JP2009045111A - Column for photopheresis process, photopheresis process system and photopheresis process method - Google Patents
Column for photopheresis process, photopheresis process system and photopheresis process method Download PDFInfo
- Publication number
- JP2009045111A JP2009045111A JP2007211481A JP2007211481A JP2009045111A JP 2009045111 A JP2009045111 A JP 2009045111A JP 2007211481 A JP2007211481 A JP 2007211481A JP 2007211481 A JP2007211481 A JP 2007211481A JP 2009045111 A JP2009045111 A JP 2009045111A
- Authority
- JP
- Japan
- Prior art keywords
- photopheresis
- column
- excitation light
- porous body
- skeleton
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 30
- 230000005284 excitation Effects 0.000 claims abstract description 38
- 210000001124 body fluid Anatomy 0.000 claims abstract description 30
- 239000010839 body fluid Substances 0.000 claims abstract description 29
- 210000004369 blood Anatomy 0.000 claims description 34
- 239000008280 blood Substances 0.000 claims description 34
- 210000000265 leukocyte Anatomy 0.000 claims description 29
- 210000004027 cell Anatomy 0.000 claims description 20
- 230000001678 irradiating effect Effects 0.000 claims description 10
- 239000011148 porous material Substances 0.000 claims description 8
- 238000003980 solgel method Methods 0.000 claims description 7
- 238000001330 spinodal decomposition reaction Methods 0.000 claims description 7
- 238000003672 processing method Methods 0.000 claims description 6
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 5
- 229910052753 mercury Inorganic materials 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 4
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 210000003743 erythrocyte Anatomy 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000001506 immunosuppresive effect Effects 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 238000001879 gelation Methods 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 239000003018 immunosuppressive agent Substances 0.000 description 5
- 239000000306 component Substances 0.000 description 4
- 230000006058 immune tolerance Effects 0.000 description 4
- 229940125721 immunosuppressive agent Drugs 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- 239000012503 blood component Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 206010018910 Haemolysis Diseases 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 229920000620 organic polymer Polymers 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- DWAOUXYZOSPAOH-UHFFFAOYSA-N 4-[2-(diethylamino)ethoxy]furo[3,2-g]chromen-7-one;hydrochloride Chemical compound [Cl-].O1C(=O)C=CC2=C1C=C1OC=CC1=C2OCC[NH+](CC)CC DWAOUXYZOSPAOH-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 230000002165 photosensitisation Effects 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 238000009751 slip forming Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
Abstract
Description
本発明は、いわゆるフォトフェレシス処理に利用可能なカラムに関する。また、本発明は、当該カラムを含むフォトフェレシス処理システム、及び当該カラムを用いたフォトフェレシス処理方法に関する。 The present invention relates to a column that can be used for so-called photopheresis processing. The present invention also relates to a photopheresis processing system including the column and a photopheresis processing method using the column.
人体の持つ免疫は、人体を細菌・ウイルス、癌、寄生虫等の外敵（寄生体）から防御する役割を担っており、免疫は人間が生きていく上で不可欠な機構であると言える。しかしながら、一方で免疫反応は、アトピー性皮膚炎や乾癬等の皮膚病、関節リュウマチや全身性エリテマトーデス等の膠原病等の自己免疫疾患を引き起こす原因ともなる。自己免疫疾患とは、本来は細菌・ウイルスや腫瘍などの自己と異なる異物を認識し排除するための役割を持つ免疫系が、自分自身の正常な細胞や組織に対してまで過剰に反応し、攻撃を加えることで発症する症状の総称である。 The immunity of the human body plays a role in protecting the human body from external enemies (parasites) such as bacteria, viruses, cancer, and parasites, and it can be said that immunity is an indispensable mechanism for human life. However, on the other hand, the immune reaction also causes autoimmune diseases such as skin diseases such as atopic dermatitis and psoriasis, and collagen diseases such as rheumatoid arthritis and systemic lupus erythematosus. Autoimmune disease is an immune system that has a role of recognizing and eliminating foreign substances that are different from self, such as bacteria, viruses, and tumors, and reacts excessively to its own normal cells and tissues. It is a general term for symptoms that develop when an attack is applied.
昨今では、かかる免疫反応を適切に制御し、少ない副作用の下で免疫を抑制することが、現代の医学における最重要課題の一つとして挙げられている。臓器移植の分野においても、免疫反応の克服が最重要の課題であることはよく知られていることである。 Nowadays, one of the most important issues in modern medicine is to appropriately control such immune responses and suppress immunity with few side effects. In the field of organ transplantation, it is well known that overcoming the immune response is the most important issue.
このような背景の下、近年、フォトフェレシスが免疫抑制の分野で注目を集めている。フォトフェレシスとは、一般的には、体外に取り出した血液にソラレン（psolaren）誘導体等の感光医薬を添加し、活性化したＴ細胞に吸収させた後、当該血液に紫外光を照射し、感光医薬を活性化してＴ細胞をアポトーシスさせ、あるいはダメージを与えて免疫寛容を誘導し、免疫を抑制する方法である。なお、実際には、感光医薬の添加は必要条件ではなく、紫外光の波長を選択することにより、もともと生体内に存在する生体内感光物質を励起することでも、同様の処置を行うことができることが分かっている。 Against this background, photopheresis has recently attracted attention in the field of immunosuppression. Photopheresis generally involves adding a photopharmaceutical such as a psoralen derivative to blood taken out of the body, making it absorbed by activated T cells, and then irradiating the blood with ultraviolet light, This is a method of suppressing immunity by activating a photosensitizing drug to cause apoptosis of T cells or inducing immune tolerance by causing damage. Actually, the addition of a photosensitive drug is not a necessary condition, and the same treatment can be performed by exciting the in-vivo photosensitive substance originally present in the living body by selecting the wavelength of the ultraviolet light. I know.
従来の免疫抑制方法としては、免疫抑制剤を投与する方法が一般的に利用されていたが、免疫抑制剤の投与による副作用が問題視されていた。これに対し、フォトフェレシスは、前記のとおり感光医薬の添加は必ずしも必要ではない。また、仮に感光医薬を添加してフォトフェレシス処理を行う場合であって、投与した感光医薬がもし体内に戻った場合であっても、紫外光が照射されなければ当該感光医薬は活性化されないため、免疫抑制剤による免疫抑制方法と比較して副作用の可能性が非常に低いという効果を有する。このため、フォトフェレシスは、免疫抑制剤を投与する場合と比べて副作用の少ない免疫抑制法として注目を集めている。また、欧米各国では、ステロイド等の免疫抑制剤の効かない自己免疫疾患の治療や骨髄移植等の移植治療時の免疫抑制に対するフォトフェレシスの臨床応用が急速に増大している。 As a conventional immunosuppressive method, a method of administering an immunosuppressive agent has been generally used, but side effects due to administration of the immunosuppressant have been regarded as a problem. On the other hand, the photopheresis does not necessarily require the addition of a photosensitive drug as described above. In addition, even when a photopharmaceutical treatment is performed by adding a photosensitive drug, and the administered photosensitive drug returns to the body, the photosensitive drug is not activated unless irradiated with ultraviolet light. Therefore, it has the effect that the possibility of a side effect is very low compared with the immunosuppressive method using an immunosuppressive agent. For this reason, photopheresis is attracting attention as an immunosuppressive method with fewer side effects than when an immunosuppressive agent is administered. In Western countries, the clinical application of photopheresis for the treatment of autoimmune diseases in which immunosuppressive agents such as steroids are not effective and the immunosuppression during transplantation treatment such as bone marrow transplantation is rapidly increasing.
