WO2015111745A1 - 血小板製剤保存装置および血小板製剤の保存方法 - Google Patents

血小板製剤保存装置および血小板製剤の保存方法 Download PDF

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Publication number
WO2015111745A1
WO2015111745A1 PCT/JP2015/052049 JP2015052049W WO2015111745A1 WO 2015111745 A1 WO2015111745 A1 WO 2015111745A1 JP 2015052049 W JP2015052049 W JP 2015052049W WO 2015111745 A1 WO2015111745 A1 WO 2015111745A1
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Prior art keywords
platelet
platelet preparation
equation
prp
storage
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PCT/JP2015/052049
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English (en)
French (fr)
Japanese (ja)
Inventor
敦子 本馬
俊昌 落合
宮本　篤
光也 白石
丸山　征郎
Original Assignee
三菱重工業株式会社
国立大学法人鹿児島大学
大塚製薬株式会社
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Publication of WO2015111745A1 publication Critical patent/WO2015111745A1/ja

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F29/00—Mixers with rotating receptacles
    • B01F29/10—Mixers with rotating receptacles with receptacles rotated about two different axes, e.g. receptacles having planetary motion
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F29/00—Mixers with rotating receptacles
    • B01F29/30—Mixing the contents of individual packages or containers, e.g. by rotating tins or bottles
    • B01F29/33—Mixing the contents of individual packages or containers, e.g. by rotating tins or bottles by imparting a combination of movements to two or more containers

Definitions

  • the present invention relates to a platelet preparation storage device and a method for storing a platelet preparation.
  • platelet preparation for transfusion used for patients who need transfusion of platelets. If the transfusion platelet preparation is not stored in a state of horizontal shaking, the permeation of oxygen becomes insufficient, and the metabolism of platelets becomes anaerobic, resulting in a decrease in pH, a decrease in platelet function, and the like. Therefore, platelet preparations for transfusion are stored, for example, using a horizontal shaker, a horizontal and rotating shaker, etc. (see, for example, Patent Document 1). In addition, the platelet preparation for blood transfusion generally has an expiration date of 4 days after blood collection.
  • the storage conditions for platelet preparations for transfusion are other preparations such as red blood cell preparations (21 days after blood collection, storage temperature: 2 to 6 ° C.) and plasma preparations (one year after blood collection, storage temperature: -20 ° C. or less) It is strict compared to blood products, and the expiration date of platelet preparations for blood transfusion is also short compared to other blood products.
  • the present applicant also uses target cells in a simulated microgravity environment generated by multiaxial rotation as an apparatus for proliferating and culturing bone marrow stromal cells (BMSCs) or mesenchymal stem cells (MSCs) in an undifferentiated state.
  • BMSCs bone marrow stromal cells
  • MSCs mesenchymal stem cells
  • the present invention is made in view of the above, and an object of the present invention is to provide a platelet preparation storage device and a storage method of a platelet preparation which can suppress the functional deterioration of the platelet preparation.
  • the rotating device includes a holding unit for holding the platelet preparation container, and a first rotating body connected to the holding unit and holding the holding unit, and the first rotating body for the first rotation.
  • a first drive unit configured to rotate around an axis
  • a second rotating body configured to rotatably hold the first rotating body around the first rotation axis, and an axial center of the first rotation axis;
  • a leg portion rotatably held about a second rotation axis having an axial direction different from the direction, and a second drive portion rotating the second rotation body around the second rotation axis; It is preferable to have.
  • the platelet preparation storage unit has a pair of partition parts for partitioning a plurality of the platelet preparation storage containers inside the platelet preparation storage unit.
  • the holding portion preferably includes a pair of facing holding plates and a plurality of connecting portions for connecting the holding plate and the first rotating body, and is preferably formed in a box shape.
  • the present invention is characterized in that the platelet preparation storage container for storing a sample containing platelets is rotated in the n-axis direction (n is an integer of 2 or more), and the platelets are preserved while suppressing aggregation of the platelets. It is a storage method of a platelet preparation to be used.
  • the rotating device includes a holding unit for holding the platelet preparation container, and a first rotating body connected to the holding unit and holding the holding unit, and the first rotating body for the first rotation.
  • a first drive unit configured to rotate around an axis
  • a second rotating body configured to rotatably hold the first rotating body around the first rotation axis, and an axial center of the first rotation axis;
  • a leg portion rotatably held about a second rotation axis having an axial direction different from the direction, and a second drive portion rotating the second rotation body around the second rotation axis; It is preferable to have.
