Peristaltic micropump with replaceable pump headThe present invention relates to a device for injecting a medicament into the human or animal body by means of a motor-driven pump head which is simple and quick to replace.
Many drugs must be injected into the body. This is especially true for those drugs that are inactivated or substantially inactivated when administered orally. These drugs include, in particular, proteins (e.g. insulin, growth hormones, interferons), carbohydrates (e.g. heparin), antibodies or most vaccines. For in vivo injection, syringes, medication pens or drug pumps are mainly used.
A conventional insulin injection device is an insulin syringe. Since the start of insulin therapy, insulin syringes have been used, but in recent years, especially in germany, insulin syringes have been gradually replaced due to the introduction of insulin pens. Nevertheless, syringes are currently irreplaceable, for example when an insulin pen is lost or damaged, and many diabetics use syringes in conjunction with insulin pens. The advantage is maintenance free and easy availability, especially on trips.
Insulin syringes differ in their identity and scale according to the insulin concentration U40 or U100 to be used. The insulin may be taken from a vial or a pre-filled cartridge for an insulin pen. This allows mixing of different types of insulin and reduces the number of injections necessary. Special care must be taken to avoid air bubbles when drawing insulin into the syringe. The directly visible insulin dose drawn in allows the user to easily check the amount of insulin injected. Nevertheless, for error-free administration with insulin syringes, skilled and regular use is necessary.
Another injection device that is currently very widely used throughout the world, especially in europe, is the insulin pen.
The medical device was marker-pen sized, developed in the mid 80's of the 20 th century, and was primarily used for more intensive insulin therapy. A significant innovation compared to insulin syringes is the use of replaceable medicament containers. This container, also called a carpule or cartridge, is filled with insulin when supplied by the manufacturer and inserted into an insulin pen prior to use. When the pen is operated, the injection needle pierces the sealing disk of the cartridge and completes a parenteral injection of the preselected dose to administer the insulin. During injection, the injection and release mechanism produces an injection stroke that advances a plunger (plunger) or stopper in the cartridge and causes a preselected dose to be delivered into the target tissue. The mechanism typically consists of a rigid plunger rod (plungerstem) having a length corresponding to the stroke of the cartridge stopper.
Insulin pens are classified into disposable insulin pens and reusable insulin pens. For disposable insulin pens, the cartridge and the metering mechanism form a unit that is pre-manufactured by the manufacturer and after the cartridge is emptied, the cartridge and the metering mechanism are disposed of together. The metering mechanism is no longer used. Reusable pens have increased demands on the user compared to pre-loaded pens. Therefore, when changing the cartridge, the plunger rod has to be retracted to the starting position. Depending on its mode, this is done by twisting or sliding the plunger rod and simultaneously actuating a specific function of the metering mechanism. Due to the everyday use and high mechanical stress, malfunctions such as plunger rod sticking may occasionally occur, so that the user has to perform this operation very carefully.
Reusable insulin pens can also be divided into manual pens and semi-automatic pens. In the case of a manual pen, the user applies a force with the finger to actuate the injection button and thereby determine the duration and progress of the injection. In contrast, with a semi-automatic insulin pen, the spring that stores the energy necessary for the injection is manually tightened prior to use. During the actual injection step, the user releases the spring. The injection speed is fixed by the force of the spring and therefore cannot be adjusted to the individual needs.
DE 19745999 discloses a compact tube pump with a particularly small construction. The tubing pump is said to consist of a delivery head, a delivery head drive, a rotational speed controller, and other components and accessories, and is characterized by the pump head and associated drive being easily removable from the housing and replaceable by the same, similar, or different means.
A significant drawback of this arrangement is that the pump head can only be removed from the housing with the drive. This means that conventional pump head replacement to maintain therapy (as clean and sterile as possible) is expensive, inconvenient and impractical.
The present invention relates to a device for moving a liquid containing a drug in dissolved or suspended form, said device being in particular composed of at least:
a) a motor;
b) a reservoir;
c) a pump head driven by the motor from a) through which liquid is transported out of the reservoir;
d) control electronics
Wherein the pump head is equipped with an interface that is removable and re-connectable to the motor from a) and/or the reservoir from b) and/or the control electronics from d).