フォトフェレシス処理を実行するに際しては、前記のようにＴ細胞に紫外光を照射する必要がある。しかしながら、血液中には、白血球の一種であるＴ細胞の他に赤血球が含まれている。赤血球に含まれるヘモグロビンは、紫外光に対して大きな吸光度を示す性質を持つ。このため、赤血球を含んだ状態で血液に対して紫外光を照射した場合、赤血球中のヘモグロビンによって照射された紫外光が吸収される結果、真に照射したいＴ細胞に対して効果的に紫外光を照射できないという問題を有する。また、Ｔ細胞に対して必要なエネルギ量の紫外光を照射するためには、紫外光照射手段から高い強度の紫外光を照射する必要があり、このような高強度の紫外光が血中成分に照射されることで、赤血球の溶血や血漿蛋白の変成等の悪影響が生じる可能性がある。 When performing the photopheresis treatment, it is necessary to irradiate the T cells with ultraviolet light as described above. However, blood contains red blood cells in addition to T cells, which are a type of white blood cell. Hemoglobin contained in erythrocytes has the property of exhibiting a large absorbance to ultraviolet light. Therefore, when ultraviolet light is irradiated to blood in a state containing red blood cells, the ultraviolet light irradiated by hemoglobin in the red blood cells is absorbed, and as a result, ultraviolet light is effectively applied to the T cells to be truly irradiated. Has a problem that it cannot be irradiated. Further, in order to irradiate T cells with ultraviolet light having a necessary energy amount, it is necessary to irradiate high intensity ultraviolet light from the ultraviolet light irradiation means, and such high intensity ultraviolet light is emitted from blood components. May cause adverse effects such as red blood cell hemolysis and plasma protein degeneration.
このため、従来のフォトフェレシス処理の実行に際しては、患者から採血した血液に感光医薬を添加後、当該血液を遠心分離して白血球のみを取り出した状態で厚さ数ｍｍ程度の平たい容器内に入れ、かかる容器を介して紫外光を照射する。その後、赤血球や血漿と再混合し、再び患者の体内に戻すという複雑な手順を必要とする。下記特許文献１には、かかる処理に要する時間の短縮化を可能にする血液分離装置が開示されている。 For this reason, when performing the conventional photopheresis process, after adding a photosensitive medicine to blood collected from a patient, the blood is centrifuged and only white blood cells are taken out and placed in a flat container having a thickness of about several mm. Then, irradiate with ultraviolet light through such a container. After that, it requires a complicated procedure of re-mixing with red blood cells and plasma and returning it to the patient. Patent Document 1 below discloses a blood separation device that can shorten the time required for such processing.
従来のフォトフェレシス処理方法によれば、上記のような複雑な手順を必要とするため、患者の体力的負担の増大や、医療コストの高騰等の問題を有しており、フォトフェレシスそのものの普及の妨げとなっている。 According to the conventional photopheresis processing method, since the complicated procedure as described above is required, there are problems such as an increase in physical burden on the patient and a rise in medical costs. Has become a hindrance to the spread of.
本発明は、上記の問題点に鑑み、複雑な処理を要することなくフォトフェレシス処理の実行を可能にするフォトフェレシス処理用カラムを提供することを目的とし、ひいては、フォトフェレシスによる治療の普及を促進することを目的とするものである。また、本発明は、前記フォトフェレシス処理用カラムを含むフォトフェレシス処理システム、並びに前記フォトフェレシス処理用カラムを用いたフォトフェレシス処理方法を提供することを目的とする。 An object of the present invention is to provide a column for photopheresis processing that enables execution of photopheresis processing without requiring complicated processing in view of the above problems. The purpose is to promote dissemination. Another object of the present invention is to provide a photopheresis processing system including the photopheresis processing column, and a photopheresis processing method using the photopheresis processing column.
上記目的を達成するための本発明に係るフォトフェレシス処理用カラムは、励起光の照射目標となる細胞を含む体液が投入される投入口と、投入された前記体液が排出される排出口と、前記投入口と前記排出口の間を連通する貫通孔部、及び前記励起光を透過する性質を示す骨格部で構成された多孔質体と、を備えてなり、前記貫通孔部の孔径が前記細胞の最大径より大きく、前記多孔質体の外側から照射された前記励起光を前記骨格部内に受光可能に構成されていることを第１の特徴とする。 In order to achieve the above object, a photopheresis processing column according to the present invention comprises an input port into which a body fluid containing cells to be irradiated with excitation light is input, and an output port through which the input body fluid is discharged. A through-hole portion communicating between the input port and the discharge port, and a porous body composed of a skeleton portion exhibiting a property of transmitting the excitation light, and the hole diameter of the through-hole portion is A first feature is that the excitation light, which is larger than the maximum diameter of the cell and irradiated from the outside of the porous body, can be received in the skeleton.
本発明に係るフォトフェレシス処理用カラムの上記第１の特徴構成によれば、遠心分離を行うことなくフォトフェレシスを実現することができる。すなわち、本発明に係るフォトフェレシス処理用カラムの投入口から、照射目標となる細胞を含む体液を投入することで、貫通孔部内を前記体液が流動中において、孔部の内壁を構成する骨格部と照射目標となる細胞との間に、体液中の別の細胞等が入り込む可能性が低下する。従って、かかる状態下で、多孔質体の外側から励起光を照射することで、体液中の別の細胞によって励起光が吸収されることが少なく、多孔質体の骨格部を介して目標となる細胞に対して効率的に照射することができる。よって、遠心分離によって目標となる細胞のみを体液から取り出すことなく、従来のフォトフェレシス処理において遠心分離した照射目標の細胞に照射するのと同程度あるいはそれよりも少ないエネルギ量の励起光を照射することで、照射目標となる細胞に対して励起光を照射することができる。 According to the first characteristic configuration of the photopheresis processing column according to the present invention, photopheresis can be realized without performing centrifugation. That is, by introducing a body fluid containing cells to be irradiated from the inlet of the photopheresis processing column according to the present invention, the skeleton constituting the inner wall of the hole while the body fluid is flowing in the through hole The possibility that another cell or the like in the body fluid enters between the part and the cell to be irradiated is reduced. Therefore, by irradiating the excitation light from the outside of the porous body under such a state, the excitation light is hardly absorbed by another cell in the body fluid, and becomes a target through the skeleton part of the porous body. The cells can be irradiated efficiently. Therefore, without removing only the target cells from the body fluid by centrifugation, the irradiation light is irradiated with the same or less energy as the irradiation target cells centrifuged in the conventional photopheresis process. By doing so, it is possible to irradiate the excitation light to the cells to be irradiated.
