JPWO2019160134A1 - Container for cell pharmaceutical products - Google Patents

Abstract

Provided is a means for enabling administration of a cytopharmaceutical preparation in an amount containing an appropriate number of cells according to the body weight of the patient or subject to the patient or subject by a simple operation. The container 1 for a cell pharmaceutical product of the present invention includes a container body 10 having an internal space 14 capable of accommodating the cell pharmaceutical product L, and a lead-out portion 20 having a lead-out port 21 communicating with the internal space 14 of the container body 10. The container body 10 is provided with a first scale display unit 100 that displays the dose of the cytopharmaceutical preparation L corresponding to the weight of the patient or the subject to be administered, and the position of the liquid level A in the container body 10 is the first. It is characterized in that the dose of the cytopharmaceutical preparation L suitable for the weight of the patient or the subject can be visually recognized depending on whether or not it is located on the scale display unit 100 of 1.

Description

The present invention relates to a container for a cell pharmaceutical product used for accommodating the cell pharmaceutical product and administering it to a patient, and a method for preparing the cell pharmaceutical product.

In the medical field, when administering a drug containing a pharmaceutical compound or vitamin to a patient, the drug bag containing the drug solution is hung on the hook of the drip stand, and the drug solution is dropped from the drug bag by natural drop. , The drug solution is directly introduced into the patient's body through an injection needle placed in the patient's static artery. In recent years, various administration forms have been reported in addition to the conventional administration methods described above.

For example, in Patent Document 1, a part of a first syringe having a label related to a dose to the body weight of a patient is sent into a drug container, the first syringe is filled to the dose, and the drug is filled. It describes how to administer to a patient. According to Patent Document 1, this method does not require calculation or association of drug doses with respect to the patient's body weight.

Further, in Patent Document 2, in a drug solution bag provided with a bag body having a chamber in which the drug solution can be enclosed, a marker indicating the weight of the patient corresponding to the dose of the drug solution to be administered is attached to the outer surface of the bag body. It is stated that it may be done. In Patent Document 2, after confirming the weight of the patient, the medical worker sandwiched the bag body with a clip according to the marker of the drug solution bag of this embodiment, and prepared the drug solution at a dose corresponding to the weight of the patient. Above, it is described to be administered to the patient.

Further, Patent Document 3 describes a medical container provided with a first scale display unit for displaying the amount of liquid in the soft bag and a second scale display unit for displaying the amount of liquid in the bag above the liquid level. It is described that the medical worker can administer the drug to the patient after confirming the presence or absence of mixed injection with other drugs using the second scale display portion of the medical container as an index.

Special Table 2015-508321 JP-A-2017-164421 JP-A-2007-260252

When a cell medicine preparation containing cells used for cell medicine is administered to a patient, the cell medicine preparation is a cell suspension, so that the cells have an uneven density in the container, and the cells are precipitated and settled. In consideration of aggregation, the appropriate cell dose (cell number and cell density) according to the weight of the patient must be accurately administered to the patient.

Therefore, as a method of administering to the patient an appropriate dose of cells according to the weight of the patient, the present inventors obtain the number of cells according to the weight of the patient from the first container containing the cell medicine preparation. A method was examined in which the preparation was taken out with a syringe, transferred to another second container, diluted with physiological saline to an appropriate cell density, and then the entire amount in the second container was administered to the patient. However, in this method, when the cell medicine preparation is transferred from the first container to the second container via the syringe, the cells stay near the outlet in the syringe, so that the cells in the second container are retained. We have found the problem of reduced numbers and the potential for cell death due to pressure in deriving the cell suspension from the syringe. We also found that the cell density in the second container cannot be properly adjusted because the physiological saline remains in the syringe even when diluted with the physiological saline. Therefore, in order to solve the above problems, the administration methods described in Patent Documents 1 to 3 have been further investigated.

The first syringe having the indication related to the dose to the patient's body weight described in Patent Document 1 can avoid the measurement error by the indication described in the syringe, but the cells are suspended in the syringe. There is a problem that cells die due to the pressure when introducing the liquid. Further, in the case of a cytopharmaceutical preparation, since cells precipitate and aggregate according to the elapsed time, it is necessary to flow the inside of the container, but the syringe is made of a hard material and is suspended. Since the space cannot be retained in the syringe, there is a problem that an appropriate cell density cannot be maintained at the time of administration.

Further, in the drug solution bag described in Patent Document 2, it is possible to divide the drug solution in the drug solution bag into doses according to the weight of the patient by sandwiching the drug solution bag with a clip, but in the case of a cell medicine preparation, , The cells in the drug solution bag settle and aggregate depending on the elapsed time. Therefore, even if the entire container is rubbed to flow the entire cell pharmaceutical product, it is impossible to flow the entire cell pharmaceutical product because the drug solution bag is sandwiched between the clips, and the entire cell pharmaceutical product is excessive. There is a problem that the clip comes off from the chemical bag when a large amount of pressure is applied.

Further, the medical container described in Patent Document 3 has a cell suspension by a first scale display unit for displaying the amount of liquid in the soft bag and a second scale display unit for displaying the amount of liquid in the bag above the liquid level. Although it is possible to confirm the presence or absence of mixed injection with other drugs other than the turbid solution, there is a problem that there is no means for confirming the appropriate cell dose according to the weight of the patient.

In view of the above problems, the present invention makes it possible to accurately grasp the appropriate cell dose according to the body weight of a patient and administer the cell pharmaceutical product to the patient by a simple operation when the cell pharmaceutical preparation is administered to the patient. The purpose is to provide a means of enabling.

Surprisingly, the present inventors can accurately grasp the appropriate cell dose according to the weight of the patient and administer it to the patient with a simple operation by using a container for a cell pharmaceutical product having the following characteristics. The present invention has been completed by finding a method for preparing a cell pharmaceutical preparation that can be administered to a patient by a simple operation by using the cell pharmaceutical preparation container.

(1) A container for cell pharmaceutical products
A container body with an internal space that can hold liquid,
A lead-out unit that communicates with the internal space of the container body,
The container body is provided with a first scale display unit that displays the dose of the cell pharmaceutical preparation corresponding to the body weight of the patient or the subject to be administered.
The container in which the dose of the cell pharmaceutical preparation suitable for the body weight of the patient or the subject can be visually recognized depending on whether or not the liquid level position in the container body is located on the first scale display portion.
(2) The container according to (1), wherein the numerical value of the first scale display unit is displayed so as to increase toward the lead-out unit of the container body.
(3) Further, the container body is provided with a second scale display unit that displays the amount of liquid for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and the liquid level position in the container body is the first. The container according to (1) or (2), wherein the cell concentration of the cytopharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether or not the container is located on the scale display portion of 2.
(4) Further, the container body is provided with a third scale display unit that displays the amount of liquid to be filled with the cell pharmaceutical preparation, and the liquid level position in the container body is located at the third scale display unit. The container according to any one of (1) to (3), wherein the number of cells of the cell pharmaceutical preparation to be introduced into the container body can be visually recognized depending on whether or not the container is used.
(5) Further, the container body is provided with a fourth scale display unit that displays the amount of liquid in the container, and depending on whether or not the liquid level position of the container body is located on the fourth scale display unit. The container according to any one of (1) to (4), wherein the amount of the cell pharmaceutical preparation remaining in the container body can be visually recognized.
(6) The container according to (5), wherein the numerical value of the fourth scale display unit is displayed so as to decrease toward the lead-out unit of the container body.
(7) Further, the container body is provided with a fifth scale display unit for displaying the number of cells of the cell pharmaceutical preparation administered to the patient or the subject, and the liquid level position in the container body is the fifth scale. The container according to any one of (1) to (6), wherein the number of cells of the cell pharmaceutical preparation administered to the patient or the subject can be visually recognized depending on whether or not the container is located on the display unit.
(8) The container according to (7), wherein the numerical value of the fifth scale display unit is displayed so as to increase in the direction of the lead-out unit of the container body.
(9) The container body has a second scale display unit that displays the amount of liquid that dilutes the cell pharmaceutical product with a pharmaceutically acceptable drug, and a third that displays the amount of liquid that fills the cell pharmaceutical product. Equipped with a scale display
The cell concentration of the cell-pharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether or not the liquid level position in the container body is located on the second scale display portion.
The number of cells of the cell pharmaceutical product to be introduced into the container body can be visually recognized depending on whether or not the liquid level position in the container body is located on the third scale display portion.
The container according to any one of (1) to (8), wherein the second scale display unit is provided on a parallel line of the third scale display unit.
(10) The container according to any one of (1) to (9), further comprising an introduction portion that communicates with the internal space of the container body.
(11) The container according to (10), wherein the introduction portion is provided at the upper end portion of the container body facing the lead-out portion.
(12) The container according to any one of (1) to (11), wherein the container body is made of a flexible material.

