JP2023125342A - Storage device and cell transplantation unit - Google Patents

Abstract

To secure the sufficient strength for puncture in a melting needle having a void for storing an implant therein.SOLUTION: A storage device includes a needle-like part which includes a water-soluble polymer and has a shape that can pierce a living body. A needle weight ratio of the needle-like part to the needle-like part having a storage hole for demarcating a region configured to store an object in the needle-like part is between 30% and 60%. The length of the long axis of the needle of the needle-like part is between 0.5 mm and 3 mm.SELECTED DRAWING: Figure 2

Description

TECHNICAL FIELD The present invention relates to a storage device used for placing a target object into a living body, and a cell transplant unit.

Techniques have been developed in which cell masses obtained by culturing cells collected from a living body are transplanted into the skin or subcutaneously of the living body. For example, attempts have been made to regenerate hair by purifying a cell group that contributes to the formation of hair follicles, which are the organs that produce hair, and transplanting this cell group into the skin.

Hair follicles are formed by the interaction of epithelial cells and mesenchymal cells. For good hair regeneration, it is desirable that the transplanted cell product become a hair follicle with a normal tissue structure and good hair-forming ability. Therefore, various research and development efforts are being conducted on methods for producing cell groups capable of forming hair follicles (see, for example, Patent Documents 1 to 4).

International Publication No. 2017/073625 International Publication No. 2012/108069 Japanese Patent Application Publication No. 2008-29331 Special table 2019-535705 publication

Transplantation of cells, etc. is performed by making a transplant wound in the target tissue with a scalpel or the like, and inserting the transplant using tweezers, etc. However, if the transplant is small, the transplantation procedure is difficult and often results in a decrease in transplant efficiency. was. One of the reasons for this was that after inserting the implant, when pulling out an instrument such as tweezers from the implant wound, the implant would come off at the same time. To prevent this, devices have been proposed in which the needle itself dissolves to accommodate and deliver the implant. These dissolvable containment devices have a structure in which a water-soluble needle has a cavity-like accommodating portion for accommodating the implant. In order to accommodate the implant smoothly and smoothly in the needle, it is desirable to have a larger accommodating part, but when the accommodating part is made larger, there is a problem that not only does the formability of the needle deteriorate, but also the strength of the needle decreases. .

On the other hand, if the accommodating portion is made smaller, the needle strength increases, but the amount of the accommodated material decreases, and the opening when accommodating the implant is likely to be clogged. The needle strength must be able to withstand the compressive force in the long axis direction of the needle during puncture, and also the force in the horizontal direction to the needle to hold the needle tip perpendicular to the skin just before puncturing. . Therefore, the needle is required to have a certain strength against vertical and horizontal forces.

From the above, the present invention is a dissolvable containment device, which has a containment portion large enough to accommodate the implant smoothly in the needle, and which can withstand puncture of the skin from both vertical and horizontal directions with respect to the needle. The purpose of the present invention is to provide a containment device that has a strength of a certain degree.

A containment device for solving the above problems is a containment device used for placing an object in a living body, and includes a needle-like part that contains a water-soluble polymer and has a shape that can pierce the living body. The needle-like part has an accommodation hole for dividing a region configured to accommodate the object inside the needle-like part, and the needle-like part does not have the accommodation hole. It is characterized in that the needle weight ratio to the solid needle made of the material is 30% or more and 60% or less.

In the above configuration, the needle weight ratio may be 45% or more and 60% or less.

In the above configuration, the length of the long axis of the needle of the needle-like portion may be 0.5 mm or more and 3 mm or less.

In the above structure, the surface or inside of the accommodation hole may be coated with another substance constituting the needle-like portion.

In the above configuration, the accommodation hole may open at the base end of the needle-shaped portion.

