WO1997046274A1 - Implantable drug pump - Google Patents

Implantable drug pump Download PDF

Info

Publication number
WO1997046274A1
WO1997046274A1 PCT/DE1997/000986 DE9700986W WO9746274A1 WO 1997046274 A1 WO1997046274 A1 WO 1997046274A1 DE 9700986 W DE9700986 W DE 9700986W WO 9746274 A1 WO9746274 A1 WO 9746274A1
Authority
WO
WIPO (PCT)
Prior art keywords
pump
insulin
pump according
medication
glucose
Prior art date
Application number
PCT/DE1997/000986
Other languages
German (de)
French (fr)
Inventor
Siegfried Kallert
Erhard Weidlich
Brigitte Stroetmann
Original Assignee
Siemens Aktiengesellschaft
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Siemens Aktiengesellschaft filed Critical Siemens Aktiengesellschaft
Publication of WO1997046274A1 publication Critical patent/WO1997046274A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/14244—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14276—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body specially adapted for implantation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A61M5/1723—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure

Definitions

  • the invention relates to an implantable medication pump, for example an insulin pump, in which a continuous insulin fusion over the course of the day is adapted to the fluctuating glucose oil load in such a way that a constant glucose concentration in the blood is ensured within the scope of the physiological spread.
  • the hitherto known plans for the use of glucose concentration-dependent insulin pumps are all based on the establishment of a technical control loop in which the current glucose concentration in the blood (or also in the liquid space of the organism dependent on it) is measured with the aid of technical sensors, and Given the dependence of these measured values, if they deviate from the target value, the insulin pump is influenced in such a way that the glucose concentration value is returned to the target value.
  • An implantable glucose sensor is known, for example, from US Pat. No. 5,101,814. It comprises living cells which react to different glucose concentrations with a different electrical activity. The electrical activity is transmitted wirelessly out of the body and measured, for example, by electrodes or optically recognized by electrochromic dyes.
  • insulin is already released when the food is presented intensely, when seeing, smelling and especially when tasting food and when chyme is in the intestine, ie not only after absorption and appearance in the blood , as in the known technical controls for insulin release.
  • the object of the present invention is therefore to provide a medicament pump and in particular an insulin pump which, similar to nature, does so before the measurable change in the concentration of a substance
  • the body's intact reflex arches ie physiological receptors
  • the body's own glucose receptors can be used as sensors.
  • the implantable medication pump becomes similar to the natural one
  • Insulin release by the ß-cells in the healthy organism deliver the medication (e.g. insulin) to the body in the correct amount even before changing a relevant substance concentration (e.g. the glucose concentration).
  • the medication e.g. insulin
  • a relevant substance concentration e.g. the glucose concentration
  • the invention is based on the fact that, for example, in many cases of diabetes the disease is due to a defect in the ⁇ -cells producing the insulin, the reflex bow of the organism for activating these cells being still intact in most cases.
  • the medicament pump according to the invention uses this reflex arc, is controlled by the body's own control circuit (for example the insulin delivery system) and thus provides an optimal physiological medication supply. It therefore not only uses the natural receptors, but also the entire downstream neuronal system Processing apparatus, both of which are already possible other disturbance variables acting on the substance concentration anticipatory a l s also taken into account in a measuring manner, even including learning processes.
  • G Egens t he at dd invention is an implantable drug- pump for patients with intact reflex arc but defective O rganen the en d okrinen hydrogen generation, so to Eigensub- stanzabge b ung, wherein the control of the discharge amount, duration time of said un d drug pump to the excitations of the vegetati ⁇ ven N ervenfasern of the reflex arc between the endogenous S sensors an d the defective organs is coupled.
  • the coupling takes-acres vegetative nerve fibers un the drug pump via electrodes d instead. It is pra kt severally, when the surface of the electrode in the way b lic k au fd ie h o h e electrical capacitance they have Müs ⁇ sen to register all action potentials femporos ges t a e lt t. T he fempor ⁇ e surface may additionally be aomother from a turned b ever discourseen material. In these ab eckung d drugs can be incorporated, which are then targeted courts t and be precisely metered to the nerve fiber and given the body.
  • the efferent fibers between the central nervous system and the ⁇ cells of the pancreas are particularly suitable as vegetative nerve fibers in the sense of the present invention. However, it may be sufficient to use the excitations of an easily accessible vegetative nerve and to use the organism's ability to learn. This possible configuration is part of the invention.
  • the action potentials of the nerve fiber are understood as excitation in the sense of this invention.
  • the coupling of the medication pump to the nerve fiber by means of an electrode is preferably carried out with metal (e.g. platinum iridium) or carbon, the finely porous surface being made, for example, of black or platinum sponge, titanium nitride, titanium carbide or activated carbon. Fabric can exist.
  • the tissue-compatible material that is used to cover the electrode surface should be ion-conductive in order to be able to pass on the action potentials or excitations of the nerve fiber. Therefore, oiocompatible, ion-conducting membranes, such as Mafion, are suitable.
  • the invention should not be restricted by the material of the electrode cover, however, since it is conceivable to produce covers of such a small thickness that the ion conductivity of the material no longer plays a role.
  • Medicines in particular include those that facilitate the healing phase of the electrode on the nerve fiber, such as antibiotics or corticoids.
  • the single figure shows a basic circuit diagram of an insulin pump according to the invention.
  • nerve 1 comes from the central nervous system.
  • the action potentials of such efferent nerve fibers are based on the excitations of the afferent nerve fibers from the various glucose receptors of the body and their neuronal processing in the central nervous system.
  • Nerve 1 is encompassed by electrode 2.
  • a differential amplifier 3 is connected to the electrode, which amplifies the incoming Emzel action potentials (AP) and leads them to the integrator 5.
  • the mean value of the temporal density of action potentials is determined in the integrator 5.
  • U f (number of AP / unit of time)
  • the insulin pump 6 becomes thereby activated to emit a certain Insuim current, which in turn is directly proportional to the span previously reached the Insulp pump
  • the insulin current strength which is released by the insulin pump according to the invention, is controlled directly by the excitation of the nerve 1.
  • the insulin supply according to the invention takes place before the glucose reaches the blood via the intestinal absorption. In the case of glucose absorption, there is then a substantially smaller increase in the blood glucose concentration.
  • the device according to the invention is characterized in that the intact parts of the physiological functional circuit of the patient to be treated control the device. This allows the development of technical glucose sensors and their implants tation be waived.
  • the blood sugar control becomes physiological, which means that the controlled variable (here the blood sugar concentration) does not have to deviate from the target value in order to initiate counter-regulatory measures (insulin release), but that even before the controlled variable deviates from the target value , counteracting the expected deviation, action is started.
  • the device according to the invention After the device according to the invention is used, for example, in diabetics with an intact reflex arch but defective ⁇ -cells, it can serve as a replacement for the pancreas and other organ implants.
  • the multiple problems of transplantation which e.g. connected with the immune system
  • the device according to the invention can be used for mass application and thus, unlike pancreatic transplantations, also for the therapy of a large number of diabetic or sick people with a defective organ that releases endocrine substances.

