WO2019160134A1

WO2019160134A1 - Container for cell pharmaceutical preparation

Info

Publication number: WO2019160134A1
Application number: PCT/JP2019/005792
Authority: WO
Inventors: 拡敏松田
Original assignee: 株式会社カネカ
Priority date: 2018-02-19
Filing date: 2019-02-18
Publication date: 2019-08-22
Also published as: JPWO2019160134A1; JP7240336B2

Abstract

The present invention provides a means by which a cell pharmaceutical preparation, in an amount including the appropriate number of cells according to the weight of a patient or a subject, can be administered to the patient or the subject with a simple operation. A container 1 for a cell pharmaceutical preparation according to the present invention is characterized by comprising: a container body 10 having an inner space 14 in which a cell pharmaceutical preparation L can be accommodated; and a discharge unit 20 in which a discharge port 21 communicating with the inner space 14 of the container body 10 is formed, wherein the container body 10 is provided with a first scale indication part 100 that indicates the cell pharmaceutical preparation L dosage corresponding to the weight of a patient or a subject to be dosed, and the cell pharmaceutical preparation L dosage appropriate for the weight of the patient or the subject can be visually checked according to whether or not the liquid surface A level inside the container body 10 is at the first scale indication part 100.

Description

Container for cell medicine preparation

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

When administering drugs containing pharmaceutical compounds or vitamins to patients in medical settings, hang the drug bag containing the drug solution on the hook of the drip stand and drop the drug solution from the drug bag by natural fall. The drug solution is directly introduced into the patient's body through the injection needle placed in the patient's static artery. In recent years, in addition to the conventional administration methods described above, various administration forms have been reported.

For example, in Patent Document 1, a part of a first syringe having an indication related to a dose with respect to a patient's body weight is fed into a drug container, the first syringe is filled to the dose, and the drug is loaded. A method of administration to a patient is described. According to Patent Document 1, in this method, there is no need to calculate or relate the drug dose to the patient's body weight.

Further, in Patent Document 2, in a drug solution bag including a bag body having a drug chamber capable of enclosing a drug solution, a marker indicating the patient's weight corresponding to the dose of the drug solution to be administered is attached to the outer surface of the bag body. It is described that it may be done. In Patent Document 2, after confirming the weight of the patient, the medical staff prepared the drug according to the weight of the patient by sandwiching the bag body with a clip according to the marker of the drug bag of this aspect. Above, it is described to be administered to a patient.

Furthermore, Patent Document 3 describes a medical container including a first scale display unit that displays the amount of liquid in the soft bag and a second scale display unit that displays the amount of liquid in the bag above the liquid level. It is described that a medical worker can administer a drug to a patient after confirming the presence or absence of mixed injection with another drug using the second scale display part of the medical container as an index.

Special table 2015-508321 gazette JP 2017-164421 A JP 2007-260252 A

When a cell pharmaceutical preparation containing cells used for cell therapy is administered to a patient, since the cell pharmaceutical preparation is a cell suspension, the cells have a non-uniform density in the container, and the cells are precipitated and In consideration of aggregation, an appropriate cell dose (cell number and cell density) corresponding to the patient's body weight must be accurately administered to the patient.

Therefore, as a method of administering an appropriate dose of cells according to the patient's body weight to the patient, the present inventors obtained the number of cells according to the patient's body weight from the first container containing the cell pharmaceutical preparation. After taking out from a formulation with a syringe, transferring to another 2nd container and further diluting to the appropriate cell density with the physiological saline, the method of administering the whole quantity in the said 2nd container to a patient was examined. However, in this method, when the cell pharmaceutical preparation is transferred from the first container to the second container through the syringe, the cells in the second container are retained in the vicinity of the lead-out portion in the syringe. It has been found that the number of cells decreases, and furthermore, cells may be killed by pressure when the cell suspension is drawn from the syringe. Moreover, when diluting with the physiological saline, the physiological saline remained in a syringe, and also the problem that the cell density in a 2nd container cannot be prepared appropriately was discovered. Therefore, the administration methods described in Patent Documents 1 to 3 were further examined to solve the above problems.

The first syringe having the indication related to the dose relative to the patient's body weight described in Patent Document 1 can avoid measurement errors by the indication described in the syringe, but the cell suspension in the syringe can be avoided. There is a problem that cells are killed by the pressure when the liquid is introduced. Furthermore, in the case of a cell pharmaceutical preparation, since the cells precipitate and aggregate according to the elapsed time, it is necessary to flow in the container, but the syringe is composed of a hard material and is suspended. Since this space cannot be held in the syringe, there is a problem that an appropriate cell density cannot be maintained at the time of administration.

In addition, the drug solution bag described in Patent Document 2 can 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. Depending on the elapsed time, the cells in the drug solution bag precipitate and aggregate. Therefore, even if the whole cell pharmaceutical preparation is made to flow by swallowing the entire container or the like, since the drug solution bag is sandwiched between the clips, it is impossible to make the whole cell pharmaceutical preparation flow, and excessive There is a problem that if the pressure is applied, the clip will come off the chemical bag.

In addition, the medical container described in Patent Document 3 includes a first scale display unit that displays the amount of liquid in the soft bag and a second scale display unit that displays the amount of liquid in the bag above the liquid level. Although it is possible to confirm the presence of mixed injection with other drugs other than the suspension, there is a problem that there is no means for confirming an appropriate dose of cells according to the weight of the patient.

In view of the above problems, in the case of administering a cell pharmaceutical preparation to a patient, the present invention accurately grasps an appropriate dose of cells according to the weight of the patient and administers it to the patient with a simple operation. It aims to provide a means to enable.

Surprisingly, the inventors of the present invention can accurately grasp the appropriate dose of cells according to the patient's body weight and can be administered to the patient with a simple operation using a container for cell pharmaceutical preparation having the following characteristics: In addition, the inventors have found a method by which a cell pharmaceutical preparation that can be administered to a patient can be prepared by a simple operation by using the container for cell pharmaceutical preparation, thereby completing the present invention.

