melt PE particles and add calcium peroxide microcapsules, extrude and mix them, and cast them into an oxygen-generating layer.

[0018] S2. A mixed solution of SiO2 and PVP is coated onto the outer surface of the oxygen generation layer and cured to form a porous membrane.

[0019] S3. Melt PP particles and add lithium hydroxide microcapsules, extrude and mix them, and cast them into a carbon dioxide absorption layer.

[0020] S4. The oxygen generating layer and the PE side of the isolation film are hot-melt bonded together, and the carbon dioxide absorbing layer and the PE side of the isolation film are hot-melt bonded together.

[0021] S5. Stack the two layers of separation film that have been composited in S4 and weld the three peripheries of the separation film to form a bag;

[0022] S6. Insert the connecting tube into the opening of the bag body in S5 and weld it.

[0023] By adopting the above technical solution, the preservation bag can be successfully manufactured.

[0024] Optionally, the separator is made by hot pressing molten PE particles and a porous PTFE membrane at a temperature of 175-185℃, a pressure of 9-11 MPa, and a hot pressing time of 55-65 seconds.

[0025] By adopting the above technical solution, a seamless combination of PTFE and PE can be achieved.

[0026] Optionally, the hot melt bonding in S4 specifically includes the following steps.

[0027] S41. Spray hot melt adhesive between the two films to be laminated;

[0028] S42. Perform pre-bonding at a temperature of 78-82℃, a pressure of 1.8-2.2Mpa, and a time of 9-11s;

[0029] S43, perform main fusion at a temperature of 127-133℃, a pressure of 4.6-5.4 MPa, and a time of 43-47 seconds;

[0030] S44. Perform shaping and cooling at a temperature of 58-62℃, a pressure of 0.9-1.1Mpa, and a time of 27-33s.

[0031] By adopting the above technical solution, the three-stage combination process makes the microcapsules less prone to damage.

[0032] Optionally, after completing the hot-melt bonding in step S4, the two composite films are welded around their perimeter.

[0033] By adopting the above technical solution, it is less likely that the oxygen generation layer and the isolation membrane, as well as the carbon dioxide release layer and the periphery of the isolation membrane, will warp.

[0034] In summary, this application includes at least the following beneficial effects:

[0035] The calcium peroxide microcapsules in the oxygen generation layer absorb moisture from the environment to produce oxygen, which is then delivered to the platelets between the two separating membranes via the separating membrane. The lithium hydroxide microcapsules in the carbon dioxide absorption layer absorb carbon dioxide between the two separating membranes, so that the platelets in the bag can always maintain a good state of aerobic respiration, prolonging the platelet storage time. It is also convenient to use and does not require vacuuming or oxygen filling. Attached Figure Description

[0036] Figure 1 This is a structural diagram of the platelet preservation bag of this application;

[0037] Figure 2 This is a schematic diagram of the cross-sectional structure of a platelet preservation bag along its thickness.

[0038] Explanation of reference numerals in the attached diagram: 1. Bag body; 2. Connecting tube; 3. Separating membrane; 4. Oxygen generating layer; 5. Carbon dioxide absorbing layer; 51. Porous membrane. Detailed Implementation

[0039] The present application will be further described in detail below with reference to the accompanying drawings.

[0040] This application discloses a platelet preservation bag, referring to... Figure 1 It includes a bag 1 with an internal space for platelets to enter, and a connecting tube 2 made of polycarbonate is fixedly connected to one side of the bag 1.

[0041] Reference Figure 2 The cross-section along the thickness direction of the bag body 1 sequentially includes a porous membrane 51, an oxygen generating layer 4, two separating membranes 3, and a carbon dioxide absorbing layer 5. The porous membrane 51 is a SiO2 / PVP composite membrane. The oxygen generating layer 4 is a PE membrane with embedded calcium peroxide microcapsules. The separating membranes 3 are PTFE / PE composite membranes, with the PE surfaces of the two separating membranes 3 being close to each other. The carbon dioxide absorbing layer 5 is a PP membrane with embedded lithium hydroxide microcapsules.