In the above configuration, the water-soluble polymer includes carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, polyacrylic acid polymer, polyacrylamide, polyethylene oxide, pullulan, alginate, starch. , pectin, chitosan, chitosan succinamide, oligochitosan, chondroitin sulfate, poly(2-ethyl-2-oxazoline), poly(2-methyl-2-oxazoline), carboxyvinyl polymer, dextran, dextrin, cellulose, chitin , galactan, collagen, atelocollagen, gelatin, reosane, xanthan gum, casein, polyvinylpyrrolidone, hyaluronic acid, glucomannan, polymalic acid, and curdlan.

A cell transplantation unit for solving the above problem is a cell transplantation unit used for placing a group of cells in a living body, which contains a water-soluble polymer and has a needle-like shape that can pierce the living body. and a needle weight ratio of the needle-like part to the needle-like part having an accommodation hole for dividing a region configured to accommodate the object inside the needle-like part is 30%. It is characterized by being 60% or less.

According to the present invention, when placing a target in a living body, the needle has a housing portion large enough to accommodate the implant smoothly, and the implant can be placed into the skin both vertically and horizontally with respect to the needle. A containment device can be provided that has enough strength to withstand puncture.

FIG. 1 is a diagram showing a cross-sectional structure of a storage device according to an embodiment. FIG. 1 is a diagram showing a cross-sectional structure of a cell transplant unit of one embodiment. The figure which shows the cross-sectional structure of the accommodation device of a modification. FIG. 3 is a diagram showing a procedure for arranging a target object using a cell transplantation unit according to an embodiment. FIG. 3 is a diagram showing a procedure for arranging a target object using a cell transplantation unit according to an embodiment. FIG. 3 is a diagram showing a procedure for arranging a target object using a cell transplantation unit according to an embodiment.

One embodiment of a storage device and a cell transplant unit will be described with reference to the drawings. The accommodation device of this embodiment is configured to be able to accommodate a target object such as a cell group, and is used to place the target object in a living body. The area where the target object is placed is within the tissue of the living body, for example, at least one of intradermal and subcutaneous areas, or an organ. In this embodiment, the term "living body" includes not only the body and tissue of a living organism, but also a biological model that is an artificial product that imitates the body or tissue of a living organism. That is, the accommodation device of this embodiment can be used not only for arranging objects with respect to living things but also with respect to biological models.

[Containment device]
As FIG. 1 shows, the containment device 10 comprises a needle-shaped portion 20 extending along one direction. The needle-like part 20 has an accommodation hole 15 that is a hole for dividing a space inside the needle-like part 20 for accommodating an object. The accommodation hole 15 opens at the base end of the needle-shaped portion 20 . Furthermore, the accommodation device 10 may include a substrate portion 11 that is integrally formed with the needle-like portion 20 . The substrate portion 11 has a plate shape that extends from the base end of the needle-like portion 20 in a direction perpendicular to the direction in which the needle-like portion 20 extends. In other words, the substrate portion 11 supports the base end portion of the needle-like portion 20.

Specifically, the substrate portion 11 has a first surface 11F and a second surface 11R, which is a surface opposite to the first surface 11F, and the needle-shaped portion 20 extends from the first surface 11F. The accommodation hole 15 is open to the second surface 11R.

By providing the substrate portion 11, it is easy to hold the storage device 10 by holding the substrate portion 11 with another instrument or the like. Therefore, it becomes easier to move the accommodation device 10 or to stab the accommodation device 10 into a living body.

In addition, since the substrate portion 11 is provided, when the stored object is put into the accommodation hole 15 from the opening 17, the substrate portion 11 prevents the stored object from adhering to the surface of the needle-shaped portion 20. It can be suppressed. Therefore, the needle-like part 20 is prevented from dissolving before it is inserted into the living body.

The substrate portion 11 can hold the needle-like portion during puncturing, and can also be expected to have the effect of preventing droplets from being scattered around when a physiologically active substance is accommodated in the void. Particularly when handling a water-soluble base material, it is desirable to include the substrate section 11 because if the base material adheres to the needle-like section, the needle-like section may dissolve. Further, the surface of the substrate on the side where the void is open may be coated with a water-insoluble material. The water-insoluble material is preferably a material that is sparingly soluble in water, undergoes changes such as melting, dissolution, and decomposition in vivo, and is biocompatible.