従って、本発明に係るフォトフェレシス処理用カラムを用いてフォトフェレシスを行う場合、予め体液を遠心分離する必要がないため、その後に分離された体液成分を再び混合する必要がなく、これによって処置に要する時間を大幅に短縮することができ、患者に対する負担を大幅に軽減することができる。また、従来は遠心分離を行うのに必要であった遠心分離装置が不要となるため、大がかりなシステムを必要とせず、大幅にコストを削減することができる。これによって、医療コストが削減されるとともに、フォトフェレシスによる治療法の普及の促進につながる。 Therefore, when performing photopheresis using the photopheresis processing column according to the present invention, it is not necessary to centrifuge the body fluid in advance, so that it is not necessary to mix the separated body fluid components again. The time required for the treatment can be greatly reduced, and the burden on the patient can be greatly reduced. In addition, since a centrifuge that has been conventionally necessary for performing centrifugation is not required, a large-scale system is not required, and the cost can be greatly reduced. This reduces medical costs and promotes the spread of treatment by photopheresis.
また、本発明に係るフォトフェレシス処理用カラムは、上記第１の特徴構成に加えて、前記多孔質体がケイ酸を主成分とすることを第２の特徴とする。 In addition to the first characteristic configuration, the photopheresis processing column according to the present invention has a second characteristic that the porous body contains silicic acid as a main component.
また、本発明に係るフォトフェレシス処理用カラムは、上記第１または第２の特徴構成に加えて、前記骨格部が三次元網目構造を有することを第３の特徴とする。 In addition to the first or second characteristic configuration, the photopheresis processing column according to the present invention has a third characteristic that the skeleton has a three-dimensional network structure.
また、本発明に係るフォトフェレシス処理用カラムは、上記第３の特徴構成に加えて、前記多孔質体が、スピノーダル分解ゾル−ゲル法により製造されたものであることを第４の特徴とする。 Moreover, the photopheresis processing column according to the present invention has the fourth characteristic that, in addition to the third characteristic configuration, the porous body is manufactured by a spinodal decomposition sol-gel method. To do.
本発明に係るフォトフェレシス処理用カラムの上記第４の特徴構成によれば、簡易な方法によって所望の孔径を有する多孔質体を製造することができる。 According to the fourth characteristic configuration of the photopheresis processing column according to the present invention, a porous body having a desired pore diameter can be produced by a simple method.
また、本発明に係るフォトフェレシス処理用カラムは、上記第１〜第４のいずれか一の特徴構成に加えて、前記励起光を透過する性質を示す筒状体によって前記多孔質体の周囲が覆われており、前記筒状体の外側から照射された前記励起光を前記骨格部内に受光可能に構成されていることを第５の特徴とする。 Further, the photopheresis processing column according to the present invention includes a cylindrical body having a property of transmitting the excitation light in addition to any one of the first to fourth characteristic configurations described above. The fifth feature is that the excitation light irradiated from the outside of the cylindrical body is received in the skeleton portion.
本発明に係るフォトフェレシス処理用カラムの上記第５の特徴構成によれば、多孔質体の最も外側の表面にも孔部が形成されている場合であっても、励起光の照射効率を低下させることなく、投入口から投入された体液が当該孔部を介して外部に流出するのを防止することができる。 According to the fifth characteristic configuration of the photopheresis processing column according to the present invention, the irradiation efficiency of the excitation light can be improved even when the hole is formed on the outermost surface of the porous body. Without lowering, it is possible to prevent body fluid introduced from the introduction port from flowing out through the hole.
また、本発明に係るフォトフェレシス処理用カラムは、上記第１〜第５のいずれか一の特徴構成に加えて、前記細胞が白血球であり、前記体液が血液であり、前記励起光が紫外光または波長５００ｎｍ以下の可視光であり、前記多孔質体が、水銀圧入法による測定の下で平均孔径１５〜５０μｍを示す貫通孔部を有することを第６の特徴とする。 The photopheresis processing column according to the present invention, in addition to any one of the first to fifth features, is characterized in that the cells are leukocytes, the body fluid is blood, and the excitation light is ultraviolet. A sixth feature is that the porous body has light or visible light having a wavelength of 500 nm or less, and the porous body has a through-hole portion having an average pore diameter of 15 to 50 μm under measurement by a mercury intrusion method.
上記第６の特徴構成を有するフォトフェレシス処理用カラムを用いることにより、予め患者から採取した血液を遠心分離して白血球のみを採取することなく、白血球に含まれるＴ細胞に対して紫外光または波長５００ｎｍ以下の可視光が照射されて免疫寛容を誘導することができる。 By using the photopheresis processing column having the sixth feature, blood collected in advance from a patient is centrifuged to collect only white blood cells, and ultraviolet light or T cells contained in white blood cells are collected. Irradiation with visible light having a wavelength of 500 nm or less can induce immune tolerance.
また、上記目的を達成するための本発明に係るフォトフェレシス処理用システムは、上記第１〜第６のいずれか一の特徴構成のフォトフェレシス処理用カラムと、前記フォトフェレシス処理用カラムの外側から前記骨格部に対して前記励起光を照射可能な励起光照射手段と、を備えることを特徴とする。 In order to achieve the above object, a photopheresis processing system according to the present invention includes a photopheresis processing column having any one of the first to sixth characteristics, and the photopheresis processing column. Excitation light irradiation means capable of irradiating the skeleton part with the excitation light from the outside.
また、上記目的を達成するための本発明に係るフォトフェレシス処理方法は、上記第１〜第６のいずれか一の特徴構成のフォトフェレシス処理用カラムが有する前記投入口から前記体液を投入し、前記体液が前記貫通孔部内を流動中に、前記フォトフェレシス処理用カラムの外側から前記骨格部に対して前記励起光を照射することで、前記骨格部を介して前記体液中の前記細胞に対して前記励起光を照射することを特徴とする。 In addition, the photopheresis processing method according to the present invention for achieving the above object is to supply the body fluid from the input port of the photopheresis processing column having any one of the first to sixth characteristic configurations. Then, while the body fluid is flowing in the through-hole portion, the excitation light is applied to the skeleton portion from the outside of the photopheresis processing column, whereby the body fluid in the body fluid is passed through the skeleton portion. The cell is irradiated with the excitation light.
本発明に係るフォトフェレシス処理用カラム、フォトフェレシス処理システムを用いることで、複雑な処理を要することなくフォトフェレシス処理の実行を可能にすることができ、これによって、フォトフェレシスによる治療の普及の促進に貢献することができる。また、 By using the photopheresis processing column and the photopheresis processing system according to the present invention, it is possible to execute the photopheresis processing without requiring complicated processing. Can contribute to the promotion of dissemination. Also,
以下において、本発明に係るフォトフェレシス処理用カラム、フォトフェレシス処理システム、並びにフォトフェレシス処理方法（以下、それぞれ適宜「本発明カラム」、「本発明システム」、並びに「本発明方法」と称する）の実施形態について図１〜図３の各図を参照して説明する。 In the following, the photopheresis processing column, the photopheresis processing system, and the photopheresis processing method according to the present invention (hereinafter referred to as “the present column”, “the present system”, and “the present method” respectively) 1) will be described with reference to FIGS.