  • the platelet preparation storage device of the present invention By using the platelet preparation storage device of the present invention, it is possible to suppress the functional deterioration of the platelet preparation. By using the method for storing a platelet preparation of the present invention, it is possible to suppress the decrease in the function of the platelet preparation.
  • FIG. 1 is a view showing an example of a platelet preparation storage device according to an embodiment of the present invention.
  • FIG. 2 is a view showing a platelet preparation storage container and a platelet preparation storage unit.
  • FIG. 3 is an explanatory view showing a coordinate system defined for the platelet preparation storage device.
  • FIG. 4 shows platelet count of platelet-rich plasma (PRP) immediately after blood collection and PRP after storage by the method of Example 1 and Comparative Examples 1 and 2.
  • FIG. 5 shows the mean platelet volume (MPV) of PRP immediately after blood collection and PRP after storage by the method of Example 1 and Comparative Examples 1 and 2.
  • FIG. 1 is a view showing an example of a platelet preparation storage device according to an embodiment of the present invention.
  • FIG. 2 is a view showing a platelet preparation storage container and a platelet preparation storage unit.
  • FIG. 3 is an explanatory view showing a coordinate system defined for the platelet preparation storage device.
  • FIG. 4 shows platelet count of platelet-rich plasma
  • FIG. 6 is a graph showing the platelet distribution width (PDW) of PRP immediately after blood collection and PRP after storage by the methods of Example 1 and Comparative Examples 1 and 2.
  • FIG. 7 is a diagram showing the clot retraction rate of PRP immediately after blood collection and PRP after storage by the methods of Example 1 and Comparative Examples 1 and 2.
  • FIG. 8 is a diagram showing hypotonic shock recovery rates of PRP immediately after blood collection and PRP after storage by the methods of Example 1 and Comparative Examples 1 and 2.
  • FIG. 9 is a diagram showing the platelet aggregation reaction of PRP immediately after blood collection and PRP after storage by the method of Example 1 and Comparative Examples 1 and 2.
  • FIG. 10 is a diagram showing platelet counts of PRP immediately after blood collection and PRP after storage by the method of Example 2 and Comparative Example 3.
  • FIG. 11 is a diagram showing MPV of PRP immediately after blood collection and PRP after storage by the method of Example 2 and Comparative Example 3.
  • FIG. 12 is a diagram showing PDW of PRP immediately after blood collection and PRP after storage by the method of Example 2 and Comparative Example 3.
  • FIG. 13 is a diagram showing the platelet aggregation reaction of PRP immediately after blood collection and PRP after storage by the method of Example 2 and Comparative Example 3.
  • FIG. 1 is a view showing an example of a platelet preparation storage device according to an embodiment of the present invention.
  • FIG. 2 is a view showing a platelet preparation storage container and a platelet preparation storage unit.
  • the platelet preparation storage device 10 includes a three-dimensional crinostat (rotation device) 11 and a platelet preparation storage unit 12.
  • a three-dimensional crinostat (rotation device) 11 and a platelet preparation storage unit 12.
  • platelets of animals such as humans and rabbits are used as the platelet preparation.
  • the three-dimensional cryostat 11 includes a holding unit 13, an inner frame (first rotating body) 14, an outer frame (second rotating body) 15, a leg 16, a first motor (first drive unit) 17, and a second motor
  • the second drive unit 18 is provided.
  • the holding unit 13 holds the platelet preparation storage unit 12.
  • the holding portion 13 includes a pair of facing holding plates 13a and a plurality of connecting portions 13b, and is formed in a box shape.
  • the pair of holding plates 13 a is a flat plate, and is disposed so as to face the inner frame 14 at a position sandwiching the inner frame 14 therebetween. That is, the two holding plates 13a are arranged in parallel with each other in the direction in which the faces (front faces) having the largest area face each other.
  • One end of the connection portion 13 b is connected to the inner frame 14, and the other end is connected to one of the holding plates 13 a.
  • the connecting portion 13b is connected to any one of four corners of the holding plate 13a.
  • the connecting portion 13 b is fixed to the holding plate 13 a by a screw. Each of the four corners of the holding plate 13a is connected to the connecting portion 13b.
  • the holding plate 13a is fixed to the inner frame 14 by the connecting portion 13b.
  • the holding portion 13 fixes the two holding plates 13a to the inner frame 14 by the plurality of connecting portions 13b.
  • the platelet preparation housing unit 12 is disposed in a space surrounded by the two holding plates 13a.
  • the holding unit 13 fixes the platelet preparation container 12 between the pair of holding plates 13 a by sandwiching the platelet preparation container 12 with the pair of holding plates 13 a.