Abstract

The invention relates to an implantable drug pump which uses the reflex arc which is still intact in many patients (for example diabetics) between the endogenous receptors and the cells, producing the material to be secreted, for controlling drug release. Consequently, practically physiological drug release is achieved thereby controlling the feared late symptoms, for example diabetes, in a particularly effective manner.

Description

Beschreibungdescription
Implantierbare MedikamentpumpeImplantable medication pump
Die Erfindung betrifft eine implantierbare Medikamentpumpe, beispielsweise eine Insulmpumpe, bei der eine kontinuierli¬ che Insulmmfusion über den Tagesablauf jeweils der schwan¬ kenden Glukoseoelastung derart angepaßt wird, daß eine im Rahmen physiologischer Streubreite konstante Glukosekonzen- tration im Blut gewährleistet ist.The invention relates to an implantable medication pump, for example an insulin pump, in which a continuous insulin fusion over the course of the day is adapted to the fluctuating glucose oil load in such a way that a constant glucose concentration in the blood is ensured within the scope of the physiological spread.
Die bisher bekannten Plane für den Einsatz von glukosekonzen- trationsabhangigen Insulinpumpen basieren alle auf dem Aufbau eines tecnmscnen Regelkreises, bei dem die aktuelle Glukose- konzentration im Blut (oder auch m davon abhangigen Flussig- keitsraumen des Organismus) mit Hilfe technischer Sensoren gemessen wird, und bei dem m Abhängigkeit dieser Meßwerte, falls sie vom Sollwert abweichen, die Insulmpumpe so beein¬ flußt wird, daß der Glukosekonzentrationswert auf den Soll- wert zurückgeführt wird.The hitherto known plans for the use of glucose concentration-dependent insulin pumps are all based on the establishment of a technical control loop in which the current glucose concentration in the blood (or also in the liquid space of the organism dependent on it) is measured with the aid of technical sensors, and Given the dependence of these measured values, if they deviate from the target value, the insulin pump is influenced in such a way that the glucose concentration value is returned to the target value.
Diesen bisher Dekannten Losungen haften folgende Mangel anThese previous solutions have the following shortcomings
- Es gibt keine, hinreichend lange funktionstüchtigen und lm- plantierbaren technischen Sensoren für die Messung αer Glu¬ kosekonzentration im Blut undThere are no sufficiently long, functional and implantable technical sensors for measuring the blood glucose concentration and
- Insulin wird erst nach erfolgter Abweichung der Glukosekon- zentration im Blut freigesetzt- Insulin is only released after the glucose concentration in the blood has deviated
Dabei weicht diese technische Steuerung der Insulinabgane in¬ sofern von der physiologischen Steuerung ab, als sie keinen antizipatorischen Steuerungsanteil hat, d.h. keine Steuerung, bei der es nicht erst zu einer wesentlicnen Änderung der Sollgroße kommt Ein implantierbarer Glukosesensor ist beispielsweise aus der US-5 101 814 bekannt. Er umfaßt lebende Zellen, die auf un¬ terschiedliche Glukosekonzentrationen mit einer unterschied¬ lichen elektrische Aktivität reagieren. Die elektrische Akti- vität wird drahtlos aus dem Körper heraus übermittelt und zum Beispiel durch Elektroden gemessen oder optisch durch elek- trochrome Farbstoffe erkannt.This technical control of the insulin waste deviates from the physiological control insofar as it has no anticipatory control component, ie no control in which there is no significant change in the target size An implantable glucose sensor is known, for example, from US Pat. No. 5,101,814. It comprises living cells which react to different glucose concentrations with a different electrical activity. The electrical activity is transmitted wirelessly out of the body and measured, for example, by electrodes or optically recognized by electrochromic dyes.
Komplette geschlossene Regelsysteme zur glukosekonzentrati- onsabhängigen Insulindosierung werden zum Beispiel in derComplete closed control systems for glucose concentration-dependent insulin dosing are, for example, in the
US-5 474 552 oder in der WO/28878 vorgeschlagen, wobei Insu¬ linpumpen oder andere Dosiervorrichtungen in Abhängigkeit von der durch einen Glukosesensor gemessenen Glukosekonzentration für eine entsprechende Insulindosierung sorgen.No. 5,474,552 or proposed in WO / 28878, insulin pumps or other metering devices providing a corresponding insulin metering depending on the glucose concentration measured by a glucose sensor.