A device is made up of one or more components connected together and is used for a specific purpose. The purpose may be determined by the particular type of application. One purpose is for example for injecting a medicament, in particular insulin, into the human or animal body.
The interface between the pump head and the motor functionally connects these two components. This functional connection involves converting the motion of the motor into pumping work. Various forms of energy may be provided to the motor for this purpose. In this connection, it is preferably operated by batteries (single use or rechargeable) or household current (voltage can be regulated by an inserted adapter) and/or solar cells. The pumping work is used to transport the liquid out of the reservoir. For this purpose, an interface exists between the pump head and the reservoir. The interface is designed so that movement of the liquid (which transports the liquid out of the reservoir) can be initiated, maintained and terminated by appropriate operation or control of the motor and/or pump head. The conduit is contained within the above-described interface. The connection should be designed to be liquid-tight. There is also an interface between the pump head and the control electronics. The interface is used to transmit sensor data (e.g., from a flow sensor, temperature sensor, "glucose sensor," or other sensor) to the control electronics. The interface may have an electrical, optical, wireless configuration. The control electronics may be used to maintain the operational status of the equipment, coordinate the various components, exchange and process operational data between the various components, exchange and input information related to the user, or monitor normal operational functions and safety related to the user.
The pump head interface to the motor, reservoir and control electronics features easy and quick release and reattachment. Ease of release and attachment is for the average operator of the above-described device who has previously read the accompanying specification. Simple release of the interface can be performed as follows: for example by detaching the parts, by pressing and subsequently rotating the parts, by moving a lever, sliding a slide button or pressing a button to disengage from the locking mechanism, and also by unscrewing, detaching, etc. Simple connection of the interface can be performed by pushing, sliding, twisting, screwing, coupling, fastening, moving a lever, and the like. The simple detachment and connection of the interface is particularly present when the detachment and connection takes place without tools but only by physical effort of the user (e.g. patient, medical staff), which is in particular done by movements of the arms, hands and/or fingers.
In a preferred embodiment, the invention resides in an apparatus as described above, wherein after operation (i.e. actuation of the apparatus), the pump head is replaced with another pump head.
After using the device in an "on, maintenance and off cycle" of the pump head for operation, the pump head is replaced in each case, in particular every time, or every second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth or longer interval. When the pump head capacity decreases, the pump head is replaced. Especially in applications where cleaning and/or a minimal number of microbial organisms are important (e.g. in medical treatment), the pump head should be replaced often, i.e. after each or every two uses.
In another preferred embodiment, the invention resides in a device as described above, wherein the pump head carries a needle. The needle refers to a medical injection needle. The syringe needle includes: a cannula (usually made of metal) through which a liquid or gas can be injected or aspirated into or out of the human or animal body; and a fixing means attached to the top of the cannula and by means of which the needle can be fixed to a syringe, a catheter, a medical pump, a medication pen (e.g. an insulin pen) or other medical device. The needle carried by the pump head is particularly useful for injecting a liquid (e.g. an insulin preparation) from a reservoir into the human or animal body.
In another preferred embodiment, the invention resides in an apparatus as described above wherein the motor comprises a micromotor. Micromotors are characterized by small dimensions. The length is 3-0.5cm, the width is 0.5-1.5cm, and the height is 0.5-1.5 cm. The micromotors used in the device according to the invention are based in particular on electromagnetic drives.
In another preferred embodiment, the present invention resides in a device as described above wherein the reservoir consists of a commercially available cartridge for holding the medicament. The cartridge may be used for a variety of medicaments. Known cartridges (also referred to as vials) are those containing insulin as a solution or suspension and a mixture of different insulins of various types (e.g. slow acting such as Lantus (time of arrival) or fast acting such as Apidra or standard effect such as an insulin) or amounts (e.g. amounts of 100i.u., 200i.u., 300i.u., 500i.u., 1000i.u., or others). An insulin cartridge (insulin vial) is used for injecting insulin to a human body by a syringe and an insulin pen, or for continuously supplying insulin to a human body by an insulin pump. The manufacturer of the insulin cartridge is in particular Xenof-Anthrate (Sanofi-Aventis). Commercial delivery of insulin cartridges is commonly performed by pharmacies in most countries.
