DE4002559A1 - Artificial organs, esp. pancreas - comprising interconnected sensor and reactor for secreting biologically active substances - Google Patents
Artificial organs, esp. pancreas - comprising interconnected sensor and reactor for secreting biologically active substancesInfo
- Publication number
- DE4002559A1 DE4002559A1 DE19904002559 DE4002559A DE4002559A1 DE 4002559 A1 DE4002559 A1 DE 4002559A1 DE 19904002559 DE19904002559 DE 19904002559 DE 4002559 A DE4002559 A DE 4002559A DE 4002559 A1 DE4002559 A1 DE 4002559A1
- Authority
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- Germany
- Prior art keywords
- reactor
- sensor
- implanted
- active substances
- biologically active
- 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.)
- Ceased
Links
- 210000000056 organ Anatomy 0.000 title claims abstract description 17
- 239000013543 active substance Substances 0.000 title claims abstract description 14
- 230000003248 secreting effect Effects 0.000 title abstract description 4
- 210000000496 pancreas Anatomy 0.000 title abstract description 3
- 210000003462 vein Anatomy 0.000 claims abstract description 7
- 210000001367 artery Anatomy 0.000 claims abstract description 5
- 229940088597 hormone Drugs 0.000 claims abstract description 4
- 239000005556 hormone Substances 0.000 claims abstract description 4
- 239000000463 material Substances 0.000 claims abstract description 4
- 230000002503 metabolic effect Effects 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 4
- 210000002889 endothelial cell Anatomy 0.000 claims abstract description 3
- 210000005033 mesothelial cell Anatomy 0.000 claims abstract description 3
- 210000004027 cell Anatomy 0.000 claims description 9
- 239000012510 hollow fiber Substances 0.000 claims description 6
- 230000028327 secretion Effects 0.000 claims description 5
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 8
- 239000008103 glucose Substances 0.000 abstract description 8
- 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 abstract description 8
- 102000004877 Insulin Human genes 0.000 abstract description 4
- 108090001061 Insulin Proteins 0.000 abstract description 4
- 229940125396 insulin Drugs 0.000 abstract description 4
- 210000004153 islets of langerhan Anatomy 0.000 abstract description 4
- 230000010412 perfusion Effects 0.000 abstract description 4
- 229920001296 polysiloxane Polymers 0.000 abstract description 2
- 210000005084 renal tissue Anatomy 0.000 abstract description 2
- 239000000835 fiber Substances 0.000 abstract 2
- 239000012528 membrane Substances 0.000 abstract 2
- 238000011067 equilibration Methods 0.000 abstract 1
- 238000009792 diffusion process Methods 0.000 description 4
- 230000002124 endocrine Effects 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000001817 pituitary effect Effects 0.000 description 2
- 241000766026 Coregonus nasus Species 0.000 description 1
- 208000005422 Foreign-Body reaction Diseases 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/022—Artificial gland structures using bioreactors
Landscapes
- Health & Medical Sciences (AREA)
- Transplantation (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
Die Erfindung betrifft ein extrakorporales oder implantierbares und aus semipermeablem Material gestaltetes bio-artifizielles Organ, das zur Sekre tion von biologisch aktiven Substanzen fähig ist. Dieses bio-artifizielle Organ besteht aus einem in die Arterie oder in die Vene implantierten Sensor teil (meistens eine Hohlfaser mit der Beschichtung von Endo- und Mesothelial zellen) und aus einem extrakorporalen oder einem implantierten Reaktorteil (meistens eine oder mehrere Hohlfasern, mit Zellen, die biologisch aktive Sub stanzen sezernieren können), welche so miteinander verbunden sind, daß der Durchfluß von biologischen Signalen und von metabolischen Substanzen möglich ist.The invention relates to an extracorporeal or implantable and semi-permeable material designed bio-artificial organ that is used for secretion tion of biologically active substances. This bio-artificial Organ consists of a sensor implanted in the artery or vein part (mostly a hollow fiber with the coating of endo- and mesothelial cells) and from an extracorporeal or an implanted reactor part (usually one or more hollow fibers, with cells that are biologically active sub can secrete), which are connected so that the Flow of biological signals and of metabolic substances possible is.
Das vorgegebene bio-artifizielle Organ soll vor allem die Funktion der beschä digten endokrinen Organe (z. B. Langerhansche Inseln des endokrinen Teils des Pankreas, Nebenschilddrüse, Hypophyse usw.) ersetzen. Es kann auch in allen Situationen, wo die Sekretion der biologisch aktiven Substanzen nötig ist, angewandt werden.The specified bio-artificial organ is primarily intended to function as a dam endocrine organs (e.g. Langerhan islands of the endocrine part of the Replace pancreas, parathyroid, pituitary, etc.). It can also be used in all Situations where the secretion of the biologically active substances is necessary be applied.