Solche Systeme werden auch für die kontinuierliche Dosierung anderer Medikamente vorgeschlagen.Such systems are also proposed for the continuous dosing of other drugs.
Bei der physiologischen Steuerung des intakten Organismus kommt es schon zur Insulinausschüttung bei intensiver Vor¬ stellung von Speisen, beim Sehen, Riechen und vor allem beim Schmecken von Speisen und beim Aufenthalt von Speisebrei im Darm, also nicht erst nach der Resorption und dem Erscheinen im Blut, wie nach den bekannten technischen Steuerungen zur Insulinfreigabe.In the physiological control of the intact organism, insulin is already released when the food is presented intensely, when seeing, smelling and especially when tasting food and when chyme is in the intestine, ie not only after absorption and appearance in the blood , as in the known technical controls for insulin release.
Aufgabe der vorliegenden Erfindung ist es daher, eine Medika¬ mentpumpe und insbesondere eine Insulinpumpe zur Verfügung zu stellen, die, ähnlich wie die Natur es macht, bereits vor der meßbaren Veränderung der Konzentration eines StoffesThe object of the present invention is therefore to provide a medicament pump and in particular an insulin pump which, similar to nature, does so before the measurable change in the concentration of a substance
(insbesondere von Insulin) im Blut ein Medikament zur Ein¬ stellung dieser Konzentration abgibt. Zudem ist es Aufgabe der vorliegenden Erfindung einen stabilen Ersatz für die be¬ kannten technischen Glukoεesensoren zu finden.(in particular insulin) releases a drug in the blood to adjust this concentration. It is also an object of the present invention to find a stable replacement for the known technical glucose sensors.
Allgemeine Erkenntnis der Erfindung ist: 1. An Stelle der bisher vorgesehenen technischen Sensoren für einen Stoff können die körpereigenen intakten Reflexbogen, also physiologischen Rezeptoren weiterhin benutzt werden, um die Dosierung eines Medikaments zu steuern. Zum Beispiel kon- nen m solchen Fällen, bei denen der Diabetes durch Ausfall von ß-Zellen bedingt ist, die körpereigenen Glukoserezeptoren als Sensoren genutzt werden.General knowledge of the invention is: 1st In place of the technical sensors previously provided for a substance, the body's intact reflex arches, ie physiological receptors, can continue to be used to control the dosage of a drug. For example, in cases where diabetes is caused by the failure of ß cells, the body's own glucose receptors can be used as sensors.
2. Bei Verwendung dieser körpereigenen Sensoren wird die ltn- plantierbare Medikamentpumpe -ähnlich wie bei der naturlichen2. When these body sensors are used, the implantable medication pump becomes similar to the natural one
Insulinfreisetzung durch die ß-Zellen im gesunden Organismus- das Medikament (z.B. Insulin) schon vor der Veränderung einer relevanten Stoffkonzentration (z.B der Glukosekonzencration) in richtiger Menge an den Korper abgeben.Insulin release by the ß-cells in the healthy organism - deliver the medication (e.g. insulin) to the body in the correct amount even before changing a relevant substance concentration (e.g. the glucose concentration).
Damit ist es möglich, ein defektes Organ zur Eigensubstanzab- gebung, zum Beispiel die Pankreas durch die erfindungsgemaße Medikamentpumpe zu ersetzen und dabei den naturlichen Regel¬ kreis über die körpereigenen Sensoren beizubehalten. So ist es zum Beispiel möglich, die Glukosekonzentration des Blutes so zu regeln, daß sie den normalen physiologischen Verhalt¬ nissen besonders gut entspricht, so daß auch eine besonders wirksame Eindämmung der so gefurchteten Spatschaden zu erwar¬It is thus possible to replace a defective organ for self-delivery, for example the pancreas, with the medicament pump according to the invention and to maintain the natural control loop via the body's own sensors. For example, it is possible to regulate the blood glucose concentration in such a way that it corresponds particularly well to the normal physiological conditions, so that particularly effective containment of the dreaded spar damage can be expected