(1) A container for cell pharmaceutical preparation,
A container body having an internal space capable of holding a liquid;
A lead-out portion communicating with the internal space of the container body;
The container body includes a first scale display unit for displaying a dose of a cell pharmaceutical preparation corresponding to the weight of a patient or subject to be administered,
The said container which can visually recognize the dosage of the said cell pharmaceutical formulation suitable for a patient or a test subject's body weight by whether the liquid level position in the said container main body is located in a said 1st scale display part.
(2) The container according to (1), wherein the numerical value of the first scale display part is displayed so as to increase toward the direction of the lead-out part of the container main body.
(3) The container body further includes a second scale display unit that displays a liquid volume for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and the liquid surface position in the container body is the first level. The container according to (1) or (2), wherein the cell concentration of the cell pharmaceutical preparation to be administered to a patient or a subject can be visually recognized depending on whether or not it is positioned on the scale display part 2.
(4) Furthermore, the container body includes a third scale display unit that displays the amount of the liquid filled with the cell pharmaceutical preparation, and the liquid level position in the container body is located in 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 introduced into the container body can be visually recognized depending on whether or not.
(5) Furthermore, the container body includes a fourth scale display unit that displays the amount of liquid in the container, and whether or not the liquid level position of the container body is located in 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 confirmed.
(6) The container according to (5), in which the numerical value of the fourth scale display unit is displayed so as to decrease toward the direction of the outlet part of the container body.
(7) Furthermore, the container body includes a fifth scale display unit that displays the number of cells of the cell pharmaceutical preparation administered to a patient or a 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 a patient or a subject can be visually recognized depending on whether or not it is positioned on the display unit.
(8) The container according to (7), wherein the numerical value of the fifth scale display part is displayed so as to increase toward the direction of the lead-out part of the container main body.
(9) The container main body displays a second scale display portion for displaying a liquid amount for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and a third scale for displaying the liquid amount for filling the cell pharmaceutical preparation. And a scale display
Whether or not the liquid surface position in the container body is located in the second scale display unit, the cell concentration of the cell pharmaceutical preparation to be administered to a patient or a subject can be visually confirmed,
Whether or not the liquid level position in the container body is located in the third scale display unit, the number of cells of the cell pharmaceutical preparation to be introduced into the container body can be visually confirmed,
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 including an introduction portion communicating with the internal space of the container body.
(11) The container according to (10), wherein the introduction part is provided at an upper end part of the container body facing the lead-out part.
(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,
Corresponding to the body of a container filled with a cell pharmaceutical preparation and having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container body, and the weight of a patient or subject to be administered provided in the container body A first scale display for displaying the dose of the cell pharmaceutical preparation to be performed, and a second scale display for displaying the amount of liquid used for diluting the cell pharmaceutical preparation provided in the container body with a pharmaceutically acceptable drug The method comprising the step of filling a cell pharmaceutical preparation container comprising a portion with a pharmaceutically acceptable drug until the liquid level reaches the second scale display section of the container body.
(14) A method for preparing a cell pharmaceutical preparation,
A container main body having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container main body, and a dose of a cell pharmaceutical preparation provided in the container main body corresponding to the weight of a patient or subject to be administered A first scale display unit for displaying, a second scale display unit for displaying a liquid volume for diluting the cell pharmaceutical preparation provided in the container main body with a pharmaceutically acceptable drug, and a container main body. Until the liquid level reaches the third scale display portion of the container main body in the cell pharmaceutical preparation container having a third scale display portion for displaying the amount of the liquid filled with the cell pharmaceutical preparation. Filling, and
Filling the container filled with a cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display part of the container body.

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

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

FIG. 1 is a diagram showing a cell pharmaceutical preparation container according to the first embodiment of the present invention. FIG. 2 is a diagram showing a state in which the cell pharmaceutical preparation container according to the first embodiment of the present invention is suspended and the cell pharmaceutical preparation is accommodated in the internal space. FIG. 3 suspends the cell pharmaceutical preparation container according to the first embodiment of the present invention, stores the cell pharmaceutical preparation in the internal space as shown in FIG. 2, and then administers the cell pharmaceutical preparation to the patient through the outlet. It is a figure which shows the state at the time. FIG. 4 shows a state in which the cell pharmaceutical preparation container according to the first embodiment of the present invention is suspended and the internal space is filled with the high-concentration cell pharmaceutical preparation until the liquid level is positioned at the third scale display section. It is a figure which shows a state. FIG. 5 suspends the cell pharmaceutical preparation container according to the first embodiment of the present invention, and after filling the internal space with a high concentration cell pharmaceutical preparation as shown in FIG. It is a figure which shows a state when it further fills until a liquid level is located in a 2nd scale display part, and mixes and it prepares a cell pharmaceutical formulation. FIG. 6 is a view showing a container for cell pharmaceutical preparation according to a second embodiment of the present invention. FIG. 7 is a view showing a cell pharmaceutical preparation container according to a third embodiment of the present invention. FIG. 8 is a schematic view showing an example of a 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>
The cell pharmaceutical preparation is a pharmaceutical preparation containing medically and / or pharmaceutically acceptable cells, specifically, medically and / or pharmaceutically acceptable cells and pharmaceutically acceptable drugs. A pharmaceutical preparation containing The cell pharmaceutical preparation is preferably a container for cell pharmaceutical preparation according to the present invention described later. In the present specification, “container” may be referred to as “bag” in some cases.

In addition, cell medicine preparations include salts, vitamins, amino acids, polysaccharides, dimethyl sulfoxide, buffer, albumin, medium, cell cryoprotectant CP-1 (manufactured by Kyokuto Pharmaceutical Co., Ltd.), BAMBANKER as necessary. (Manufactured by Lymphoctec), STEM-CELLBANKER (manufactured by Nippon Zenyaku Kogyo Co., Ltd.), ReproCryo RM (manufactured by Reprocell), CryoNovo (manufactured by Akron Biotechnology), MSC Freezing Solution (Biological IndustryCriticalS) Manufactured) and the like.

The medium in the present invention is not particularly limited as long as it is a medium composed of a component composition that allows cells to survive. However, BME medium, BGJb medium, CMRL1066 medium, Glasgow MEM medium, Improved MEM Zinc Option medium, IMDM medium (Iscove medium) 's Modified Dulbecco's Medium), Medium 199 medium, Eagle MEM medium, αMEM medium, DMEM medium (Dulbecco's Modified Eagle's Medium), Ham F10 medium, Ham F12 medium, RPMI 1640' medium, FMI 1640 'medium And mixed media thereof (for example, DMEM / F12 medium (Dulbecco's Modified Eagle's Medium / Nutrient Mixtu) e F-12 Ham)), CHO-S-SFM II ( Life Technologies Japan, Ltd.), Hybridoma-SFM (Life Technologies Japan, Ltd.), eRDF Dry Powdered Media (Life Technologies Japan, ^Ltd.), UltraCULTURE TM (BioWhittaker Inc. ), UltraDOMA ^™ (BioWhittaker), UltraCHO ^™ (BioWhittaker), UltraMDCK ^™ (BioWhittaker) and the like can be used. A medium such as STEMPRO (registered trademark) hESC SFM (Life Technologies Japan), mTeSR1 (Veritas), TeSR2 (Veritas) can be used.

In addition to cells, cell pharmaceutical preparations are various additives for increasing storage stability, isotonicity, absorbability and / or viscosity, for example, emulsifiers, dispersants, buffers, preservatives, wetting agents. Agents, antioxidants, chelating agents, thickeners, gelling agents, pH adjusting agents and the like. Examples of the thickener include, but are not limited to, HES, dextran, methylcellulose, xanthan gum, carboxymethylcellulose, hydroxypropylcellulose, and the like. The concentration of the thickener depends on the selected thickener, but can be arbitrarily set within a range of concentrations that are safe when administered to a patient or subject and achieve a desired viscosity.