(13) A method for preparing a cell pharmaceutical preparation.
Corresponds to a container body filled with a cytopharmaceutical preparation and having an internal space capable of holding a liquid, a lead-out unit communicating with the internal space of the container body, and the weight of the patient or subject to be administered provided in the container body. A first scale display unit for displaying the dose of the cell pharmaceutical product to be used, and a second scale display for displaying the amount of liquid for diluting the cell pharmaceutical product with a pharmaceutically acceptable drug provided in the container body. The method comprising a step of filling a container for a cytopharmaceutical product provided with a portion with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body.
(14) A method for preparing a cell pharmaceutical preparation.
A container body having an internal space capable of holding a liquid, a lead-out unit communicating with the internal space of the container body, and a dose of a cytopharmaceutical preparation corresponding to the weight of the patient or subject to be administered provided in the container body. A first scale display unit for displaying, a second scale display unit provided on the container body for displaying the amount of liquid for diluting the cytopharmaceutical preparation with a pharmaceutically acceptable drug, and the container body are provided. In a container for a cell pharmaceutical product provided with a third scale display unit for displaying the amount of liquid to be filled with the cell pharmaceutical product, the cell pharmaceutical product is placed in the container body until the liquid level reaches the third scale display unit. The filling process and
The method comprising a step of filling the container filled with a cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body.

This specification includes the disclosure content of Japanese Patent Application No. 2018-026959, which is the basis of the priority of the present application.

According to the container for a cell pharmaceutical product of the present invention, it is possible to accurately grasp the appropriate cell dose according to the body weight of the patient and to administer the cell to the patient with a simple operation. Further, according to the method for preparing a cell-pharmaceutical preparation of the present invention, it is possible to prepare a cell-pharmaceutical preparation that can be administered to a patient by a simple operation.

FIG. 1 is a diagram showing a container for a cell pharmaceutical product according to the first embodiment of the present invention. FIG. 2 is a diagram showing a state in which the cell pharmaceutical product container according to the first embodiment of the present invention is suspended and the cell pharmaceutical product is housed in the internal space. FIG. 3 shows that the container for the cell pharmaceutical product according to the first embodiment of the present invention is suspended, the cell pharmaceutical product is stored in the internal space as shown in FIG. 2, and then the cell pharmaceutical product is administered to the patient through the outlet. It is a figure which shows the state at the time. FIG. 4 shows a case where the container for the cell pharmaceutical product according to the first embodiment of the present invention is suspended and the internal space is filled with the high-concentration cell pharmaceutical product until the liquid level is located on the third scale display portion. It is a figure which shows the state. FIG. 5 shows a pharmaceutically acceptable drug after suspending the cell pharmaceutical product container according to the first embodiment of the present invention and filling the internal space with the high-concentration cell pharmaceutical product as shown in FIG. It is a figure which shows the state when the liquid surface is further filled until it is located at the position of the 2nd scale display part, and is mixed and the cell pharmaceutical product is prepared. FIG. 6 is a diagram showing a container for a cell pharmaceutical product according to a second embodiment of the present invention. FIG. 7 is a diagram showing a container for a cell pharmaceutical product according to a third embodiment of the present invention. FIG. 8 is a schematic view showing an example of the hollow fiber separation membrane module.

Hereinafter, embodiments of the present invention will be specifically described, but the following description is for facilitating the understanding of the present invention, and the scope of the present invention is not limited to the following embodiments. Other embodiments in which those skilled in the art appropriately replace the configurations of the following embodiments are also included in the scope of the present invention.

<Terms and materials>
A cell-pharmaceutical preparation is a pharmaceutical preparation containing medically and / or pharmaceutically acceptable cells, specifically, a medically and / or pharmaceutically acceptable cell and a pharmaceutically acceptable drug. It is a pharmaceutical preparation containing and. As the cell pharmaceutical preparation, it is preferable to use the container for the cell pharmaceutical preparation according to the present invention described later. In this specification, the term "container" may be referred to as "bag".

In addition, the cell pharmaceutical preparations include salts, vitamins, amino acids, polysaccharides, dimethylsulfoxide, buffer, albumin, medium, CP-1 (manufactured by Far East Pharmaceutical Co., Ltd.), which is a cell cryoprotectant, and BAMBANKER, as required. (Limpotech), STEM-CELLBANKER (Nippon Zenyaku Kogyo), ReproCryo RM (Reprocell), CryoNovo (Acron Biotechnology), MSC Freezing Solution (Biological Technology) ) Etc. can be included.

The medium in the present invention is not particularly limited as long as it is a medium having a component composition in which cells can survive, but it is not particularly limited, but it is BME medium, BGJb medium, CMRL1066 medium, Glasgow MEM medium, Improved MEM Zinc Option medium, IMDM medium (Iscover) 's Modified Dulvecco's Medium), Medium 199 medium, Eagle MEM medium, αMEM medium, DMEM medium (Dulvecco's Modified Eagle's Medium), ham F10 medium, ham F12 medium, RPMIs 1640 medium And their mixed medium (for example, DMEM / F12 medium (Dulvecco's Modified Eagle's Medium / Nutrient Mixture F-12 Ham)), CHO-S-SFM II (Life Technologies Japan Co., Ltd.), Hybridoma-SFM (Life). Technologies Japan, Ltd.), eRDF Dry Powdered Media (Life Technologies Japan, ^Ltd.), UltraCULTURE TM (BioWhittaker, ^Inc.), UltraDOMA TM (BioWhittaker, ^Inc.), UltraCHO TM (BioWhittaker ^Inc.), be used UltraMDCK TM (BioWhittaker Inc.) it can. Mediums such as STEMPRO® hESC SFM (Life Technologies Japan Co., Ltd.), mTeSR1 (Veritas), TeSR2 (Veritas) and the like can be used.

In addition to cells, cytopharmaceutical formulations also contain various additives for increasing storage stability, isotonicity, absorbability and / or viscosity, such as emulsifiers, dispersants, buffers, preservatives, wetsers. It may contain an agent, an antioxidant, a chelating agent, a thickener, a gelling agent, a pH adjusting agent and the like. Examples of the thickener include, but are not limited to, HES, dextran, methyl cellulose, xanthan gum, carboxymethyl cellulose, hydroxypropyl cellulose and the like. The concentration of the thickener depends on the thickener selected, but can be arbitrarily set within a range of concentrations that are safe when administered to the patient or subject and that achieve the desired viscosity.

Further, the cell pharmaceutical preparation may contain an immunosuppressive agent, an antibiotic, an albumin preparation, a vitamin preparation, an anti-inflammatory agent and the like, which are components having activity as a medicine. Examples of the anti-inflammatory agent include, but are not limited to, 5-aminosalicylic acid preparations, steroid preparations, immunosuppressants, biologics and the like. Examples of the above-mentioned 5-aminosalicylic acid preparation include, but are not limited to, salazosulfapyridine and mesalazine. Examples of the above-mentioned steroid preparation include, but are not limited to, cortisone, prednisolone, methylprednisolone and the like. Examples of the above-mentioned immunosuppressive agent include tacrolimus, cyclosporine, methotrexate, azatiprin, 6-mercaptopurine and the like, and examples of the above-mentioned biologics include infliximab, adalimumab, ustekinumab, sexualumab and ixekizumab. , Brodalmab, tocilizumab, vedorizumab, filgotinib, golimumab, sertrizumab pegol, abatacept, etanercept, and the like, but not limited to these.

The pH of the cell pharmaceutical preparation of the present invention can be near neutral pH, for example, pH 6.5 or higher or pH 7.0 or higher, and pH 8.5 or lower or pH 8.0 or lower. Not limited to these.

The volume (mL) of the cell-pharmaceutical preparation is adjusted to the cell concentration (cells / mL) at which the safety of the patient or subject is confirmed when the cell-pharmaceutical preparation is administered to the patient or subject. It is the capacity, which is the capacity per bag. The volume of the cytopharmaceutical preparation is not particularly limited, but for example, 1 mL or more, 2 mL or more, 3 mL or more, 4 mL or more, 5 mL or more, 6 mL or more, 7 mL or more, 8 mL or more, 9 mL or more, 10 mL or more, 15 mL or more, 20 mL or more, 25 mL. 30 mL or more, 35 mL or more, 40 mL or more, 45 mL or more, 50 mL or more, 55 mL or more, 60 mL or more, 65 mL or more, 70 mL or more, 75 mL or more, 80 mL or more, 85 mL or more, 90 mL or more, 95 mL or more, 100 mL or more, and more. 5000 mL or less, 4000 mL or less, 3000 mL or less, 2000 mL or less, 1000 mL or less, 900 mL or less, 800 mL or less, 700 mL or less, 600 mL or less, 500 mL or less, 400 mL or less, 300 mL or less, 200 mL or less, 150 mL or less.