Bisherige Versuche der Bildung der bio-artifizielen Organe, welche biologisch aktive Substanzen sezernieren, waren vor allem zur Konstruktion von semiperme ablen Diffusionskammern begrenzt. Diese Kammern enthielten Zellen, die biolo gisch aktive Substanzen produzierten (Jolley und Mitarb., 1977; Gates und Lazarus, 1977; Theodoru und Howell 1979; Bodziony und Mitarb., 1985; Bodziony und Stanosek, 1985; Kojima und Mitarb., 1987). Previous attempts at the formation of bio-artificial organs, which are biological Secreting active substances were primarily for the construction of semiperme limited diffusion chambers limited. These chambers contained cells that were biolo genetically active substances (Jolley et al., 1977; Gates and Lazarus, 1977; Theodoru and Howell 1979; Bodziony and co-workers, 1985; Bodziony and Stanosek, 1985; Kojima et al., 1987).
Bio-artifizielle Organe, mit Zellen, die biologisch aktive Substanzen sezer nieren und mit der Umgebung nur auf dem Weg der Diffusion kommunizieren, was im Fall der semipermeablen Kammern stattfindet, können leider nicht die auf sie gesetzten Erwartungen erfüllen. Unzureichender Zufluß der Nähr stoffe (Garvey und Mitarb., 1979), die Fremdkörperreaktion (Theodoru und Mitarb., 1980; Bodziony und Stanosek, 1985) und die verlangsamte Übertragung des biologischen Signals (Theodoru und Howell, 1979) sind Hauptursachen für die Einstellung der Hormonsekretion und das Absterben der Zellen.Bio-artificial organs, with cells that secrete biologically active substances kidneys and communicate with the environment only by diffusion, Unfortunately, what happens in the case of semi-permeable chambers cannot meet the expectations placed on them. Inadequate nutrient inflow substances (Garvey and co-workers, 1979), the foreign body reaction (Theodoru and Coworker, 1980; Bodziony and Stanosek, 1985) and the slowed down transmission of the biological signal (Theodoru and Howell, 1979) are the main causes of the cessation of hormone secretion and cell death.
Die Konstruktion eines extrakorporalen oder implantierbaren bio-artifiziellen Organs, das zur Sekretion von biologisch aktiven Substanzen fähig ist. Dieses Organ soll aus einem in die Arterie oder in die Vene implantierten Sensorteil, das schnellen Austausch von biologischen Signalen und von metabolischen Sub stanzen durch die Ultrafiltration ermöglicht und aus einem extrakorporealen oder einem implantierten Reaktorteil mit Zellen, die biologisch aktive Sub stanzen produzieren, bestehen. Beide Teile sollen so verbunden werden, daß die Übertragung von biologischen Signalen und von Nährstoffen weniger als 15 min dauert.The construction of an extracorporeal or implantable bio-artificial Organ capable of secreting biologically active substances. This Organ should consist of a sensor part implanted in the artery or vein, the rapid exchange of biological signals and of metabolic sub punching made possible by ultrafiltration and from an extracorporeal or an implanted reactor part with cells that are biologically active sub produce, pass. Both parts should be connected so that the transmission of biological signals and nutrients less than Takes 15 min.
Diese Aufgabe wird erfindungsmäßig dadurch gelöst, daß das entsprechend der vorherigen Patentanmeldung (Bodziony, 1989) angefertigte Sensorteil mit dem Reaktorteil, wie auf dem Bild 1 und 2 gezeigt, durch die Silikonkapillaren verbunden ist. Der Durchfluß des Perfusionsmedium ist durch die entsprechende Pumpe in dieser Weise erzwungen, daß es zuerst im Sensorteil auf dem Weg der Ultrafiltration und Diffusion zum Austausch von Nährstoffen und von biologi schen Signalen (z. B. Glukose, Ca++) kommt und danach das mit dem Plasma bio chemisch ausgeglichene Medium zum Reaktorteil überpumpt wird. Im Reaktorteil (meistens eine oder mehrere Hohlfasern) sind die allo- oder xenogenen Zellen, die biologisch aktive Substanzen produzieren, in dieser Weise von außen oder von innen angebracht, daß ihre mehrjährige Funktion möglich ist. Die entspre chenden biologisch aktiven Substanzen beeinflussen meistens das Niveau des biologischen Signals (z. B. senkt das Insulin die Konzentration von Glukose, Parathormon erhöht die Konzentration von Ga++, usw.) und schließen nach der Ultrafiltration und Diffusion aus dem Reaktorteil die Rückkopplungsschleife. This object is achieved in terms that the previous according to the patent application (Bodziony, 1989)-built sensor part with the part of the reactor, as shown on the figure 1 and 2, is connected by the Silikonkapillaren. The flow of the perfusion medium is forced by the corresponding pump in such a way that it first comes to the exchange of nutrients and biological signals (e.g. glucose, Ca ++ ) in the sensor part on the way of ultrafiltration and diffusion and then that with the plasma bio-chemically balanced medium is pumped over to the reactor part. In the reactor part (usually one or more hollow fibers), the allo- or xenogenic cells that produce biologically active substances are attached from the outside or from the inside in such a way that their multi-year function is possible. The corresponding biologically active substances mostly influence the level of the biological signal (e.g. insulin lowers the concentration of glucose, parathyroid hormone increases the concentration of Ga ++ , etc.) and closes the feedback loop after ultrafiltration and diffusion from the reactor part .