In another preferred embodiment, the invention resides in a device as described above wherein the liquid comprises insulin. The insulins provided may be of different types (e.g. slow acting such as Lantus or fast acting such as Apidra or standard curative such as instrumentan) or amounts (e.g. 100i.u., 200i.u., 300i.u., 500i.u., 1000i.u., or other amounts) which may be as solutions or suspensions and mixtures of different insulins. Insulin may be of animal origin or produced by genetic manipulation.
The present invention relates to the use of a device in one or more embodiments as described above for injecting a substance into the human or animal body. Said substance is in particular insulin in a solution or suspension. Here, injection is distinguished in particular from feeding by a pump. For injection, the substance (usually in a previously fixed total volume) is introduced into the body with a syringe or a medication pen (e.g. an insulin pen) within a short time (e.g. 5-60 seconds). The medication pen is in contact with the body only during direct injection. The substance is supplied by the drug pump for a long period of time (from 60 seconds up to several hours) and the drug pump is usually attached to the body.
The invention also relates to the manufacture of a device according to one or more of the embodiments described above, wherein
a) Providing a motor;
b) providing a reservoir;
c) providing a pump head;
d) assembling the individual components according to a) to c) to obtain a functional unit.
Assembling the device according to the invention to obtain a functional unit means manufacturing the device according to the invention in a ready-to-operate state. After the start of operation, the functional unit of the device according to the invention can remove liquid from the reservoir, in particular by the action of the pump head driven by the motor. In another possible use of the functional unit, the removed liquid may be injected by the pump head into the human or animal body.
The invention also relates to a medical device for injecting a drug into a human or animal body, the medical device comprising inter alia:
a) housing and/or
b) An adjustment mechanism for presetting an amount of a drug to be delivered by a medical device, and/or
c) Display device and/or
d) A release mechanism for initiating and completing an injection;
it also comprises at least one device according to the invention in one or more of the embodiments described above.
Medical devices for injecting medication, in particular pens. Pens are known in particular for the injection of insulin (insulin pens). Insulin pens are commercially available in drug stores. Currently, examples of insulin pens on the market are the Optilick, Optipen Pro, Optiset and insulin pens of other manufacturers.
The housing is the housing of the medical device, which may contain a protective cap, depending on the design. The housing may be made of plastic or metal. It typically has an elongated shape, typically containing a recess, mouth or window, containing an internal cavity, and is adapted to receive and position other components.
The adjustment mechanism makes it possible to preset the amount of medicament which is to be injected later on. The adjustment mechanism may be mechanically or electronically operated. The adjustment mechanism is designed so that the preset amount of medicament can be corrected until the actual injection is completed.
The display device is used for displaying the preset amount of the medicine to be injected. Which may be displayed mechanically or in the form of an LCD display device. The release mechanism includes the removal of any air bubbles (which are necessary before the actual injection is performed) and the initiation of the injection process by appropriate activation of the motor and/or pump head until the injection is completed. The medical device according to the invention may comprise a second display means or further display means.
The first or second or further display means may be used to display the current status of the device during injection, e.g. remaining amount, temperature, glucose level, etc. The display means may display the progress of the injection, for example, by means of a progress bar.
In a preferred embodiment, the medical device comprises at least one means for storing and/or processing data and/or signals and at least one interface for transferring data and/or signals to and/or from an external technical unit, for example consisting of a PC equipped with a program for storing and/or processing data and/or signals, which external technical unit is configured for storing and/or processing data and/or signals.
The medical device as described above is particularly useful for injecting insulin or GLP-1 or heparin, such as cloisonx (Lovenox). The insulin may be long-acting, short-acting, mixed or normal acting insulin of animal or human origin or produced by conventional or genetic manipulation, and may be in the form of a solution or suspension.
In one or more of its embodiments, the medical device according to the present invention may be used for the prevention and/or treatment of a physical disease and/or dysfunction by means of a substance with reduced or lost pharmacological activity in the gastrointestinal tract.