The cell concentration (cells / mL) of the cell-pharmaceutical preparation can obtain a therapeutic effect on the disease when the cell-pharmaceutical preparation is administered to the patient or subject as compared with the patient or subject to which the cell-pharmaceutical preparation is not administered. The concentration of cells contained in a cell pharmaceutical product. The cell concentration of the cytopharmaceutical preparation is not particularly limited, but for example, 1 × 10 ⁴ cells / mL or more, 2 × 10 ⁴ cells / mL or more, 3 × 10 ⁴ cells / mL or more, 4 × 10 ⁴ cells / mL or more, 5 × 10 ⁴ cells / mL or more, 6 × 10 ⁴ cells / mL or more, 7 × 10 ⁴ cells / mL or more, 8 × 10 ⁴ cells / mL or more, 9 × 10 ⁴ cells / mL or more, 1 × 10 ⁵ cells / ML or more, 2 × 10 ⁵ cells / mL or more, 3 × 10 ⁵ cells / mL or more, 4 × 10 ⁵ cells / mL or more, 5 × 10 ⁵ cells / mL or more, 6 × 10 ⁵ cells / mL or more, 7 × 10 ⁵ cells / mL or more, 8 × 10 ⁵ cells / mL or more, 9 × 10 ⁵ cells / mL or more, 1 × 10 ⁶ cells / mL or more, and 1 × 10 ¹⁵ cells / mL or less, 1 × 10 ¹⁴ cells / mL or less, 1 × 10 ¹³ cells / mL or less, 1 × 10 ¹² cells / mL or less, 1 × 10 ¹¹ cells / mL or less, 1 × 10 ¹⁰ cells / mL or less, 1 × 10 ⁹ cells / mL or less Below, 9 × 10 ⁸ cells / mL or less, 8 × 10 ⁸ cells / mL or less, 7 × 10 ⁸ cells / mL or less, 6 × 10 ⁸ cells / mL or less, 5 × 10 ⁸ cells / mL or less, 4 × 10 ⁸ cells / mL or less, 3 × 10 ⁸ cells / mL or less, 2 × 10 ⁸ cells / mL or less, 1 × 10 ⁸ cells / mL or less, 9 × 10 ⁷ cells / mL or less, 8 × 10 ⁷ cells / mL or less , 7 × 10 ⁷ cells / mL or less, 6 × 10 ⁷ cells / mL or less, 5 × 10 ⁷ cells / mL or less, 4 × 10 ⁷ cells / mL or less, 3 × 10 ⁷ cells / mL or less, 2 × 10 ⁷ cells / mL or less, 1 × 10 ⁷ cells / mL or less. In addition to the above, it can be appropriately determined depending on the administration form, administration method, purpose of use, age, weight, symptom and the like of the patient or subject.

The number of cells (cells) of a cell-pharmaceutical preparation is the number of cells that can obtain a therapeutic effect on a disease when the cell-pharmaceutical preparation is administered to a patient or subject as compared with a patient or subject to which the cell-pharmaceutical preparation is not administered. Is. The number of cells in the cytopharmaceutical preparation is not particularly limited, but for example, 1 × 10 ⁴ cells or more, 2 × 10 ⁴ cells or more, 3 × 10 ⁴ cells or more, 4 × 10 ⁴ cells or more, 5 × 10 ⁴ cells or more, 6 × 10 ⁴ cells or more, 7 × 10 ⁴ cells or more, 8 × 10 ⁴ cells or more, 9 × 10 ⁴ cells or more, 1 × 10 ⁵ cells or more, 2 × 10 ⁵ cells or more, 3 × 10 ⁵ cells or more, 4 × 10 ⁵ cells or more, 5 × 10 ⁵ cells or more, 6 × 10 ⁵ cells or more, 7 × 10 ⁵ cells or more, 8 × 10 ⁵ cells or more, 9 × 10 ⁵ cells or more, 1 × 10 ⁶ cells or more, and 1, × 10 ¹⁵ cells or less, 1 × 10 ¹⁴ cells or less, 1 × 10 ¹³ cells or less, 1 × 10 ¹² cells or less, 1 × 10 ¹¹ cells or less, 1 × 10 ¹⁰ cells or less, 1 × 10 ⁹ cells or less, 9 × 10 ⁸ cells or less, 8 × 10 ⁸ cells or less, 7 × 10 ⁸ cells or less, 6 × 10 ⁸ cells or less, 5 × 10 ⁸ cells or less, 4 × 10 ⁸ cells or less, 3 × 10 ⁸ cells or less, 2 × 10 ⁸ cells or less, 1 × 10 ⁸ cells or less, 9 × 10 ⁷ cells or less, 8 × 10 ⁷ cells or less, 7 × 10 ⁷ cells or less, 6 × 10 ⁷ cells or less, 5 × 10 ⁷ cells or less, 4 × It is 10 ⁷ cells or less, 3 × 10 ⁷ cells or less, 2 × 10 ⁷ cells or less, and 1 × 10 ⁷ cells or less. In addition to the above, it can be appropriately determined depending on the administration form, administration method, purpose of use, age, weight, symptom and the like of the patient or subject.

The dose of the cell-pharmaceutical preparation (cells / kg) is a patient who can obtain a therapeutic effect on the disease when the cell-pharmaceutical preparation is administered to the patient or the subject as compared with the patient or the subject who does not receive the cell-pharmaceutical preparation. Alternatively, it is the number of cells per 1 kg of the body weight of the subject. The dose of the cell medicine preparation is not particularly limited, but for example, 1 × 10 ⁴ cells / kg or more, 1 × 10 ⁵ cells / kg or more, 5 × 10 ⁵ cells / kg or more, 1 × 10 ⁶ cells / kg or more, 2 × 10 ⁶ cells / kg or more, 4 × 10 ⁶ cells / kg or more, 6 × 10 ⁶ cells / kg or more, or 8 × 10 ⁶ cells / kg or more, and 1 × 10 ¹² cells / kg or less, 1 × 10 ¹¹ cells / kg or less, 1 × 10 ¹⁰ cells / kg or less, 1 × 10 ⁹ cells / kg or less, 5 × 10 ⁸ cells / kg or less, 1 × 10 ⁸ cells / kg or less, 8 × 10 ⁷ cells / kg or less. It is kg or less, 6 × 10 ⁷ cells / kg or less, 4 × 10 ⁷ cells / kg or less, or 2 × 10 ⁷ cells / kg or less.

The type of cell is not particularly limited as long as it is a medically and / or pharmaceutically acceptable cell, and for example, a pluripotent stem cell (artificial pluripotent stem cell (iPS cell), embryonic stem cell (ES cell), etc. GS cells, which are pluripotent stem cells derived from the testis, EG cells derived from primordial germ cells of the fetus, Muse cells derived from bone marrow, etc.), somatic stem cells (bone marrow, adipose tissue, dental pulp, placenta, egg membrane, umbilical cord blood) , Membranous stem cells, hematopoietic stem cells, nerve stem cells, etc. derived from sheep membrane, chorionic villi, etc.), leukocytes, monospheres, granulocytes, lymphocytes (T cells, B cells, NK cells, etc.), giant nuclei, macrophages, nerves Examples thereof include cells, myocardial cells, myocardial progenitor cells, hepatocytes, liver progenitor cells, α cells, β cells, γ cells, fibroblasts, chondrocytes, corneal cells, vascular endothelial cells, vascular endothelial progenitor cells, and peri-cells. , The cell may be in a form in which a gene is introduced or a form in which a target gene on the genome is knocked down.

The cells used in the present invention are typically humans, such as rodents such as mice, rats and hamsters, primates such as gorillas, chimpanzees and marmosets, as well as dogs, cats, rabbits, cows and horses. , Sheep, goats and other livestock or pets and other mammals.

The pharmaceutically acceptable drug in the cytopharmaceutical preparation is not particularly limited as long as it is an aqueous medium that can maintain the cells in a form that can be used as a drug and can be administered to animals such as humans. The pharmaceutically acceptable drug may be mixed with the cell pharmaceutical product at the stage of manufacturing as a pharmaceutical product, or may be mixed with the cell pharmaceutical product at the stage of administering the cell pharmaceutical product to the patient or subject. .. The pharmaceutically acceptable drug is not particularly limited, and examples thereof include physiological saline, electrolyte solution, Ringer's solution, high-calorie infusion solution, glucose solution, water for injection, amino acid electrolyte and the like. Pharmaceutically acceptable drugs include salts, vitamins, amino acids, polysaccharides, dimethyl sulfoxide, buffers, albumin, medium, and cell cryoprotectant CP-1 (Far East Pharmaceutical Industry Co., Ltd.), if necessary. , BAMBANKER (made by Lymphotec), STEM-CELLBANKER (made by Nippon Zenyaku Kogyo), ReproCryo RM (made by Reprocell), CryoNovo (made by Amino Biotechnology), MSC Freezing Solution (manufactured by Biotechnology) It may include CryoStor (manufactured by HemaCare) and the like. The medium is not particularly limited as long as it is a medium having a component composition that can be administered to animals such as humans, but BME medium, BGJb medium, CMRL1066 medium, Glasgow MEM medium, Eagle's MEM Zinc Option medium, and the like. IMDM medium (Iscover's Modified Dulvecco's Medium), Medium 199 medium, Eagle MEM medium, αMEM medium, DMEM medium (Dulvecco's Modified Medium RP Medium, F10 medium, ham F10 medium, ham F10 medium) 's medium, and a mixed medium thereof (for example, DMEM / F12 medium (Dulvecco's Modified Eagle's Medium / Nutrition Mix F-12 Ham)), CHO-S-SFM II (Life Technologies Japan Co., Ltd.), Hybridoma. -SFM (Life Technologies Japan, Ltd.), eRDF Dry Powdered Media (Life Technologies Japan, ^Ltd.), UltraCULTURE TM (BioWhittaker, ^Inc.), UltraDOMA TM (BioWhittaker, ^Inc.), UltraCHO TM (BioWhittaker, ^Inc.), UltraMDCK TM (BioWhittaker Inc.) Can be used. Examples thereof include media such as STEMPRO (registered trademark) hESC SFM (Life Technologies Japan Co., Ltd.), mTeSR1 (Veritas), and TeSR2 (Veritas).