Furthermore, 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 active ingredients as a medicine. Examples of the anti-inflammatory agent include, but are not limited to, 5-aminosalicylic acid preparations, steroid preparations, immunosuppressants, biological preparations and the like. Examples of the 5-aminosalicylic acid preparation include, but are not limited to, salazosulfapyridine and mesalazine. Examples of the steroid preparation include, but are not limited to, cortisone, prednisolone, methylprednisolone, and the like. Examples of the immunosuppressive agent include tacrolimus, cyclosporine, methotrexate, azathypurine, 6-mercaptopurine and the like, and examples of the biological preparation include infliximab, adalimumab, ustekinumab, secukinumab, ixekizumab. , Brodalumab, tocilizumab, vedolizumab, filgotinib, golimumab, certolizumab pegol, abatacept, etanercept, and the like, but are not limited thereto.

The pH of the cell pharmaceutical preparation of the present invention can be a neutral pH, for example, pH 6.5 or more or pH 7.0 or more, and can be pH 8.5 or less or pH 8.0 or less. It is 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 the subject is confirmed when the cell pharmaceutical preparation is administered to the patient or the subject. Capacity, and the capacity per bag. The volume of the cell pharmaceutical preparation is not particularly limited. 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, 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 It is.

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 a patient or subject as compared to a patient or subject who is not administered the cell pharmaceutical preparation. It is the density | concentration of the cell contained in a cell pharmaceutical formulation. The cell concentration of the cell pharmaceutical preparation is not particularly limited. 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 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, 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 ce ls / 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, or less 1 × ¹⁰ 7 cells / mL is there. In addition to the above, it can be determined as appropriate depending on the administration form, administration method, purpose of use, and the age, weight, and symptoms of the patient or subject.

The number of cells (cells) of a cell pharmaceutical preparation refers to 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 compared to a patient or subject not administered with the cell pharmaceutical preparation. It is. The number of cells of the cell pharmaceutical preparation is not particularly limited. 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 × More than 10 ⁵ cells, more than 5 × 10 ⁵ cells, more than 6 × 10 ⁵ cells, more than 7 × 10 ⁵ cells, more than 8 × 10 ⁵ cells, more than 9 × 10 ⁵ cells, more than 1 × 10 ⁶ cells, 1 × 10 ¹⁵ cells or less, 1 × 10 ¹⁴ cells or less, 1 × 10 ¹³ cells or less, 1 × 10 ¹² below 1 cells, below 1 × 10 ¹¹ cells, below 1 × 10 ¹⁰ cells, below 1 × 10 ⁹ cells, below 9 × 10 ⁸ cells, below 8 × 10 ⁸ cells, below 7 × 10 ⁸ cells, below 6 × 10 ⁸ cells. Below, 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 × 10 ⁷ cells or less, 3 × 10 ⁷ cells or less, 2 × 10 ⁷ cells or less, 1 × 10 ⁷ cells or less is there. In addition to the above, it can be determined as appropriate depending on the administration form, administration method, purpose of use, and the age, weight, and symptoms of the patient or subject.

The dose (cells / kg) of the cell pharmaceutical preparation is such that when the cell pharmaceutical preparation is administered to a patient or subject, a therapeutic effect on the disease can be obtained as compared to a patient or subject not administering the cell pharmaceutical preparation. Or the number of cells per kg body weight of the subject. The dose of the cell pharmaceutical preparation is not particularly limited. 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 kg or less, 6 × ¹⁰ 7 cells / kg or less, is 4 × ¹⁰ 7 cells / kg or less, or 2 × ¹⁰ 7 cells / kg or less

The cell type is not particularly limited as long as it is a medically and / or pharmaceutically acceptable cell. For example, pluripotent stem cells (artificial pluripotent stem cells (iPS cells), embryonic stem cells (ES cells), GS cells, testicular-derived pluripotent stem cells, EG cells derived from fetal primordial germ cells, Muse cells derived from bone marrow, etc.), somatic stem cells (bone marrow, adipose tissue, dental pulp, placenta, egg membrane, umbilical cord blood) Mesenchymal stem cells, hematopoietic stem cells, neural stem cells, etc. derived from amniotic membrane, chorion, etc.), leukocytes, monocytes, granulocytes, lymphocytes (T cells, B cells, NK cells, etc.), megakaryocytes, macrophages, nerves Examples include cells, cardiomyocytes, myocardial progenitor cells, hepatocytes, liver progenitor cells, α cells, β cells, γ cells, fibroblasts, chondrocytes, corneal cells, vascular endothelial cells, vascular endothelial progenitor cells, pericytes, etc. The cells are in a gene-transfected form or Such target genes on Nom may be knocked down form to.

The cells used in the present invention are typically humans, for example, rodents such as mice, rats, hamsters, primates such as gorillas, chimpanzees, marmosets, and dogs, cats, rabbits, cows, horses. It may be derived from livestock such as sheep and goats or mammals such as pets.

The pharmaceutically acceptable drug in the cell pharmaceutical preparation is not particularly limited as long as it is an aqueous medium that can maintain cells in a form usable as a medicine and can be administered to animals such as humans. The pharmaceutically acceptable drug may be mixed with the cell pharmaceutical preparation at the stage of production as a pharmaceutical preparation, or may be mixed with the cell pharmaceutical preparation at the stage of administering the cell pharmaceutical preparation to a patient or subject. . Although it does not specifically limit as a pharmacologically acceptable chemical | medical agent, For example, a physiological saline, electrolyte solution, Ringer's solution, a high-calorie infusion solution, glucose solution, water for injection, an amino acid electrolyte etc. are mentioned. Pharmaceutically acceptable drugs include CP-1, which is a salt, vitamins, amino acids, polysaccharides, dimethyl sulfoxide, buffer, albumin, medium, and cell cryoprotectant as necessary. ), BAMBANKER (manufactured by Linphotech), STEM-CELLBANKER (manufactured by Nippon Zenyaku Kogyo Co., Ltd.), ReproCryo RM (manufactured by Reprocell), CryoNovo (manufactured by Akron Biotechnology), MSC Freezing Solution (BiologicInd.) CryoStor (manufactured by HemaCare) and the like may be included. The medium is not particularly limited as long as it is a medium composed of a component composition that can be administered to animals such as humans, but BME medium, BGJb medium, CMRL 1066 medium, Glasgow MEM medium, Improved MEM Zinc Option medium, IMDM medium (Iscove's Modified Dulbecco's Medium), Medium 199 medium, Eagle MEM medium, αMEM medium, DMEM medium (Dulbecco's Modified Eagle's Medium), Ham F10 medium, Ham F10 medium, Ham F10 medium, Ham F10 medium, Ham F10 medium, Ham 16 medium 's medium, and mixed media thereof (for example, DMEM / F12 medium (Dulbecco's Modified Eagle's Medium / Nutrient Mi ture F-12 Ham)), CHO-S-SFM II ( Life Technologies Japan, Ltd.), Hybridoma-SFM (Life Technologies Japan, Ltd.), eRDF Dry Powdered Media (Life Technologies Japan, ^Ltd.), UltraCULTURE TM (BioWhittaker Inc. ), UltraDOMA ^™ (BioWhittaker), UltraCHO ^™ (BioWhittaker), UltraMDCK ^™ (BioWhittaker) and the like can be used. Examples of the medium include STEMPRO (registered trademark) hESC SFM (Life Technologies Japan), mTeSR1 (Veritas), TeSR2 (Veritas).