  • the holding unit 13 supports and fixes the platelet preparation storage container 12 by screwing, but the mechanism by which the holding unit 13 supports and fixes the platelet preparation storage container 12 is not particularly limited. You may fix by methods other than screwing. Moreover, the distance between the pair of holding plates 13a facing each other can be adjusted to an arbitrary length by adjusting the length of the connecting portion 13b. For this reason, the holding unit 13 can be appropriately adjusted to an arbitrary length in accordance with the length and the like of the platelet preparation storage container 12 sandwiched by the holding unit 13.
  • the inner frame 14 is a rectangular frame.
  • the inner frame 14 holds the platelet preparation container 12 via the holder 13.
  • the inner frame 14 rotates around the first rotation axis ⁇ .
  • the first rotation axis ⁇ is an axis passing through the rotation axis of the first motor 17.
  • the rotation direction of the inner frame 14 may be either clockwise or counterclockwise.
  • the outer frame 15 is a rectangular frame formed of four side portions 15a, and the holding portion 13 and the inner frame 14 are disposed inside the frame.
  • the outer frame 15 holds a pair of opposing side portions 15 a of the four side portions 15 a so that the inner frame 14 can rotate around the first rotation axis ⁇ .
  • the outer frame 15 is held by the leg portion 16 so that the other pair of opposing side portions 15a among the four side portions 15a can rotate around the second rotation axis ⁇ .
  • the second rotation axis ⁇ is an axis in a direction orthogonal to the first rotation axis ⁇ .
  • the rotation direction of the outer frame 15 may be either clockwise or counterclockwise.
  • the legs 16 hold the outer frame 15 so that it can rotate around the second rotation axis ⁇ .
  • the legs 16 are fixed to the mount 19.
  • the first motor 17 rotates the inner frame 14 around the first rotation axis ⁇ .
  • the first motor 17 is provided outside the one side portion 15 a of the pair of side portions 15 a.
  • the first motor 17 rotates the inner frame 14 around the first rotation axis ⁇ through a power transmission mechanism such as a gear, a belt or the like.
  • the second motor 18 is provided on one leg 16 of the pair of legs 16.
  • the second motor 18 rotates the outer frame 15 around the second rotation axis ⁇ via a power transmission mechanism such as a gear, a belt or the like.
  • the first rotation axis ⁇ and the second rotation axis ⁇ are substantially orthogonal to each other.
  • the inner frame 14, the outer frame 15 and the leg portion 16 constitute a gimbal mechanism which can be tilted in any direction by combining the first rotation axis ⁇ and the second rotation axis ⁇ orthogonal to each other.
  • the first rotation axis ⁇ and the second rotation axis ⁇ are not limited to be provided to be orthogonal to each other, but the first rotation axis ⁇ and the second rotation axis ⁇ have a predetermined angle. It may be provided.
  • the platelet preparation storage unit 12 is a container capable of storing a plurality of platelet preparation storage containers 21.
  • the platelet preparation storage container 21 is a container for storing a platelet preparation, and includes a sample enclosing unit 23 for enclosing the platelet preparation.
  • the platelet preparation storage container 21 is provided with a lid 26 which can be removed from the platelet preparation storage container 21 in the sample enclosing unit 23. After the platelet preparation is enclosed in the sample enclosure 23, the platelet enclosure 23 can be closed by the lid 26.
  • the platelet preparation is stored in the inside of the platelet preparation storage container 21 by the platelet preparation being enclosed in the sample enclosing unit 23.
  • the method for sealing the platelet preparation in the sample sealing portion 23 is not limited to the method of providing the removable lid 26 in the sample sealing portion 23.
  • the sample sealing portion 23 is provided with an openable lid, and the sample sealing portion The platelet preparation may be enclosed in 23.
  • the platelet preparation storage unit 12 includes a plurality of dividers 24 inside the platelet preparation storage unit 12.
  • the partitions 24 are formed at intervals corresponding to the width of the platelet preparation storage container 21.
  • the platelet preparation storage container 12 can hold the platelet preparation storage container 21 inside by inserting the platelet preparation storage container 21 between the dividers 24 and 24.
  • the platelet preparation storage unit 12 divides and stores the plurality of platelet preparation storage containers 21 by the partition unit 24, the position of the platelet preparation storage container 21 in the platelet preparation storage unit 12 can be fixed, and The platelet preparation storage container 21 can be easily attached and detached.
  • the platelet preparation container 12 is in the vicinity of the intersection of the first rotation axis ⁇ and the second rotation axis ⁇ .
  • the platelet preparation housing unit 12 is held by the holding unit 13, and thus rotates integrally with the inner frame 14.