In one or more of its embodiments, the medical device according to the invention may be particularly useful for the treatment of diabetes, e.g. by administration of GLP-1.
In one or more of its embodiments, the medical device according to the invention may additionally be used for the administration of peptide hormones (such as, inter alia, glucagon, thyroxine, pituitary hormones, hypothalamic hormones, leptin) or growth hormones (such as, for example, human growth hormone).
In one or more of its embodiments, the medical device according to the present invention may also be used for administration of heparin (e.g. low molecular weight heparin) and/or troxacillin.
Finally, in one or more of its embodiments, the medical device according to the invention may be used for the administration of vaccines (such as, inter alia, live or killed vaccines; vaccines for the treatment of influenza, measles, mumps, polio, rabies, tetanus, pertussis, immunodeficiency diseases) and/or for the administration of antibodies (such as monoclonal or polyclonal antibodies for the treatment of bacterial or viral infections, immune system dysfunction, allergies, cancer, etc.).
The invention also relates to the manufacture of a medical device for injecting a drug into a human or animal body, wherein
a) Providing a housing;
b) providing an adjustment mechanism for presetting an amount of a drug to be delivered by the medical device;
c) providing a display device;
d) providing a release mechanism;
e) providing possible electronic components;
f) providing a device according to the invention in at least one or more of the embodiments described above;
g) assembling the individual components of a) to f) to obtain a functional unit.
The device consists of one or more components and is used for specific medical purposes, in particular for injecting substances into the human or animal body. A component is composed of one or more elements and is used to implement technical or non-technical functions. It is technical if the function involves the transfer of force, work, energy, material (substance), data, and/or signals, the maintenance of structure and/or form, or the storage of substances or information. It is non-technical if the function involves the input or output of information to or from a user of the device or involves the input or output of a substance to or from a user of the device.
A component may be, for example, a part of a technical device, which component provides part of the functionality relating to the overall functionality of the device.
The component is for example a reservoir. The reservoir may be a replaceable cartridge containing a substance, in particular a drug, such as insulin. The replaceable cartridge may be particularly suitable for use in an insulin pen or other device for injecting a medicament into a human or animal body. Another example of a technical component is a device or a pump for pumping. Further examples of technical components are, in particular, syringes, needles, plunger rods, metering elements, mechanical displays, tubes, gaskets, batteries, motors, actuators (transmissions), electronic displays, electronic memories or electronic controllers. The meaning of the object in connection with the technical installation is in particular the movement of liquid from one place to another. For example, one purpose is to move the liquid volume from the reservoir to the outflow conduit. The object may also be to inject a drug into the human or animal body.
One component may be technically connected to one or more other components to achieve one purpose together. A technical connection is, for example, a connection of components adapted to transmit force, work, energy, material (substance), data and/or signals. The components may be connected, for example, by mechanical couplings, fixed mechanical connections (gluing, screwing, riveting, via linkage, etc.), gears, latches, interlocks, wires, optical waveguides, wireless connections, electromagnetic fields, light beams, etc.
Injection is the introduction of a substance, in particular a liquid, into the human or animal body through a cannula together with a syringe or a device with comparable functionality, such as in particular a pen. In particular, subcutaneous, intramuscular, intravenous, intradermal and intraarticular injections are well known. Subcutaneous injections are performed under the skin and are relatively easy to achieve, are not very painful and can be performed by the patient himself. Intramuscular injection is into muscle. This is usually done by medical staff, since in this case there is a greater risk, for example painful periosteal damage. Intravenous injections were performed directly through the vein after venipuncture.
In intradermal injection, the drug is delivered directly beneath the dermis. In intra-articular injection, a fluid is injected into the joint. Injecting a substance into the human or animal body is to be distinguished from introducing the substance, in particular by means of a drug pump, infusion or other type of continuous supply that occurs over a certain time.
