JPWO2019169089A5 - - Google Patents
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- JPWO2019169089A5 JPWO2019169089A5 JP2020545290A JP2020545290A JPWO2019169089A5 JP WO2019169089 A5 JPWO2019169089 A5 JP WO2019169089A5 JP 2020545290 A JP2020545290 A JP 2020545290A JP 2020545290 A JP2020545290 A JP 2020545290A JP WO2019169089 A5 JPWO2019169089 A5 JP WO2019169089A5
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- macrocapsule
- barrier
- glucomannan
- composition
- sulfate
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- 239000000203 mixture Substances 0.000 claims description 62
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 36
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2S,3S,4S,5S,6R)-2-[(2R,3S,4R,5R,6S)-6-[(2R,3S,4R,5S,6S)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2R,4R,5S,6R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 claims description 34
- 229920002581 Glucomannan Polymers 0.000 claims description 34
- 229940046240 glucomannan Drugs 0.000 claims description 34
- 239000001913 cellulose Substances 0.000 claims description 18
- 229920002678 cellulose Polymers 0.000 claims description 18
- 229940005550 Sodium alginate Drugs 0.000 claims description 12
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 12
- MSXHSNHNTORCAW-UHFFFAOYSA-M sodium 3,4,5,6-tetrahydroxyoxane-2-carboxylate Chemical compound [Na+].OC1OC(C([O-])=O)C(O)C(O)C1O MSXHSNHNTORCAW-UHFFFAOYSA-M 0.000 claims description 12
- 235000010413 sodium alginate Nutrition 0.000 claims description 12
- 239000000661 sodium alginate Substances 0.000 claims description 12
- 230000001225 therapeutic Effects 0.000 claims description 11
- 229920000371 poly(diallyldimethylammonium chloride) polymer Polymers 0.000 claims description 10
- 206010012601 Diabetes mellitus Diseases 0.000 claims description 8
- 102000004877 Insulin Human genes 0.000 claims description 6
- 108090001061 Insulin Proteins 0.000 claims description 6
- WDIHJSXYQDMJHN-UHFFFAOYSA-L Barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 claims description 4
- 229910052788 barium Inorganic materials 0.000 claims description 4
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium(0) Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L cacl2 Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 238000006116 polymerization reaction Methods 0.000 claims description 4