［本発明システム及び本発明方法の説明］
図１は、本発明システムの概略構成を示す概念的ブロック図である。図１に示される本発明システム１０は、本発明カラム１及び紫外光照射手段２を備える。本発明カラム１は、後述するように、照射目標となる白血球を含む血液が投入される投入口１２、投入口１２より投入された血液が流動する多孔質体１１、及び多孔質体１１を通過した血液が排出される排出口１３を備え、その外周は紫外光を透過する性質を示す筒状体１６で覆われている。また、紫外光照射手段２は、多孔質体１１に対して外部から紫外光２１を照射可能に構成されている。
[Description of the system and method of the present invention]
FIG. 1 is a conceptual block diagram showing a schematic configuration of the system of the present invention. The inventive system 10 shown in FIG. 1 includes the inventive column 1 and the ultraviolet light irradiation means 2. As will be described later, the column 1 of the present invention passes through an inlet 12 into which blood containing white blood cells serving as an irradiation target is introduced, a porous body 11 through which blood introduced through the inlet 12 flows, and the porous body 11 The outer periphery is covered with a cylindrical body 16 having a property of transmitting ultraviolet light. The ultraviolet light irradiation means 2 is configured to be able to irradiate the porous body 11 with ultraviolet light 21 from the outside.
図２は、本発明カラム１を構成する多孔質体１１の概略構成を示すＳＥＭ（Scanning Electron Microscope：走査型電子顕微鏡）写真である。図２に示されるように、多孔質体１１は、三次元網目構造の一体化した骨格部１４で構成され、骨格部１４の間隙において三次元網目状に連通する貫通孔部１５を備える。 FIG. 2 is a SEM (Scanning Electron Microscope) photograph showing a schematic configuration of the porous body 11 constituting the column 1 of the present invention. As shown in FIG. 2, the porous body 11 includes a skeleton part 14 having an integrated three-dimensional network structure, and includes a through-hole part 15 that communicates in a three-dimensional network in the gap between the skeleton parts 14.
骨格部１４は、ケイ酸（シリカ）を主成分とする石英ガラス多孔質体で構成される。また、貫通孔部１５は、水銀圧入法による測定の下で平均１５〜５０μｍの孔径を有する。このような骨格部１４と貫通孔部１５とで構成される多孔質体１１が、投入口１２と排出口１３の間に介装されており、貫通孔部１５によって投入口１２と排出口１３の間が連通される。すなわち、貫通孔部１５は多孔質体１１内を網目状に貫通するように構成されている。このため、投入口１２から投入された血液は、多孔質体１１内の貫通孔部１５を通って排出口１３へ導かれる。 The skeleton 14 is made of a silica glass porous body mainly composed of silicic acid (silica). Moreover, the through-hole part 15 has an average hole diameter of 15-50 micrometers under the measurement by a mercury intrusion method. The porous body 11 composed of the skeleton portion 14 and the through hole portion 15 is interposed between the inlet port 12 and the outlet port 13, and the inlet port 12 and the outlet port 13 are formed by the through hole portion 15. Between the two. That is, the through-hole portion 15 is configured to penetrate the porous body 11 in a mesh shape. For this reason, the blood input from the input port 12 is guided to the discharge port 13 through the through hole portion 15 in the porous body 11.
図３は、多孔質体１１に血液を投入した状態を示す概念図であり、多孔質体１１内の２つの貫通孔部１５とその周りの骨格部１４を模式的に示している。図３（ａ）は、血液の通流方向に垂直な断面で切断したときの模式的概念図、図３（ｂ）は、血液の通流方向に平行な断面で切断したときの模式的概念図である。 FIG. 3 is a conceptual diagram showing a state in which blood is introduced into the porous body 11, and schematically shows the two through-hole portions 15 in the porous body 11 and the skeleton portion 14 around it. 3A is a schematic conceptual diagram when cut in a cross section perpendicular to the blood flow direction, and FIG. 3B is a schematic concept when cut in a cross section parallel to the blood flow direction. FIG.
多孔質体１１に対して血液が投入された状態で紫外光照射手段２から紫外光２１が照射されると、図３に示されるように、この紫外光２１が、三次元網目構造を構成する骨格部１４を介して貫通孔部１５内を流動する血液に照射される。すなわち、骨格部１４は紫外光２１の導波路を構成する。そして、図３に示されるように、この貫通孔部１５内を流動する血液３０に含まれる白血球３１に対してこの紫外光２１が照射される。なお、図３では、説明の都合上、血液３０に含まれる成分として、白血球３１と赤血球３２のみを図示しており、他の成分を省略している。 When ultraviolet light 21 is irradiated from the ultraviolet light irradiation means 2 in a state where blood is introduced into the porous body 11, as shown in FIG. 3, the ultraviolet light 21 forms a three-dimensional network structure. The blood flowing through the through hole 15 is irradiated through the skeleton 14. That is, the skeleton part 14 constitutes a waveguide of the ultraviolet light 21. Then, as shown in FIG. 3, the ultraviolet light 21 is irradiated to the white blood cells 31 contained in the blood 30 flowing in the through-hole portion 15. In FIG. 3, for convenience of explanation, only the white blood cells 31 and the red blood cells 32 are shown as components contained in the blood 30, and other components are omitted.
一般的に赤血球３２の径は８μｍ程度であるのに対し、白血球３１の径は１５μｍ程度の大きさを示す。このため、水銀圧入法による測定の下で平均孔径１５〜５０μｍを示す貫通孔部１５内を血液３０が流動中に、貫通孔部１５内において、貫通孔部１５の内壁を構成する骨格部１４と白血球３１との間に赤血球３２が入り込む確率は大きく低下する。特に、貫通孔部１５の孔径が白血球３１の径よりも大きく、且つ、白血球３１の径と比べて大きく離れた値でない場合には、貫通孔部１５の内壁を構成する骨格部１４と白血球３１との隙間が狭くなるため、かかる隙間内に赤血球３２が入り込む可能性は大幅に減少する。 In general, the diameter of red blood cells 32 is about 8 μm, while the diameter of white blood cells 31 is about 15 μm. For this reason, the skeleton part 14 which comprises the inner wall of the through-hole part 15 in the through-hole part 15 in the through-hole part 15 in the through-hole part 15 in the through-hole part 15 which shows the average hole diameter of 15-50 micrometers under the measurement by a mercury intrusion method. The probability that the red blood cell 32 enters between the white blood cell 31 and the white blood cell 31 is greatly reduced. In particular, when the hole diameter of the through-hole portion 15 is larger than the diameter of the leukocyte 31 and is not a value far apart from the diameter of the leukocyte 31, the skeleton portion 14 and the leukocyte 31 constituting the inner wall of the through-hole portion 15 are used. Therefore, the possibility that red blood cells 32 enter the gap is greatly reduced.