The patient and the subject are typically humans, but for example, rodents such as mice, rats, hamsters, primates such as gorillas, chimpanzees, marmosets, and dogs, cats, rabbits, cows, horses, sheep It may be a non-human animal such as a domestic animal such as a goat or a mammal such as a pet animal.

The cell pharmaceutical preparation accommodated in the container for cell pharmaceutical preparation according to the present invention is led out through a later-described outlet and administered to a patient. The route of administration to the patient is not particularly limited, and can be, for example, subcutaneous injection, intralymphatic injection, intravenous injection, intraarterial injection, intraperitoneal injection, intrathoracic injection, direct local injection, and the like.

The administration frequency of the cell pharmaceutical preparation of the invention is such a frequency that a therapeutic effect can be obtained for the disease when administered to a patient or subject. The specific administration frequency can be appropriately determined depending on the administration form, administration method, purpose of use, and the age, weight, and symptoms of the patient or subject. For example, once every 4 weeks, once every 3 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 such a period that 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, and the age, weight, and symptoms of the patient or subject. 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 a subject is not particularly limited. For example, immediately after onset, within N days from onset (N represents an integer of 1 or more), immediately after diagnosis, within N days from diagnosis (N represents 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 just 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 degrees 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 thawed rapidly at 37 ° C. and used.

A container for a cell pharmaceutical preparation according to the present invention includes at least a container main body having an internal space capable of containing a liquid cell pharmaceutical preparation, and a lead-out portion formed with a lead-out port communicating with the internal space of the container main body. It only has to be.

The container body is preferably formed of a flexible material.
At least a part of the container main body can be made of a transparent or translucent material so that the liquid level position of the internal cell pharmaceutical preparation can be visually confirmed. In particular, it is preferable that the container main body is formed of a transparent or translucent material in a portion including the first to fifth scale display portions.

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 hydrogenated product thereof, and styrene. -Flexible resins such as thermoplastic elastomers such as isoprene-styrene copolymers or hydrogenated products thereof, and mixtures of thermoplastic elastomers and softeners such as polyolefin and ethylene-ethyl acrylate.

When the container main body is formed of a flexible resin, the container main body is formed by blow molding the resin, and the peripheral portion is formed by opposingly arranging two sheets mainly composed of the resin. A container main body formed by fusing, a container main body formed by folding one sheet formed of the resin and fusing a peripheral edge, and an opening 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 may be, for example, 0.2 mm to 0.6 mm. The container body is preferably a bag-like container in which at least a part of the wall surface is formed by a sheet mainly composed of the resin, and particularly preferably, the two sheets are arranged to face each other and the peripheral portion is heated. It is a bag-like container formed into a bag shape by fusing or bonding with an adhesive.

The cell pharmaceutical preparation container according to the present invention is preferably formed so that the stored cell pharmaceutical preparation can be led out through the outlet and administered to the patient in a suspended state.

The lead-out part provided in the cell pharmaceutical preparation container according to the present invention is not particularly limited as long as a lead-out port communicating with the internal space of the container body is formed. Typically, the lead-out part can be constituted by a tube containing a flow path through which a liquid can pass.

The lead-out part preferably has a structure in which the lead-out port is sealed so as to communicate with the outside. Examples of such a structure include a luer lock and a needleless port.

The size of the outlet provided in the outlet may be any dimension that allows the cell pharmaceutical preparation containing cells to pass through.

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

The cell pharmaceutical preparation container according to the present invention preferably further comprises an introduction part in which an introduction port for communicating the internal space of the container body with the outside is formed. The introduction port may be used as a route for supplying a cell pharmaceutical preparation or a material for preparing the cell pharmaceutical preparation (for example, the pharmaceutically acceptable drug described above) to the internal space of the container body. it can.

The introduction part is not particularly limited as long as an introduction port communicating with the internal space of the container body is formed. Typically, the introduction portion can be constituted by a tube including a flow path through which a liquid can pass.

In addition, the introduction unit may have a structure in which the introduction port is sealed so as to communicate with the outside. Examples of such a structure include a luer lock and a needleless port. Furthermore, the introduction part may be irreversibly sealed after supplying necessary materials to the internal space.

In addition, the number of introduction portions is not limited to one, and may be, for example, two, three, four, five, six, seven, eight, nine, ten or more, The internal space of the container body may be filled and mixed with the cell pharmaceutical preparation and the pharmaceutically acceptable drug via separate introduction parts. For example, when preparing a cell pharmaceutical preparation, the container for cell pharmaceutical preparation of the present invention includes a first introduction part for introducing the cell pharmaceutical preparation into the internal space, and a pharmaceutically acceptable drug in the internal space. And a second introduction part for introduction into the system.

The characteristics of the container for cell pharmaceutical preparation of the present invention include one or more selected from the first to fifth scale display parts in the container body. Each scale display unit is configured by one or more identification displays such as a visible line, a character, a sign, and a color. The identification display may be a print on the container body, a protrusion and / or a depression formed on the container body, or a combination of printing and a protrusion and / or a depression. .

The 1st scale display part in the container for cell medicine preparations of this invention displays the dosage of the cell medicine preparation corresponding to the body weight of the patient or a test subject administered to the said container main body, The liquid in the said container main body Depending on whether or not the surface position is located on the first scale display section, it is possible to visually recognize the dosage of the cell pharmaceutical preparation suitable for the weight of the patient or the subject. More specifically, the first scale display unit is a patient or subject obtained by dividing the dose (cells / kg) of the cell pharmaceutical preparation from the cell concentration (cells / mL) contained in the cell pharmaceutical preparation. The dose (kg / mL) of the cell pharmaceutical preparation suitable for body weight is displayed as a scale corresponding to the liquid volume (mL) of the cell pharmaceutical preparation. For example, cell medicine corresponding to the body weight of a patient or a subject is arranged stepwise according to the value obtained by dividing the dose of the cell medicine preparation from the cell concentration of the cell medicine preparation and the liquid volume of the cell medicine preparation. In order to make it easy to visually recognize the dosage of the preparation, the body weight of the patient or subject to be administered such as 10 kg, 20 kg, 30 kg, etc. may be displayed as a numerical value near the scale. Moreover, what is necessary is just to design the dosage of the cell pharmaceutical formulation corresponding to a patient's or test subject's body weight suitably for every cell concentration of the cell pharmaceutical formulation administered to a patient or a test subject.

The numerical value of the first scale display unit is not particularly limited. 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, etc. may be selected.

It is preferable that the numerical value of the first scale display portion is displayed so as to increase in the direction of the outlet portion of the container body. The numerical value interval in the first scale display section is not particularly limited, and may be appropriately designed according to the type of cell to be administered, disease, container shape, container material, container capacity, and the like.