Die Erfindung knüpft an der Tatsache an, daß zum Beispiel bei vielen Fallen von Diabetes die Krankheit auf einen Defekt der das Insulin produzierenden ß-Zellen zurückzuführen ist, wobei der Reflexbogen des Organismus zur Aktivierung dieser Zellen m den meisten Fallen noch intakt ist. Die erfindungsgemaße Medikamentpumpe bedient sich dieses Reflexbogens, wird vom körpereigenen Regelkreis (z.B dem Insulmabgabe-System) ge¬ steuert und erbringt so eine optimale physiologische Medika- mentversorgung Sie nutzt also nicht nur die naturlichen Re- zeptoren, sondern zusä tzli ch den gesamten nachgeεchalteten neuronalen Verarbeitungsapparat, der auch schon mögliche an¬ dere auf die Stoffkonzentration einwirkende Störgrößen sowohl antizipatorisch als auch messend berücksichtigt, ja sogar Lernprozesse einschließt.The invention is based on the fact that, for example, in many cases of diabetes the disease is due to a defect in the β-cells producing the insulin, the reflex bow of the organism for activating these cells being still intact in most cases. The medicament pump according to the invention uses this reflex arc, is controlled by the body's own control circuit (for example the insulin delivery system) and thus provides an optimal physiological medication supply. It therefore not only uses the natural receptors, but also the entire downstream neuronal system Processing apparatus, both of which are already possible other disturbance variables acting on the substance concentration anticipatory a l s also taken into account in a measuring manner, even including learning processes.
Gegenstand der Erfindung ist eine implantierbare Medikament- pumpe für Patienten mit intaktem Reflexbogen aber defekten Organen zur endokrinen Stofferzeugung, also zur Eigensub- stanzabgebung, bei der die Steuerung der Abgabemenge, -dauer und -zeit der Medikamentpumpe an die Erregungen der vegetati¬ ven Nervenfasern des Reflexbogens zwischen den körpereigenen Sensoren und den defekten Organen gekoppelt ist. G Egens t he at dd invention is an implantable drug- pump for patients with intact reflex arc but defective O rganen the en d okrinen hydrogen generation, so to Eigensub- stanzabge b ung, wherein the control of the discharge amount, duration time of said un d drug pump to the excitations of the vegetati¬ ven N ervenfasern of the reflex arc between the endogenous S sensors an d the defective organs is coupled.
In der Regel findet die Kopplung zwiscnen den vegetativen Nervenfasern und der Medikamentpumpe über Elektroden statt. Es ist praktisch, wenn die Oberfläche der Elektroden im Hin- blick auf die hohe elektrische Kapazität, die sie haben müs¬ sen, um alle Aktionspotentiale zu registrieren, femporos gestaltet ist. Die femporόεe Oberflache kann zusätzlich von einem gewebeverträglichen Material aogedeckt sein. In diese Abdeckung können Medikamente eingelagert sein, die dann ziel- gerichtet und fein dosiert an die Nervenfaser und den Körper abgegeben werden.In general, the coupling takes-acres vegetative nerve fibers un the drug pump via electrodes d instead. It is pra kt severally, when the surface of the electrode in the way b lic k au fd ie h o h e electrical capacitance they have Müs ¬ sen to register all action potentials femporos ges t a e lt t. T he femporόεe surface may additionally be aogedeckt from a turned b everträglichen material. In these ab eckung d drugs can be incorporated, which are then targeted courts t and be precisely metered to the nerve fiber and given the body.
Im Sinne dieser Erfindung wird als Reflexoogen zwischen den körpereigenen intakten Sensoren und den defekten Organen der endokrinen Stofferzeugung der Reflexoogen bezeichnet, der I m S held T his invention is referred to as Reflexoogen between the kö rpereigenen intact sensors and the defective organs of s d o k rinen St o ff generation of Reflexoogen, the
1. die physiologischen Rezeptoren in Mund (z.B. Glukoserezep- toren) und Dünndarm, aber auch in Leber und Gehirn und 1st the p h en h ysiologisc receptors in the mouth (eg Glukoserezep- t Oren) an d the small intestine, but also in the liver and brain and
2. die dazugehörigen afferenten Nervenfasern von den Rezepto¬ ren zum Zentralnervensystem und zum Gehirn, 3. die neuronale Verarbeitung im Gehirn, im Zentralnervensy¬ stem und in den vegetativen Ganglien sowie 2nd T he d azugehörigen afferent nerve fibers from the Rezepto ¬ ren to Z s t ra l nervous system and brain; 3. the neural processing in the brain, in Zentralnervensy ¬ s t em an d in the autonomic ganglia and
4. die effεrenten Nervenfasern zu den endokrin produzierenden Zellen im (defekten) Organ umfaßt. 4th d ie effεrenten nerve fibers to the endocrine producing Z e l s in the (defective) member comprises.
Unter ß-Zellen im Sinne der vorliegenden Erfindung bezie¬ hungsweise einer bevorzugten Ausführung der Erfindung werden die ß-Zellen des Pankreas verstanden, die das körpereigene Insulin produzieren und ausschütten.Under ß-Ze l len in the sense of the present invention rela ¬ h ungsweise a preferred embodiment of the invention are Understand the pancreatic beta cells that produce and release the body's insulin.