[0042] This application also discloses a method for manufacturing platelet preservation bags, which specifically includes the following steps.

[0043] S1. Melt PE particles at 195-205℃ and add calcium peroxide microcapsules, extrude, mix and cast to form oxygen generation layer 4, with the film thickness of oxygen generation layer 4 controlled at 0.38-0.42mm.

[0044] The preparation process of calcium peroxide microcapsules can be as follows: First, calcium peroxide powder with a particle size ≤5μm is mixed with a polyvinyl alcohol solution with a concentration of 9.5-10.5% at a mass ratio of 1:3. The mixture is stirred in a 40℃ water bath to form a suspension. Then, polylactic acid dissolved in dichloromethane is added dropwise to the suspension. The polylactic acid concentration is 15%, and the mass ratio of calcium peroxide to polylactic acid is 1:2. The mixture is treated with ultrasonic emulsification at a power of 200W and a frequency of 20kHz for 10 minutes to form an oil-in-water emulsion. The emulsion is then transferred to a spray dryer with an inlet air temperature of 120℃ and an outlet air temperature of 60℃ to finally obtain spherical calcium peroxide microcapsules with a diameter of 6-10μm and a shell thickness of 1-1.2μm.

[0045] S2. A mixed solution of SiO2 with a particle size of 19-21 nm and PVP with a concentration of 10% is coated on the outer surface of the oxygen generation layer 4. The coating thickness is 0.08-0.12 mm. After curing at room temperature for at least 12 h, a porous membrane 51 is formed.

[0046] S3. Melt PP granules at 187-193℃ and add lithium hydroxide microcapsules, extrude and mix, and cast into carbon dioxide absorption layer 5. The thickness of carbon dioxide absorption layer 5 is 0.32-0.37mm.

[0047] The preparation process of lithium hydroxide microcapsules can be as follows: First, lithium hydroxide powder with a particle size ≤3μm is dispersed in an ethanol solution of Tween-80 with a concentration of 1%, and then a xylene solution of ethylene-vinyl acetate copolymer with a concentration of 10% is added. The mass ratio of lithium hydroxide to ethylene-vinyl acetate copolymer is 1:1.5. Droplets are generated by a microfluidic device at a flow rate of 0.5mL / min. The microcapsules are then dried and cured in a vacuum oven at 50℃ for 4 hours to obtain lithium hydroxide microcapsules with a diameter of 7-13μm.

[0048] S4. The oxygen generating layer 4 and the PE surface of the isolation membrane 3 are thermally melt-bonded together, and the carbon dioxide absorption layer 5 and the PE surface of the isolation membrane 3 are thermally melt-bonded together. After the thermal melt bonding is completed, high-frequency welding is performed on the four sides where the oxygen generating layer 4 and the isolation membrane 3 are bonded together, as well as on the four sides where the carbon dioxide absorption layer 5 and the isolation membrane 3 are bonded together. The welding power is about 27MHz and the power is 2kW.

[0049] The hot melt composite process specifically includes the following steps.

[0050] S41. Spray polyurethane hot melt adhesive between the two films to be laminated, with a coating amount of 8g / m². 2 .

[0051] S42. Perform pre-bonding at a temperature of 78-82℃, a pressure of 1.8-2.2Mpa, and a time of 9-11s.

[0052] S43. Perform the main fusion at a temperature of 127-133℃, a pressure of 4.6-5.4 MPa, and a time of 43-47 seconds.

[0053] S44. Perform shaping and cooling at a temperature of 58-62℃, a pressure of 0.9-1.1Mpa, and a time of 27-33s.

[0054] In addition, the separator 3 is made by hot pressing molten PE particles and porous PTFE membrane. The separator 3 has a thickness of 0.05 mm, a temperature of 175-185℃, a pressure of 9-11 MPa, and a hot pressing time of 55-65 s.

[0055] S5. The two layers of separation film 3 that have been composited in S4 are stacked together and the three peripheries of the separation film 3 are laser welded with a power of about 150w to form the bag body 1.