Specific materials include, for example, oils and fats and higher alcohols. Examples of fats and oils include saturated fatty acids, olive oil, oleic acid, rapeseed oil, palm oil, cocoa butter, petrolatum, liquid lanolin, beeswax, liquid paraffin, and the like. Examples of higher alcohols are stearyl alcohol, 1-hexadecanol, and the like. In addition, if there is a substrate during puncture, the impact of the puncture will escape to the substrate instead of the needle, so the size of the substrate portion 11 should be 625 mm ² or less per needle, or it should be processed so that only the needle can pass through during puncture. It would be good to have it done.

The shape of the needle 20 is not particularly limited as long as the tip of the needle 20 has a shape that allows it to pierce the tissue in which the object is placed. From the viewpoint of increasing the ease with which the needle-like part 20 sticks into a living body, it is preferable that the tip of the needle-like part 20 be sharp. For example, the needle-shaped portion 20 may have a shape such as a conical shape or a pyramid shape, in which the width decreases from the base end to the distal end. Alternatively, the needle-shaped portion 20 may have a shape in which a cylinder is cut diagonally with respect to its extending direction, or a shape in which a cone extends from the top surface of the cylinder. It may have a shape with a smaller width.

The thinner the needle-like part 20 is, the smaller the mark formed when the needle-like part 20 is inserted into a living body, while the thicker the needle-like part 20 is, the more flexible the size and amount of objects that can be accommodated. is enhanced. From the viewpoint of suppressing the expansion of the above-mentioned marks and increasing the restrictions on objects that can be accommodated, the outer shape of the needle-like part 20 is When the inscribed virtual circle is used as a reference circle, the radius of the reference circle is preferably 50 μm or more and 2000 μm or less, more preferably 400 μm or more and 800 μm or less. Note that the width direction is a direction perpendicular to the direction in which the needle-like portion 20 extends, and the width of the needle-like portion 20 is the length of the needle-like portion 20 in the width direction.

The needle-shaped portion 20 is formed from a material that dissolves in water. The main component of the needle portion 20 is a water-soluble polymer. The material of the needle-like part 20 is such that the needle-like part 20 has a strength that allows it to pierce the tissue in which the object is placed, and that the needle-like part 20 dissolves within the tissue after piercing the tissue. The material is selected from materials with which the needle-like portion 20 can be formed.

Examples of water-soluble polymers included in the material of the needle portion 20 include carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, polyacrylic acid polymer, polyacrylamide, polyethylene oxide, Pullulan, alginate, starch, pectin, chitosan, chitosan succinamide, oligochitosan, chondroitin sulfate, poly(2-ethyl-2-oxazoline), poly(2-methyl-2-oxazoline), carboxyvinyl polymer, dextran , dextrin, cellulose, chitin, galactan, collagen, atelocollagen, gelatin, leozane, xanthan gum, casein, polyvinylpyrrolidone, hyaluronic acid, glucomannan, polymalic acid, curdlan, etc. The needle-shaped portion 20 may be formed from a single material among these materials, or may be formed from a mixture of a plurality of materials. The main component of the needle-like part 20 is the material with the highest content ratio in the needle-like part 20.

The depth of the accommodation hole 15 may be selected depending on the target depth at which the object is placed. However, from the viewpoint of suppressing the object from coming out from the opening 17 after being accommodated, the depth of the accommodating section 15 is preferably 50 μm or more, so that it is possible to easily insert the object to the vicinity of the bottom of the accommodating section 15. From this point of view, it is preferable that the depth of the accommodating portion 15 is 3000 μm or less. Note that the length of the needle-shaped portion 20 is not particularly limited as long as it is longer than the accommodation hole 15.