The cannula is essentially a hollow needle, which is typically made of metal (e.g., steel, stainless steel, gold, silver, platinum). The end of the cannula is typically sharpened by grinding at an angle. The cannula may be pointed and/or sharpened at one end and blunt at the other end, but it may also be pointed and/or sharpened at both ends. At one of the two ends of the cannula there is a conical attachment, usually made of e.g. plastic, by means of which the hollow needle is mounted, e.g. by pushing or screwing, onto a medical device, such as a syringe, a medication pen (in particular an insulin pen), a medication container or a medication pump. The cannula together with a functionally associated syringe, pen, pump or other medical device suitable for the purpose is used for removing liquid from or supplying liquid to the human or animal body.
The diameter (outer diameter) of the cannula is generally indicated by mm or No. (No. 18 ═ 1.2 mm; No. 20 ═ 0.9 mm; No. 21 ═ 0.8 mm; No. 22 ═ 0.7 mm; No. 23 ═ 0.6 mm; No. 25 ═ 0.5 mm; No. 27 ═ 0.4 mm). Another parameter characterizing a casing is its length. Typical lengths of the cannula are 40mm, 30mm, 25mm, 8mm, 6mm and others.
Medical devices are in particular devices for injecting a substance into the human or animal body. In addition to a syringe, it may be a medication pen, such as an insulin pen, for the device for injection. The drug pen is adapted for various forms and purposes and is commercially available from different manufacturers (e.g. Optiklick, Optipen, Optiset).
Each insulin pen must meet various requirements relating to ease of operation so that it can be used safely and without malfunction. The basic requirement is to display the pre-selected dose and the amount remaining in the cartridge. Furthermore, the setting of the dose and the completion of the injection process should be made audible, tactile and visible. The safety requirement is particularly caused by the limited perception capabilities of elderly type 2 diabetic patients.
In addition to insulin pens using needles, needle-less injection systems are also used for insulin therapy. The present example of an injection system using a needle-less needle isInjex injection system for AG. For this injector, insulin is injected into the adipose layer of the skin through a microneedle (microneedle) using extremely high pressure. For this purpose, the elastic spring is manually tensioned before the injection, so that it stores the necessary injection energy. In this case, the substance to be injected is distributed evenly and conically in the adipose tissue.
A non-negligible advantage of this device is the needle-less injection of the drug, which in some patients lowers the psychological suppression threshold for insulin administration. In addition, needle-less injection avoids infection at the puncture site. The disadvantage compared to conventional insulin pens is shown to be the transfer of insulin into a specific cartridge, the greater mass of such devices compared to and the inclusion of other accessories for tightening the spring.
Insulin pumps, unlike insulin syringes, are fully automated infusion systems for continuous subcutaneous injection of insulin. The insulin pump is approximately cigarette pack sized and is permanently carried on the body. Short-acting insulin is injected into the skin tissue through a catheter and a needle located in the skin according to a program preset by the patient. The task of an insulin pump is to mimic the pancreas to continuously deliver insulin to lower blood glucose levels, but not to regulate blood glucose in a closed-loop control manner. These pumps are advantageous because they provide a continuous and regulated supply of insulin, particularly for people who are engaged in physical activity and who have a large variation in daily activities. Insulin pump therapy can be used to compensate for large variations in blood glucose, for example in diabetic patients with significant DAWN phenomenon, who can be controlled by conventional methods with only increased effort. One disadvantage is that severe metabolic disturbances may occur when the insulin supply is interrupted due to a lack of insulin depot in the human body. Insulin pumps are commercially available in various technical configurations and as technology develops devices with syringe-like containers have emerged. Like a pen with a needle, insulin is present in a reservoir with a removable stopper. The movable stopper is moved by a motor driven plunger rod.
Since insulin is fully automated and continuously delivered, the pump is equipped with a number of safety systems to protect the user from malfunctions with serious consequences. However, this does not mean that the responsible and intended (anticipatory) use of the device is not necessary.
In accordance with further technological developments in the current injection devices and medical and microsystem technology, there is a clear trend towards fully automated miniaturized drug metering systems. Further developments may be directed to implantable and extracorporeal drug metering systems. The goal of implantable insulin pumps is to free a diabetic patient from daily injections of insulin without the need to wear an external device on the body.