  • the inner frame 14 is rotated about the first rotation axis ⁇ by the first motor 17, and the outer frame 15 is rotated about the second rotation axis ⁇ by the first motor 17. Rotate 2 axes.
  • the three-dimensional clinostat 11 combines the first rotation axis ⁇ and the second rotation axis ⁇ and rotates the platelet preparation storage container 21 in three dimensions to generate a pseudo weightless state.
  • the three-dimensional crinostat 11 can maintain the quality of the platelet preparation by placing the platelet preparation in a pseudo-gravity state, and can prolong the storage period of the platelet preparation.
  • the present inventors disperse the platelets in the platelet preparation. It can be made to stir uniformly with a fixed load in three dimensions.
  • the three-dimensional crinostat 11 can reduce stress given to platelets as compared with the case where a platelet preparation is shaken horizontally using a generally used horizontal shaker. Thereby, since the three-dimensional crinostat 11 can suppress the function decrease of the platelet aggregation action and can store the platelet preparation, the quality of the platelet preparation can be maintained and the storage period of the platelet preparation can be extended. Think of what you can do.
  • platelet count in platelet preparation for example, platelet count in platelet preparation, mean platelet volume (MPV), platelet distribution width (PDW), clot retraction rate, hypotonic shock recovery rate and platelets Aggregation reaction etc. are mentioned.
  • MPV and PDW are indicators of changes in platelet morphology.
  • the platelet count, MPV and PDW are measured, for example, using an automatic blood cell counter known to date.
  • the clot retraction rate is an indicator of platelet function.
  • the clot retraction rate is determined by adding a predetermined amount of a thrombin solution to a platelet preparation and measuring after a predetermined time has elapsed.
  • the hypotonic shock recovery rate is determined by adding distilled water to a platelet preparation and measuring the change in platelet morphology and the recovery state after a predetermined time as a change in turbidity.
  • the platelet aggregation reaction is determined by adding a predetermined concentration (for example, 10 ⁇ M) of adenosine diphosphate (ADP) to a platelet preparation and measuring the aggregation reaction by turbidimetry.
  • the three-dimensional crinostat 11 rotates the platelet preparation storage container 12 by two axes, but it is not limited to this.
  • the platelet preparation storage container 12 further has a plurality of rotating shafts (for example, , N-axis rotation: n is an integer of 2 or more, preferably an integer of 2 or more and 10 or less, more preferably an integer of 2 or more and 5 or less, and still more preferably 2). You may do it. Even in this case, as in the case of the two-axis rotation, the direction of the gravity acting on the platelets in the platelet preparation is dispersed by the rotation of the platelet preparation storage container 12, and the platelets are uniformly agitated in a three-dimensional constant load. Can.
  • FIG. 3 is an explanatory view showing a coordinate system defined by the platelet preparation storage device 10.
  • the first rotation axis ⁇ and the second rotation axis ⁇ correspond to the X 0 axis and the Y 0 axis.
  • a stationary reference coordinate system ⁇ P 0 , X 0 , Y 0 , Z 0 ⁇ fixed to the gantry 19 is defined.
  • a coordinate system ⁇ P 1 , X 1 , Y 1 , Z 1 ⁇ fixed to the outer frame 15 is defined, and a coordinate system ⁇ P 2 , X 2 , Y 2 fixed to the inner frame 14 , Z 2 ⁇ is defined.
  • the X 0 axis and the Y 0 axis point in the horizontal direction, and the Z 0 axis is vertically downward.
  • the platelet preparation storage device 10 further includes a rotation angle detector 31, a rotation angle detector 32, and a control device 35 having a motor control unit (motor controller) 33 and a track generation unit 34.
  • the rotation angle detector 31 detects a rotation angle ⁇ around the Y 0 axis with respect to the mount 19 of the outer frame 15, and outputs the detected rotation angle ⁇ S to the motor control unit 33.
  • the rotation angle detector 32 detects a rotation angle ⁇ around the X 1 axis with respect to the outer frame 15 of the inner frame 14, and outputs the detected rotation angle ⁇ S to the motor control unit 33.
  • the trajectory generation unit 34 outputs the rotation angle command ⁇ * and the rotation angle command ⁇ * to the motor control unit 33.
  • the motor control unit 33 outputs the torque command ⁇ ⁇ * to the motor controller 33 so that the detected rotation angle ⁇ S matches the rotation angle command ⁇ * so that the detected rotation angle ⁇ S matches the rotation angle command ⁇ *.
  • the torque command ⁇ ⁇ * is output to the motor controller 34.
  • the motor controller 33 rotates the outer frame 15 around the Y 0 axis as the torque command tau theta *.