The structure of the accommodation hole 15 is not particularly limited as long as it is open on the second surface 11R of the needle-like portion 20, but it may be open not only on the second surface 11R of the needle-like portion 20 but also on the side surface of the needle-like portion 20. This should be avoided as it may cause the implant to leak or not maintain sufficient strength. The shape of the cavity of the accommodation hole 15 is such that the cross-sectional area increases toward the opening, which is suitable for smoothly accommodating the implant. On the other hand, even if the jar shape is slightly constricted near the opening, it is convenient because the stored implant is less likely to leak out of the gap due to the impact of puncturing or the like. In particular, since impact tends to concentrate on the needle base during puncturing, a certain degree of thickness is required regardless of the shape of the space in the accommodation hole 15. Specifically, unless the thinnest part has a thickness of 25 μm or more, it cannot withstand the impact of puncturing.

[Cell transplant unit]
Referring to FIG. 2, a configuration in which the object is a group of cells and the storage device 10 is used for cell transplantation will be described. The accommodation device 10 in which the cell group is accommodated is a cell transplant unit. Note that the storage device in which the object is stored is a storage unit, and the cell transplantation unit is an example of a storage unit.

As shown in FIG. 2, the cell transplant unit 100 includes a storage device 10 and a cell group 30. Further, the accommodating portion 15 also accommodates an auxiliary liquid 31 together with the cell group 30, and the auxiliary liquid 31 surrounds the cell group 30. The cell group 30 and the auxiliary liquid 31 are contents contained in the storage device 10.

Cell group 30 includes a plurality of cells. For example, cell group 30 includes one or more cell clusters. A cell mass is an aggregate of multiple cells. The cell mass may be an aggregate of a plurality of aggregated cells or an aggregate of a plurality of cells connected by intercellular bonds. Alternatively, the cell group 30 may be composed of a plurality of dispersed cells. Further, the cells constituting the cell group 30 may be undifferentiated cells or cells that have completed differentiation, and the cell group 30 may include undifferentiated cells and differentiated cells. It's okay to stay. The cell group 30 is, for example, a spheroid, an primordium, a tissue, an organ, an organoid, a mini-sized organ, or the like.

The cell group 30 has the ability to affect tissue formation in the living body by being placed in the living body. An example of a cell mass included in such a cell group 30 is a cell aggregate containing cells having stem cell properties. The cell group 30 contributes to hair growth or growth by being placed intradermally or subcutaneously, for example. Specifically, the cell group 30 has the ability to function as a hair follicular organ, the ability to differentiate into a hair follicular organ, the ability to induce or promote the formation of a hair follicular organ, or the ability to induce or promote the formation of hair in a hair follicular organ. have the ability to promote, etc. Furthermore, the cell group 30 may include cells that contribute to hair color control, such as pigment cells or stem cells that differentiate into pigment cells. Furthermore, the cell group 30 may include vascular cells.

A specific example of the cell group 30 is a hair follicle primordium, which is a primitive hair follicle organ. The hair follicle primordium includes a cell mass consisting of mesenchymal cells and a cell mass consisting of epithelial cells, and these two types of cell masses are in contact with each other. In the hair follicle organ, dermal papilla cells contained in mesenchymal cell clusters induce differentiation of hair follicle epithelial stem cells contained in epithelial cell clusters, and hair matrix cells are formed in the formed hair bulb. Hair is formed by repeated division. Hair follicle primordia are a group of cells that differentiate into these hair follicle organs.

Hair follicle primordia are produced by, for example, mesenchymal cells originating from mesenchymal tissues such as dermal papillae and epithelial cells originating from epithelial tissues located in the bulge region, the base of the hair bulb, etc., under predetermined conditions. It is formed by culturing to form cell clusters and bringing these cell clusters into contact. However, the method for producing hair follicle primordia is not limited to the above-mentioned example. Furthermore, the origin of the mesenchymal cells and epithelial cells used to produce the hair follicle primordium is not limited, and these cells may be cells derived from the hair follicle organ, or may be derived from the hair follicle organ. The cells may be derived from a different organ or may be cells derived from pluripotent stem cells.