- 239000004677 Nylon Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229920001778 nylon Polymers 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 210000000683 Abdominal Cavity Anatomy 0.000 claims 1
- 210000002747 Omentum Anatomy 0.000 claims 1
- 210000004369 Blood Anatomy 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 210000004153 Islets of Langerhans Anatomy 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 230000001058 adult Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Description
インスリン依存性糖尿病の成人ヒト対象は、開示されたマクロカプセル化島細胞を含む治療有効量の組成物を含む移植片を、網に固定された対象の網ポーチ内に、または腹腔内に受ける。
対象は血糖値について評価される。対象は、対象の血糖値が安定していることを確認するため、治療上有効な数のマクロカプセル化細胞の移植後に監視される。対象をさらに、経時的にグリコシル化ヘモグロビン、および糖尿病の併存症についてスクリーニングする。 本発明の実施形態として例えば以下を挙げることができる。
［実施形態１］
複数の治療用細胞を包含する少なくとも２つのマクロカプセルを含むデバイスであって、前記マクロカプセルが、円筒形状および少なくとも１．５ｍｍの直径を含む、デバイス。
［実施形態２］
前記マクロカプセルが、少なくとも１つのバリアを含み、前記バリアが、
（ａ）硫酸セルロースおよびグルコマンナンもしくは硫酸グルコマンナン、または
（ｂ）アルギン酸ナトリウム、を含む、実施形態１に記載のデバイス。
［実施形態３］
前記マクロカプセルが、第２のバリアをさらに含み、前記第１のバリアが、前記第２のバリア内に包含される、実施形態１または実施形態２に記載のデバイス。
［実施形態４］
前記マクロカプセルが、１枚の外科用メッシュに取り付けられる、実施形態１～３のいずれかに記載のデバイス。
［実施形態５］
前記外科用メッシュが、ナイロンである、実施形態４に記載のデバイス。
［実施形態６］
前記外科用メッシュが、円形である、実施形態４に記載のデバイス。
［実施形態７］
前記外科用メッシュが、長円形である、実施形態４に記載のデバイス。
［実施形態８］
前記外科用メッシュが、前記デバイスを宿主内の適切な部位に取り付けるためのタブを含む、実施形態４に記載のデバイス。
［実施形態９］
複数のマクロカプセルが、前記外科用メッシュに取り付けられる、実施形態４～８のいずれかに記載のデバイス。
［実施形態１０］
前記マクロカプセルが、前記メッシュの周りに放射状に配置される、実施形態９に記載のデバイス。
［実施形態１１］
前記マクロカプセルが、前記メッシュに沿って並置される、実施形態９に記載のデバイス。
［実施形態１２］
前記マクロカプセルが、前記メッシュの反対側を延びるように配置される、実施形態９に記載のデバイス。
［実施形態１３］
糖尿病の治療を、それを必要とする対象において行う方法であって、糖尿病の対象に、実施形態１～１２のいずれかに記載のデバイスを移植することを含み、前記デバイスが、前記対象の大網内または腹腔内に移植される、方法。
［実施形態１４］
糖尿病の治療を、それを必要とする対象において行うことに使用するための、実施形態１～１２のいずれかに記載のデバイス。
［実施形態１５］
糖尿病の治療のための医薬品の製造における実施形態１～１２のいずれかに記載のデバイスの使用。
［実施形態１６］
複数の治療用細胞を包含するマクロカプセルを含む組成物であって、前記マクロカプセルが少なくとも１つのバリアを含み、前記バリアが、
（ａ）硫酸セルロースおよびグルコマンナンもしくは硫酸グルコマンナン、または
（ｂ）アルギン酸ナトリウム、を含み、
前記マクロカプセルが、少なくとも１つの他のマクロカプセルも取り付けられる１枚の外科用メッシュに取り付けられる、組成物。
［実施形態１７］
前記治療用細胞が、インスリン産生細胞である、実施形態１６に記載の組成物。
［実施形態１８］
第２のバリアをさらに含む、実施形態１６または実施形態１７に記載の組成物。
［実施形態１９］
前記第２のバリアが、硫酸セルロースおよびグルコマンナンまたは硫酸グルコマンナンを含む、実施形態１８に記載の組成物。
［実施形態２０］
前記第２のバリアが、グルコマンナンまたは硫酸グルコマンナンを含まない、実施形態１８に記載の組成物。
［実施形態２１］