The 2nd scale display part in the container for cell medicine preparations of this invention displays the liquid quantity which dilutes the said cell medicine preparation with the pharmacologically acceptable chemical | medical agent, The liquid level position in the said container main body is It is possible to visually recognize the cell concentration of the cell pharmaceutical preparation to be administered to a patient or a subject depending on whether or not the second scale display unit is located. More specifically, the second scale display unit displays the liquid amount (mL) that is filled with a pharmaceutically acceptable drug from the cell concentration (cells / mL) and the liquid amount (mL) of the cell pharmaceutical preparation before mixing. ), And the amount of liquid of the cell pharmaceutical preparation before mixing and the amount of liquid of the pharmaceutically acceptable drug to be filled is displayed as a scale, and the cell medicine to be administered to the patient or subject It is a mark line which shows the final position of the liquid level of a formulation. Therefore, by mixing the cell pharmaceutical preparation and a pharmaceutically acceptable drug using the mark line, the cell concentration of the cell pharmaceutical preparation to be administered to a patient or a subject can be easily prepared, and the second The cell concentration of the cell pharmaceutical preparation administered to the patient or subject can be visually recognized by the scale display unit.

The 3rd scale display part in the container for cell medicine preparations of this invention displays the liquid quantity with which the said cell medicine preparation is filled, and the liquid level position in the said container main body is a said 3rd scale display part. Depending on whether or not it is positioned, it is possible to visually recognize the number of cells of the cell pharmaceutical preparation introduced into the container body. More specifically, the third scale display unit displays the amount (mL) of the liquid to be filled with the cell pharmaceutical preparation as a scale, and the liquid of the cell pharmaceutical preparation to be filled in the container for cell pharmaceutical preparation. It is a mark line which shows the final position of a surface. Therefore, it is possible to simply fill the cell pharmaceutical preparation using the mark line and to confirm the cell concentration (cells / mL) and the filling amount (mL) of the cell pharmaceutical preparation to be filled. The number of cells (cells) of the cell pharmaceutical preparation to be introduced becomes visible.

The 4th scale display part in the container for cell medicine preparations of the present invention displays the amount of liquid in the container, and whether the liquid level position of the container body is located in the 4th scale display part or not. This makes it possible to visually recognize the amount of the cell pharmaceutical preparation remaining in the container body. More specifically, a 4th scale display part displays the liquid volume (mL) which the container for cell pharmaceutical preparations can accommodate as a scale in steps. For example, liquids such as 100 mL, 200 mL, and 300 mL are arranged near the scale so that the amount of liquid that can be accommodated in the container for cell pharmaceutical preparation is arranged in stages and the remaining liquid volume in the container is easily visible. The quantity may be displayed as a numerical value.

The numerical value of the fourth scale display section 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, 45 mL, 50 mL, 55 mL, 60 mL, 65 mL, 70 mL, 75 mL, 80 mL, 85 mL, 90 mL, 95 mL, 100 mL, 150 mL, 200 mL, 300 mL, 400 mL, 500 mL, 600 mL, 700 mL, 800 mL, 900 mL, 1000 mL, 2000 mL, 3000 mL, 4000 mL, Any one or more such as 5000 mL may be selected.

It is preferable that the numerical value of the fourth scale display part is displayed so as to decrease toward the direction of the outlet part of the container body. The numerical value interval in the fourth scale display section is not particularly limited, and may be appropriately designed according to the type of cell to be administered, disease, container shape, container material, container capacity, and the like.

The 5th scale display part in the container for cell medicine preparations of this invention displays the cell number of the said cell medicine preparation administered to a patient or a test subject, and the liquid level position in the said container main body is said 5th. It is possible to visually recognize the number of cells of the cell pharmaceutical preparation administered to a patient or a subject depending on whether or not it is positioned on the scale display section. More specifically, the fifth scale display unit is obtained by multiplying the cell concentration (cells / mL) contained in the cell pharmaceutical preparation and the liquid amount (mL) of the cell pharmaceutical preparation administered to the patient or subject. The number of cells (cells) of the cell pharmaceutical preparation administered to a patient or subject is displayed as a scale corresponding to the liquid volume (mL) of the cell pharmaceutical preparation. For example, cells that are administered to a patient or a subject are arranged in stages according to the numerical value obtained by multiplying the cell concentration of the cell pharmaceutical preparation by the amount of the liquid of the cell pharmaceutical preparation to be administered and the liquid amount of the cell pharmaceutical preparation. In order to make the number of cells of the pharmaceutical preparation easy to see, 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. Also good.

Although it does not specifically limit as a numerical value of the said 5th scale display part, 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, 1 × 10 ¹⁰ cells, 1 × 10 ¹¹ cells, 1 × 10 ¹² cells, 1 × 10 ¹³ cells, 1 × 10 Any one or more of ¹⁴ cells, 1 × 10 ¹⁵ cells, etc. may be selected.

It is preferable that the numerical value of the fifth scale display part is displayed so as to increase in the direction of the outlet part of the container body. The numerical interval in the fifth scale display section is not particularly limited, and may be appropriately designed according to the type of cell to be administered, disease, container shape, container material, container capacity, and the like.

The container for cell pharmaceutical preparation of the present invention is prepared by mixing an empty form that does not contain a liquid such as a cell pharmaceutical preparation, a form containing a cell pharmaceutical preparation, and a mixture of a cell pharmaceutical preparation and a pharmaceutically acceptable drug. Can be distributed in various forms such as a form in which the prepared cell medicine preparation is accommodated, a form in which only the cell medicine preparation for preparing the cell medicine preparation is accommodated. The cell pharmaceutical preparation for preparing a cell pharmaceutical preparation is a cell pharmaceutical preparation containing cells at a higher concentration than the cell concentration in a cell pharmaceutical preparation prepared for treating a disease of a patient or a subject. . In the present specification, “a cell pharmaceutical preparation for preparing a cell pharmaceutical preparation” may be referred to as a “high concentration cell pharmaceutical preparation” in some cases.

The cell pharmaceutical preparation or the high-concentration cell pharmaceutical preparation may be processed using a cell suspension processing apparatus 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 storing it. The container 810 has an upstream head portion 814 in which a liquid supply port 811 to be supplied to the hollow fiber separation membrane 801 is formed, and a processing liquid outlet port 812 from which the liquid processed by the hollow fiber separation membrane 801 is led out. And a body portion 816 in which a filtrate outlet 813 for connecting the formed downstream side head portion 815 and leading out the filtrate in the hollow fiber separation membrane 801 is formed.

Inside the trunk portion 816, a large number of bundles 802 of hollow fiber separation membranes 801 and a bundle 802 of hollow fiber separation membranes 801 at the upstream end of the trunk portion 816 are connected to the upstream open end 803 of the hollow fiber separation membrane 801. Is fixed so as to face the upstream head portion 814, and the upstream resin layer portion 821 between the adjacent hollow fiber separation membranes 801 and the gap between the bundle 802 and the inner peripheral surface of the barrel 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 the gap between 802 and the inner peripheral surface of the body portion 816 is disposed. The upstream end of the trunk 816 is crowned by the upstream head 814, and the downstream end of the trunk 816 is crowned by the downstream head 815. With this configuration, the supply port 811 and the treatment liquid outlet 812 are continuous through the space inside the hollow fiber separation membrane 801, and the filtrate outlet 813 is different from the supply port 811 and the treatment liquid outlet 812. The hollow fiber separation membrane 801 is separated by a membrane wall and has a non-continuous structure.