Furthermore, in addition to the mesenchymal cell mass and the epithelial mesenchymal cell mass, the cell group 30 may include a cell mass that contributes to engraftment and improvement of function. Examples of such cell clusters include cell clusters related to hair color, cell clusters containing vascular cells, and cell clusters that release growth factors.

Note that the object accommodated in the accommodation device 10 may include, together with the cell group 30, a member that assists in the transplantation and engraftment of the cell group 30. An example of such a member is a gel bead that provides sustained release of growth factors.

The auxiliary liquid 31 is a fluid that assists in maintaining the activity of the cell group 30 within the accommodation hole 15 and in supporting the engraftment of the cell group 30 after being placed in the living body. For example, the auxiliary liquid 31 surrounds the cell group 30 and suppresses contact between the cell group 30 and the inner surface of the accommodation hole 15, thereby assisting in maintaining the activity of the cell group 30. Alternatively, the auxiliary fluid 31 may contain components similar to body fluids of a living body and may assist in maintaining the activity and engraftment of the cell group 30 by enveloping the cell group 30 or providing nutrients to the cell group 30. Good too.

The auxiliary liquid 31 contains an aqueous material as a main component. The main component of the auxiliary liquid 31 is the material with the highest content rate in the auxiliary liquid 31. Specific examples of the auxiliary fluid 31 are pure water, physiological saline, and the like. Further, the auxiliary liquid 31 may contain an additive that lowers the vapor pressure of water. Examples of additives that reduce the vapor pressure of water are gelatin, agar, sodium alginate, pullulan, gellan gum, hydroxypropyl cellulose, collagen, etc.

The auxiliary liquid 31 may be made of a single material, or may be a mixture of a plurality of materials. Further, the auxiliary liquid 31 may be a low viscosity fluid or a high viscosity fluid. Note that the auxiliary fluid 31 does not need to surround the entire circumference of the cell group 30. For example, the cell group 30 may be arranged at the bottom of the accommodation hole 15, and the auxiliary liquid 31 may cover the cell group 30 in a region from above the cell group 30 to the opening 17.

As shown in FIG. 3 , the containment device 10 may include a seal 40 . The sealing part 40 closes the opening 17 in a state in which the object is accommodated. The sealing portion 40 extends along the surface located at the proximal end of the needle-like portion 20 or along the second surface 11R of the substrate portion 11. The sealing portion 40 is made of a material that does not dissolve in water.

The sealing portion 40 before closing the opening 17 may be managed separately from the needle portion 20 and the substrate portion 11, or may be connected to the end of the substrate portion 11 or the like. For example, the sealing part 40 is a resin sheet having an adhesive surface, and the resin sheet is attached to the needle part 20 or the substrate part 11 so as to cover the opening 17, so that the sealing part 40 is attached to the opening 17. may be placed on top. Alternatively, the sealing portion 40 may be formed by applying an oil-based sealant to cover the opening 17 . The sealant is, for example, an oily cream such as petrolatum. It is preferable that the sealing part 40 is capable of closely adhering to the surface of the tissue on which the object is placed.

By providing the sealing portion 40, it is possible to suppress leakage of the stored object due to vibrations during transportation of the storage device 10, impact when the storage device 10 punctures a living body, or the like.

[Method for manufacturing containment device and cell transplant unit]
The needle-like part 20 is formed by filling a solution containing the material for the needle-like part 20 into a mold having a recess corresponding to the shape of the desired needle-like part 20, solidifying the filling by drying, and then releasing the mold. Manufactured.