前記マクロカプセルの直径が、少なくとも１．５ｍｍである、実施形態１６～２０のいずれかに記載の組成物。
［実施形態２２］
前記マクロカプセルの前記直径が、少なくとも２．０ｍｍである、実施形態１６～２１のいずれかに記載の組成物。
［実施形態２３］
前記アルギン酸ナトリウムが、二価カチオンであるバリウム（ＢａＣｌ
２
）またはカルシウム（ＣａＣｌ
２
）と重合される、実施形態１６～２２のいずれかに記載の組成物。
［実施形態２４］
前記硫酸セルロースが、ポリ（ジアリルジメチルアンモニウムクロリド）（ｐＤＡＤＭＡＣ）と重合された、実施形態１６～２２のいずれかに記載の組成物。
［実施形態２５］
前記マクロカプセルが、ｐＤＡＤＭＡＣとの重合後、ポリメチレン－コ－グアニジン（ＰＭＣＧ）で洗浄された、実施形態２４のいずれかに記載の組成物。
［実施形態２６］
前記マクロカプセルが、少なくとも約１１ｃｍの長さである、実施形態１６～２５のいずれかに記載の組成物。
［実施形態２７］
前記マクロカプセルが、１ｃｍ当たり少なくとも約５０，０００個の細胞を含む、実施形態１６～２６のいずれかに記載の組成物。
［実施形態２８］
前記マクロカプセルが、円筒状である、実施形態１６～２７のいずれかに記載の組成物。
［実施形態２９］
複数の治療用細胞を包含するマクロカプセルを含む組成物であって、前記マクロカプセルが、少なくとも第１のバリアおよび第２のバリアを含み、前記第１のバリアが、前記第２のバリア内に包含され、前記マクロカプセルが、少なくとも１．５ｍｍの直径を有し、前記マクロカプセルが、少なくとも１つの他のマクロカプセルも取り付けられる１枚の外科用メッシュに取り付けられる、組成物。
［実施形態３０］
前記マクロカプセルの直径が、少なくとも２．０ｍｍである、実施形態２９に記載の組成物。
［実施形態３１］
前記治療用細胞が、インスリン産生細胞である、実施形態２９または実施形態３０に記載の組成物。
［実施形態３２］
前記第２のバリアが、硫酸セルロースおよびグルコマンナンまたは硫酸グルコマンナンを含む、実施形態２９～３１のいずれかに記載の組成物。
［実施形態３３］
前記第１および第２のバリアの両方が、硫酸セルロースおよび硫酸グルコマンナンを含む、実施形態２９～３２のいずれかに記載の組成物。
［実施形態３４］
前記硫酸セルロースが、ｐＤＡＤＭＡＣと重合された、実施形態３２～３３のいずれかに記載の組成物。
［実施形態３５］
前記マクロカプセルが、ｐＤＡＤＭＡＣとの重合後にＰＭＣＧで洗浄された、実施形態３４に記載の組成物。
［実施形態３６］
前記第２のバリアが、グルコマンナンまたは硫酸グルコマンナンを含まない、実施形態２９～３１のいずれかに記載の組成物。
［実施形態３７］
前記第１のバリアが、アルギン酸ナトリウムを含む、実施形態２９～３２のいずれかに記載の組成物。
［実施形態３８］
前記アルギン酸ナトリウムが、二価カチオンであるバリウム（ＢａＣｌ
２
）またはカルシウム（ＣａＣｌ
２
）と重合される、実施形態３７に記載の組成物。
［実施形態３９］
前記マクロカプセルが、少なくとも約１１ｃｍの長さである、実施形態２９～３８のいずれかに記載の組成物。
［実施形態４０］
前記マクロカプセルが、１ｃｍ当たり少なくとも約５０，０００個の細胞を含む、実施形態２９～３９のいずれかに記載の組成物。
［実施形態４１］
前記マクロカプセルが、円筒状である、実施形態２９～４０のいずれかに記載の組成物。
［実施形態４２］
複数の治療用細胞を包含するマクロカプセルを含む組成物であって、前記マクロカプセルが、円筒形状および少なくとも１．５ｍｍの直径を含み、前記マクロカプセルが、少なくとも１つの他のマクロカプセルも取り付けられる１枚の外科用メッシュに取り付けられる、組成物。
［実施形態４３］
前記マクロカプセルが、少なくとも第１のバリアおよび第２のバリアを含み、前記第１のバリアが、前記第２のバリア内に包含される、実施形態４２に記載の組成物。
［実施形態４４］
前記第１のバリアが、
（ａ）硫酸セルロースおよびグルコマンナンもしくは硫酸グルコマンナン、または
（ｂ）アルギン酸ナトリウム、を含む、実施形態４３に記載の組成物。
［実施形態４５］
前記第２のバリアが、硫酸セルロースおよびグルコマンナンまたは硫酸グルコマンナンを含む、実施形態４３または実施形態４４に記載の組成物。
［実施形態４６］
前記治療用細胞が、インスリン産生細胞である、実施形態４２～４５のいずれかに記載の組成物。
［実施形態４７］
前記マクロカプセルが、少なくとも約１１ｃｍの長さである、実施形態４２～４６のいずれかに記載の組成物。
［実施形態４８］
前記マクロカプセルが、１ｃｍ当たり少なくとも約５０，０００個の細胞を含む、実施形態４２～４７のいずれかに記載の組成物。
Adult human subjects with insulin-dependent diabetes mellitus receive a graft containing a therapeutically effective amount of the disclosed macroencapsulated islet cells in a net-fixed net pouch or intraperitoneally.