Insulin pens focus on important ergonomic and safety properties in EN ISO standard 11608. This again includes the geometry/material properties of the insulin cartridge and the pen needle. Thus, the handling and operation of the pen is substantially consistent for the user and independent of the model.
The contents of EN ISO standard 11608, which are expressly incorporated into this disclosure by reference, relate to insulin pens, insulin cartridges and needles.
In the design of the pen, some significant differences were found among the pens of different manufacturers. The reason for this is for example that it is designed for different target groups (children, elderly). These differences are particularly limited in the injection and release mechanisms because of the requirements of EN ISO standard 11608. The dose selector and the dose display device are mainly ergonomically compliant and are generated from the general design conditions of the respective model.
An important functional element of insulin pens is the injection mechanism. Which determines the type and size of the pen and the design of the release mechanism and the dose selector. The mechanism converts the preset dose on the dose selector into an injection stroke of the bung in the cartridge using injection energy from the release mechanism. This energy is transmitted directly into the injection mechanism or through a motion-modifying actuator.
For injection mechanisms in the shape of a plunger rod, variations in form are technically feasible.
In insulin pens currently available on the market, solutions with rigid (e.g. threaded shaft, rack) or flexible (e.g. curved rack, curved compression spring) designs have been established. Other possible configurations such as telescopic plunger rods (e.g. screw mechanisms, belt and chain drives, hydraulic drives, shaft drives) are not employed in insulin pens currently commercially available.
The design solutions of the rigid and flexible types vary widely and depend on the type of pen, i.e. reusable pen or disposable pen. The plunger rod used is a threaded shaft or a rack or a combination of the two. In the dose selector, the angle of rotation corresponding to the dose is preset with the aid of a stopper (dead) device and is transmitted to the injection mechanism via a subsequent screw mechanism and gear and converted into an injection stroke.
Drug delivery is performed by the described injection stroke and the resulting stopper movement. The amount of liquid delivered depends on the injection stroke and the inner diameter of the cartridge. To avoid dosage errors, the bubbles must be completely removed according to the manufacturer and EN ISO standard 11608. Furthermore, after delivery of the liquid, it is necessary to wait long enough to ensure a steady state, i.e. a normal pressure of the liquid in the cartridge and a relaxation of the stopper.
The drug reservoir (also referred to as a cartridge) affects the structural and functional structure of the medication pen. In this regard, partial functions may be distinguished, first a protection function for the drug, then a delivery function, and finally a coupling function with the drug pen injection system. The protective function is achieved by the cartridge as a whole, i.e. by the stopper, the glass body and the sealing disc. The drug delivery function is imparted by a bung which is displaced with the aid of an injection mechanism and causes a change in volume in the cartridge. Finally, the coupling function with the injection system is produced by sealing means (e.g. a sealing disc). In automatic medication pens, such as automatic insulin pens, the injection energy is provided by a driver with a subsequent actuator. Furthermore, an energy supply and control unit is required.
In the injection mechanism of the present invention, the medicament (e.g. insulin) is not delivered by displacing the stopper with the injection mechanism, but by introducing the pump means. The pump device is inserted between the cartridge and the injection system and is provided with a suitable interface.
The pump device may be equipped with a flow sensor. The flow sensor is in direct contact with a drug, e.g. insulin, thereby placing additional requirements, such as reduced organism count, sterility, biocompatibility, among others.
When applying this functional principle, many variables (e.g. the liquid pressure in the drug reservoir) are changed compared to conventional injection drug pens (e.g. insulin pens), because when the drug is sucked out, a sub-atmospheric pressure is created.
Insulin cartridges are used as primary packages for medicaments and have to meet high standards. The criteria relate to accuracy of cartridge dimensions and compatibility with other components related to dosage accuracy. EN ISO standard 11608-3 addresses these requirements and describes the basic aspects and geometry/material construction without unnecessary limitations to cartridge shape. Also, it is necessary to ensure that the cartridge is impermeable to the drug.
The cartridge is composed of a number of sub-assemblies. The main component is a cylinder of medicinal glass that is highly neutral and chemically resistant to insulin. The surface quality of the cylinder is improved by a siliconizing treatment before filling. This surface treatment reduces the sliding and dislodging force of the stopper, increases dosage accuracy and reduces dissolution of glass components during long term storage. In this regard, the degree of silicidation is related to the level of plug friction, and the sensitivity of insulin to silicone sets the limit of silicidation.