Das oben beschriebene bio-artifizielle Organ ermöglicht die mit dem positiven und negativen Feedback regulierte Sekretion der biologisch aktiven Substanzen. Das angewandte semipermeable Material ist als sog. biomechanische Barriere benutzt (Bodziony und Mitarb., 1985), was die Verwendung von allo- und xeno genen Zellen möglich macht. Der Gegenstand der Erfindung ist durch die Her stellung des bio-artifiziellen Organs mit allo- oder xenogenen Zellen, die biologisch aktive Substanzen produzieren, gewerblich anwendbar. Dieses bioartifizielle Organ kann die Funktion der beschädigten endokrinen Organe (z. B. Langerhanssche Inseln, Nebenschilddrüse, Hypophyse) ersetzen.The bio-artificial organ described above enables those with the positive and negative feedback regulated secretion of the biologically active substances. The semi-permeable material used is a so-called biomechanical barrier used (Bodziony and Mitarb., 1985), what the use of allo- and xeno gene cells possible. The object of the invention is through the Her Position of the bio-artificial organ with allo- or xenogenic cells that Produce biologically active substances, industrially applicable. This bioartificial organ can damage the function of damaged endocrine organs (e.g. Langerhans Islands, parathyroid gland, pituitary).
Abb. 1 und 2 zeigen in einer experimentellen (Abb. 1) und in einer klinischen Situation das implantierbare bio-artifizielle Organ. Ein in die Vene implan tiertes Sensorteil (A - Hohlfaser mit der Beschichtung von Zellen, die mehr jährige Implantation in Arterien und Venen ermöglichen) ist durch Silikon kapillaren (C) mit einem in das Nierengewebe implantierten Reaktorteil (B) verbunden. Dieses Reaktorteil enthält allogene Langerhanssche Inseln, die Insulin, Glukagon und Somatostatin, wichtigste Hormone des Kohlenhydratstoff wechsels sezernieren. Das Perfusionsmedium wird durch die Pumpe (D) in Bewegung gesetzt und zuerst wird das Sensorteil perfundiert, wo die biochemische Aus gleichung mit dem Plasma stattfindet. Danach werden die isolierten Langerhan sschen Inseln im Reaktorteil (B) perfundiert. Diese Inseln antworten auf die Erhöhung der Konzentration der Glukose im Perfusionsmedium mit der entspre chenden Insulinfreisetzung, die so lange dauert, bis die Glukosekonzentration wieder gesunken ist. Die Antwort auf eine intravenöse Glukosebelastung dauert weniger als 10 min, was die präzise Regulierung der Glukose- und Insulinkon zentration ermöglicht. Fig. 1 and 2 show the implantable bio-artificial organ in an experimental ( Fig. 1) and in a clinical situation. A sensor part implanted in the vein (A - hollow fiber with the coating of cells that allow years of implantation in arteries and veins) is connected by silicone capillaries (C) to a reactor part (B) implanted in the kidney tissue. This part of the reactor contains allogeneic Langerhans islands, which secrete insulin, glucagon and somatostatin, the most important hormones of the carbohydrate metabolism. The perfusion medium is set in motion by the pump (D) and first the sensor part is perfused, where the biochemical equation with the plasma takes place. The isolated Langerhan islands in the reactor part (B) are then perfused. These islands respond to the increase in the concentration of glucose in the perfusion medium with the corresponding insulin release, which lasts until the glucose concentration has decreased again. The response to an intravenous glucose load takes less than 10 minutes, which enables precise regulation of the glucose and insulin concentration.