Subjects are assessed for blood glucose levels. Subjects will be monitored after transplantation of a therapeutically effective number of macroencapsulated cells to ensure that the subject's blood glucose levels are stable. Subjects are further screened for glycosylated hemoglobin over time, and comorbidities of diabetes. Examples of embodiments of the present invention include the following.
[Embodiment 1]
A device comprising at least two macrocapsules comprising a plurality of therapeutic cells, wherein the macrocapsules have a cylindrical shape and a diameter of at least 1.5 mm.
[Embodiment 2]
The macrocapsule comprises at least one barrier, wherein the barrier is:
(A) Cellulose sulfate and glucomannan or glucomannan sulfate, or
(B) The device according to embodiment 1, comprising sodium alginate.
[Embodiment 3]
The device according to embodiment 1 or 2, wherein the macrocapsule further comprises a second barrier, wherein the first barrier is encapsulated within the second barrier.
[Embodiment 4]
The device according to any one of embodiments 1 to 3, wherein the macrocapsule is attached to a single surgical mesh.
[Embodiment 5]
The device according to embodiment 4, wherein the surgical mesh is nylon.
[Embodiment 6]
The device according to embodiment 4, wherein the surgical mesh is circular.
[Embodiment 7]
The device according to embodiment 4, wherein the surgical mesh is oval.
[Embodiment 8]
The device of embodiment 4, wherein the surgical mesh comprises a tab for attaching the device to a suitable site in the host.
[Embodiment 9]
The device according to any of embodiments 4-8, wherein the plurality of macrocapsules are attached to the surgical mesh.
[Embodiment 10]
9. The device of embodiment 9, wherein the macrocapsules are arranged radially around the mesh.
[Embodiment 11]
The device according to embodiment 9, wherein the macrocapsules are juxtaposed along the mesh.
[Embodiment 12]
9. The device of embodiment 9, wherein the macrocapsule is arranged so as to extend on the opposite side of the mesh.
[Embodiment 13]
A method of treating diabetes in a subject in need thereof, comprising transplanting the device according to any one of embodiments 1-12 into the subject of diabetes, wherein the device is a large subject. A method of being implanted intraretally or intraperitoneally.
[Embodiment 14]
The device according to any one of embodiments 1-12, for use in treating diabetes in a subject in need thereof.
[Embodiment 15]
Use of the device according to any of embodiments 1-12 in the manufacture of a pharmaceutical product for the treatment of diabetes.
[Embodiment 16]
A composition comprising a macrocapsule comprising a plurality of therapeutic cells, wherein the macrocapsule comprises at least one barrier.
(A) Cellulose sulfate and glucomannan or glucomannan sulfate, or
(B) Containing sodium alginate,
A composition in which the macrocapsule is attached to a surgical mesh to which at least one other macrocapsule is also attached.
[Embodiment 17]
The composition according to embodiment 16, wherein the therapeutic cell is an insulin-producing cell.
[Embodiment 18]
The composition according to embodiment 16 or 17, further comprising a second barrier.
[Embodiment 19]
The composition according to embodiment 18, wherein the second barrier comprises cellulose sulfate and glucomannan or glucomannan sulfate.
[Embodiment 20]
The composition according to embodiment 18, wherein the second barrier does not contain glucomannan or glucomannan sulfate.