[0056] S6. Insert the connecting tube 2 into the opening of the bag body 1 in S5 and perform resonant friction welding.

[0057] The following description uses specific examples and comparative models.

[0058] Example 1:

[0059] A platelet storage bag includes a bag body 1 with an internal space for platelets to enter, and a connecting tube 2 made of polycarbonate fixedly connected to one side of the bag body 1. The cross-section of the bag body 1 along its thickness direction sequentially includes a porous membrane 51, an oxygen generating layer 4, two separating membranes 3, and a carbon dioxide absorbing layer 5. The porous membrane 51 is a SiO2 / PVP composite membrane. The oxygen generating layer 4 is a PE membrane with embedded calcium peroxide microcapsules. The separating membranes 3 are PTFE / PE composite membranes, with the PE surfaces of the two separating membranes 3 approaching each other. The carbon dioxide absorbing layer 5 is a PP membrane with embedded lithium hydroxide microcapsules.

[0060] A method for manufacturing platelet preservation bags includes the following steps.

[0061] S1. PE particles are melted at 200℃ and calcium peroxide microcapsules are added. The mixture is then extruded, kneaded, and cast into an oxygen generation layer 4. The thickness of the oxygen generation layer 4 is controlled at 0.4 mm.

[0062] S2. A mixed solution of SiO2 with a particle size of 20 nm and PVP with a concentration of 10% is coated on the outer surface of the oxygen generation layer 4. The coating thickness is 0.1 mm. After curing at room temperature for 12 h, a porous membrane 51 is formed.

[0063] S3. Melt PP granules at 190°C and add lithium hydroxide microcapsules, extrude and mix, and cast into carbon dioxide absorption layer 5 with a thickness of 0.35 mm.

[0064] S4. The oxygen generating layer 4 and the PE surface of the isolation membrane 3 are thermally melt-bonded together, and the carbon dioxide absorption layer 5 and the PE surface of the isolation membrane 3 are thermally melt-bonded together. After the thermal melt bonding is completed, high-frequency welding is performed on the four sides where the oxygen generating layer 4 and the isolation membrane 3 are bonded together, and on the four sides where the carbon dioxide absorption layer 5 and the isolation membrane 3 are bonded together. The welding power is 27MHz and the power is 2kW.

[0065] The hot melt composite process specifically includes the following steps.

[0066] S41. Spray polyurethane hot melt adhesive between the two films to be laminated, with a coating amount of 8g / m². 2 .

[0067] S42. Perform pre-bonding at a temperature of 78℃, a pressure of 1.8 MPa, and a time of 9 seconds.

[0068] S43. Perform the main fusion at a temperature of 127℃, a pressure of 4.6 MPa, and a time of 43 seconds.

[0069] S44. Perform a shaping and cooling process at a temperature of 58℃, a pressure of 0.9 MPa, and a time of 27 seconds.

[0070] In addition, the separator 3 is made by hot pressing molten PE particles and porous PTFE membrane at a temperature of 175°C, a pressure of 9 MPa, and a hot pressing time of 55 seconds.

[0071] S5. The two layers of separation film 3 that have been composited in S4 are stacked together and the three peripheries of the separation film 3 are laser welded with a power of 150w to form the bag body 1.

[0072] S6. Insert the connecting tube 2 into the opening of the bag body 1 in S5 and perform resonant friction welding.

[0073] Example 2:

[0074] The difference from Example 1 lies in the different parameters of the hot melt bonding method in the platelet preservation bag manufacturing method. The specific differences are as follows.

[0075] S42. Perform pre-bonding at a temperature of 82℃, a pressure of 2.2 MPa, and a time of 11 seconds.

[0076] S43. Perform the main fusion at a temperature of 133℃, a pressure of 5.4 MPa, and a time of 47 seconds.

[0077] S44. Perform a shaping and cooling process at a temperature of 62℃, a pressure of 1.1 MPa, and a time of 33 seconds.