  • the motor controller 34 rotates the inner frame 14 about the X 1 axis in accordance with the torque command tau phi *.
  • P 0 , X 0 , Y 0 , and Z 0 are formulas (Equation 1): Is represented by Here, the superscript "T” means "transposition”.
  • R Y is a coordinate transformation matrix representing rotation about the Y 0 axis
  • equation (Equation 4) Is represented by
  • R X is a coordinate transformation matrix representing rotation about the X 1 axis
  • equation (5) Is represented by
  • the trajectory generation unit 34 outputs, to the motor control unit 33, a rotation angle command ⁇ * and a rotation angle command ⁇ * respectively indicating ⁇ (t) and ⁇ (t).
  • ⁇ (t) and ⁇ (t) are equations (11) for time t, predetermined period T, predetermined coefficients b 1 and b 2k + 1 , and predetermined positive integers k, M and N: Is represented by Here, M and N are equations (12) for any positive integer m: Meet. Also, b 1 and b 2k + 1 have an equation (Equation 13): Solution of
  • the experimenter determines the cycle T such that the experiment time is a positive integer multiple of the cycle T, and rotates the rotation around the Y 0 axis and the rotation around the X 1 axis during the cycle T, respectively.
  • the parameters M and N may be determined depending on
  • the infinite-order differential function at an arbitrary time t is also continuous, so that the rotation angle around Y 0 and around X 1 axis, rotation angular velocity, rotation angular acceleration Is prevented from changing rapidly. Therefore, when the platelet preparation storage device 10 is operated, generation of vibration is prevented.
  • Equation 16 the components of gravitational acceleration g x , g Y and g Z are expressed by the equation (Equation 16): Is represented by Therefore, the conditions under which the gravity given by the equation (Equation 14) is temporally canceled are the equations (Equation 17) to the equation (Equation 19): Is represented by Also, the condition of uniform dispersion of gravity given by equation (Equation 15) is equation (Equation 20): Is represented by
  • Equation 25 If the rotational angular velocity about the Y 0 axis is constant as shown in, it is examined whether the conditions of the equations (17) to (19) and the equations (21) to (23) are satisfied.
  • Equation (21) is not satisfied as shown in
  • Equation 27 As shown in the figure, when the rotational angular velocity around the X 1 axis is constant, it is examined whether the conditions of the equations (17) to (19) and the equations (21) to (23) are satisfied. Do.
  • Equation 29 It is calculated as
  • Equation 28 The sin 2 ⁇ included in the fourth term on the right side of the equation (Equation 28) is an even function. Then, since the outer frame 15 rotates M around the Y 0 axis during the period T, the fundamental angular frequency of sin ⁇ is 2 ⁇ M / T, so the fundamental angular frequency of sin 2 ⁇ in which sin ⁇ is squared is 4 ⁇ M / It becomes T. At this time, since sin 2 ⁇ can be generally expressed by a Fourier series of even functions, equation (Equation 30): Is represented by Here, the coefficients a 0 and a m, equation (31): Is represented by
  • Equation 33 As shown in, the fourth term of the right side of the equation (Equation 28) is zero.
  • equation (34) Is obtained.
  • equation (34) is rearranged, it has the same form as equation (21).
  • Equation 22 ⁇ (t) satisfying equation (21) is determined by defining ⁇ (t) by equation (27) under the boundary conditions for each period shown in equation (24), the determined ⁇ (T) simultaneously satisfies the equation (Equation 22).
  • Equation 36 Is represented by
  • Equation 37 The sin ⁇ (t) represented by the equation (Equation 37) satisfies the equation (Equation 17). Since the outer frame 15 rotates M around the Y 0 axis during the period T, sin ⁇ is represented by a Fourier series having 2 ⁇ M / T as the fundamental angular frequency, so sin ⁇ (t) can be expressed by the equation (Equation 37) It is clear that the equation (17) holds, even in the case where the equation (17) is not used. Further, since cos ⁇ is also expressed by a Fourier series having 2 ⁇ M / T as the fundamental angular frequency, equation (18) holds, and equation (12) holds for any positive integer m. Equations (Equation 19) also hold true if the rotational speeds M and N are selected.
  • Equation 41 the solution of coefficients b 1 and b 2k + 1 is Equation 41. Is represented by
  • a method of storing a platelet preparation according to an embodiment of the present invention will be described.
  • the method of storing a platelet preparation according to the present embodiment is performed using a three-dimensional crinostat 11 in a predetermined temperature range.
  • the platelet preparation is not particularly limited as long as it can be used for blood transfusion, and generally, platelet rich plasma (PRP), which is a plasma obtained by concentrating platelets from peripheral blood. It is synonymous.