[Embodiment 21]
The composition according to any one of embodiments 16 to 20, wherein the macrocapsule has a diameter of at least 1.5 mm.
[Embodiment 22]
The composition according to any of embodiments 16-21, wherein the macrocapsule has a diameter of at least 2.0 mm.
[Embodiment 23]
The composition according to any one of embodiments 16 to 22, wherein the sodium alginate is polymerized with the divalent cation barium (BaCl 2 ) or calcium (CaCl 2 ).
[Embodiment 24]
The composition according to any one of embodiments 16 to 22, wherein the cellulose sulfate is polymerized with poly (diallyldimethylammonium chloride) (pDADMAC).
[Embodiment 25]
The composition according to any of embodiments 24, wherein the macrocapsules were washed with polymethylene-co-guanidine (PMCG) after polymerization with pDADMAC.
[Embodiment 26]
The composition according to any of embodiments 16-25, wherein the macrocapsules are at least about 11 cm in length.
[Embodiment 27]
The composition according to any of embodiments 16-26, wherein the macrocapsule comprises at least about 50,000 cells per cm.
[Embodiment 28]
The composition according to any one of embodiments 16 to 27, wherein the macrocapsule is cylindrical.
[Embodiment 29]
A composition comprising a macrocapsule comprising a plurality of therapeutic cells, wherein the macrocapsule comprises at least a first barrier and a second barrier, wherein the first barrier is within the second barrier. A composition comprising, wherein the macrocapsule has a diameter of at least 1.5 mm and the macrocapsule is attached to one surgical mesh to which at least one other macrocapsule is also attached.
[Embodiment 30]
29. The composition of embodiment 29, wherein the macrocapsule has a diameter of at least 2.0 mm.
[Embodiment 31]
The composition according to embodiment 29 or 30, wherein the therapeutic cell is an insulin-producing cell.
[Embodiment 32]
The composition according to any of embodiments 29-31, wherein the second barrier comprises cellulose sulfate and glucomannan or glucomannan sulfate.
[Embodiment 33]
The composition according to any of embodiments 29-32, wherein both the first and second barriers comprise cellulose sulfate and glucomannan sulfate.
[Embodiment 34]
The composition according to any one of embodiments 32 to 33, wherein the cellulose sulfate is polymerized with pDADMAC.
[Embodiment 35]
The composition according to embodiment 34, wherein the macrocapsules were washed with PMCG after polymerization with pDADMAC.
[Embodiment 36]
The composition according to any of embodiments 29-31, wherein the second barrier does not contain glucomannan or glucomannan sulfate.
[Embodiment 37]
The composition according to any of embodiments 29-32, wherein the first barrier comprises sodium alginate.
[Embodiment 38]
13. The composition of embodiment 37, wherein the sodium alginate is polymerized with the divalent cations barium (BaCl 2 ) or calcium (CaCl 2 ).
[Embodiment 39]
The composition according to any of embodiments 29-38, wherein the macrocapsules are at least about 11 cm in length.
[Embodiment 40]
The composition according to any of embodiments 29-39, wherein the macrocapsule comprises at least about 50,000 cells per cm.
[Embodiment 41]
The composition according to any one of embodiments 29-40, wherein the macrocapsule is cylindrical.
[Embodiment 42]
A composition comprising a macrocapsule comprising a plurality of therapeutic cells, wherein the macrocapsule comprises a cylindrical shape and a diameter of at least 1.5 mm, and the macrocapsule is also attached to at least one other macrocapsule. A composition that attaches to a single surgical mesh.
[Embodiment 43]
42. The composition of embodiment 42, wherein the macrocapsule comprises at least a first barrier and a second barrier, wherein the first barrier is encapsulated within the second barrier.
[Embodiment 44]
The first barrier is
(A) Cellulose sulfate and glucomannan or glucomannan sulfate, or
(B) The composition according to embodiment 43, which comprises sodium alginate.