Patients and subjects are typically humans, such as rodents such as mice, rats and hamsters, primates such as gorillas, chimpanzees and marmosets, as well as dogs, cats, rabbits, cows, horses and sheep. , A domestic animal such as a goat, or a non-human animal such as a mammal such as a pet animal.

The cell-pharmaceutical preparation contained in the cell-pharmaceutical preparation container according to the present invention is derived through an outlet described later and administered to a patient. The route of administration to the patient is not particularly limited, and may be, for example, subcutaneous injection, intralymph node injection, intravenous injection, intraarterial injection, intraperitoneal injection, intrathoracic injection, direct local injection, or the like.

The administration frequency of the cell-pharmaceutical preparation of the present invention is such that when administered to a patient or a subject, a therapeutic effect can be obtained for the disease. The specific administration frequency can be appropriately determined depending on the administration form, administration method, purpose of use, age, body weight, symptom, etc. of the patient or subject, and is, for example, once every four weeks and once every three weeks. , Once every two weeks, once a week, twice a week, three times a week, four times a week, five times a week, six times a week, or seven times a week is there.

The administration period of the cell pharmaceutical preparation of the present invention is a period during which a therapeutic effect can be obtained for a disease when administered to a patient or a subject. The specific administration period can be appropriately determined depending on the administration form, administration method, purpose of use, age, body weight, symptom, etc. of the patient or subject, and for example, 1 week, 2 weeks, 3 weeks, 4 weeks. 5 weeks, 6 weeks, 7 weeks, or 8 weeks.

The timing of administering the cell pharmaceutical preparation of the present invention to a patient or subject is not particularly limited, but for example, immediately after the onset, within N days from the onset (N indicates an integer of 1 or more), immediately after the diagnosis, and within N days from the diagnosis. (N indicates an integer of 1 or more), before remission, during remission, after remission, before relapse, during relapse, after relapse, and the like.

The cell pharmaceutical preparation of the present invention can be stored in a frozen state until immediately before use. The cryopreservation temperature is preferably -30 ° C or lower, -40 ° C or lower, -50 ° C or lower, -80 ° C or lower, -90 ° C or lower, -100 ° C or lower, -150 ° C or lower, -180 ° C or lower, or-. It is 196 ° C. (liquid nitrogen temperature) or less. When the cell pharmaceutical preparation of the present invention is administered to a patient or subject, it can be rapidly thawed and used at 37 ° C.

The container for a cell pharmaceutical product according to the present invention includes at least a container body having an internal space capable of accommodating a liquid cell pharmaceutical product and a lead-out portion having an outlet for communicating with the internal space of the container body. You just have to.

The container body is preferably made of a flexible material.
The container body can be made of at least a transparent or translucent material so that the liquid level position of the cytopharmaceutical preparation inside can be visually recognized. In particular, it is preferable that the portion of the container body provided with the first to fifth scale display portions is formed of a transparent or translucent material.

Specific examples of the flexible material include soft vinyl chloride, vinyl chloride, polyurethane, ethylene-vinyl acetate copolymer, polyolefin such as polyethylene and polypropylene, styrene-butadiene-styrene copolymer or its hydrogenated product and styrene. Examples thereof include thermoplastic elastomers such as a-isoprene-styrene copolymer or a hydrogenated product thereof, and flexible resins such as a mixture of a thermoplastic elastomer and a softening agent such as polyolefin and ethylene-ethyl acrylate.

When the container body is made of a flexible resin, the container body is formed by blow-molding the resin, and the container body and two sheets containing the resin as a main component are arranged to face each other and the peripheral portion thereof. The container body formed by fusing the resin, the container body formed by folding back one sheet formed of the resin and fusing the peripheral edge portion, and the opening of a tubular shape formed by extrusion molding using the resin. It may be in various forms such as a container body formed by fusing the peripheral edges. The thickness of the sheet is not particularly limited, but can be, for example, 0.2 mm to 0.6 mm. The container body is preferably a bag-shaped container in which at least a part of the wall surface is formed by a sheet containing the resin as a main component, and particularly preferably, the two sheets are arranged facing each other and the peripheral edge portion is heated. It is a bag-shaped container formed in a bag shape by fusing or joining with an adhesive.

It is preferable that the container for the cell pharmaceutical product according to the present invention is formed so that the contained cell pharmaceutical product can be taken out through the outlet and administered to the patient in a suspended state.

The lead-out portion provided in the container for a cell pharmaceutical product according to the present invention may have a lead-out port that communicates with the internal space of the container body, and its shape is not particularly limited. Typically, the outlet can be configured by a tube containing a flow path through which the liquid can pass.

The lead-out unit preferably has a structure in which the lead-out port is closed so that it can communicate with the outside. Examples of such a structure include a luer lock and a needleless port.

The size of the lead-out port provided in the lead-out unit may be any size as long as the cell pharmaceutical preparation containing cells can pass through.

The number of out-licensing units is not limited to one, and may be, for example, two, three, four, five, six, seven, eight, nine, ten or more, and the like.

The container for a cell pharmaceutical product according to the present invention preferably further includes an introduction portion in which an introduction port for communicating the internal space of the container body and the outside is formed. The introduction port can be used as a route for supplying a cell pharmaceutical product or a material for preparing the cell pharmaceutical product (for example, the above-mentioned pharmaceutically acceptable drug) to the internal space of the container body. it can.

The introduction portion may be formed with an introduction port that communicates with the internal space of the container body, and its shape is not particularly limited. Typically, the introduction can be constructed by a tube containing a flow path through which the liquid can pass.

Further, the introduction portion may have a structure in which the introduction port is closed so as to communicate with the outside. Examples of such a structure include a luer lock and a needleless port. Further, the introduction portion may be irreversibly sealed after supplying the necessary material to the internal space.

Further, the number of introduction portions is not limited to one, and may be, for example, a plurality of introduction portions such as 2, 3, 4, 5, 6, 6, 7, 8, 9, 10 or more. The internal space of the container body may be filled with the cytopharmaceutical preparation and the pharmaceutically acceptable drug via separate introduction portions and mixed. For example, when preparing a cell-pharmaceutical preparation, the container for the cell-pharmaceutical preparation of the present invention has a first introduction part for introducing the cell-pharmaceutical preparation into the internal space and a pharmaceutically acceptable drug in the internal space. It may be provided with a second introduction part for introducing into.

The feature of the container for a cell pharmaceutical product of the present invention is that the container body is provided with one or more selected from the first to fifth scale display portions. Each scale display unit is composed of one or more identification displays such as visible lines, characters, signs, and colors. The identification display may be printed on the container body, may be protrusions and / or dents formed on the container body, or may be a combination of printing and protrusions and / or dents. ..

The first scale display portion of the container for the cell pharmaceutical product of the present invention displays the dose of the cell pharmaceutical product corresponding to the weight of the patient or the subject to be administered to the container body, and the liquid in the container body. Depending on whether or not the surface position is located on the first scale display portion, it is possible to visually recognize the dose of the cell pharmaceutical preparation suitable for the weight of the patient or the subject. More specifically, the first scale display portion is a patient or subject determined by dividing the dose of the cell pharmaceutical product (cells / kg) from the cell concentration (cells / mL) contained in the cell pharmaceutical product. The dose (kg / mL) of the cell-pharmaceutical preparation suitable for the body weight is displayed as a scale according to the liquid volume (mL) of the cell-pharmaceutical preparation. For example, the scale is arranged stepwise according to the value obtained by dividing the dose of the cell-pharmaceutical product from the cell concentration of the cell-pharmaceutical product and the liquid volume of the cell-pharmaceutical preparation, and the cell-pharmaceutical corresponding to the weight of the patient or subject In order to make the dose of the formulation easy to see, the weight of the patient or subject to be administered such as 10 kg, 20 kg, 30 kg may be displayed as a numerical value near the scale. In addition, the dose of the cell-pharmaceutical preparation corresponding to the weight of the patient or subject may be appropriately designed for each cell concentration of the cell-pharmaceutical preparation to be administered to the patient or subject.

The numerical value of the first scale display unit is not particularly limited, but for example, 0 kg, 5 kg, 10 kg, 15 kg, 20 kg, 25 kg, 30 kg, 35 kg, 40 kg, 45 kg, 50 kg, 55 kg, 60 kg, 65 kg, 70 kg, 75 kg, Any one or more of 80 kg, 85 kg, 90 kg, 95 kg, 100 kg and the like may be selected.

It is preferable that the numerical value of the first scale display unit is displayed so as to increase toward the lead-out unit of the container body. The interval between the numerical values in the first scale display unit is not particularly limited, and may be appropriately designed according to the type of cells to be administered, the disease, the shape of the container, the material of the container, the capacity of the container, and the like.

The second scale display portion of the cell pharmaceutical product container of the present invention indicates the amount of liquid for diluting the cell pharmaceutical product with a pharmaceutically acceptable drug, and the liquid level position in the container body is set. It is possible to visually recognize the cell concentration of the cell-pharmaceutical preparation to be administered to the patient or the subject depending on whether or not it is located on the second scale display portion. More specifically, the second scale display is the amount of liquid (mL) filled with a pharmaceutically acceptable drug based on the cell concentration (cells / mL) and the liquid volume (mL) of the cytopharmaceutical preparation before mixing. ) Is calculated, and the liquid volume obtained by adding the liquid volume of the cytopharmaceutical preparation before mixing and the liquid volume of the pharmaceutically acceptable drug to be filled is displayed as a scale, and the cell drug to be administered to the patient or subject is displayed. It is a marker line indicating the final position of the liquid surface of the formulation. Therefore, by mixing the cell-pharmaceutical preparation and the pharmaceutically acceptable drug using the marker line, the cell concentration of the cell-pharmaceutical preparation to be administered to the patient or the subject can be easily adjusted, and the second The scale display makes it possible to visually recognize the cell concentration of the cell pharmaceutical product to be administered to the patient or the subject.