- 1. Bodziony J., Gasior U., Stanosek J.: Funktionsbeurteilung isolierter Langerhansscher Inseln in semipermeablen Kammern. Z. exp. Chir. Transplant. künstl. Organe, 1985, 18/4, 204-214.1. Bodziony J., Gasior U., Stanosek J .: Functional evaluation of isolated Langerhans Islands in semi-permeable chambers. Z. exp. Chir. Transplant. artificial Organs, 1985, 18/4, 204-214.
- 2. Bodziony J., Stanosek J.: Die Behandlung des Diabetes durch Implantationen von isolierten Langerhansschen Inseln in semipermeablen Kammern. Z. exp. Chir. Transplant. künstl. Organe, 1985, 18/4, 215-223.2. Bodziony J., Stanosek J .: Treatment of diabetes by implantation of isolated Langerhans islands in semi-permeable chambers. Z. exp. Chir. Transplant. artificial Organs, 1985, 18/4, 215-223.
- 3. Bodziony J.: Hohlfaser mit der Beschichtung von Zellen, die mehrjährige Implantation in Arterien und Venen ermöglichen. Deutsches Patentamt, Patent anmeldung Nr. P 39 41 873.1.3. Bodziony J .: hollow fiber with the coating of cells, the perennial Allow implantation in arteries and veins. German Patent Office, patent application no.P 39 41 873.1.
- 4. Gates R.J., Lazarus N.R.: Reversal of streptozotocin-induced diabetes in rats by intraperitoneal implantation of encapsulated neonatal rabbit pan creatic tissue. Lancet, 1977, 17, 1257-1259.4. Gates R.J., Lazarus N.R .: Reversal of streptozotocin-induced diabetes in rats by intraperitoneal implantation of encapsulated neonatal rabbit pan creative tissue. Lancet, 1977, 17, 1257-1259.
- 5. Garvey J.F.W., Morris P.J., Finch D.R.A., Millard P.R., Poole M.: Experi mental pancreas transplantation. Lancet, 1979, 971-972.5. Garvey J.F.W., Morris P.J., Finch D.R.A., Millard P.R., Poole M .: Experi mental pancreas transplantation. Lancet, 1979, 971-972.
- 6. Jolley W.B., Hinshaw D.B., Call T.W., Alrord L.S.: Xenogeneic pancreatic islet transplantation in proteolytic enzyme-bounded diffusion chambers in diabetic rats. Transplantation Proceedings, 1979, 9/1, 363-365.6. Jolley W.B., Hinshaw D.B., Call T.W., Alrord L.S .: Xenogeneic pancreatic islet transplantation in proteolytic enzyme-bounded diffusion chambers in diabetic rats. Transplantation Proceedings, 1979, 9/1, 363-365.
- 7. Kojima Y., Fukushima W., Note M., Kinoshita H., Nahagawara G.: Xenogeneic pancreatic islet transplantation using a millipore diffusion chamber. Trans plantation Proceedings, 1987, 19/1, 981-983.7. Kojima Y., Fukushima W., Note M., Kinoshita H., Nahagawara G .: Xenogeneic pancreatic islet transplantation using a millipore diffusion chamber. Trans plantation proceedings, 1987, 19/1, 981-983.
- 8. Theodoru N.A., Howell S.L.: An assesment of diffusion chambers for use in pancreatic islet cell transplantation. Transplantation, 1979, 27/5, 350- 352.8. Theodoru N.A., Howell S.L .: An assesment of diffusion chambers for use in pancreatic islet cell transplantation. Transplantation, 1979, 27/5, 350- 352.