The cartridge is sealed at both ends with a resilient sealing member, a stopper and a sealing disc. In this regard, the key point is that it exhibits mechanical impermeability under a variety of stress conditions and is microbiologically impermeable to all organisms over long-term testing. Another key point is the maximum blocking force allowed and the number of punctures of the sealing disk by the cannula.
The pen needle is a disposable sterile product for introducing insulin from the cartridge into the target tissue. Similar to cartridges, the requirements are also strict, since the actual functioning of an insulin pen can only be accomplished by the cooperation of these two components. The needle consists of a cannula that is ground at both ends and that is placed in the cartridge connection part. The optimal abrasion of the cannula makes it possible to insert it into the target tissue of the patient substantially painlessly and also causes only slight tissue damage during withdrawal. Also, the cartridge sealing disk is pierced without causing significant breakage. This is a mandatory requirement, since the impermeability of the cartridge must also be ensured when the needle is periodically replaced. The connection part of the cartridge ensures that it can be securely mounted on the insulin pen.
After two or more uses, the pen needle should be replaced after each injection for sterility reasons, even if it shows signs of wear that are hardly visible to the eye. In addition, crystallized insulin may clog the needle. Furthermore, if a temperature change occurs, air may enter the cartridge, also causing a dosage error. In this regard, a temperature change of only 15K would cause up to 15 μ l of air to enter the cartridge.
Microfluidics is a branch of microsystem technology and includes the design, preparation, use and study of microsystems that manipulate and process the amount of fluid across a channel of 1 μm to 1mm in diameter. Microfluidic systems are used in medical technology, biochemistry, chemical engineering and analysis, and microreaction technology. These microsystems may have dimensions in the millimeter and centimeter range, since for practical applications it is the amount of fluid that is important and not the size of the microfluidic system. Furthermore, due to the small fluid volume and generally small system size, this type of system appears to be significantly different from conventional fluid systems. Miniaturization is accompanied by changes in fluid flow behavior because of the surface-related effects and the preponderance of electrostatic and electrokinetic forces. Thus, new methods are needed for the design, preparation and characterization of microfluidic components such as micropumps and sensors. The constant energy density of the actuator causes its output to drop, making it mismatched with conventional components in the macro scale (macro sector). For this reason, external actuators are often used, which sometimes greatly increases the size of the overall system. In addition, the physical and chemical properties of the delivered particles and molecules also limit the miniaturization of microfluidic components.
Diabetes is a condition in which the body itself is unable to produce and properly use any or sufficient amounts of insulin. Insulin is required to transport glucose from the blood to the cells of the body. Blood glucose levels remained constant over a narrow range (60-100 mg% or 3.33-5.55 mmol/l). It can be achieved by the interaction of the two hormones insulin and glucagon.
Diabetes is diagnosed after blood withdrawal using suitable laboratory equipment. For a definitive diagnosis, it is necessary to detect elevated blood glucose levels at least two different time periods.
Diabetes is a term used when the glucose level measured in plasma exceeds a specified value in at least one of the indicated cases:
a) fasting blood glucose is-7.0 mmol/l or 126mg/dl
b) Blood glucose two hours after administration of 75mg glucose (oral glucose tolerance test) -11.1mmol/l or 200mg/dl
c) Blood glucose 11.1mmol/l or 200mg/dl with severe thirst (polydipsia), frequent urination (polyuria) or weight loss.
Untreated diabetes results in elevated blood glucose levels, which can lead to a number of symptoms and end-stage consequences such as polyneuropathy, microangiopathy, macroangiopathy, retinopathy, nephropathy, and the like. When the non-enzymatic glycation of erythrocytes (HbA1c levels) is low, there is less risk of diabetes leading to late-stage damage.
Diabetic coma is a life-threatening acute diabetic complication. In such cases, blood glucose levels may exceed 1000mg/dl with excessive blood acidity (metabolic acidosis). Diabetic coma can be particularly triggered by infection, ingestion of too much carbohydrate, alcohol abuse, or incorrect insulin dosage.