[Embodiment 45]
The composition according to embodiment 43 or 44, wherein the second barrier comprises cellulose sulfate and glucomannan or glucomannan sulfate.
[Embodiment 46]
The composition according to any of embodiments 42-45, wherein the therapeutic cell is an insulin-producing cell.
[Embodiment 47]
The composition according to any of embodiments 42-46, wherein the macrocapsules are at least about 11 cm in length.
[Embodiment 48]
The composition according to any of embodiments 42-47, wherein the macrocapsule comprises at least about 50,000 cells per cm.
Claims (34)
前記マクロカプセルが、第１のバリア、および前記第１のバリアを包含する第２のバリアを含み、
前記第１のバリアが、
（ａ）硫酸セルロースおよびグルコマンナンもしくは硫酸グルコマンナン、または
（ｂ）アルギン酸ナトリウム、を含み、
前記マクロカプセルが、円筒形状および少なくとも１．５ｍｍの直径を有し、
前記マクロカプセルが、前記１枚の外科用メッシュに取り付けられる、デバイス。 A device containing a single surgical mesh and multiple macrocapsules containing multiple therapeutic cells.
The macrocapsule comprises a first barrier and a second barrier comprising the first barrier.
The first barrier is
(A) Cellulose sulfate and glucomannan or glucomannan sulfate, or
(B) Containing sodium alginate ,
The macrocapsule has a cylindrical shape and a diameter of at least 1.5 mm .
A device in which the macrocapsule is attached to the single surgical mesh .
（ａ）硫酸セルロースおよびグルコマンナンもしくは硫酸グルコマンナン、または
（ｂ）アルギン酸ナトリウム、を含み、
前記マクロカプセルが、少なくとも１つの他のマクロカプセルも取り付けられる１枚の外科用メッシュに取り付けられ、
前記マクロカプセルの直径が、少なくとも１．５ｍｍである、組成物。 A composition comprising a cylindrical macrocapsule comprising a plurality of insulin-producing therapeutic cells, wherein the macrocapsule comprises a first barrier and a second barrier , wherein the first barrier comprises.
(A) Cellulose sulfate and glucomannan or glucomannan sulfate, or (b) sodium alginate,
The macrocapsule is attached to a surgical mesh to which at least one other macrocapsule is also attached .
A composition in which the diameter of the macrocapsule is at least 1.5 mm .
前記マクロカプセルが、少なくとも第１のバリアおよび第２のバリアを含み、前記第１のバリアが、前記第２のバリア内に包含され、
前記第１のバリアが、
（ａ）硫酸セルロースおよびグルコマンナンもしくは硫酸グルコマンナン、または
（ｂ）アルギン酸ナトリウム、を含む、組成物。 A composition comprising a macrocapsule containing at least about 50,000 therapeutic cells for insulin production per cm , wherein the macrocapsule has a cylindrical shape , a length of at least about 11 cm, and a diameter of at least 1.5 mm. Containing, said macrocapsule is attached to one surgical mesh to which at least one other macrocapsule is also attached .
The macrocapsule comprises at least a first barrier and a second barrier, wherein the first barrier is encapsulated within the second barrier.
The first barrier is
(A) Cellulose sulfate and glucomannan or glucomannan sulfate, or
(B) A composition comprising sodium alginate .