Als vegetative Nervenfasern im Sinne der vorliegenden Erfin- düng eignen sich insbesondere die efferenten Fasern zwischen dem Zentralnervensystem und den ß-Zellen des Pankreas. Even¬ tuell genügt es aber, die Erregungen eines leichter zugängli¬ chen vegetativen Nervs zu verwenden und die Lernfähigkeit des Organismus zu nutzen. Diese mögliche Ausgestaltung ist Be- standteil der Erfindung.The efferent fibers between the central nervous system and the β cells of the pancreas are particularly suitable as vegetative nerve fibers in the sense of the present invention. However, it may be sufficient to use the excitations of an easily accessible vegetative nerve and to use the organism's ability to learn. This possible configuration is part of the invention.
Als Erregung im Sinne dieser Erfindung werden die Aktionspo- tentiale der Nervenfaser verstanden.The action potentials of the nerve fiber are understood as excitation in the sense of this invention.
Die Ankopplung der Medikamentpumpe an die Nervenfaser mit¬ tels einer Elektrode erfolgt bevorzugt mit Metall (z. B. Pla¬ tin-Iridium) oder Kohlenstoff, wobei die feinporös gestaltete Oberfläche beispielsweise aus Plantmschwarz oder Platin¬ schwamm, Titannitrid, Titankarbid oder aktiviertem Kohlen- Stoff bestehen kann. Das gewebeverträgliche Material, das zur Abdeckung der Elektrodenoberfläche eingesetzt wird, sollte lonenleitend sein, um die Aktionspotentiale oder Erregungen der Nervenfaser weitergeben zu können. Deshalb sind dafür oiokompatible, lonenleitende Membranen, wie beispielsweise Mafion, geeignet Die Erfindung soll aber durch das Material der Elektrodenabdeckung nicht eingeschränkt werden, da es denkbar ist, Abdeckungen so geringer Dicke herzustellen, daß die Ionenleitfahigkeit des Materials keine Rolle mehr spielt.The coupling of the medication pump to the nerve fiber by means of an electrode is preferably carried out with metal (e.g. platinum iridium) or carbon, the finely porous surface being made, for example, of black or platinum sponge, titanium nitride, titanium carbide or activated carbon. Fabric can exist. The tissue-compatible material that is used to cover the electrode surface should be ion-conductive in order to be able to pass on the action potentials or excitations of the nerve fiber. Therefore, oiocompatible, ion-conducting membranes, such as Mafion, are suitable. The invention should not be restricted by the material of the electrode cover, however, since it is conceivable to produce covers of such a small thickness that the ion conductivity of the material no longer plays a role.
Als Medikamente werden insbesondere solche eingelagert, die die Einheilungsphase der Elektrode an der Nervenfaser er¬ leichtern, wie beispielsweise Antibiotika oder Corticoide.Medicines in particular include those that facilitate the healing phase of the electrode on the nerve fiber, such as antibiotics or corticoids.
Die vorstehenden Definitionen beziehen sich sowohl auf die Beschreibung als auch auf die Patentansprüche und die Erläu¬ terungen zu der Figur . Im folgenden soll die Erfindung nun anhand eines Beispiels dargestellt werden: Die einzige Figur zeigt ein Prinzipschaltbild einer erfin¬ dungsgemäßen Insulmpumpe. Ganz links im Bild ist der Nerv 1 zu sehen, der vom Zentralnervensystem kommt. Auf den Erregun- gen der afferenten Nervenfasern von den verschiedenen Gluko¬ serezeptoren des Körpers und deren neuronale Verarbeitung im Zentralnervensystem beruhen die Aktionspotentiale solcher ef- ferenten Nervenfasern. Nerv 1 wird von der Elektrode 2 um¬ faßt. An die Elektrode schließt sich ein Differenzverstärker 3 an, der die eintreffenden Emzel-Aktionspotentiale (AP) verstärkt und zum Integrator 5 leitet .The above definitions relate both to the description and to the claims and the explanations for the figure. In the following, the invention will now be illustrated using an example: The single figure shows a basic circuit diagram of an insulin pump according to the invention. On the far left of the picture is nerve 1, which comes from the central nervous system. The action potentials of such efferent nerve fibers are based on the excitations of the afferent nerve fibers from the various glucose receptors of the body and their neuronal processing in the central nervous system. Nerve 1 is encompassed by electrode 2. A differential amplifier 3 is connected to the electrode, which amplifies the incoming Emzel action potentials (AP) and leads them to the integrator 5.
Im Integrator 5 wird der Mittelwert der zeitlichen Dichte von Aktionspotentialen festgestellt. Die Leitung vom Integrator 5 zur eigentlichen Insulinpumpe 6 übertragt dann die Anzahl der Aktionspotentiale pro Zeiteinheit (oder die resultierende Spannung U) als Funktion der Anzahl der Aktionspotentiale pro Zeiteinheit ( U= f (Anzahl AP/Zeitemheit) zur Insulinpumpe 6. Die Insulmpumpe 6 wird dadurch zu einer Abgabe einer be- stimmten Insuim-Stromstärke aktiviert, die ihrerseits direkt proportional zu der vorher zur Insulmpumpe gelangten Span¬