  • PRP platelet rich plasma
  • platelet preparations contain 0.2 ⁇ 10 11 platelets per unit in citrated plasma.
  • the platelet preparation storage container is not particularly limited as long as it is a container capable of stably storing platelets, but (a list of possible materials for the container can be mentioned) Among the materials of (1), preferred ones are preferred.
  • the predetermined temperature range is not particularly limited as long as it is an optimum temperature range for storing the blood preparation, but in general, when the blood preparation is a platelet preparation, the optimum temperature range is 22 ° C ⁇ 2 ° C. In addition, when the blood preparation is an erythrocyte preparation, the optimum temperature range is 4 ° C ⁇ 2 ° C. When the blood product is a plasma product, the optimum temperature range is -20 ° C or less. In the present embodiment, the optimum temperature range is 22 ° C. ⁇ 2 ° C., since platelet preparations are stored. This temperature range may be called room temperature.
  • the platelet preparation is enclosed in the sample enclosure 23 of at least one platelet preparation storage container 21. Thereafter, at least one platelet preparation storage container 21 is accommodated in the platelet preparation accommodation unit 12. Thereafter, the three-dimensional clinostat 11 is operated to rotate the platelet preparation storage unit 12 by two axes.
  • the platelet preparation storage container 21 can be rotated in three dimensions, so that platelets in the platelet preparation can be stored while being uniformly stirred in a three-dimensional constant load.
  • the platelets in the platelet preparation are rotated in three dimensions and uniformly stirred with a constant load, so that the platelet preparation is horizontalized using the horizontal shaking method.
  • the stress applied to platelets can be reduced as compared to the case of shaking. Therefore, since the platelet preparation can be stored while suppressing aggregation of platelets, the quality of the platelet preparation can be maintained and the storage period of the platelet preparation can be extended.
  • the platelet preparation storage unit 12 is held by the inner frame 14 before storing the platelet preparation storage container 21 in the platelet preparation storage unit 12, but the invention is not limited to this. After the platelet preparation storage container 21 is accommodated in the platelet preparation accommodation unit 12, the platelet preparation accommodation unit 12 may be held on the inner frame 14.
  • the platelet preparation storage container 21 is stored while being rotated using the three-dimensional crinostat 11 is described, but the present invention is not limited to this.
  • the platelet preparation storage container 21 may be stored while being rotated using a multi-dimensional, rotatable rotation device.
  • the platelet preparation is stored using the three-dimensional crinostat 11
  • the invention is not limited to this, and in addition to platelets, for example, anticoagulant, storage solution And platelet preparations such as red blood cell preparations and blood plasma preparations, culture solutions containing human, animal or plant cells, artificial organs and the like.
  • Example 1 After collecting blood (100 ml) from a Japanese white rabbit, it was centrifuged for 10 minutes with a centrifugal gravity of about 400 G, and platelet-rich plasma (PRP), which is the supernatant from which precipitated red blood cells were removed, was collected. .
  • the collected PRP was stored at room temperature for 72 hours in a state (three-dimensional rotation condition) in which it was housed and rotated in the housing member 22 installed in the three-dimensional clinostat 11 in Opticell (manufactured by NUNC). .
  • room temperature is a temperature range optimum for storing a platelet preparation, and means a range of 20 ° C. or more and 24 ° C. or less.
  • Comparative Examples 1 and 2 In the comparative example 1, it carried out like Example 1 except having changed the storage conditions of PRP into the state (stationary condition) which rested. Comparative Example 2 is the same as Example 1 except that the storage condition of PRP is changed to a state of horizontal shaking (horizontal shaking condition: manufactured by BC-730 BIO CRAFT) and stored by two-dimensional movement. went.
  • ⁇ Evaluation method Platelet count, mean platelet volume (MPV), platelet distribution width (PDW), clotting regression rate, hypotonic shock recovery rate with PRP immediately after blood collection and PRP after storage by the method of each example and comparative example And platelet aggregation reaction was measured and evaluated by the following method.
  • Platelet count mean platelet volume (MPV), platelet distribution width (PDW)
  • MPV mean platelet volume
  • PDW platelet distribution width
  • the platelet count, MPV and PDW were measured using an automatic blood cell counter (F-820, Sysmex Corporation) with PRP immediately after blood collection and PRP after storage by the methods of the respective Examples and Comparative Examples. Eleven platelet samples and MPV were prepared and the average value was calculated. PDW made eight samples and calculated the average value.
  • the hypotonic shock recovery rate was measured by PRP immediately after blood collection and the change in turbidity of PRP after storage by the method of each example and comparative example.