[0078] Example 3:

[0079] The difference from Example 1 is that the manufacturing conditions of the isolation membrane 3 in the platelet preservation bag manufacturing method are different, and the specific differences are as follows.

[0080] The hot-pressing temperature of the separator 3 is 185℃, the pressure is 11 MPa, and the hot-pressing time is 65 seconds.

[0081] Comparative Example 1:

[0082] The difference from Example 1 is that the cross-section of the platelet preservation bag 1 along its thickness direction includes a PE film, two PTFE / PE composite films, and a PP film. Oxygen is filled between the PE film and the PTFE / PE composite film, and the oxygen pressure is greater than or equal to 10 kPa. A vacuum is drawn between the PP film and the PTFE / PE composite film, and the vacuum degree is less than or equal to 1.3 kPa.

[0083] Comparative Example 2:

[0084] The difference from Example 1 is that the oxygen generation layer 4 of the platelet preservation bag does not have a porous membrane 51.

[0085] Comparative Example 3:

[0086] The difference from Example 1 is that the hot melt bonding in a method for manufacturing a platelet preservation bag specifically includes the following steps.

[0087] S41. Spray hot melt adhesive between the two films to be laminated.

[0088] S42. Perform the main fusion at a temperature of 127℃, a pressure of 4.6 MPa, and a time of 52 seconds.

[0089] S43. Perform a shaping and cooling process at a temperature of 58℃, a pressure of 0.9Mpa, and a time of 27s.

[0090] Comparative Example 4:

[0091] The difference from Example 1 is that the hot melt bonding in a method for manufacturing a platelet preservation bag specifically includes the following steps.

[0092] S41. Spray polyurethane hot melt adhesive between the two films to be laminated.

[0093] S42. Perform pre-bonding at a temperature of 78℃, a pressure of 1.8 MPa, and a time of 9 seconds.

[0094] S43. Perform the main fusion at a temperature of 127℃, a pressure of 4.6 MPa, and a time of 43 seconds.

[0095] S44. Perform a shaping and cooling process at room temperature and pressure for 27 seconds.

[0096] Reference group:

[0097] Use Terumo® platelet preservation bags instead of one of the platelet preservation bags in this application.

[0098] Eight platelet preservation bags obtained from each embodiment, comparative example, and reference group were selected as samples for the following experiments.

[0099] For interlayer bonding strength testing, a 10×50mm strip sample was taken from the central area of ​​each platelet storage bag, and the bonding strength was tested using a universal testing machine in accordance with the standard ASTM D1876.

[0100] Platelet preservation testing involved selecting platelets from 20 healthy volunteers, homogenizing them, and then injecting 30 ml of platelet suspension into each of the embodiment, comparative example, and control group's platelet preservation bags. The bags were then stored at a constant temperature of 20-24°C with shaking. After seven days, three indicators were measured: CD62P expression rate, GPⅠbα retention rate, and LDH release. Lower CD62P expression rate, higher GPⅠbα retention rate, and lower LDH release indicated better platelet preservation and a longer preservation time. Furthermore, if any two of the three platelet indicators met the following criteria—CD62P expression rate greater than 30%, GPⅠbα retention rate less than 70%, and LDH release greater than 200 U / L—it indicated that the corresponding platelets were inactivated, thus determining the effective preservation days of platelets per platelet preservation bag.

[0101] The specific results are shown in the table below.

[0102]

[0103] Based on Examples 1 to 3, Comparative Example 1, and the reference group, it can be seen that filling one side of the platelet storage bag with oxygen in the comparative example makes the platelets more susceptible to contact with a high-oxygen environment, causing oxidative stress and resulting in a reduction in the platelet storage time.

[0104] As can be seen from Examples 1 to 3 and Comparative Example 2, the porous membrane 51 can effectively regulate water vapor, making it less likely for the calcium peroxide microcapsules in the oxygen generation layer 4 to undergo explosive reactions, thereby avoiding platelet oxidative stress and prolonging platelet preservation time.