The third scale display unit in the container for the cell pharmaceutical product of the present invention displays the amount of liquid to be filled with the cell pharmaceutical product, and the liquid level position in the container body is on the third scale display unit. Depending on whether or not it is located, it is possible to visually recognize the number of cells of the cell pharmaceutical preparation to be introduced into the container body. More specifically, the third scale display unit displays the amount (mL) of the liquid to be filled in the cell pharmaceutical product as a scale, and the liquid of the cell pharmaceutical product to be filled in the container for the cell pharmaceutical product. It is a marker line indicating the final position of the surface. Therefore, it is possible to easily fill the cell-pharmaceutical preparation using the mark line, and the cell concentration (cells / mL) and filling amount (mL) of the cell-pharmaceutical preparation to be filled can be confirmed. The number of cells (cells) of the cell pharmaceutical preparation to be introduced becomes visible.

The fourth scale display unit in the container for a cell pharmaceutical product of the present invention displays the amount of liquid in the container, and whether or not the liquid level position of the container body is located on the fourth scale display unit. Thereby, it becomes possible to visually recognize the amount of the liquid amount of the cell pharmaceutical preparation remaining in the container body. More specifically, the fourth scale display unit gradually displays the amount of liquid (mL) that can be accommodated in the container for the cell pharmaceutical product as a scale. For example, the amount of liquid that can be accommodated in the container for cell pharmaceutical products is arranged stepwise as a scale, and in order to make it easier to see the amount of residual liquid in the container, liquids such as 100 mL, 200 mL, and 300 mL are placed near the scale. The quantity may be displayed as a numerical value.

The numerical value of the fourth scale display is not particularly limited, but for example, 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 15 mL, 20 mL, 25 mL, 30 mL, 35 mL, 40 mL, etc. 45mL, 50mL, 55mL, 60mL, 65mL, 70mL, 75mL, 80mL, 85mL, 90mL, 95mL, 100mL, 150mL, 200mL, 300mL, 400mL, 500mL, 600mL, 700mL, 800mL, 900mL, 1000mL, 2000mL, 3000mL, 4000mL, Any one or more such as 5000 mL may be selected.

It is preferable that the numerical value of the fourth scale display unit is displayed so as to decrease toward the lead-out unit of the container body. The interval between the numerical values in the fourth scale display unit is not particularly limited, and may be appropriately designed according to the type of cells to be administered, the disease, the shape of the container, the material of the container, the capacity of the container, and the like.

The fifth scale display portion of the container for the cell pharmaceutical product of the present invention indicates the number of cells of the cell pharmaceutical product to be administered to the patient or the subject, and the liquid level position in the container body is the fifth. It is possible to visually recognize the number of cells of the cell-pharmaceutical preparation administered to the patient or the subject depending on whether or not the cell is located on the scale display portion of. More specifically, the fifth scale display portion is obtained by multiplying the cell concentration (cells / mL) contained in the cell medicine preparation and the liquid volume (mL) of the cell medicine preparation administered to the patient or subject. The number of cells (cells) of the cell medicine preparation administered to the patient or the subject is displayed as a scale according to the liquid volume (mL) of the cell medicine preparation. For example, cells administered to a patient or subject by arranging the scale stepwise according to the numerical value obtained by multiplying the cell concentration of the cell pharmaceutical product and the liquid volume of the cell pharmaceutical product and the liquid volume of the cell pharmaceutical product. In order to make it easier to see the number of cells in the pharmaceutical product, the number of cells administered to a patient or subject such as 1 × 10 ⁴ cells, 2 × 10 ⁴ cells, 3 × 10 ⁴ cells, etc. is displayed as a numerical value near the scale. May be good.

The numerical value of the fifth scale display unit is not particularly limited, but for example, 1 × 10 ⁴ cells, 2 × 10 ⁴ cells, 3 × 10 ⁴ cells, 4 × 10 ⁴ cells, 5 × 10 ⁴ cells, 6 ×. 10 ⁴ cells, 7 × 10 ⁴ cells, 8 × 10 ⁴ cells, 9 × 10 ⁴ cells, 1 × 10 ⁵ cells, 2 × 10 ⁵ cells, 3 × 10 ⁵ cells, 4 × 10 ⁵ cells, 5 × 10 ⁵ cells, 6 × 10 ⁵ cells, 7 × 10 ⁵ cells, 8 × 10 ⁵ cells, 9 × 10 ⁵ cells, 1 × 10 ⁶ cells, 1 × 10 ⁷ cells, 1 × 10 ⁸ cells, 1 × 10 ⁹ cells, Any one or more of 1 × 10 ¹⁰ cells, 1 × 10 ¹¹ cells, 1 × 10 ¹² cells, 1 × 10 ¹³ cells, 1 × 10 ¹⁴ cells, 1 × 10 ¹⁵ cells, and the like may be selected.

It is preferable that the numerical value of the fifth scale display unit is displayed so as to increase in the direction of the lead-out unit of the container body. The interval between the numerical values in the fifth scale display unit is not particularly limited, and may be appropriately designed according to the type of cells to be administered, the disease, the shape of the container, the material of the container, the capacity of the container, and the like.

The container for a cell pharmaceutical product of the present invention is prepared by an empty form that does not contain a liquid such as a cell pharmaceutical product, a form that contains a cell pharmaceutical product, or a mixture of the cell pharmaceutical product and a pharmaceutically acceptable drug. It can be distributed in various forms such as a form containing the prepared cell-pharmaceutical preparation and a form containing only the cell-pharmaceutical preparation for preparing the cell-pharmaceutical preparation. The cell-pharmaceutical preparation for preparing the cell-pharmaceutical preparation is a cell-pharmaceutical preparation containing cells at a higher concentration than the cell concentration in the cell-pharmaceutical preparation prepared for treating the disease of the patient or the subject. .. Further, in the present specification, "a cell-pharmaceutical preparation for preparing a cell-pharmaceutical preparation" may be paraphrased as "a high-concentration cell-pharmaceutical preparation".

The cell pharmaceutical preparation or the high-concentration cell pharmaceutical preparation may be one treated using a cell suspension processing device including a hollow fiber separation membrane module. An example of the hollow fiber separation membrane module is shown in FIG. The hollow fiber separation membrane module 800 includes a hollow fiber separation membrane 801 and a storage container 810 for accommodating the hollow fiber separation membrane module 801. The storage container 810 has an upstream temporal region 814 in which a supply port 811 for the liquid supplied to the hollow fiber separation membrane 801 is formed, and a processing liquid outlet port 812 from which the liquid treated by the hollow fiber separation membrane 801 is led out. Includes a body portion 816 that connects to the formed downstream temporal region 815 and has a filtrate out-out port 813 that leads out the filtrate in the hollow fiber separation membrane 801.

Inside the body portion 816, a bundle 802 of a large number of hollow fiber separation membranes 801 and at the upstream end of the body portion 816, a bundle 802 of the hollow fiber separation membrane 801 is provided, and an upstream opening end 803 of the hollow fiber separation membrane 801 is provided. On the upstream side resin layer portion 821 and the body portion 816, which are fixed so as to face the upstream side head 814 and fill the gap between the adjacent hollow fiber separation membranes 801 and the gap between the bundle 802 and the inner peripheral surface of the body portion 816. At the downstream end, the bundle 802 of the hollow fiber separation membrane 801 is fixed so that the downstream opening end 804 of the hollow fiber separation membrane 801 faces the downstream head 815, and between the adjacent hollow fiber separation membranes 801 and the bundle. A downstream resin layer portion 822 that fills a gap between the 802 and the inner peripheral surface of the body portion 816 is arranged. The upstream end of the body 816 is crowned by the upstream head 814, and the downstream end of the body 816 is crowned by the downstream head 815. With this configuration, the supply port 811 and the treatment liquid outlet port 812 are continuous with each other through the space inside the hollow fiber separation membrane 801. The filtrate discharge port 813 is different from the supply port 811 and the treatment liquid outlet port 812. It is separated by a membrane wall constituting the hollow fiber separation membrane 801 and has a non-continuous structure.

The bundle 802 of the hollow fiber separation membrane 801 is preferably a bundle of about 10 to 1000 hollow fiber separation membranes 801.

As the resin material constituting the hollow fiber separation membrane 801, a synthetic polymer material can be preferably used from the viewpoint of material safety and stability. Of these, polysulfone-based or cellulosic-based hydrophilic polymer materials can be more preferably used. Further, polyether sulfone and cellulose ester can be most preferably used from the viewpoint of material safety, stability and availability.