  • the change of the turbidity was measured by the change of the turbidity for 5 minutes measured using CAF-100 (manufactured by JASCO Corporation) by adding 0.2 mL of distilled water to 0.4 mL of PRP.
  • the change in turbidity immediately after adding distilled water was taken as 100%, and the rate at which the turbidity was recovered after 5 minutes was taken as the hypotonic shock recovery rate.
  • the hypotonic shock recovery rate was determined by preparing eight samples and averaging them.
  • the platelet agglutination reaction was carried out by turbidifying the agglutination reaction by adding 10 ⁇ M of adenosine diphosphate (ADP) to PRP immediately after blood collection and 0.4 mL of PRP after storage according to the method of each example and comparative example. It was measured. Platelet agglutination reaction prepared eight samples and calculated the average value.
  • ADP adenosine diphosphate
  • FIG. 4 is a diagram showing the evaluation results of platelet counts of PRP immediately after blood collection and PRP after storage by the methods of Example 1 and Comparative Examples 1 and 2.
  • FIG. 5 is a graph showing PRP immediately after blood collection and
  • FIG. 6 is a diagram showing the evaluation results of MPV with PRP after storage by the methods of Example 1 and Comparative Examples 1 and 2.
  • FIG. 6 shows PRP immediately after blood collection, Example 1, and Comparative Example 1
  • FIG. 7 shows the evaluation results of PDW with PRP after storage by the method 2
  • FIG. 7 shows PRP immediately after blood collection and PRP after storage by the methods of Example 1 and Comparative Examples 1 and 2.
  • FIG. 8 is a diagram showing the evaluation results of the blood clot retraction rate, and FIG. 8 shows the hypotonic shock recovery rates of PRP immediately after blood collection and PRP after storage by the methods of Example 1 and Comparative Examples 1 and 2.
  • FIG. 9 shows the PRP immediately after blood collection, Example 1, and Comparative Example 1, Is a graph showing evaluation results of the platelet aggregation reaction with PRP after storage at ways.
  • Example 1 was closer to the platelet count of PRP immediately after blood collection than Comparative Examples 1 and 2. Decreased platelet count is an indicator of platelet damage.
  • PRP platelet count
  • Comparative Example 1 the platelet count tends to decrease compared to that immediately after blood collection (see Comparative Example 1), so platelet preparations are stored under static conditions. If so, it is possible that platelet destruction has occurred.
  • PRP was stored at room temperature for 72 hours under horizontal shaking conditions or three-dimensional rotation conditions, a tendency to suppress the decrease in platelet count was observed compared to when platelet preparations were stored under static conditions (implementation See Example 1 and Comparative Example 2).
  • MPV and PDW As shown in FIG. 5 and FIG. 6, MPV and PDW of PRP after storage using any of the storage methods of Example 1 and Comparative Examples 1 and 2 are values close to MPV and PDW of PRP immediately after blood collection. And hardly changed. MPV and PDW are indicators of changes in platelet morphology. Therefore, it was found that even if PRP was stored at room temperature for 72 hours under three-dimensional rotation conditions instead of the standing condition and the horizontal shaking condition, the platelet morphology could be maintained in the same manner as the conventional storage method.
  • Example 1 was a value almost similar to the hypotonic shock recovery rate of PRP immediately after blood collection, and was almost the same value as Comparative Examples 1 and 2.
  • PRP was stored at room temperature for 72 hours under three-dimensional rotation conditions instead of the standing condition and the horizontal shaking condition, almost the same function as the PRP immediately after blood collection could be maintained.
  • Platelet aggregation reaction As shown in FIG. 9, the platelet aggregation reaction of PRP after storage using any of the storage methods of Example 1 and Comparative Examples 1 and 2 was a value lower than that of PRP immediately after blood collection. However, the platelet aggregation response of PRP after storage was higher in Example 1 than in Comparative Examples 1 and 2. Platelet aggregation is an indicator of platelet function, as platelet aggregation is an important response to hemostasis. When PRP is stored under static conditions or horizontal shaking conditions, it can be said that the function involved in platelet aggregation reaction is reduced as compared to PRP immediately after blood collection.
  • Example 2 PRP was collected in the same manner as in Example 1 except that human (five adult males in their twenties and forties) blood was used. The collected PRP was stored for 7 days in a state of being accommodated and rotated in an accommodation member 22 installed in a three-dimensional crinostat 11 in Opticell (manufactured by NUNC) (three-dimensional rotation condition).