Figure imgf000008_0001
The mean value of the temporal density of action potentials is determined in the integrator 5. The line from the integrator 5 to the actual insulin pump 6 then transfers the number of action potentials per unit of time (or the resulting voltage U) as a function of the number of action potentials per unit of time (U = f (number of AP / unit of time) to the insulin pump 6. The insulin pump 6 becomes thereby activated to emit a certain Insuim current, which in turn is directly proportional to the span previously reached the Insulp pump
Figure imgf000008_0001
Anhand dieser Figur ist klar erkennbar, daß die Insulmstrom- starke, die von der erfindungsgemaßen Insulmpumpe freigege¬ ben wird, direkt durch die Erregung des Nerven 1 gesteuert wird. Genau wie bei der gesunden Natur des Körpers findet bei der erfindungsgemaßen Insulinversorgung die Ausschüttung schon statt, bevor die Glukose über die Darmresorption m das Blut gelangt. Bei der Glukoseresorption kommt es dann zu ei¬ nem wesentlich geringerem Anstieg der Glukosekonzentration im Blut.It can be clearly seen from this figure that the insulin current strength, which is released by the insulin pump according to the invention, is controlled directly by the excitation of the nerve 1. Just as with the healthy nature of the body, the insulin supply according to the invention takes place before the glucose reaches the blood via the intestinal absorption. In the case of glucose absorption, there is then a substantially smaller increase in the blood glucose concentration.
Das erfindungsgemäße Gerat zeichnet sich dadurch auε, daß die intakten Teile des physiologischen Funktionskreises des zu therapierenden Patienten das Gerat steuern. Dadurch kann auf die Entwicklung technischer Glukosesensoren und deren Implan- tation verzichtet werden. Mit dem erfindungsgemaßen Gerat wird die Blutzuckerregelung physiologisch, was bedeutet, daß die Regelgroße (hier die Blutzuckerkonzentration) nicht erst vom Sollwert abweichen muß, damit gegenregulatorisch wirkende Maßnahmen eingeleitet werden (Insulinfreisetzung) , sondern daß schon vor der Abweichung der Regelgroße vom Sollwert ei¬ ne, der zu erwartenden Abweichung entgegenwirkende, Aktion gestartet wird.The device according to the invention is characterized in that the intact parts of the physiological functional circuit of the patient to be treated control the device. This allows the development of technical glucose sensors and their implants tation be waived. With the device according to the invention, the blood sugar control becomes physiological, which means that the controlled variable (here the blood sugar concentration) does not have to deviate from the target value in order to initiate counter-regulatory measures (insulin release), but that even before the controlled variable deviates from the target value , counteracting the expected deviation, action is started.
Als Ergebnis wird die Abweichung des Blutzuckergehaltes von der normalen Konzentration geringer sein als mit Herkömmli¬ chen Insulinpumpen Dies wiederum hat zur Folge, daß Spat- schaden vermindert werden oder gar nicht eintretenAs a result, the deviation of the blood sugar content from the normal concentration will be less than with conventional insulin pumps. This in turn has the consequence that spade damage is reduced or does not occur at all
Nachdem das erfindungsgemaße Gerat beispielsweise bei Diabe¬ tikern mit intaktem Reflexbogen aber defekten ß-Zellen einge¬ setzt wird, kann es als Ersatz für die Pankreas- und andere Organimplantationen dienen. Dabei entfallen die mannigfachen Probleme von Transplantationen, die z.B. mit dem Immunsystem zusammenhangen Das erfindungsgemaße Gerat kann zur Massenan- wendung eingesetzt werden und damit, anders als die Pankreas- Tranεplantationen, auch zur Therapie einer großen Anzahl Dia¬ beteskranker oder Kranker mit einem defekten endokrin Stoffe ausschüttenden Organ. After the device according to the invention is used, for example, in diabetics with an intact reflex arch but defective β-cells, it can serve as a replacement for the pancreas and other organ implants. The multiple problems of transplantation, which e.g. connected with the immune system The device according to the invention can be used for mass application and thus, unlike pancreatic transplantations, also for the therapy of a large number of diabetic or sick people with a defective organ that releases endocrine substances.