The bundle 802 of hollow fiber separation membranes 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 the safety and stability of the material. Among these, polysulfone-based or cellulose-based hydrophilic polymer materials can be more preferably used. Furthermore, polyethersulfone and cellulose ester can be most suitably used because of the safety, stability, and availability of the material.

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 passes through the micropores provided in the membrane wall of the hollow fiber separation membrane 801 while filling the space inside the hollow fiber separation membrane 801, and is contaminated outside the hollow fiber separation membrane 801. And a filtrate containing a liquid medium is led out, 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 treatment of passing the cell suspension through the space inside the hollow fiber separation membrane in this way as necessary, the cell suspension is washed, concentrated, and / or replaced with a medium. It is possible to prepare a cellular pharmaceutical formulation of a composition or a high concentration cellular pharmaceutical formulation.

An example of a method for preparing a cell pharmaceutical preparation according to the present invention is as follows:
Corresponding to the body of a container filled with a cell pharmaceutical preparation and having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container body, and the weight of a patient or subject to be administered provided in the container body A first scale display for displaying the dose of the cell pharmaceutical preparation to be performed, and a second scale display for displaying the amount of liquid used for diluting the cell pharmaceutical preparation provided in the container body with a pharmaceutically acceptable drug At least a step of filling a pharmacologically acceptable drug in a cell pharmaceutical preparation container having a portion until the liquid level reaches the second scale display portion of the container body. 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 section as an index. In this example of the preparation method, examples of the cell pharmaceutical preparation pre-filled in the cell pharmaceutical preparation container include the above-mentioned “cell pharmaceutical preparation for preparing a cell pharmaceutical preparation” or “high concentration cell pharmaceutical preparation”. The cell medicine preparation container filled with the cell medicine preparation may be a cell medicine preparation container that is distributed in a form containing only the cell medicine preparation for preparing the cell medicine preparation, or an empty container. It may be prepared by a user filling a cell pharmaceutical preparation that is distributed in the form with a cell pharmaceutical preparation for preparing the cell pharmaceutical preparation. 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 a method for preparing a cell pharmaceutical preparation according to the present invention is:
A container main body having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container main body, and a dose of a cell pharmaceutical preparation provided in the container main body corresponding to the weight of a patient or subject to be administered A first scale display unit for displaying, a second scale display unit for displaying a liquid volume for diluting the cell pharmaceutical preparation provided in the container main body with a pharmaceutically acceptable drug, and a container main body. Until the liquid level reaches the third scale display portion of the container main body in the cell pharmaceutical preparation container having a third scale display portion for displaying the amount of the liquid filled with the cell pharmaceutical preparation. Filling, and
Filling the container filled with the cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display part of the container body. In the first half step of this example of the preparation method, the cell pharmaceutical preparation containing the intended number of cells can be filled into the cell pharmaceutical preparation container by a simple operation using the third scale display section as an index. In the latter half of this example of the preparation method, a pharmaceutical cell preparation having an intended cell concentration to be administered to a patient or subject can be easily prepared using the second scale display section as an index. In this example of the preparation method, examples of the cell pharmaceutical preparation to be filled in the first step include the above-mentioned “cell pharmaceutical preparation for preparing a cell pharmaceutical preparation” or “high concentration cell pharmaceutical preparation”. 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, based on specific embodiments, the characteristics of the method for preparing a cell pharmaceutical preparation using the container for cell pharmaceutical preparation according to the present invention and the container for cell pharmaceutical preparation according to the present invention will be described. It is not limited to these embodiments.

<First Embodiment>
FIG. 1 shows a cell pharmaceutical preparation container 1 (hereinafter sometimes referred to as “container 1”) according to a 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 a bag body in which a pair of generally rectangular first resin sheet 11 and second resin sheet 12 are arranged to face each other and the peripheral edge portions are joined by thermal fusion. The 1st resin sheet 11 and the 2nd resin sheet 12 are sheets which have 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 at least a part thereof is made of a transparent or translucent material so that the liquid level position of the internal cell pharmaceutical preparation can be visually observed. ing. In addition, it is preferable that the inner surfaces of the first resin sheet 11 and the second resin sheet 12 are pear-finished because the remaining liquid can be reduced during administration of the cell pharmaceutical preparation.

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

The lead-out part 20 communicates the internal space 14 of the container body 10 with the outside, and a lead-out pipe 22 in which a lead-out port 21 serving as a path for leading the liquid contained in the internal space 14 to the outside is formed, and the lead-out part 20 And a luer lock 23 for sealing the outlet of the tube 22 so as to allow communication.

The first introduction part 30 communicates the internal space 14 of the container body 10 with the outside, and a first introduction port 31 serving as a path for introducing material from the outside into the internal space 14 is formed inside. An introduction pipe 32 and a luer lock 33 that blocks the inlet of the first introduction pipe 32 so as to communicate with each other are provided.

The second introduction part 40 communicates the internal space 14 of the container body 10 with the outside, and a second introduction port 41 serving as a path for introducing a material from the outside into the internal space 14 is formed inside. An introduction pipe 42 and a luer lock 43 that seals the inlet of the second introduction pipe 42 so as to communicate with each other are provided.

The container main body 10 has a substantially rectangular shape, and the lead-out portion 20 includes a first resin sheet 11 and a second resin whose one end of the lead-out pipe 22 is on one side in the longitudinal direction of the container main body 10. It arrange | positions between the sheet | seats 12, the 1st resin sheet 11 and the 2nd resin sheet 12 of the circumference | surroundings are joined by heat sealing | fusion, and are integrated with the container main body 10. FIG. Similarly, in the first introduction part 30 and the second introduction part 40, one end of the first introduction pipe 32 and the second introduction pipe 42 is the other end in the longitudinal direction of the container body 10, respectively. It is disposed 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 the first resin sheet 11 and the second resin sheet 12 are joined together by heat fusion so as to be integrated with the container body 10. It has become. That is, the 1st introduction part 30 and the 2nd introduction part 40 are arranged at the end of container body 10 opposite to the end by which derivation part 20 is arranged.

In the first embodiment, the through holes 15 and 15 are formed in the outer portions of the container body 10 on the side where the first introduction part 30 and the second introduction part 40 are arranged, on the outer side of the fusion part 13. Is formed. The container 1 is hung on a support such as a hook through the through holes 15, 15 so that the first introduction part 30 and the second introduction part 40 are positioned at the upper end in the vertical direction, and the lead-out part 20 is It can be hung so that it may be located in the lower end part of a perpendicular direction.

As shown in FIG. 1, when the container 1 is suspended so that the lead-out portion 20 is vertically downward, the opening 21 </ b> A on the internal space 14 side of the lead-out port 21 of the lead-out portion 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 located below the fusion portion 13 surrounding the internal space 14 in the vertical direction is located upward in the vertical direction as it moves away from the opening 21A in the horizontal direction. It is preferable to be formed so as to be positioned. With this configuration, the cell pharmaceutical preparation is accommodated in the internal space 14, the container 1 is suspended so that the lead-out portion 20 is vertically downward, and the cell pharmaceutical preparation is led out from the lead-out port 21 of the lead-out portion 20. When administered to a subject, since the cells do not stay in the portion 13A and easily move toward the opening 21A, a cell pharmaceutical preparation containing an intended amount of cells can be administered to the patient or subject.