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| JP2023198977A JP2024026164A (en) | 2018-03-01 | 2023-11-24 | Macro-capsulated therapeutic cell, device, and method for using the same |
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| US201862637085P | 2018-03-01 | 2018-03-01 | |
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| PCT/US2019/019980 WO2019169089A1 (en) | 2018-03-01 | 2019-02-28 | Macro-encapsulated therapeutic cells, devices, and methods of using the same |
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| US (1) | US11141508B2 (en) |
| EP (1) | EP3758722A1 (en) |
| JP (2) | JP2021515756A (en) |
| KR (1) | KR20200128409A (en) |
| CN (1) | CN112203667A (en) |
| AU (1) | AU2019228529A1 (en) |
| CA (1) | CA3092356A1 (en) |
| IL (1) | IL276979B2 (en) |
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| WO2024081310A1 (en) | 2022-10-11 | 2024-04-18 | Sigilon Therapeutics, Inc. | Engineered cells and implantable elements for treatment of disease |
| WO2024081309A1 (en) | 2022-10-11 | 2024-04-18 | Sigilon Therapeutics, Inc. | Engineered cells and implantable elements for treatment of disease |
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| US4743545A (en) | 1984-08-09 | 1988-05-10 | Torobin Leonard B | Hollow porous microspheres containing biocatalyst |
| US5545423A (en) * | 1991-11-25 | 1996-08-13 | Vivorx, Inc. | Cytoprotective, biocompatible, retrievable macrocapsule containment systems for biologically active materials |
| JPH05154195A (en) * | 1991-12-06 | 1993-06-22 | Sekisui Chem Co Ltd | Hybrid type artificial pancreas |
| US5334640A (en) | 1992-04-08 | 1994-08-02 | Clover Consolidated, Ltd. | Ionically covalently crosslinked and crosslinkable biocompatible encapsulation compositions and methods |
| ES2179839T3 (en) | 1992-11-16 | 2003-02-01 | Univ Brown Res Found | MICROPOROUS MACROCAPSULES. |
| JPH08507747A (en) * | 1992-12-30 | 1996-08-20 | クローバー コンソリデイテッド，リミテッド | Reusable macroencapsulation system that protects biologically active material packets and is biocompatible |
| US20050180957A1 (en) * | 2004-01-16 | 2005-08-18 | Scharp David W. | Method of using fibrin-bound angiogenic factors to stimulate vascularization of transplant site of encapsulated cells |
| DE102005011367B4 (en) * | 2005-03-11 | 2010-12-09 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Process for the preparation of cellulose sulphate with improved properties |
| US20080292690A1 (en) | 2006-04-07 | 2008-11-27 | Technology Center | Multi-membrane immunoisolation system for cellular transplant |
| US20070237749A1 (en) * | 2006-04-07 | 2007-10-11 | Wang Taylor G | Multi-membrane immunoisolation system for cellular transplant |
| WO2010032242A1 (en) | 2008-09-17 | 2010-03-25 | Beta O2 Technologies Ltd. | Optimization of alginate encapsulation of islets for transplantation |
| EP3290061B1 (en) * | 2009-08-28 | 2020-06-10 | Sernova Corporation | Methods and devices for cellular transplantation |
| JP6234485B2 (en) * | 2013-03-07 | 2017-11-22 | ヴィアサイト インコーポレイテッド | 3D large capacity cell encapsulation device assembly |
| US9555007B2 (en) | 2013-03-14 | 2017-01-31 | Massachusetts Institute Of Technology | Multi-layer hydrogel capsules for encapsulation of cells and cell aggregates |
| US10493107B2 (en) * | 2014-06-09 | 2019-12-03 | Cornell University | Implantable therapeutic delivery system and methods thereof |
| US10426735B2 (en) * | 2014-08-01 | 2019-10-01 | Massachusetts Institute Of Technology | Modified alginates for anti-fibrotic materials and applications |
| US9408807B2 (en) | 2015-01-13 | 2016-08-09 | Taylor Gun-Jin Wang | Semi-permeable encapsulation system with tapered conduits for diabetes reversal |
| WO2016187225A1 (en) | 2015-05-17 | 2016-11-24 | Massachusetts Institute Of Technology | Multi-layer hydrogel capsules for encapsulation of cells and cell aggregates |
| CA3058369A1 (en) * | 2017-04-06 | 2018-10-11 | Seraxis, Inc. | Macro-encapsulated therapeutic cells and methods of using the same |
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