By controlling the filling and drying of the solution so that air bubbles gather in the center of the filler that becomes the needle-like part 20, voids are formed inside the needle-like part 20. This allows the accommodation hole 15, which is the void, to be formed. Alternatively, after the filling is solidified with a pin-shaped structure having a shape corresponding to the accommodation hole 15 inserted into the center of the filling, the structure may be removed. Thereby, a gap, which is the accommodation hole 15, can be formed in the portion where the pin-shaped structure was located. In this case, the solution dries along the mold depending on the balance between surface tension and wettability of the mold, so by controlling the amount of base material when adding the base solution, it is possible to form a void inside the needle. This method is the simplest, hassle-free manufacturing method that can reliably obtain the desired shape. Note that when the accommodation device 10 includes the substrate section 11, the substrate section 11 is also formed at the same time as the needle-shaped section 20.

In addition to the above-mentioned method, there is also a method of drying while centrifuging as a method of controlling the shape of the void, and it is possible to control the depth of the void, in particular. Although the drying process can be shortened by heating, etc., if the material dries rapidly, the voids will not open on the back surface of the needle and air bubbles will likely be left behind inside the needle. Therefore, it is necessary to appropriately control the drying time by controlling the temperature and humidity. In addition to this, it is also possible to mold the accommodating part by incorporating a mold for molding it, and in this case, there is a high degree of freedom in designing the shape of the accommodating part.

The stored object may be stored in the storage hole 15 by a method depending on the properties of the stored object. As an example, a case will be described in which a cell group 30 including a cell mass and an auxiliary liquid 31 are accommodated.

First, the auxiliary liquid 31 is filled into the accommodation hole 15 . For example, the auxiliary liquid 31 may be injected using a nozzle, or the auxiliary liquid 31 may be poured into the opening 17 by applying a vacuum or using a centrifuge. May be filled.

Subsequently, the cell group 30 is placed into the accommodation hole 15. For example, if the cell group 30 is dropped toward the opening 17, the cell group 30 will sink due to gravity. At this time, in order to facilitate accommodation of the cell group 30, a centrifuge may be used, or a rod-shaped or pipe-shaped instrument may be used to push the cell group 30 to move the cell group 30 toward the bottom.

Although the cell group 30 does not necessarily need to be submerged to near the bottom of the housing portion 26, it is preferable that the cell group 30 is placed closer to the bottom because it becomes difficult for the cell group 30 to leak. If the needle-shaped portion 20 is transparent, the cell group 30 can be accommodated while confirming the position of the cell group 30 within the accommodation hole 15 . When the storage device 10 includes the sealing part 40, the opening 17 is covered with the sealing part 40 after the stored object is stored.

The void ratio of the accommodation hole 15 can be easily determined as the needle weight ratio by manufacturing accommodation devices 10 of the same size and measuring their relative weights to the needles. In this case, since it can be determined as the weight ratio of the voids in the accommodation hole 15 without being affected by the density of the accommodation device 10, it is a constant value even if the constituent materials are different. Any other method may be used as long as the weight ratio of the voids in the accommodation hole 15 can be determined. For example, since the needle weight ratio is almost equal to the volume ratio, the void volume of the accommodation hole 15 can be directly determined using a laser microscope or the like. The ratio to the volume may also be determined. Further, the housing device 10 points from the needle base to the needle tip, and excludes the other parts. For example, if a plurality of needles exist on a film-like base material, it is necessary to cut out each needle from the base material and measure it.

Note that the inside of the cavity of the accommodation hole 15 may be coated with a water-insoluble material, but since the mechanical influence on the needle is slight, it is excluded from the needle weight when calculating the needle weight ratio.

[How to place objects]
With reference to FIGS. 4 to 6, a method for arranging a target object using the storage device 10 will be described using an example in which the target object is a cell group 30. That is, the method for arranging the object described above is a method for transplanting cells using the cell transplant unit 100.

As shown in FIG. 4, first, the needle-like part 20 of the cell transplantation unit 100 is pressed against the target tissue Sk where the cell group 30 is arranged, so that the needle-like part 20 is inserted into the target tissue Sk. The target tissue Sk is, for example, skin. At this time, an applicator may be used that assists the needle 20 to enter the target tissue Sk by adjusting the force applied to the needle 20 and the direction of the needle 20. When the accommodation device 10 has the substrate part 11, it is easy to make the applicator hold the cell transplant unit 100. Note that while the needle-shaped portion 20 is stuck in the target tissue Sk, the substrate portion 11 does not enter into the target tissue Sk but is placed on the surface of the target tissue Sk.