かかる状態の下で、紫外光照射手段２が多孔質体１１の外側から多孔質体１１に向かって紫外光２１を照射した場合について検討する。照射された紫外光２１は、筒状体１６を透過して多孔質体１１に伝達される。多孔質体１１を構成する骨格部１４が上記のように石英ガラス多孔質体で形成される場合、石英ガラスは紫外光を透過する性質を有するため、上述のように骨格部１４に対して照射された紫外光２１は骨格部１４内を透過して貫通孔部１５内を流動する血液３０内に伝達される。なお、骨格部１４を構成する石英ガラス多孔質体が、ガラス中のヒドロキシル基の除去の為の熱処理を行っていない場合、レンズ用の石英ガラスに比べれば透過性は低くなるが、かかる場合であっても、体液に比べれば吸光度は非常に低く、紫外光に対する透過性は高い。 In this state, the case where the ultraviolet light irradiation means 2 irradiates the ultraviolet light 21 from the outside of the porous body 11 toward the porous body 11 will be considered. The irradiated ultraviolet light 21 passes through the cylindrical body 16 and is transmitted to the porous body 11. When the skeleton part 14 constituting the porous body 11 is formed of a porous silica glass body as described above, the quartz glass has a property of transmitting ultraviolet light, so that the skeleton part 14 is irradiated as described above. The ultraviolet light 21 transmitted through the skeleton part 14 is transmitted into the blood 30 flowing in the through-hole part 15. In addition, when the quartz glass porous body which comprises the frame | skeleton part 14 has not performed the heat processing for the removal of the hydroxyl group in glass, compared with quartz glass for lenses, although permeability becomes low, in such a case, Even if it exists, the light absorbency is very low compared with a body fluid, and the transmittance | permeability with respect to ultraviolet light is high.
また、前述したように貫通孔部１５の内壁を構成する骨格部１４と白血球３１との隙間に赤血球３２が入り込むこと可能性は低く、特に貫通孔部１５の孔径と白血球３１の径が近い場合には、白血球３１は貫通孔部１５の内壁に近接して貫通孔部１５内を流動することとなる。このため、骨格部１４を透過した紫外光の一部は、貫通孔部１５内を流動する血液３０中の赤血球３２によって吸収されることなく白血球３１に伝達され、照射される。これによって、白血球３１、特にＴ細胞に紫外光が照射されることで免疫寛容が誘導される。紫外光照射処理が施された血液は、その後さらに多孔質体１１内を流動後、排出口１３から排出される。 In addition, as described above, it is unlikely that the red blood cells 32 enter the gap between the skeleton portion 14 constituting the inner wall of the through-hole portion 15 and the white blood cells 31, particularly when the diameter of the through-hole portion 15 is close to the diameter of the white blood cell 31. In other words, the leukocytes 31 flow in the through-hole portion 15 close to the inner wall of the through-hole portion 15. For this reason, a part of the ultraviolet light transmitted through the skeleton part 14 is transmitted to the leukocytes 31 without being absorbed by the erythrocytes 32 in the blood 30 flowing in the through-hole part 15 and irradiated. Thereby, immune tolerance is induced by irradiating the leukocytes 31, particularly T cells, with ultraviolet light. The blood that has been subjected to the ultraviolet light irradiation treatment is further discharged from the discharge port 13 after flowing in the porous body 11.
このように、本発明システム１によれば、患者から採取した血液を投入口１２に投入し、多孔質体１１内を流動中に紫外光照射手段２によって当該血液に対して紫外光照射が施されることで、血液中のＴ細胞に免疫寛容が誘導される。そして、紫外光照射後の血液を排出口１３から採取して再度患者の体内に戻すことで、患者の免疫力を抑制することができる。 As described above, according to the system 1 of the present invention, blood collected from a patient is introduced into the inlet 12, and the blood is irradiated with ultraviolet light by the ultraviolet light irradiation means 2 while flowing in the porous body 11. As a result, immune tolerance is induced in T cells in the blood. And the blood after ultraviolet light irradiation is extract | collected from the discharge port 13, and a patient's immunity can be suppressed by returning to a patient's body again.
つまり、本発明システム１によれば、血液中の白血球に対して紫外光を照射するに際し、当該血液に含まれる赤血球による紫外光の吸収による照射能力の低下を考慮する必要がないため、血液分離装置を用いて予め白血球のみを取り出す必要がなく、さらには分離された血液成分を処置後に再び混合する必要もない。このため、処置に要する時間を大幅に短縮することができ、患者に対する負担を大幅に軽減することができる。また、従来は遠心分離を行うのに必要であった血液分離装置が不要となるため、大がかりなシステムを必要とせず、大幅にコストを削減することができる。これによって、医療コストが削減されるとともに、フォトフェレシスによる治療法の普及の促進につながる。 That is, according to the system 1 of the present invention, when irradiating the white blood cells in the blood with ultraviolet light, it is not necessary to consider a decrease in irradiation ability due to absorption of the ultraviolet light by the red blood cells contained in the blood. It is not necessary to extract only white blood cells in advance using the apparatus, and further, it is not necessary to mix the separated blood components again after the treatment. For this reason, the time required for the treatment can be greatly shortened, and the burden on the patient can be greatly reduced. In addition, since a blood separation device that has conventionally been necessary for performing centrifugation is unnecessary, a large-scale system is not required, and the cost can be greatly reduced. This reduces medical costs and promotes the spread of treatment by photopheresis.
なお、本発明システム１を用いてフォトフェレシスを行う場合、血液３０が多孔質体１１内を流動中に、当該血液３０に対して紫外光照射手段２から紫外光を照射するため、図３に示すように、現実的には白血球３１のみならず赤血球３２その他の血中成分にも紫外光が照射されることとなる。しかし、上述のように、白血球３１に対して照射される紫外光は、骨格部１４を介して直接照射される構成であり、紫外光の吸光度の高い赤血球３２を介して照射される可能性が極めて低い。このため、赤血球３２によって紫外光が吸光されることを考慮して予め紫外光照射強度を高める必要はなく、従来のように遠心分離により白血球のみを取り出して紫外光照射を行う場合と同等、あるいはそれ以下の強度で紫外光照射を行うことができる。このため、赤血球の溶血や血漿蛋白の変成等の問題を誘発することがない。 In addition, when performing photopheresis using the system 1 of the present invention, the blood 30 is irradiated with ultraviolet light from the ultraviolet light irradiation means 2 while the blood 30 is flowing in the porous body 11, so that FIG. As shown in FIG. 3, in reality, not only the white blood cells 31 but also the red blood cells 32 and other blood components are irradiated with ultraviolet light. However, as described above, the ultraviolet light irradiated to the leukocytes 31 is configured to be directly irradiated via the skeleton part 14, and may be irradiated via the red blood cells 32 having a high absorbance of ultraviolet light. Very low. For this reason, it is not necessary to increase the ultraviolet light irradiation intensity in advance considering that the ultraviolet light is absorbed by the red blood cells 32, which is equivalent to the case where only the white blood cells are extracted by centrifugation as in the conventional case, or the ultraviolet light irradiation is performed. Irradiation with ultraviolet light can be performed at an intensity lower than that. Therefore, problems such as red blood cell hemolysis and plasma protein degeneration are not induced.