Claims

Patentansprüche claims
1. Implantierbare Medikamentpumpe für Patienten mit intaktem Reflexbogen aber defekten Organen zur Eigensubstanzabgebung, bei der die Steuerung der Abgabemenge, -dauer und -zeit der Medikamentpumpe an die Erregungen der vegetativen Nervenfa¬ sern des Reflexbogens zwischen den körpereigenen Sensoren und den defekten Organen gekoppelt ist.1. Implantable medication pump for patients with an intact reflex arch but defective organs for self-delivery, in which the control of the quantity, duration and time of the medication pump is coupled to the excitation of the vegetative nerve fibers of the reflex arch between the body's own sensors and the defective organs.
2. Pumpe nach Anspruch 1, bei der die Erregungen einer vege¬ tativen Nervenfaser mittels einer an die Nervenfaser gekop¬ pelten Elektrode registrierbar sind.2. Pump according to claim 1, in which the excitations of a vegetative nerve fiber can be registered by means of an electrode coupled to the nerve fiber.
3. Pumpe nach Anspruch 2, bei der die Oberfläche der Elektro- de feinporös gestaltet und mit einem gewebeverträglichen Ma¬ terial abgedeckt ist.3. Pump according to claim 2, in which the surface of the electrode is made finely porous and is covered with a tissue-compatible material.
4. Pumpe nach Anspruch 3, bei der die gewebeverträgliche Ab¬ deckung Medikamente trägt und abgibt.4. Pump according to claim 3, wherein the tissue-compatible cover carries and delivers medication.
5. Pumpe nach einem der Ansprüche 1 bis 4, dadurch gekenn¬ zeichnet, daß sie eine Insulinpumpe ist. 5. Pump according to one of claims 1 to 4, characterized gekenn¬ characterized in that it is an insulin pump.
PCT/DE1997/000986 1996-05-30 1997-05-15 Implantable drug pump WO1997046274A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19621770.9 1996-05-30
DE1996121770 DE19621770C1 (en) 1996-05-30 1996-05-30 Implantable insulin pump

Publications (1)

Publication Number Publication Date
WO1997046274A1 true WO1997046274A1 (en) 1997-12-11

Family

ID=7795718

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1997/000986 WO1997046274A1 (en) 1996-05-30 1997-05-15 Implantable drug pump

Country Status (2)

Country Link
DE (1) DE19621770C1 (en)
WO (1) WO1997046274A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019207007A1 (en) * 2018-04-24 2019-10-31 Imperial College Of Science, Technology & Medicine Artificial pancreas with neural signal input