[0105] As can be seen from Examples 1 to 3 and Comparative Examples 3 to 4, the lack of pre-bonding leads to a high breakage rate for both calcium peroxide microcapsules and lithium hydroxide microcapsules, both of which easily damage platelets. Furthermore, the absence of shaping and cooling, coupled with ambient pressure and temperature cooling, results in a rapid temperature drop, causing residual stress accumulation between the two composite film layers. This leads to microcracks at the interface, subsequently causing gas channel collapse and an imbalance in oxygen and carbon dioxide exchange, ultimately affecting platelet storage time.

[0106] The above are all preferred embodiments of this application, and are not intended to limit the scope of protection of this application. Therefore, all equivalent changes made in accordance with the structure, shape and principle of this application should be covered within the scope of protection of this application.

Claims

1. A platelet storage bag, comprising a bag body (1) fixedly connected to the periphery to form a space on the central side for storing platelets, and a connecting tube (2) communicating within the bag body (1) for platelet circulation, characterized in that: The bag (1) includes two layers of isolation membrane (3) that are in contact with platelets and allow gas to pass through only, an oxygen generating layer (4) and a carbon dioxide absorbing layer (5) that are composited one-to-one on opposite surfaces of the two isolation membranes (3), with calcium peroxide microcapsules embedded in the oxygen generating layer (4) and lithium hydroxide microcapsules embedded in the carbon dioxide absorbing layer (5).

2. The platelet preservation bag according to claim 1, characterized in that: The separator (3) is a PTFE / PE composite membrane.

3. The platelet preservation bag according to claim 1, characterized in that: The oxygen generating layer (4) is a PE film, and the carbon dioxide absorbing layer (5) is a PP film.

4. A platelet preservation bag according to claim 1, characterized in that: The oxygen generation layer (4) has a porous membrane (51) on the surface away from the isolation membrane (3), and the porous membrane (51) is a SiO2 / PVP composite membrane.

5. A method for manufacturing a platelet preservation bag, comprising manufacturing a platelet preservation bag as described in any one of claims 1-4, characterized in that: Specifically, the steps include the following: S1. Melt PE particles and add calcium peroxide microcapsules, extrude and mix them and cast them into an oxygen generation layer (4). S2. A mixed solution of SiO2 and PVP is scraped onto the outer surface of the oxygen generation layer (4), and a porous membrane (51) is formed after curing. S3. Melt PP particles and add lithium hydroxide microcapsules, extrude and mix them and cast them into a carbon dioxide absorption layer (5). S4. The oxygen generating layer (4) and the PE surface of the isolation membrane (3) are hot-melted and bonded together; the carbon dioxide absorbing layer (5) and the PE surface of the isolation membrane (3) are hot-melted and bonded together. S5. Stack the two layers of isolation film (3) that have been composited in S4 and weld the three peripheries of the isolation film (3) to form the bag body (1). S6. Insert the connecting tube (2) into the opening of the bag body (1) in S5 and weld it.

6. A method for manufacturing a platelet preservation bag according to claim 5, characterized in that: The isolation membrane (3) is made by hot pressing molten PE particles and porous PTFE membrane at a temperature of 175-185℃, a pressure of 9-11 MPa, and a hot pressing time of 55-65s.

7. A method for manufacturing a platelet preservation bag according to claim 5, characterized in that: The hot melt bonding process in S4 specifically includes the following steps: S41. Spray hot melt adhesive between the two films to be laminated; S42. Perform pre-bonding at a temperature of 78-82℃, a pressure of 1.8-2.2Mpa, and a time of 9-11s; S43, perform main fusion at a temperature of 127-133℃, a pressure of 4.6-5.4 MPa, and a time of 43-47 seconds; S44. Perform shaping and cooling at a temperature of 58-62℃, a pressure of 0.9-1.1Mpa, and a time of 27-33s.

8. A method for manufacturing a platelet preservation bag according to claim 5, characterized in that: After the hot melt bonding is completed in step S4, the two composite films are welded around their perimeter.

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