［本発明カラムの説明］
次に、本発明カラム１の構成及びその製造方法について説明する。図２に示したように、本発明カラム１は、三次元網目構造を有した骨格部１４と、その骨格部１４によって囲まれた貫通孔部１５とを有してなる多孔質体１１、及び多孔質体１１の外周を覆う筒状体１６を備える。
[Description of the column of the present invention]
Next, the configuration of the column 1 of the present invention and the manufacturing method thereof will be described. As shown in FIG. 2, the column 1 of the present invention includes a porous body 11 having a skeleton portion 14 having a three-dimensional network structure, and a through-hole portion 15 surrounded by the skeleton portion 14, and A cylindrical body 16 that covers the outer periphery of the porous body 11 is provided.
以下、多孔質体１１のスピノーダル分解ゾル−ゲル法を用いた製造方法につき、説明を行う。 Hereinafter, the manufacturing method using the spinodal decomposition sol-gel method of the porous body 11 will be described.
１Ｍ（体積モル濃度）硝酸水溶液１０ｍｌに対して添加物としてｄ−ソルビトールを約０．３５〜約１．０ｇ加えたものにポリエチレングリコール（分子量１０００００）１．０ｇを溶かし、テトラエトキシシラン５ｍｌを加え、均一になるまで攪拌し、４０℃の恒温槽で一晩放置してゲル化させる。その後、得られたゲルを１Ｍアンモニア水に浸し、９０℃の下で３日間反応させる。その後、ゲルを乾燥させ、加熱することで石英ガラスからなる多孔質体１１が得られる。なお、この条件下で多孔質体１１を製造した場合、当該多孔質体１１が有する貫通孔部１５の孔径は水銀圧入法により測定すると１５〜５０μｍ程度である。 To 10 ml of 1M (volume molar concentration) nitric acid aqueous solution, about 0.35 to about 1.0 g of d-sorbitol was added as an additive, 1.0 g of polyethylene glycol (molecular weight 100000) was dissolved, and 5 ml of tetraethoxysilane was added. The mixture is stirred until it becomes uniform, and is left to stand in a constant temperature bath at 40 ° C. overnight for gelation. Thereafter, the gel obtained is immersed in 1M aqueous ammonia and reacted at 90 ° C. for 3 days. Then, the porous body 11 which consists of quartz glass is obtained by drying and heating a gel. In addition, when the porous body 11 is manufactured under these conditions, the pore diameter of the through-hole portion 15 included in the porous body 11 is about 15 to 50 μm when measured by a mercury intrusion method.
より具体的には、ｄ−ソルビトールを添加しなかった場合、ｄ−ソルビトールの添加量を０．２ｇとした場合、及びｄ−ソルビトールの添加量を１．０ｇとした場合において、他を同条件として多孔質体１１を製造すると、各多孔質体１１が備える貫通孔部１５の孔径は、それぞれ２μｍ、１０μｍ、５０μｍとなる。これにより、硝酸水溶液に添加するｄ−ソルビトールの添加量を調整することで、貫通孔部１５の孔径を調整できることが分かる。 More specifically, when d-sorbitol was not added, when d-sorbitol was added at 0.2 g, and when d-sorbitol was added at 1.0 g, the other conditions were the same. When the porous body 11 is manufactured, the diameters of the through-hole portions 15 included in each porous body 11 are 2 μm, 10 μm, and 50 μm, respectively. Thereby, it turns out that the hole diameter of the through-hole part 15 can be adjusted by adjusting the addition amount of d-sorbitol added to nitric acid aqueous solution.
上記の方法は、金属の有機及び無機化合物の溶液を混合して、アルコキシドの加水分解反応と脱水縮合反応によりゲル化を進行させ、かかるゲルを乾燥・加熱することで酸化物固体を作成するゾル−ゲル法を利用している。さらに、ゾル−ゲル法の出発溶液に有機高分子を混合することで、ゲル化の進行に伴って生成したシリカ重合体と有機高分子を含む溶媒とのスピノーダル分解により形成された分相構造がゲル化により固定されてμｍオーダーの細孔を有する多孔質ゲルが形成される特徴を利用したものである。すなわち、上記方法によれば、ゾル−ゲル法を用いるとともにスピノーダル分解を生じさせることで、多孔質体１１を製造することができる（スピノーダル分解ゾル−ゲル法）。 In the above method, a solution of an organic compound and an inorganic compound of a metal is mixed, gelation proceeds by hydrolysis reaction and dehydration condensation reaction of alkoxide, and an oxide solid is formed by drying and heating the gel. -The gel method is used. Furthermore, by mixing the organic polymer with the starting solution of the sol-gel method, the phase separation structure formed by spinodal decomposition of the silica polymer produced with the progress of gelation and the solvent containing the organic polymer is obtained. This utilizes the characteristic that a porous gel having pores of the order of μm is formed by gelation. That is, according to the above method, the porous body 11 can be produced by using the sol-gel method and causing spinodal decomposition (spinodal decomposition sol-gel method).
なお、上記の例では、添加するｄ−ソルビトールの添加量によって孔部の孔径が調整可能であるとしたが、ゲル化時の温度によっても孔径の調整が可能である。 In the above example, the pore diameter can be adjusted by the amount of d-sorbitol to be added, but the pore diameter can also be adjusted by the temperature at the time of gelation.
このように構成された多孔質体１１を、投入口１２と排出口１３の間に介装することで本発明カラム１を実現することができる。なお、筒状体１６は、その内径が多孔質体１１の外径よりは大きく、且つ、その多孔質体１１の外径に近い値となるような範囲内の大きさであることが好ましい。筒状体１６の内径が多孔質体１１の外径より小さいと、筒状体によって多孔質体１１を覆うことができず、一方、筒状体の内径が多孔質体の外径と比べて大きすぎると、筒状体の内壁と多孔質体の外壁との間に隙間ができてしまい、当該隙間から血液が漏れ出てしまうからである。 The column 1 of the present invention can be realized by interposing the porous body 11 thus configured between the inlet 12 and the outlet 13. The cylindrical body 16 preferably has a size within a range such that the inner diameter is larger than the outer diameter of the porous body 11 and is close to the outer diameter of the porous body 11. If the inner diameter of the cylindrical body 16 is smaller than the outer diameter of the porous body 11, the porous body 11 cannot be covered with the cylindrical body, while the inner diameter of the cylindrical body is smaller than the outer diameter of the porous body. If it is too large, a gap is formed between the inner wall of the cylindrical body and the outer wall of the porous body, and blood leaks from the gap.
また、多孔質体１１を筒状体１６内に装着する代わりに、多孔質体１１の外側面を紫外光透過性を有する物質でコーティングする構成としても良い。 Moreover, it is good also as a structure which coats the outer surface of the porous body 11 with the substance which has an ultraviolet-light transmittance instead of mounting the porous body 11 in the cylindrical body 16. FIG.
［他の実施形態］
以下に、他の実施形態について説明する。
[Other Embodiments]
Other embodiments will be described below.