(First feature)
A 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 a dose of a cell pharmaceutical preparation corresponding to the weight of a patient or subject to be administered, and the container Depending on whether or not the liquid surface position in the main body 10 is located on the first scale display unit 100, the dose of the cell pharmaceutical preparation suitable for the weight of the patient or the subject can be visually confirmed.
The function of the first scale display unit 100 will be specifically described with reference to FIGS.

FIG. 2 schematically shows a state in which a liquid cell medicine preparation L (hereinafter also 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. This is illustrated schematically. The cell concentration and liquid volume of the preparation L to be stored are controlled, and the preparation L is stored so as to have a predetermined cell concentration and liquid volume defined in advance. The first scale display unit 100 is disposed so as to extend in the vertical direction when the container 1 is suspended, and is positioned below the liquid level A of the preparation L before the start of administration when the container 1 is suspended. Numerical value scale 110 and numerical value 120 to be included. 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. 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 derivation unit 20 of the container body 10.

FIG. 3 shows the formulation L through the outlet 21 of the outlet 20 from the state in which the inner space 14 of the container body 10 of the container 1 according to the first embodiment shown in FIG. Is schematically shown in a state when it is derived and administered to a patient or 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 preparation corresponding to the weight of the patient or subject to be administered according to the position of the liquid surface A in the container body 10. The weight of the patient or subject depends on whether the position of the liquid level A of the preparation L in the container body 10 is located on the numerical scale 110 corresponding to the weight of the administration target patient or subject in the first scale display unit 100. The dosage of the preparation L suitable for can be visually confirmed. For example, if the preparation L is administered from the container 1 to a patient or subject having a weight of 65 kg, the liquid level A of the preparation L is positioned on the numerical scale 110 corresponding to the weight of 65 kg as shown in FIG. It is possible to grasp that the dosage of the preparation L suitable for the weight of the patient or the subject has been administered.

In the medical field, the weight of the patient or subject is confirmed in advance, and the liquid level A of the preparation L is passed through the outlet 21 of the outlet 20 while the container 1 is suspended. The appropriate number of cells corresponding to the weight of the patient or subject is included by a simple operation of administering to the patient or subject until reaching the numerical scale 110 indicating the weight of the patient or subject in 100 and stopping the administration at the time of arrival. An amount of a cell pharmaceutical formulation can be administered to a patient or subject. In addition, the start and stop of the administration of the preparation L through the outlet 21 of the outlet 20 are communicated by connecting a channel such as a tube downstream of the outlet 20 and further connecting the channel to the patient or subject. When administering the preparation L, 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 administration of the preparation L is started by opening the flow path, The administration of the preparation L can be stopped by closing the flow path, or the administration of the preparation L can be controlled by providing a pump in the middle of the flow path.

According to this embodiment, since it is not necessary to calculate an appropriate dose of the preparation L with respect to the weight of the patient or the subject at the medical site, the risk of erroneous dose is reduced. Further, there is no need to take out a preparation L having a dosage according to the weight of the patient or subject from the container 1 with a syringe or the like. Since L can be administered directly, 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 there are few steps, and that dose errors are unlikely to occur. Further, unlike the method of dividing a cell pharmaceutical preparation by sandwiching a drug solution bag with a clip so as to obtain a dose according to body weight as described in the cited document 2, in this embodiment, the preparation L is a container 1 Therefore, the entire formulation L can be flowed by, for example, swallowing the container 1 by hand, and the cell concentration in the formulation L can be easily maintained uniformly.

In the illustrated embodiment, the first scale display unit 100 only shows up to 70 kg as the weight of the patient or subject, but may be formed to show a larger weight. In addition, when the preparation L is administered to a patient or a subject weighing more than 70 kg and 140 kg or less using the container 1 of the illustrated embodiment, two containers 1 filled with the preparation L are prepared, The preparation 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 having a body weight of 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)
Although the preparation method of the preparation L is not particularly limited, it may be prepared inside the container 1 according to the first embodiment. For example, the high-concentration cell pharmaceutical preparation L1 and the pharmacologically in the internal space 14 of the container body 10 may be used. It may be prepared by filling and mixing the acceptable drug L2. In the container 1 according to the first embodiment to be used for the preparation of such a preparation L, as a second feature, the container body 10 is used when the inner space 14 is filled with the pharmaceutically acceptable drug L2. A second scale display unit 200 for displaying the liquid amount is provided, and the formulation L to be administered to a patient or a subject is determined depending on whether or not the position of the liquid level A in the container body 10 is located in the second scale display unit 200. The cell concentration is visible.

Specifically, using the container 1 provided with the second scale display unit 200 in the container body 10, as shown in FIG. 4, the internal space 14 of the container body 10 is first filled with the high-concentration cell pharmaceutical preparation L1. Then, as shown in FIG. 5, the pharmaceutically acceptable drug L <b> 2 can be filled until the liquid level A reaches the second scale display unit 200. In this case, the second scale display unit 200 suspends the container 1 and shows the final position of the liquid level A in the container body 10 when the internal space 14 is filled with the pharmaceutically acceptable drug L2. It is a mark line.

As shown in FIG. 4, the container 1 which concerns on 1st Embodiment of the state with which the high concentration cell pharmaceutical formulation L1 was filled beforehand is prepared, and it fills and mixes the pharmacologically acceptable chemical | medical agent L2 in a 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 main 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 intended amount of the pharmaceutically acceptable drug L2 and prepare the preparation L having the intended cell concentration.

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

When the internal space 14 of the container body 10 of the container 1 is filled with and mixed with the high-concentration cell pharmaceutical preparation L1 and the pharmaceutically acceptable drug L2, the first introduction part 30 and the second introduction part 40 One of them can be filled with the high-concentration cell pharmaceutical preparation L1 and the other with the pharmaceutically acceptable drug L2. One or both of the first introduction part 30 and the second introduction part 40 used for filling the high-concentration cell pharmaceutical preparation L1 or the pharmaceutically acceptable drug L2 are irreversibly blocked after filling. Also 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 filled with the preparation L or the high-concentration cell pharmaceutical preparation L1, and the liquid level A in the container body 10 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 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. It is a mark line which shows the position which surface A should fill.

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 unit 300. The concentration cell pharmaceutical preparation L1 can be accurately filled. Furthermore, as shown in FIG. 5, if the pharmacologically acceptable drug L2 is filled and mixed until the liquid level A reaches the second scale display unit 200, the preparation L having the intended cell concentration is prepared. be able to. Further, when the container 1 is suspended, the high-concentration cell containing an appropriate number of cells depends 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. Whether or not the pharmaceutical preparation L1 is contained can be visually confirmed.

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

In the container 1 which concerns on 1st Embodiment, since the 2nd scale display part 200 and the 3rd scale display part 300 are arrange | positioned in parallel mutually, high concentration cell pharmaceutical formulation L1 and pharmacologically acceptable. It is easy to visually check the filling amount of the medicine L2.