- 9. Theodoru N.A., Vrbova H., Tyhurst M., Howell S.L.: Problems in the use of polycarbonate diffusion chambers for syngeneic pancreatic islet transplan tations in rats. Diabetologia, 1980, 18, 313-317.9. Theodoru N.A., Vrbova H., Tyhurst M., Howell S.L .: Problems in the use of polycarbonate diffusion chambers for syngeneic pancreatic islet transplan tations in rats. Diabetologia, 1980, 18, 313-317.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19904002559 DE4002559A1 (en) | 1990-01-18 | 1990-01-30 | Artificial organs, esp. pancreas - comprising interconnected sensor and reactor for secreting biologically active substances |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19904001319 DE4001319A1 (en) | 1990-01-18 | 1990-01-18 | Implantable substitute endocrine gland with sensor and reactor - sections formed of cell-bearing fibres transferring signals and secreted prod. |
| DE19904002559 DE4002559A1 (en) | 1990-01-18 | 1990-01-30 | Artificial organs, esp. pancreas - comprising interconnected sensor and reactor for secreting biologically active substances |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE4002559A1 true DE4002559A1 (en) | 1991-10-02 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19904002559 Ceased DE4002559A1 (en) | 1990-01-18 | 1990-01-30 | Artificial organs, esp. pancreas - comprising interconnected sensor and reactor for secreting biologically active substances |
Country Status (1)
| Country | Link |
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| DE (1) | DE4002559A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4123629A1 (en) * | 1990-08-06 | 1992-02-20 | Jakob Dr Bodziony | Implantable semi-permeable bio-artificial organ - allowing biological signal and metabolic substance flow by pressure gradient |
| FR2955179A1 (en) * | 2010-01-13 | 2011-07-15 | Univ Bordeaux 1 | SENSOR FOR MEASURING INSULIN NEEDS OF A PATIENT AND METHOD FOR MANUFACTURING THE SAME |
| EP1689321B1 (en) * | 2003-11-07 | 2017-01-04 | The University of Connecticut | Artificial tissue systems and uses thereof |
Citations (5)
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|---|---|---|---|---|
| DE3422639C2 (en) * | 1984-06-19 | 1986-07-10 | Gebrüder Sulzer AG, Winterthur | Glandular prosthesis |
| GB2185408A (en) * | 1986-01-16 | 1987-07-22 | Rhode Island Hospital | Neovascularization |
| EP0259536A2 (en) * | 1986-09-11 | 1988-03-16 | BAXTER INTERNATIONAL INC. (a Delaware corporation) | Biological implant with textured surface |
| EP0286284A1 (en) * | 1987-03-30 | 1988-10-12 | Brown University Research Foundation | Semipermeable nerve guidance channels |
| WO1989007425A2 (en) * | 1988-02-17 | 1989-08-24 | Genethics Limited | Clinical developments using amniotic cells |
-
1990
- 1990-01-30 DE DE19904002559 patent/DE4002559A1/en not_active Ceased
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|---|---|---|---|---|
| DE3422639C2 (en) * | 1984-06-19 | 1986-07-10 | Gebrüder Sulzer AG, Winterthur | Glandular prosthesis |
| GB2185408A (en) * | 1986-01-16 | 1987-07-22 | Rhode Island Hospital | Neovascularization |
| DE3701148C2 (en) * | 1986-01-16 | 1989-08-31 | Rhode Island Hospital, Providence, R.I., Us | |
| EP0259536A2 (en) * | 1986-09-11 | 1988-03-16 | BAXTER INTERNATIONAL INC. (a Delaware corporation) | Biological implant with textured surface |
| EP0286284A1 (en) * | 1987-03-30 | 1988-10-12 | Brown University Research Foundation | Semipermeable nerve guidance channels |
| WO1989007425A2 (en) * | 1988-02-17 | 1989-08-24 | Genethics Limited | Clinical developments using amniotic cells |
| EP0333328A2 (en) * | 1988-02-17 | 1989-09-20 | Genethics Limited | Clinical developments using amniotic cells |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4123629A1 (en) * | 1990-08-06 | 1992-02-20 | Jakob Dr Bodziony | Implantable semi-permeable bio-artificial organ - allowing biological signal and metabolic substance flow by pressure gradient |
| EP1689321B1 (en) * | 2003-11-07 | 2017-01-04 | The University of Connecticut | Artificial tissue systems and uses thereof |
| FR2955179A1 (en) * | 2010-01-13 | 2011-07-15 | Univ Bordeaux 1 | SENSOR FOR MEASURING INSULIN NEEDS OF A PATIENT AND METHOD FOR MANUFACTURING THE SAME |
| WO2011086105A1 (en) * | 2010-01-13 | 2011-07-21 | Universite De Bordeaux 1 | Sensor for measuring the activity of beta-pancreatic cells or of islets of langerhans, manufacture and use of such a sensor |
| AU2011206641B2 (en) * | 2010-01-13 | 2016-06-09 | Centre National De La Recherche Scientifique | Sensor for measuring the activity of beta-pancreatic cells or of islets of Langerhans, manufacture and use of such a sensor |
| AU2011206641A8 (en) * | 2010-01-13 | 2016-07-07 | Centre National De La Recherche Scientifique | Sensor for measuring the activity of beta-pancreatic cells or of islets of Langerhans, manufacture and use of such a sensor |
| US9962113B2 (en) | 2010-01-13 | 2018-05-08 | Universite De Bordeaux 1 | Sensor for measuring the activity of beta-pancreatic cells or of islets of langerhans, manufacture and use of such a sensor |
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