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4146029A (en) * 1974-04-23 1979-03-27 Ellinwood Jr Everett H Self-powered implanted programmable medication system and method
EP0481583A2 (en) * 1990-10-15 1992-04-22 Cardiac Pacemakers, Inc. Method and apparatus for cardioverter/pacer utilizing neurosensing
US5305745A (en) * 1988-06-13 1994-04-26 Fred Zacouto Device for protection against blood-related disorders, notably thromboses, embolisms, vascular spasms, hemorrhages, hemopathies and the presence of abnormal elements in the blood

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5101814A (en) * 1989-08-11 1992-04-07 Palti Yoram Prof System for monitoring and controlling blood glucose
US5569186A (en) * 1994-04-25 1996-10-29 Minimed Inc. Closed loop infusion pump system with removable glucose sensor
US5474552A (en) * 1994-06-27 1995-12-12 Cb-Carmel Biotechnology Ltd. Implantable drug delivery pump

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4146029A (en) * 1974-04-23 1979-03-27 Ellinwood Jr Everett H Self-powered implanted programmable medication system and method
US5305745A (en) * 1988-06-13 1994-04-26 Fred Zacouto Device for protection against blood-related disorders, notably thromboses, embolisms, vascular spasms, hemorrhages, hemopathies and the presence of abnormal elements in the blood
EP0481583A2 (en) * 1990-10-15 1992-04-22 Cardiac Pacemakers, Inc. Method and apparatus for cardioverter/pacer utilizing neurosensing

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019207007A1 (en) * 2018-04-24 2019-10-31 Imperial College Of Science, Technology & Medicine Artificial pancreas with neural signal input
US11923063B2 (en) 2018-04-24 2024-03-05 Imperial College Innovations Limited Artificial pancreas with neural signal input

Also Published As

Publication number Publication date
DE19621770C1 (en) 1998-01-02

Similar Documents

Publication Publication Date Title
DE69533549T2 (en) IMPLANTABLE PUMP FOR THE ADMINISTRATION OF A MEDICINE
DE19756872B4 (en) Device for administering an infusion and / or perfusion to a patient
DE60028569T2 (en) CLOSED REGULATORY FOR THE INFUSION OF INSULIN
DE60302264T2 (en) Medication delivery system with control loop
DE69827513T2 (en) ARRANGEMENT FOR THE TREATMENT OF NEURODEEGENERATIVE DISORDER BY INFUSION OF NERVE GROWTH FACTORS IN THE BRAIN
Akkina et al. GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice
DE60036306T2 (en) SYSTEM FOR THE ADMINISTRATION OF MEDICAMENTS WITH A CHANGED RATE
DE69826005T2 (en) APPARATUS FOR INCREASING GLUCOSE PRODUCTION BY STIMULATING PANCREATIC BETA CELLS
Wood et al. Circadian rhythm in cerebrospinal fluid noradrenaline of man and monkey
Kamal et al. Synaptic transmission changes in the pyramidal cells of the hippocampus in streptozotocin-induced diabetes mellitus in rats
DE3435647A1 (en) DEVICE FOR PROSPECTIVE AUTOMATIC DETERMINATION OF INDIVIDUAL-SPECIFIC GLUCOSE REGULATION PARAMETERS
DE10006044A1 (en) System, useful for administering hormone for blood glucose regulation of patient, comprises regulation unit with controller for processing measured data, and device for administering hormone
EP2438861B1 (en) Medical Sensor System for Detecting at Least One Feature in At Least One Animal Body and/or Human Body
Shibata et al. Inhibitory action of insulin on suprachiasmatic nucleus neurons in rat hypothalamic slice preparations
WO1997046274A1 (en) Implantable drug pump
Benecke Verhaltenstherapie bei Adipositas
Soeldner et al. Progress towards an implantable glucose sensor and an artificial beta cell
Gosbell et al. The effects of insulin on the electroretinogram of bovine retina in vitro
DE4331934C1 (en) Implantable biosensor and drug administration arrangement and sterilisation method
DE102008032526A1 (en) Method for finding a stimulation area
Peterschmitt et al. Differential influence of the ventral subiculum on dopaminergic responses observed in core and dorsomedial shell subregions of the nucleus accumbens in latent inhibition
Held et al. Ökologie
Frutiger et al. Effect of glucoprivation on self-stimulation rate-frequency functions
DE10241550A1 (en) Method for calculating insulin dosage comprising determining actual blood sugar concentration from sample, calculating concentration variation with time and relating this to carbohydrate intake
Kretschmer Incentive motivation in humans is modulated by GLP-1 and hunger depending on insulin sensitivity

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 98500073

Format of ref document f/p: F

122 Ep: pct application non-entry in european phase