In the hollow fiber separation membrane module 800, the cell suspension supplied from the supply port 811 is introduced into the hollow fiber separation membrane 801 from the upstream opening end 803. The introduced cell suspension fills the space inside the hollow fiber separation membrane 801 and passes through the micropores provided in the membrane wall of the hollow fiber separation membrane 801 to contain impurities outside the hollow fiber separation membrane 801. A filtrate containing a liquid medium or a liquid medium is derived, and the filtrate is led out of the hollow fiber separation membrane module 800 through the filtrate outlet 813. On the other hand, the concentrated cell suspension inside the hollow fiber separation membrane 801 is led out of the hollow fiber separation membrane module 800 from the downstream opening end 804 through the treatment liquid outlet 812. By repeating the process of passing the cell suspension through the space inside the hollow thread separation membrane as necessary, the cell suspension is washed, concentrated, and / or the medium is replaced, which is the target. It is possible to prepare a cell-pharmaceutical preparation having a composition or a high-concentration cell-pharmaceutical preparation.

An example of the method for preparing a cell pharmaceutical preparation according to the present invention is
Corresponds to a container body filled with a cytopharmaceutical preparation and having an internal space capable of holding a liquid, a lead-out unit communicating with the internal space of the container body, and the weight of the patient or subject to be administered provided in the container body. A first scale display unit for displaying the dose of the cell pharmaceutical product to be used, and a second scale display for displaying the amount of liquid for diluting the cell pharmaceutical product with a pharmaceutically acceptable drug provided in the container body. At least a step of filling a container for a cytopharmaceutical preparation provided with a portion with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body is included. In this example of the preparation method, a pharmaceutical cell preparation having an intended cell concentration to be administered to a patient or a subject can be easily prepared using the second scale display portion as an index. In this example of the preparation method, examples of the cell-pharmaceutical preparation pre-filled in the container for the cell-pharmaceutical preparation include the above-mentioned "cell-pharmaceutical preparation for preparing the cell-pharmaceutical preparation" or "high-concentration cell-pharmaceutical preparation". The container for the cell pharmaceutical product filled with the cell pharmaceutical product may be a container for the cell pharmaceutical product that is distributed in a form containing only the cell pharmaceutical product for preparing the cell pharmaceutical product, or may be empty. The container for the cell pharmaceutical product distributed in the form may be prepared by the user by filling the container for the cell pharmaceutical product for preparing the cell pharmaceutical product. Specific embodiments of the cell pharmaceutical preparation, the first scale display unit, the second scale display unit, the pharmaceutically acceptable drug, and the like are as described above.

Another example of the method for preparing a cell pharmaceutical preparation according to the present invention is
A container body having an internal space capable of holding a liquid, a lead-out unit communicating with the internal space of the container body, and a dose of a cytopharmaceutical preparation corresponding to the weight of the patient or subject to be administered provided in the container body. A first scale display unit for displaying, a second scale display unit provided on the container body for displaying the amount of liquid for diluting the cytopharmaceutical preparation with a pharmaceutically acceptable drug, and the container body are provided. In a container for a cell pharmaceutical product provided with a third scale display unit for displaying the amount of liquid to be filled with the cell pharmaceutical product, the cell pharmaceutical product is placed in the container body until the liquid level reaches the third scale display unit. The filling process and
At least a step of filling the container filled with the cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body is included. In the first half step of this example of the preparation method, the cell pharmaceutical product containing the intended number of cells can be filled in the cell pharmaceutical product container by a simple operation using the third scale display portion as an index. In the latter step of this example of the preparation method, a pharmaceutical cell preparation having an intended cell concentration to be administered to a patient or a subject can be easily prepared using the second scale display portion as an index. In this example of the preparation method, as the cell-pharmaceutical preparation to be filled in the first half step, the above-mentioned "cell-pharmaceutical preparation for preparing the cell-pharmaceutical preparation" or "high-concentration cell-pharmaceutical preparation" can be exemplified. Specific embodiments of the cell pharmaceutical preparation, the first scale display unit, the second scale display unit, the third scale display unit, the pharmaceutically acceptable drug, and the like are as described above. is there.

Hereinafter, the characteristics of the cell pharmaceutical product container according to the present invention and the method for preparing the cell pharmaceutical product using the cell pharmaceutical product container according to the present invention will be described based on specific embodiments, but the scope of the present invention is the scope of the present invention. It is not limited to these embodiments.

<First Embodiment>
FIG. 1 shows a container 1 for a cell pharmaceutical product (hereinafter, may be referred to as “container 1”) according to the first embodiment of the present invention.

The container 1 includes a container main body 10, a lead-out unit 20, a first introduction unit 30, and a second introduction unit 40.

The container body 10 is formed by arranging a pair of substantially rectangular first resin sheets 11 and second resin sheets 12 so as to face each other and joining peripheral portions by heat fusion to form a bag body. The first resin sheet 11 and the second resin sheet 12 are sheets containing a flexible resin as a main component, respectively. Specific examples of the flexible resin are as described above.

The first resin sheet 11 and the second resin sheet 12 are formed so that the liquid level position of the cytopharmaceutical preparation inside can be visually observed by making at least a part of the transparent or translucent material. ing. Further, it is preferable that the inner surfaces of the first resin sheet 11 and the second resin sheet 12 are pear-processed because the residual liquid can be reduced at the time of administration of the cytopharmaceutical preparation.

The portion where the first resin sheet 11 and the second resin sheet 12 are joined by heat fusion is referred to as a fusion portion 13. In the container body 10, an internal space 14 is formed between the first resin sheet 11 and the second resin sheet 12. Note that FIG. 1 is a schematic plan view of the container 1 in a state where the internal space 14 is empty.

The lead-out unit 20 communicates the internal space 14 of the container body 10 with the outside, and leads out the lead-out pipe 22 having a lead-out port 21 formed inside which is a path for leading out the liquid contained in the internal space 14 to the outside. It is provided with a luer lock 23 that seals the outlet of the pipe 22 so as to be able to communicate with each other.

The first introduction portion 30 communicates the internal space 14 of the container body 10 with the outside, and has a first introduction port 31 formed inside which serves as a path for introducing materials from the outside into the internal space 14. It includes an introduction pipe 32 and a luer lock 33 that seals the entrance of the first introduction pipe 32 so as to communicate with each other.

The second introduction portion 40 communicates the internal space 14 of the container body 10 with the outside, and has a second introduction port 41 formed inside which serves as a path for introducing materials from the outside into the internal space 14. It includes an introduction pipe 42 and a luer lock 43 that seals the entrance of the second introduction pipe 42 so as to communicate with each other.

The container body 10 has a substantially rectangular shape, and the lead-out portion 20 has a first resin sheet 11 and a second resin having one end of the lead-out tube 22 on one end of the container body 10 in the longitudinal direction. It is arranged between the sheet 12 and the first resin sheet 11 and the second resin sheet 12 around the sheet 12 are joined by heat fusion to be integrated with the container body 10. Similarly, in the first introduction section 30 and the second introduction section 40, one end of the first introduction tube 32 and the second introduction tube 42 is the other end in the longitudinal direction of the container body 10, respectively. It is arranged between the first resin sheet 11 and the second resin sheet 12 on the side, and the first resin sheet 11 and the second resin sheet 12 around it are joined by heat fusion and integrated with the container body 10. Has been made. That is, the first introduction portion 30 and the second introduction portion 40 are arranged at the end portion of the container body 10 facing the end portion where the lead-out portion 20 is arranged.

In the first embodiment, through holes 15 and 15 are formed in both ends of the container body 10 on the side where the first introduction portion 30 and the second introduction portion 40 are arranged, outside the fusion portion 13. Is formed. By suspending the container 1 from a support such as a hook through the through holes 15 and 15, the first introduction portion 30 and the second introduction portion 40 are located at the upper end portions in the vertical direction, and the lead-out portion 20 It can be suspended so that it is located at the lower end in the vertical direction.

As shown in FIG. 1, when the container 1 is suspended so that the outlet 20 is vertically downward, the opening 21A on the side of the outlet 21 of the outlet 21 of the outlet 20 is the most in the internal space 14. The lead-out portion 20 is arranged so as to be located below, and the portion 13A of the fusion portion 13 surrounding the internal space 14 located below in the vertical direction is moved upward in the vertical direction as the distance from the opening 21A in the horizontal direction increases. It is preferably formed so as to be located. With this configuration, the cell pharmaceutical product is housed in the internal space 14, the container 1 is suspended so that the outlet 20 is vertically downward, and the cell pharmaceutical product is derived from the outlet 21 of the outlet 20 to be a patient or. When administered to a subject, the cell does not easily stay in the portion 13A and easily moves toward the opening 21A, so that the cell pharmaceutical preparation containing the intended amount of cells can be administered to the patient or the subject.

(First feature)
The first feature of the container 1 according to the first embodiment is that the container body 10 includes a first scale display unit 100 that displays the dose of the cell pharmaceutical product corresponding to the body weight of the patient or the subject to be administered. It is possible to visually recognize the dose of the cell pharmaceutical preparation suitable for the weight of the patient or the subject depending on whether or not the liquid level position in the main body 10 is located on the first scale display unit 100.
The function of the first scale display unit 100 will be specifically described with reference to FIGS. 2 and 3.