〈１〉上述の実施形態では、本発明システム１０は、紫外光照射手段２を備え、多孔質体１１の貫通孔部１５内を血液が流動中に、多孔質体１１の外側から当該手段２より紫外光を照射する構成としたが、白血球に照射する励起光は紫外光に限定されるものではなく、例えば波長４００〜５００ｎｍ程度の可視光を照射する構成としても良い。すなわち、本発明システム１０は、所定の励起光を照射する励起光照射手段２（紫外光照射手段２に相当）を備えるとともに、本発明カラム１が備える多孔質体１１の骨格部１４、並びに多孔質体１１が筒状体によって覆われる場合には当該筒状体が、励起光照射手段２から照射される励起光を透過する性質を有している構成であれば良い。また、図１では、便宜上紫外光照射手段２からあたかも一方向に紫外光２１が照射されるかのように図示されているが、本発明カラム１の外周部分に対して全方向から紫外光２１が照射される構成としても良い。 <1> In the above-described embodiment, the system 10 of the present invention includes the ultraviolet light irradiation means 2, and the means 2 from the outside of the porous body 11 while blood is flowing in the through-hole portion 15 of the porous body 11. Although it is configured to irradiate more ultraviolet light, the excitation light irradiated to the white blood cells is not limited to ultraviolet light, and may be configured to irradiate visible light having a wavelength of about 400 to 500 nm, for example. That is, the system 10 of the present invention includes the excitation light irradiation means 2 (corresponding to the ultraviolet light irradiation means 2) for irradiating predetermined excitation light, the skeleton part 14 of the porous body 11 included in the column 1 of the present invention, and the porous structure. When the material 11 is covered with the cylindrical body, the cylindrical body may be configured to have a property of transmitting the excitation light irradiated from the excitation light irradiation means 2. Further, in FIG. 1, for convenience, the ultraviolet light irradiation means 2 is illustrated as if the ultraviolet light 21 is irradiated in one direction, but the ultraviolet light 21 from all directions with respect to the outer peripheral portion of the column 1 of the present invention. It is good also as a structure irradiated.
〈２〉上述の実施形態では、免疫抑制の目的で、白血球に対して紫外光（励起光）を照射することを目的としていたため、多孔質体１１の貫通孔部１５の孔径は白血球の径よりも大きいことが前提となっていた。しかし、例えば、他の体液中に含まれる所定の細胞に対してのみ励起光を照射することを目的とするような場合であっても、同様に応用することが可能である。すなわち、照射目標となる細胞の最大径よりも大きい貫通孔部１５を有する多孔質体１１を前記の方法によって製造するとともに、投入口１２並びに排出口１３を備えて本発明カラム１を実装し、投入口１２から当該体液を投入し、貫通孔部１５内を当該体液が流動中に、本発明カラム１の外側から励起光（紫外光）照射手段２によって本発明カラム１に向かって励起光を照射した後、照射後の体液を排出口１３から採取する構成であれば、いかなる態様においても本発明が想定する範囲内である。 <2> In the above-described embodiment, for the purpose of immunosuppression, the aim was to irradiate the leukocytes with ultraviolet light (excitation light), and therefore the pore diameter of the through hole portion 15 of the porous body 11 is the diameter of the leukocytes. It was assumed that it was larger. However, for example, even when the purpose is to irradiate only predetermined cells contained in other body fluids with excitation light, the same application can be made. That is, while producing the porous body 11 having the through-hole portion 15 larger than the maximum cell diameter to be irradiated by the above method, the column 1 of the present invention is mounted with the inlet 12 and the outlet 13, The body fluid is introduced from the inlet 12, and the body fluid is flowing through the through-hole portion 15, and excitation light (ultraviolet light) irradiation means 2 emits excitation light from the outside of the column 1 of the invention toward the column 1 of the invention. As long as it is the structure which extracts the bodily fluid after irradiation from the discharge port 13 after irradiation, it is in the range which this invention assumes in any aspect.
〈３〉上述の実施形態では、本発明カラム１が備える多孔質体１１がスピノーダル分解ゾル−ゲル法によって製造された場合を例に挙げて説明した。当該方法によって製造された場合、骨格部１４は三次元網目構造となって構成される。しかしながら、本発明の目的を達成するに際しては、照射目標となる細胞の最大径よりも大きい貫通孔部１５と、その貫通孔部１５を取り囲む励起光を透過可能な骨格部１４を有する多孔質体１１でありさえすれば良く、骨格部１４は必ずしも三次元網目構造である必要はない。例えば、投入口１２から排出口１３に向かうベクトルとほぼ平行方向に複数の貫通孔部１５が連続的に複数の分岐路を有して形成される場合であっても本発明の目的を達成することができる。ただし、上述の実施形態のように三次元網目構造の骨格部１４を有することで、圧力を抑えながら貫通孔部１５内を体液を流動させることができ、体液に対して万遍なく励起光を照射することができるという効果を有する。 <3> In the above-described embodiment, the case where the porous body 11 included in the column 1 of the present invention is manufactured by the spinodal decomposition sol-gel method has been described as an example. When manufactured by this method, the skeleton 14 is configured as a three-dimensional network structure. However, in order to achieve the object of the present invention, a porous body having a through-hole portion 15 larger than the maximum diameter of a cell to be irradiated and a skeleton portion 14 that can transmit excitation light surrounding the through-hole portion 15. 11 and the skeleton 14 does not necessarily have a three-dimensional network structure. For example, the object of the present invention is achieved even when a plurality of through-hole portions 15 are continuously formed with a plurality of branch paths in a direction substantially parallel to a vector from the inlet 12 to the outlet 13. be able to. However, by having the three-dimensional network structure skeleton part 14 as in the above-described embodiment, the body fluid can flow through the through-hole part 15 while suppressing the pressure, and the excitation light is uniformly applied to the body fluid. It has the effect that it can be irradiated.
１： 本発明に係るフォトフェレシス処理用カラム
２： 紫外光照射手段
１０： 本発明に係るフォトフェレシス処理システム
１１： 多孔質体
１２： 投入口
１３： 排出口
１４： 骨格部
１５： 孔部
１６： 筒状体
２１： 紫外光
３０： 血液
３１： 白血球
３２： 赤血球
1: Photopheresis processing column according to the present invention 2: Ultraviolet light irradiation means 10: Photopheresis processing system according to the present invention 11: Porous body 12: Input port 13: Discharge port 14: Skeletal portion 15: Hole portion 16: Tubular body 21: Ultraviolet light 30: Blood 31: White blood cell 32: Red blood cell
Claims (8)
投入された前記体液が排出される排出口と、
前記投入口と前記排出口の間を連通する貫通孔部、及び前記励起光を透過する性質を示す骨格部で構成された多孔質体と、を備えてなり、
前記貫通孔部の孔径が前記細胞の最大径より大きく、
前記多孔質体の外側から照射された前記励起光を前記骨格部内に受光可能に構成されていることを特徴とするフォトフェレシス処理用カラム。 An inlet into which a body fluid containing cells to be irradiated with excitation light is introduced;
A discharge port through which the introduced body fluid is discharged;
A through-hole portion communicating between the input port and the discharge port, and a porous body composed of a skeleton portion exhibiting the property of transmitting the excitation light,
The hole diameter of the through-hole portion is larger than the maximum diameter of the cell,
The photopheresis processing column is configured to receive the excitation light irradiated from the outside of the porous body into the skeleton.