  • Comparative Example 3 is the same as Example 2 except that the storage condition of PRP is changed to a state of horizontal shaking (horizontal shaking condition: BC-730 BIO CRAFT Co., Ltd.), and storage is performed by two-dimensional movement. went.
  • FIG. 10 is a diagram showing the evaluation results of platelet counts of PRP immediately after blood collection and PRP after storage by the method of Example 2 and Comparative Example 3.
  • FIG. 11 is a graph showing PRP immediately after blood collection and Example. It is a figure which shows the evaluation result of MPV with PRP after preserve
  • FIG. 12 shows the PRP immediately after blood collection and the PRP after preserve
  • FIG. 13 shows the evaluation results of the platelet aggregation reaction between PRP immediately after blood collection and PRP after storage by the method of Example 2 and Comparative Example 3. .
  • the platelet aggregation reaction of PRP after storage using any of the storage methods of Example 2 and Comparative Example 3 has a tendency to decrease with the number of storage days, and is almost recognized after 7 days of storage. It is no longer possible.
  • the reduction rate of the platelet aggregation reaction of PRP of Comparative Example 3 is large relative to the reduction rate of the platelet aggregation reaction of Example 2 PRP, and in particular, the platelet aggregation reaction of Example 2 PRP after 5 days of storage and Comparative Example A significant difference was seen between the platelet aggregation response of 3 PRP.
  • the platelet agglutination reaction in Example 2 had a higher value than that in Comparative Example 3.
  • the PRP stored in a three-dimensional rotational condition tends to exhibit a higher agglutination reaction than the horizontal shaking condition. Since it is recognized, it can be said that it is preferable as a preservation method of PRP.
  • the platelet aggregation response to ADP is significantly higher than in horizontal shaking conditions, and it can be said that the function related to platelet aggregation is maintained. Therefore, it turned out that the fall of the function with respect to PRP immediately after blood collection can be suppressed by replacing with horizontal shaking conditions and storing PRP under three-dimensional rotation conditions.
  • the platelet preparation is stored while being rotated in three dimensions, and the agitation movement at the storage of the platelet preparation is minimized, thereby maintaining the number of platelets and preserving while suppressing aggregation of platelets.
  • it can, it can contribute to prolonging the storage period of the platelet preparation while maintaining the quality of the platelet preparation. As a result, it is possible to contribute to providing high quality platelet preparations.
  • Platelet preparation storage device 11
  • Three-dimensional crinostat (rotation device) 12
  • Platelet preparation container 13
  • Holding portion 14
  • Inner frame (first rotating body) 15
  • Outer frame (second rotating body) 16
  • legs 17
  • first motor (first drive) 18
  • Reference Signs List 19
  • gantry 21
  • platelet preparation storage container 23 sample enclosing unit 24
  • partition unit 26 lid
  • rotation angle detector 32 rotation angle detector 33
  • motor control unit 34 trajectory generator 35 controller

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CN106985276A (zh) * 2017-05-27 2017-07-28 晋江诺研机械设计有限公司 一种用于稀土矿的快速制浆装置

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CN111068364A (zh) * 2019-12-21 2020-04-28 青岛市中心血站 一种用于机采血小板解聚设备
JP7065549B1 (ja) 2022-01-06 2022-05-12 有限会社親森テクノ 撹拌装置

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JPS5833013U (ja) * 1981-08-28 1983-03-03 株式会社東芝 血液恒温庫
JPH0375829U (enrdf_load_stackoverflow) * 1989-11-22 1991-07-30
JP2010246434A (ja) * 2009-04-13 2010-11-04 Mitsubishi Heavy Ind Ltd 骨髄間質細胞及び間葉系幹細胞の培養方法、中枢神経系疾患治療用の移植細胞の製造方法
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JPS5833013U (ja) * 1981-08-28 1983-03-03 株式会社東芝 血液恒温庫
JPH0375829U (enrdf_load_stackoverflow) * 1989-11-22 1991-07-30
JP2010246434A (ja) * 2009-04-13 2010-11-04 Mitsubishi Heavy Ind Ltd 骨髄間質細胞及び間葉系幹細胞の培養方法、中枢神経系疾患治療用の移植細胞の製造方法
JP2012080874A (ja) * 2010-09-15 2012-04-26 National Institute Of Advanced Industrial Science & Technology 擬微小重力環境下での三次元組織構築方法

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106985276A (zh) * 2017-05-27 2017-07-28 晋江诺研机械设计有限公司 一种用于稀土矿的快速制浆装置
CN106985276B (zh) * 2017-05-27 2018-12-21 绍兴柯桥嘉好钰定型有限公司 一种用于稀土矿的快速制浆装置

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