FIG. 2 schematically shows a state in which a liquid cell-pharmaceutical product L (hereinafter, may be referred to as “formulation L”) is accommodated and suspended in the internal space 14 of the container body 10 of the container 1 according to the first embodiment. Illustrated. The cell concentration and liquid amount of the contained preparation L are controlled, and the preparation L is stored so as to have a predetermined cell concentration and liquid amount prescribed in advance. The first scale display unit 100 is arranged so as to extend in the vertical direction when the container 1 is suspended, and is located below the liquid level A of the preparation L before the start of administration when the container 1 is suspended. Includes a numerical scale 110 and a numerical value 120. In the illustrated example, the first scale display unit 100 includes a large scale 111 indicating the weight of the patient or subject to be administered in units of 10 kg, a medium scale 112 indicating in units of 5 kg, and a small scale 113 indicating in units of 1 kg. Includes a numerical scale 110 consisting of and a numerical value 120 indicating the weight of the patient or subject corresponding to each large scale 111. In the present embodiment, the numerical value 120 of the first scale display unit 100 is displayed so as to increase toward the lead-out unit 20 of the container body 10.

FIG. 3 shows the preparation L from the state in which the liquid preparation L is housed in the internal space 14 of the container body 10 of the container 1 according to the first embodiment shown in FIG. 2 through the outlet 21 of the out-out unit 20. Is schematically shown in the state when the above is derived and administered to a patient or a subject. When the preparation L is administered to a patient or a subject, the liquid level A in the container body 10 moves downward in the vertical direction. The first scale display unit 100 displays the dose of the cell pharmaceutical product corresponding to the body weight of the patient or the subject to be administered according to the position of the liquid level A in the container body 10. The weight of the patient or subject depends on whether or not the position of the liquid level A of the preparation L in the container body 10 is located on the numerical scale 110 of the first scale display unit 100 according to the weight of the patient or subject to be administered. The dose of the preparation L suitable for the above can be visually recognized. For example, when the preparation L is administered from the container 1 to a patient or subject weighing 65 kg, the liquid level A of the preparation L is located on the numerical scale 110 corresponding to the body weight 65 kg, as shown in FIG. It is possible to grasp that the dose of the preparation L suitable for the body weight of the patient or the subject has been administered by visually observing.

In the medical field, the weight of the patient or the subject is confirmed in advance, and with the container 1 suspended, the formulation L is delivered through the lead-out port 21 of the lead-out unit 20, and the liquid level A thereof is the first scale display unit. By a simple operation of administering to the patient or subject until the numerical scale 110 indicating the body weight of the patient or subject at 100 is reached, and stopping the administration at that point, the appropriate number of cells according to the body weight of the patient or subject is included. It becomes possible to administer an amount of a cytopharmaceutical preparation to a patient or subject. The start and stop of administration of the preparation L through the outlet 21 of the lead-out unit 20 is carried out by connecting a flow path such as a tube to the downstream of the lead-out unit 20 and further connecting the flow path to the patient or the subject. When the preparation L is administered, a mechanism (clamp, valve, etc.) for adjusting the opening and closing of the flow path is provided in the middle of the flow path, and the flow path is opened to start the administration of the preparation L. This can be done by stopping the administration of the preparation L by closing the flow path, or by providing a pump in the middle of the flow path to control the administration of the preparation L.

According to this embodiment, since it is not necessary to calculate an appropriate dose of the preparation L with respect to the body weight of the patient or the subject in the medical field, the risk of erroneous dose is reduced. Further, the preparation L of the dose according to the weight of the patient or the subject does not need to be taken out from the container 1 with a syringe or the like, and the preparation L is prepared for the patient or the subject from the container 1 containing the preparation L having a controlled cell concentration and amount. Since L can be directly administered, it is advantageous in that the stress applied to the cells is small and the risk of damaging the cells in the preparation L is low, and that the number of steps is small, so that a dose error is unlikely to occur. Further, unlike the method described in Reference 2 in which the cytopharmaceutical preparation is divided by sandwiching the drug solution bag with a clip so that the dose is adjusted according to the body weight, in the present embodiment, the preparation L is the container 1. Since it is not divided within, the whole of the preparation L can be made to flow by kneading the container 1 by hand, and it is easy to keep the cell concentration in the preparation L uniform as a whole.

In the illustrated embodiment, the first graduation display 100 shows only up to 70 kg of patient or subject weight, but may be formed to show a larger body weight. Further, when the preparation L is administered to a patient or subject having a weight of more than 70 kg and a weight of 140 kg or less using the container 1 of the illustrated embodiment, two containers 1 filled with the preparation L are prepared, and one container 1 is used. The formulation L is administered to the patient or subject until the liquid level A reaches the numerical scale corresponding to the dose to the patient or subject weighing 70 kg, and from another container 1, the excess weight of the patient or subject's weight from 70 kg. The preparation L can be administered to the patient or subject until the liquid level A reaches the numerical scale corresponding to.

(Second feature)
The method for preparing the preparation L is not particularly limited, but it may be prepared inside the container 1 according to the first embodiment. For example, in the internal space 14 of the container body 10, the high-concentration cell pharmaceutical preparation L1 is pharmaceutically represented. It may be prepared by filling and mixing with an acceptable agent L2. In order to use for the preparation of such a preparation L, in the container 1 according to the first embodiment, as a second feature, when the container body 10 fills the internal space 14 with the pharmaceutically acceptable drug L2. A second scale display unit 200 for displaying the amount of liquid is provided, and the preparation L to be administered to a patient or a subject depends on whether or not the position of the liquid level A in the container body 10 is located on the second scale display unit 200. The cell concentration can be visually recognized.

Specifically, a container 1 having a second scale display unit 200 is used in the container body 10, and the internal space 14 of the container body 10 is first filled with the high-concentration cell pharmaceutical preparation L1 as shown in FIG. After that, as shown in FIG. 5, the pharmaceutically acceptable drug L2 can be filled in the second scale display unit 200 until the liquid level A is reached. In this case, the second scale display unit 200 indicates the final position of the liquid level A in the container body 10 when the container 1 is suspended and the internal space 14 is filled with the pharmaceutically acceptable drug L2. It is a landmark line.

As shown in FIG. 4, the container 1 according to the first embodiment in which the high-concentration cell pharmaceutical preparation L1 is pre-filled is prepared, and the pharmaceutically acceptable drug L2 is filled and mixed in the medical field. When the preparation L is prepared, the cell concentration in the preparation L can be visually recognized depending on whether or not the liquid level A of the liquid in the container body 10 is located on the second scale display unit 200. By providing the second scale display unit 200, it is easy to accurately fill the pharmaceutically acceptable drug L2 in the intended amount and prepare the preparation L having the intended cell concentration.

In the illustrated embodiment, the second scale display unit 200 is a line extending in a horizontal direction when the container 1 is suspended and formed over substantially the entire direction of the container body 10, but this embodiment. Not limited to. For example, the second scale display unit 200 extends in a horizontal direction when the container 1 is suspended, but may be a line formed only in a part of the container body 10 in the above direction.

When the high-concentration cell pharmaceutical preparation L1 and the pharmaceutically acceptable drug L2 are filled and mixed in the internal space 14 of the container body 10 of the container 1, the first introduction section 30 and the second introduction section 40 One of them can be filled with the high-concentration cell pharmaceutical preparation L1 and the other can be filled with the pharmaceutically acceptable drug L2. In addition, one or both of the first introduction section 30 and the second introduction section 40 used for filling the high-concentration cell pharmaceutical preparation L1 or the pharmaceutically acceptable drug L2 is irreversibly sealed after filling. May be good.

(Third feature)
In the container 1 according to the first embodiment, the container body 10 includes a third scale display unit 300 that displays the amount of liquid to be filled with the preparation L or the high-concentration cell-pharmaceutical preparation L1, and the liquid level A of the container body 10 is provided. The third feature is that the number of cells of the preparation L or the high-concentration cell pharmaceutical preparation L1 to be introduced into the container body 10 can be visually recognized depending on whether or not the position of is located on the third scale display unit 300.

In the example shown in FIG. 4, the third scale display unit 300 suspends the container 1 and fills the internal space 14 of the container body 10 with the high-concentration cell pharmaceutical preparation L1. The surface A is a mark line indicating a position to be filled.

As shown in FIG. 4, the container 1 according to the first embodiment is filled with the high-concentration cell pharmaceutical preparation L1 until the liquid level A reaches the third scale display portion 300, so that the container 1 contains the intended number of cells. The concentration cell pharmaceutical preparation L1 can be accurately filled. Further, as shown in FIG. 5, the pharmaceutically acceptable drug L2 is filled and mixed until the liquid level A reaches the second scale display portion 200 to prepare the preparation L having the intended cell concentration. be able to. Further, when the container 1 is suspended, the high-concentration cells containing an appropriate number of cells depending on whether or not the liquid level A of the high-concentration cell pharmaceutical preparation L1 in the container body 10 is located on the third scale display unit 300. It is possible to visually check whether or not the pharmaceutical preparation L1 is contained.

In the illustrated embodiment, the third scale display unit 300 is a line extending in a horizontal direction when the container 1 is suspended and formed over substantially the entire direction of the container body 10, but this embodiment. Not limited to. For example, the third scale display unit 300 extends in a horizontal direction when the container 1 is suspended, but may be a line formed only in a part of the container body 10 in the above direction.

In the container 1 according to the first embodiment, since the second scale display unit 200 and the third scale display unit 300 are arranged in parallel with each other, they are pharmaceutically acceptable as the high-concentration cell pharmaceutical preparation L1. It is easy to visually recognize the filling amount of the drug L2.