前記筒状体の外側から照射された前記励起光を前記骨格部内に受光可能に構成されていることを特徴とする請求項１〜４のいずれか１項に記載のフォトフェレシス処理用カラム。 The periphery of the porous body is covered with a cylindrical body showing the property of transmitting the excitation light,
5. The photopheresis processing column according to claim 1, wherein the excitation light irradiated from the outside of the cylindrical body is configured to be received in the skeleton portion. 6.
前記体液が血液であり、
前記励起光が紫外光または波長５００ｎｍ以下の可視光であり、
前記多孔質体が、水銀圧入法による測定の下で平均孔径１５〜５０μｍを示す貫通孔部を有することを特徴とする請求項１〜５のいずれか１項に記載のフォトフェレシス処理用カラム。 The cell is a white blood cell;
The body fluid is blood;
The excitation light is ultraviolet light or visible light having a wavelength of 500 nm or less,
The column for photopheresis treatment according to any one of claims 1 to 5, wherein the porous body has a through-hole portion having an average pore diameter of 15 to 50 µm under measurement by a mercury intrusion method. .
前記フォトフェレシス処理用カラムの外側から前記骨格部に対して前記励起光を照射可能な励起光照射手段と、を備えることを特徴とするフォトフェレシス処理システム。 A column for photopheresis treatment according to any one of claims 1 to 6,
Excitation light irradiating means capable of irradiating the skeleton with the excitation light from the outside of the photopheresis processing column.
前記体液が前記貫通孔部内を流動中に、前記フォトフェレシス処理用カラムの外側から前記骨格部に対して前記励起光を照射することで、前記骨格部を介して前記体液中の前記細胞に対して前記励起光を照射することを特徴とするフォトフェレシス処理方法。 The body fluid is introduced from the introduction port of the photopheresis treatment column according to any one of claims 1 to 6,
While the body fluid is flowing through the through-hole portion, the cells in the body fluid are passed through the skeleton portion by irradiating the skeleton portion with the excitation light from the outside of the photopheresis column. And irradiating the excitation light to the photopheresis processing method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007211481A JP4468976B2 (en) | 2007-08-14 | 2007-08-14 | Photopheresis processing column, photopheresis processing system, and photopheresis processing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007211481A JP4468976B2 (en) | 2007-08-14 | 2007-08-14 | Photopheresis processing column, photopheresis processing system, and photopheresis processing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009045111A true JP2009045111A (en) | 2009-03-05 |
| JP4468976B2 JP4468976B2 (en) | 2010-05-26 |
Family
ID=40497918
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007211481A Active JP4468976B2 (en) | 2007-08-14 | 2007-08-14 | Photopheresis processing column, photopheresis processing system, and photopheresis processing method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4468976B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014204001A1 (en) * | 2013-06-21 | 2014-12-24 | 国立大学法人 岡山大学 | Method using abnormally-activated-cell detection to test for malignant tumors and abnormally-activated-cell apheresis-therapy apparatus |
-
2007
- 2007-08-14 JP JP2007211481A patent/JP4468976B2/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014204001A1 (en) * | 2013-06-21 | 2014-12-24 | 国立大学法人 岡山大学 | Method using abnormally-activated-cell detection to test for malignant tumors and abnormally-activated-cell apheresis-therapy apparatus |
| JPWO2014204001A1 (en) * | 2013-06-21 | 2017-02-23 | 国立大学法人 岡山大学 | Test method for malignant tumor by detecting abnormally activated cells and abnormally activated cell-removal perfusion return device |
| JP2018153195A (en) * | 2013-06-21 | 2018-10-04 | 国立大学法人 岡山大学 | Method for examining malignant tumor by abnormally activated cell detection and abnormally activated cell removal and retransfusion treatment apparatus |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4468976B2 (en) | 2010-05-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gao et al. | Functionalized MoS2 nanovehicle with near‐infrared laser‐mediated nitric oxide release and photothermal activities for advanced bacteria‐infected wound therapy | |
| Jin et al. | MRI-guided and ultrasound-triggered release of NO by advanced nanomedicine | |
| CN103528996B (en) | The preparation of a kind of gold nanorods SPR probe and the method for detecting its medicine carrying release dynamics process | |
| Zhang et al. | Heterostructures of MOFs and nanorods for multimodal imaging | |
| CN108671231B (en) | Multifunctional nano-carrier for tumor photothermal synergistic treatment and ultrasonic imaging and preparation method thereof | |
| CN109394730A (en) | A kind of erythrocyte membrane package carries gambogicacid and indocyanine green albumin nano granular and its preparation method and application altogether | |
| CN102600521A (en) | Device and method for eliminating pathogens in blood | |
| JP2009066117A (en) | Adsorption column for body fluid purifying treatment | |
| CN107308462A (en) | A kind of environment-friendly preparation method thereof of sea urchin shape nanogold and its application in tumor imaging and treatment | |
| CN106075442A (en) | There is preparation method and the purposes of the medicine carrying hollow carbon sphere of photothermal conversion effect | |
| Iresha et al. | Ultrasound-triggered nicotine release from nicotine-loaded cellulose hydrogel | |
| JP4468976B2 (en) | Photopheresis processing column, photopheresis processing system, and photopheresis processing method | |
| JP2006291193A (en) | Reformed substrate and manufacturing method thereof | |
| Mathavan et al. | Formulation buoyancy of nanoencapsulated gliclazide using primary, conjugated and deconjugated bile acids | |
| CN106433630B (en) | A kind of preparation method of fluorescence mesoporous silicon sphere | |
| JP2010082067A (en) | Method of manufacturing membrane for use in contact with biogenic substance | |
| Fang et al. | Self‐Adaptive MoO3− x Subnanometric Wires Incorporated Scaffolds for Osteosarcoma Therapy and Bone Regeneration | |
| CN109646398A (en) | A kind of nano-micelle and preparation method thereof, application | |
| CN112972705A (en) | Indocyanine green hydrogel fluorescent calibration plate and preparation method and application thereof | |
| CN105142693B (en) | Blood treatment hollow-fibre membrane and the manufacture method of this blood treatment hollow-fibre membrane | |
| US20070178436A1 (en) | Method of inactivating virus in circular blood and its applications in treating viral diseases | |
| CN102827228B (en) | Silicon phthalocyanine modified by cytidine derivative and preparation method and application thereof | |
| CN102827227B (en) | Silicon phthalocyanine modified by adenosine derivative and preparation method and application thereof | |
| WO2019203065A1 (en) | Ultraviolet irradiation method for photopheresis, micro device for photopheresis, and ultraviolet irradiation device for photopheresis | |
| Tachibana et al. | Enhanced mechanical damage to in vitro cancer cells by high-intensity-focused ultrasound in the presence of microbubbles and titanium dioxide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20090716 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090728 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090901 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100223 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100225 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130305 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130305 Year of fee payment: 3 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130305 Year of fee payment: 3 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130305 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130305 Year of fee payment: 3 |