Second Embodiment
FIG. 6 shows a cell pharmaceutical preparation container 1 (hereinafter sometimes referred to as “container 1”) according to a second embodiment of the present invention.

In the container 1 which concerns on 2nd Embodiment, the structure which is common in the container 1 which concerns on 1st Embodiment attaches | subjects the same code | symbol, and abbreviate | omits description.

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 surface A of the container body 10 is the first. The liquid amount 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 portion 4 of No. 4.

The 4th scale display part 400 is arrange | positioned so that the vertical direction may be extended when the container 1 is suspended, and the liquid of the formulation L which is the liquid accommodated in the internal space 14 of the container main body 10 when the container 1 is suspended. A numerical scale 410 and a numerical value 420 indicating the volume below the surface A are included. In the present embodiment, the numerical value 420 of the fourth scale display unit 400 is displayed so as to decrease in the direction of the derivation 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 through the outlet 21 from the container 1 containing the preparation L, the remaining liquid amount in the container 1 of the preparation L is visually recognized. can do. When the preparation L is administered from the container 1 to the patient or subject, the remaining liquid of the preparation L can be determined by knowing in advance the remaining amount of the preparation L corresponding to the appropriate dose according to the weight of the patient or subject. The dose can be confirmed based on the amount, and in addition to the confirmation based on the weight of the patient or the subject using the first scale display unit 100, the dose of the preparation L can be confirmed twice. Become. Thereby, it becomes possible to administer the preparation L containing an appropriate number of cells according to the weight of the patient or subject to the patient or subject more safely.

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

In the container 1 according to the third embodiment, the same components as those of the container 1 according to the first embodiment and the container 1 according to the second embodiment are denoted by the same reference numerals, and description thereof is 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 administered to the patient or subject to be administered. Depending on whether or not the position of the liquid level A is located in the fifth scale display section 500, the number of cells of the preparation L administered to the patient or the subject can be visually recognized.

The fifth scale display unit 500 is arranged so as to extend in the vertical direction when the container 1 is suspended, and is positioned below the liquid level A of the preparation L before starting the derivation when the container 1 is suspended. A numerical scale 110 and a numerical value 520 are included. Here, the numerical scale 110 also serves as the numerical scale 110 of the first scale display unit 100. Among 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, indicates the number of cells contained in the administered preparation L in units of 2 × 10 ⁷ , and the intermediate scale 112 indicates The body weight of the patient or subject to be administered is shown in units of 5 kg, the number of cells contained in the administered preparation L is shown in units of 1 × 10 ⁷ , and the small scale 113 is the 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 . A 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 derivation unit 20 of the container body 10.

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

By providing the fifth scale display unit 500, the liquid level of the preparation L in the container body 10 when the preparation L is derived from the container 1 containing the preparation L through the outlet 21 and administered to the patient or subject. 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 in the fifth scale display unit 500. When the preparation L is administered from the container 1 to the patient or subject, if the number of cells to be administered to the patient or subject is known in advance, the dosage is appropriate by referring to the fifth scale display unit 500. This can be confirmed, and in addition to the confirmation based on the weight of the patient or subject using the first scale display unit 100, the dosage of the preparation L can be confirmed twice. Thereby, it is possible to more safely administer the preparation L in an amount including the number of cells to be administered to the patient or subject to the patient or subject.

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

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

Claims

A cell pharmaceutical preparation container,
A container body having an internal space capable of holding a liquid;
A lead-out portion communicating with the internal space of the container body;
The container body includes a first scale display unit for displaying a dose of a cell pharmaceutical preparation corresponding to the weight of a patient or subject to be administered,
The said container which can visually recognize the dosage of the said cell pharmaceutical formulation suitable for a patient or a test subject's body weight by whether the liquid level position in the said container main body is located in a said 1st scale display part.
The container according to claim 1, wherein a numerical value of the first scale display part is displayed so as to increase toward a direction of the outlet part of the container main body.
Furthermore, the container body includes a second scale display unit that displays a liquid volume for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and a liquid level position in the container body is the second scale. The container of Claim 1 or 2 which can visually recognize the cell density | concentration of the said cell pharmaceutical formulation administered to a patient or a test subject by whether it is located in a display part.
Further, the container body includes 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 surface position in the container body is located at 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 introduced into the container main body can be visually confirmed.
Furthermore, the container body includes a fourth scale display unit that displays the amount of liquid in the container, and the container body depends on whether the liquid level position of the container body is located in the fourth scale display unit. The container according to any one of claims 1 to 4, wherein the amount of the cell pharmaceutical preparation remaining in the cell can be visually confirmed.
The container according to claim 5, wherein a numerical value of the fourth scale display part is displayed so as to decrease toward the direction of the lead-out part of the container main body.
Furthermore, the container main body includes a fifth scale display unit that displays the number of cells of the cell pharmaceutical preparation to be administered to a patient or a subject, and the liquid level position in the container main body is 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 a patient or a subject can be visually recognized depending on whether the cell is positioned.
The container according to claim 7, wherein a numerical value of the fifth scale display part is displayed so as to increase toward a direction of the lead-out part of the container main body.
The container body has a second scale display unit for displaying a liquid amount for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and a third scale display for displaying the liquid amount for filling the cell pharmaceutical preparation. With
Whether or not the liquid surface position in the container body is located in the second scale display unit, the cell concentration of the cell pharmaceutical preparation to be administered to a patient or a subject can be visually confirmed,
Whether or not the liquid level position in the container body is located in the third scale display unit, the number of cells of the cell pharmaceutical preparation to be introduced into the container body can be visually confirmed,
The container according to any one of claims 1 to 8, wherein the second scale display section is provided on a parallel line of the third scale display section.
The container according to any one of claims 1 to 9, further comprising an introduction part communicating with the internal space of the container body.
The container according to claim 10, wherein the introduction portion is provided at an 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 formulation comprising:
Corresponding to the body of a container filled with a cell pharmaceutical preparation and having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container body, and the weight of a patient or subject to be administered provided in the container body A first scale display for displaying the dose of the cell pharmaceutical preparation to be performed, and a second scale display for displaying the amount of liquid used for diluting the cell pharmaceutical preparation provided in the container body with a pharmaceutically acceptable drug The method comprising the step of filling a cell pharmaceutical preparation container comprising a portion with a pharmaceutically acceptable drug until the liquid level reaches the second scale display section of the container body.
A method for preparing a cell pharmaceutical formulation comprising:
A container main body having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container main body, and a dose of a cell pharmaceutical preparation provided in the container main body corresponding to the weight of a patient or subject to be administered A first scale display unit for displaying, a second scale display unit for displaying a liquid volume for diluting the cell pharmaceutical preparation provided in the container main body with a pharmaceutically acceptable drug, and a container main body. Until the liquid level reaches the third scale display portion of the container main body in the cell pharmaceutical preparation container having a third scale display portion for displaying the amount of the liquid filled with the cell pharmaceutical preparation. Filling, and
Filling the container filled with a cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display part of the container body.