<Second Embodiment>
FIG. 6 shows a container 1 for a cell pharmaceutical product (hereinafter, may be referred to as “container 1”) according to the second embodiment of the present invention.

In the container 1 according to the second embodiment, the configurations common to the container 1 according to the first embodiment are designated by the same reference numerals, and the description thereof will be omitted.

In the container 1 according to the second embodiment shown in FIG. 6, the container body 10 includes a fourth scale display unit 400 that displays the amount of liquid in the container body 10, and the position of the liquid level A of the container body 10 is the second. It is characterized in that the amount of liquid of the preparation L remaining in the container body 10 can be visually recognized depending on whether or not it is located on the scale display unit 400 of No. 4.

The fourth scale display unit 400 is arranged so as to extend in the vertical direction when the container 1 is suspended, and is a liquid of the preparation L which is a liquid contained in the internal space 14 of the container body 10 when the container 1 is suspended. Includes a numerical scale 410 and a numerical value 420 indicating the volume below surface A. In the present embodiment, the numerical value 420 of the fourth scale display unit 400 is displayed so as to decrease toward the lead-out unit 20 of the container body 10.

By providing the fourth scale display unit 400, when the preparation L is administered to the patient or the subject from the container 1 containing the preparation L through the outlet 21, the amount of the residual liquid of the preparation L in the container 1 can be visually recognized. can do. When the preparation L is administered from the container 1 to the patient or the subject, if the residual liquid amount of the preparation L corresponding to the appropriate dose according to the body weight of the patient or the subject is known in advance, the residual liquid of the preparation L The dose can be confirmed based on the amount, and the dose of the preparation L can be double-confirmed together with the confirmation based on the weight of the patient or the subject using the first scale display unit 100. Become. This makes it possible to more safely administer the preparation L containing an appropriate number of cells according to the body weight of the patient or subject to the patient or subject.

<Third Embodiment>
FIG. 7 shows a container 1 for a cell pharmaceutical product according to a third embodiment of the present invention (hereinafter, may be referred to as “container 1”).

In the container 1 according to the third embodiment, the configurations common to the container 1 according to the first embodiment and the container 1 according to the second embodiment are designated by the same reference numerals, and the description thereof will be omitted.

In the container 1 according to the third embodiment shown in FIG. 7, the container body 10 includes a fifth scale display unit 500 that displays the number of cells of the preparation L to be administered to the patient or the subject to be administered, and is inside the container body 10. The number of cells of the preparation L administered to the patient or the subject can be visually recognized depending on whether or not the position of the liquid level A of the liquid level A is located on the fifth scale display unit 500.

The fifth scale display unit 500 is arranged so as to extend in the vertical direction when the container 1 is suspended, and is located below the liquid level A of the preparation L before the start of derivation when the container 1 is suspended. Includes numerical scale 110 and numerical 520. Here, the numerical scale 110 also serves as the numerical scale 110 of the first scale display unit 100. Of the numerical scales 110, the large scale 111 indicates the body weight of the patient or subject to be administered in units of 10 kg, and the number of cells contained in the administered preparation L is indicated in units of 2 × 107, and the medium scale 112 indicates the unit of 2 × 10 ^7. , together indicated by 5kg units weight of the patient or subject to be administered, the number of cells contained in the administered formulation L shown in 1 × 10 ⁷ cells units, small scale 113, weight of the patient or subject to be administered Is shown in units of 1 kg, and the number of cells contained in the administered preparation L is shown in units of 2 × 10 ⁶ . The numerical value 520 indicates the number of administered cells corresponding to each large scale 111. In the present embodiment, the numerical value 520 of the fifth scale display unit 500 is displayed so as to increase in the direction of the lead-out unit 20 of the container body 10.

Although not shown, the fifth scale display unit 500 may be a scale display unit independent of the first scale display unit 100.

By providing the fifth scale display unit 500, when the preparation L is taken out from the container 1 containing the preparation L through the outlet 21 and administered to the patient or the subject, the liquid level of the preparation L in the container body 10 is provided. The number of cells administered to the patient or the subject can be visually recognized depending on whether or not the position of A is located on the numerical scale 110 corresponding to the number of administered cells on the fifth scale display unit 500. When the preparation L is administered to the patient or subject from the container 1, if the number of cells to be administered to the patient or subject is known in advance, the dose is appropriate by referring to the fifth scale display unit 500. This can be confirmed, and the dose of the preparation L can be double-confirmed together with the confirmation based on the weight of the patient or the subject using the first scale display unit 100. This makes it possible to more safely administer the preparation L in an amount containing the number of cells to be administered to the patient or subject to the patient or subject.

1: Cell pharmaceutical product container 10: Container body 14: Internal space 20: Out-out unit 21: Out-out port 30, 40: Introducing unit 31, 41: Introducing port 100: First scale display unit 200: Second scale display Part 300: Third scale display part 400: Fourth scale display part 500: Fifth scale display part L: Cell pharmaceutical product L1: Cell pharmaceutical product for preparing a cell pharmaceutical product (high-concentration cell pharmaceutical product)
L2: Pharmaceutically acceptable drug A: Liquid level

All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.

Claims (14)

A container for cell pharmaceutical products
A container body with an internal space that can hold liquid,
A lead-out unit that communicates with the internal space of the container body,
The container body is provided with a first scale display unit that displays the dose of the cell pharmaceutical preparation corresponding to the body weight of the patient or the subject to be administered.
The container in which the dose of the cell pharmaceutical preparation suitable for the body weight of the patient or the subject can be visually recognized depending on whether or not the liquid level position in the container body is located on the first scale display portion. The container according to claim 1, wherein the numerical value of the first scale display unit is displayed so as to increase in the direction of the lead-out unit of the container body. Further, the container body is provided with a second scale display unit for displaying the amount of liquid for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and the liquid level position in the container body is the second scale. The container according to claim 1 or 2, wherein the cell concentration of the cytopharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether or not the container is located on the display unit. Further, the container body is provided with a third scale display unit that displays the amount of liquid to be filled with the cell pharmaceutical preparation, and whether or not the liquid level position in the container body is located on the third scale display unit. The container according to any one of claims 1 to 3, wherein the number of cells of the cell pharmaceutical preparation to be introduced into the container body can be visually recognized. Further, the container body is provided with a fourth scale display unit that displays the amount of liquid in the container, and the container body is determined by whether or not the liquid level position of the container body is located on the fourth scale display unit. The container according to any one of claims 1 to 4, wherein the amount of the liquid amount of the cell pharmaceutical preparation remaining in the container can be visually recognized. The container according to claim 5, wherein the numerical value of the fourth scale display unit is displayed so as to decrease toward the lead-out unit of the container body. Further, the container body includes a fifth scale display unit that displays the number of cells of the cell pharmaceutical preparation to be administered to the patient or the subject, and the liquid level position in the container body is set to the fifth scale display unit. The container according to any one of claims 1 to 6, wherein the number of cells of the cell pharmaceutical preparation administered to the patient or the subject can be visually recognized depending on whether or not the container is located. The container according to claim 7, wherein the numerical value of the fifth scale display unit is displayed so as to increase in the direction of the lead-out unit of the container body. The container body has a second scale display unit that displays the amount of liquid that dilutes the cell pharmaceutical product with a pharmaceutically acceptable drug, and a third scale display that displays the amount of liquid that fills the cell pharmaceutical product. With a department
The cell concentration of the cell-pharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether or not the liquid level position in the container body is located on the second scale display portion.
The number of cells of the cell pharmaceutical product to be introduced into the container body can be visually recognized depending on whether or not the liquid level position in the container body is located on the third scale display portion.
The container according to any one of claims 1 to 8, wherein the second scale display unit is provided on a parallel line of the third scale display unit. The container according to any one of claims 1 to 9, further comprising an introduction portion that communicates with the internal space of the container body. The container according to claim 10, wherein the introduction portion is provided at the upper end portion of the container body facing the lead-out portion. The container according to any one of claims 1 to 11, wherein the container body is made of a flexible material. A method for preparing a cell pharmaceutical product.
Corresponds to a container body filled with a cytopharmaceutical preparation and having an internal space capable of holding a liquid, a lead-out unit communicating with the internal space of the container body, and the weight of the patient or subject to be administered provided in the container body. A first scale display unit for displaying the dose of the cell pharmaceutical product to be used, and a second scale display for displaying the amount of liquid for diluting the cell pharmaceutical product with a pharmaceutically acceptable drug provided in the container body. The method comprising a step of filling a container for a cytopharmaceutical product provided with a portion with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body. A method for preparing a cell pharmaceutical product.
A container body having an internal space capable of holding a liquid, a lead-out unit communicating with the internal space of the container body, and a dose of a cytopharmaceutical preparation corresponding to the weight of the patient or subject to be administered provided in the container body. A first scale display unit for displaying, a second scale display unit provided on the container body for displaying the amount of liquid for diluting the cytopharmaceutical preparation with a pharmaceutically acceptable drug, and the container body are provided. In a container for a cell pharmaceutical product provided with a third scale display unit for displaying the amount of liquid to be filled with the cell pharmaceutical product, the cell pharmaceutical product is placed in the container body until the liquid level reaches the third scale display unit. The filling process and
The method comprising a step of filling the container filled with a cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body.

Images