As shown in FIG. 5, when the needle-like part 20 enters the target tissue Sk, the needle-like part 20 comes into contact with the moisture in the tissue, thereby dissolving the needle-like part 20.

As shown in FIG. 6, as the dissolution of the needle-shaped portion 20 progresses, the accommodation device 10 collapses and disappears, leaving the accommodated cell group 30 in the target tissue Sk. The components of the needle-like part 20 are diffused and absorbed into the living body. This completes the placement of the object into the living body. Note that when the accommodation device 10 includes the substrate section 11, the substrate section 11 is dissolved by coming into contact with moisture on the surface of the target tissue Sk.

By using the accommodation device 10 of the present embodiment, the instrument is not pulled out of the living body when the object is placed in the living body, so that the object is prevented from slipping out of the living body along with the instrument. Therefore, the efficiency of arranging objects can also be improved. Further, since the object is inserted into the living body while being housed in the needle-shaped portion 20, the object can be protected from impact during insertion.

The accommodation device and cell transplant unit will be explained using specific examples.

(Production method)
A mold having a quadrangular pyramid-shaped recess was prepared, and a 5% pullulan aqueous solution was dropped into the recess as a solution for forming the needle-like part. The mold filled with this aqueous pullulan solution was then dried under ventilation for 48 hours in an environment with a temperature of 25° C. and a humidity of 30%. As drying progresses, cavities grow inside the filling of the recesses due to the balance between the wettability of the mold and the surface tension of the aqueous pullulan solution. After the drying was completed, the filling was released from the mold to obtain the needle-shaped part having the accommodation hole as the cavity. The surface located at the proximal end of the needle-like portion has a square shape with one side of 800 μm, and the length of the needle-like portion is 2.3 mm.

Samples (Examples 1 to 3, Comparative Examples 1 to 3) in which the dropping amount of 5% pullulan aqueous solution was changed as shown in Table 1 were prepared, released from the mold, observed the needle-like part, and cut out from the substrate part and measured the weight. was measured using a precision electronic balance (XP-56, Mettler Toledo). The needle weight ratio is a calculated value of the ratio of the solid needle to the weight.

<Needle strength measurement>
The needle strength of the needle bodies shown in Examples 1 to 3 and Comparative Examples 1 to 3 was measured. Using a bond tester (Dage5000, Dage), a probe was placed at a position 0.5 mm from the tip of the needle-like part cut out from the substrate at a speed of 0.6 mm/sec, and the maximum force that the needle-like part could withstand was measured. . If the needle strength is 25 g or more, it is strong enough to withstand puncturing into the skin without breakage or deformation.

<Puncture test>
The needle-like bodies shown in Examples 1 to 3 and Comparative Examples 1 to 3 were tested on a human artificial skin model (Tanak) (epidermal layer 50 μm, dermal layer 3 mm) using a load tester (MCT2150, A&D). Puncture was performed and puncturing performance was confirmed, and if the puncture broke through the film of the epidermal layer and was placed in the dermal layer at the time of puncturing, the puncture was considered successful. For each needle-shaped body, 10 puncture tests were performed, and the success rate was derived from the number of successfully punctured needles. If the puncture success rate was 60% or more, it was determined that normal puncture was possible.

<Shape of opening>
The needle-like bodies shown in Examples 1 to 3 and Comparative Examples 1 to 3 were observed with an optical microscope. As a result, when the needle weight ratio was less than 24.5%, voids opened on the side surface of the needle, and the needle could not be properly molded. Furthermore, when the needle weight ratio exceeded 60%, the opening became narrower and blockage occurred. A case where the opening did not shrink and could accommodate the contents was marked as "〇", and a case where the opening narrowed was marked as "x".

<Overall results>
In the above test results, a needle with a needle strength of 25 g or more, a puncture success rate of 60% or more, and an opening with no constriction was given an overall result of "○", and the others were given a "x".

From Table 1, it was confirmed that as the cavity becomes larger, that is, as the needle weight ratio becomes lower, the needle strength tends to decrease. Furthermore, in Comparative Example 2, the amount of the 5% pullulan aqueous solution was too small, and no needle-like portions were formed, making it impossible to measure. Furthermore, in Comparative Example 3, the needle weight ratio was low and an opening was formed at the tip of the needle-like portion, which was not a normal needle shape, so needle strength measurements and puncture tests were not performed.

When a needle with a needle weight ratio of 31.1% and a needle with a needle weight ratio of 45% were punctured into a human artificial skin model (Tanak), 4 out of 10 of the 31.1% needles were crushed during puncture, but 45% of the needles were crushed during puncture. The needle was able to puncture all needles. Therefore, it has been shown that a proportion of the needle base material of 30% or more is the minimum required for puncturing, and more preferably 45% or more to ensure sufficient strength in the vertical direction and to stably puncture. It was done.

In addition, when comparing the puncture situation and the needle strength, the needle strength was 27.4 g when the proportion of the needle base material was 31.1%, and 174.4 g when the proportion of the needle base material was 45%. That is, by setting the proportion of the needle base material to 45% or more, the needle strength becomes 174.4 g or more, which is sufficient as the needle strength in the horizontal direction with respect to the needle-like body, and stable puncture can be realized.

However, if the needle weight ratio is increased, the opening for accommodating the implant is likely to be clogged. In this regard, if the needle weight ratio is 60% or less, it is possible to have an opening large enough to accommodate the implant without being occluded.

10...Accommodation device 11...Substrate part 11R...First surface 11F...Second surface 15...Accommodation hole 17...Opening part 20...Needle-like part 30...Cell group 31...Auxiliary liquid 40...Sealing part 100...Cell transplantation unit

Claims (7)

A storage device used for placing an object in a living body, the storage device comprising:
A needle-like part containing a water-soluble polymer and having a shape capable of piercing the living body, the accommodation for dividing a region configured to contain the object into the inside of the needle-like part. the needle-like portion having a hole;
A storage device characterized in that the needle weight ratio of the needle-shaped portion is 30% or more and 60% or less. The storage device according to claim 1, wherein the needle weight ratio is 45% or more and 60% or less. The storage device according to claim 1 or 2, wherein the length of the long axis of the needle of the needle-like portion is 0.5 mm or more and 3 mm or less. Any one of claims 1 to 3, further comprising a water-insoluble part that surrounds a region in which the target object is placed within the accommodation hole, and that deforms so as to expose the target object in the living body. Containment device according to paragraph 1. The accommodation device according to any one of claims 1 to 4, wherein the accommodation hole opens at a proximal end of the needle-shaped portion. The water-soluble polymers include carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, polyacrylic acid polymer, polyacrylamide, polyethylene oxide, pullulan, alginate, starch, pectin, and chitosan. , chitosan succinamide, oligochitosan, chondroitin sulfate, poly(2-ethyl-2-oxazoline), poly(2-methyl-2-oxazoline), carboxyvinyl polymer, dextran, dextrin, cellulose, chitin, galactan, collagen , atelocollagen, gelatin, reosane, xanthan gum, casein, polyvinylpyrrolidone, hyaluronic acid, glucomannan, polymalic acid, and curdlan. containment device. A cell transplantation unit used for placing a group of cells in a living body,
A needle-like part containing a water-soluble polymer and having a shape capable of piercing the living body, the accommodation for dividing a region configured to contain the object into the inside of the needle-like part. the needle-like portion having a hole;
A cell transplantation unit characterized in that the needle weight ratio of the needle-shaped portion is 30% or more and 60% or less.