Type 1 diabetes is different from type 2 diabetes. In type 1 diabetes, there is an absolute insulin deficiency from the outset and treatment can only be achieved by administration of insulin.
Type 2 diabetes is characterized by decreased insulin sensitivity and relative insulin deficiency. In the early days, type 2 diabetes can often be treated with dietary (dietic) measures and tablets. During the course of the disorder, it often becomes necessary to replace it with insulin.
Type 2 diabetes has become a very common disease, especially in industrialized countries. The main reasons for this are believed to be overeating, lack of exercise and obesity. Exercise training and diabetes measures, especially those aimed at reducing body weight, can be effective in alleviating type 2 diabetes. In type 2 diabetes, oral hypoglycemic agents such as acarbose, biguanides, sulfonylureas, glitazone and the like may also be used. When the measures no longer last long enough to maintain blood glucose levels at or near the normal range, treatment with insulin is necessary.
Various insulin substances are available for insulin therapy. These substances are usually distinguished by the time of action or by chemical structure. Insulin analogues have different amino acids at individual positions compared to human insulin. And thus its properties may change.
Fast acting insulins include human insulin and various fast and short acting insulin analogues such as glulisine insulin (trade name: Apidra), lispro human insulin (lispro) (trade name: euprole) and insulin aspart (trade name: norand jejuni).
Slow-acting or long-acting insulins are NPH insulin (human insulin prolonged by neutral protamine zinc insulin), zinc insulin and various insulin analogs such as insulin glargine (trade name: leflus) and insulin detemir (trade name: Levemir).
In insulin therapy, mixed insulin and recently inhaled insulin may also be used.
The mixed insulin consists of fast acting insulin and long acting insulin in different mixing ratio. Typically 10/90%, 25/75%, 30/70%, 50/50% of the mixture. Insulin therapy must always be accompanied by regular measurements of blood glucose levels.
In conventional insulin therapy, a defined amount of mixed insulin is injected at a fixed time. More intensive conventional insulin therapy is mainly used to treat type 1 diabetes. In this case, long-acting insulin (basal) is used to ensure basal delivery, and rapid-acting insulin (bolus) is given at mealtimes.
Continuous subcutaneous infusion of insulin with a pump is primarily indicated for type 1 diabetes. Insulin is not injected but is delivered to the body by a small pump. The pump is present on the body for a long time. Insulin is delivered through a catheter having a cannula. Insulin pumps typically deliver fast acting insulin at equally short intervals over a long period of time.
In addition to glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1(GLP1) is one of the most important members of the incretin class. Incretins are produced in the intestine in the form of hormones and regulate blood glucose levels, in particular by stimulating insulin release in the pancreas.
The amount of gut hormone produced depends on the amount of carbohydrates taken orally. The increase in GLP1 levels after oral glucose ingestion was much higher than the increase after intravenous glucose administration. It has been shown by studies that intravenous infusion and subcutaneous injection of GLP1 can completely normalize blood glucose levels in many cases in type 2 diabetic patients. The problem is that GLP1 is inhibited by dipeptidyl peptidase IV (DPP-IV) in a very short time. Subcutaneous injection of GLP1 maintained effective plasma concentrations for only about 1-2 hours. Solutions to obtain a sustained effect of GLP1 may be found in the development of long acting GLP analogs or in the inhibition of DPP-IV with drugs.
Growth hormones are substances that stimulate the growth of humans, animals and plants. Known examples are somatotropin (human), bovine growth hormone (bovine) and auxin, gibberellic acid (plant).
Somatotropin (STH) is also known as Human Growth Hormone (HGH) and Growth Hormone (GH). STH is a peptide hormone with 191 amino acids. It is produced in the anterior pituitary under the control of somatotropin-releasing factor (SRF; GHRH; GRF) from the hypothalamus. STH is absolutely necessary for normal linear growth. Reduced production or reduced cellular response to STH results in short stature. Its overproduction can lead to gigantism or acromegaly (acromegalie).
Short stature due to growth hormone deficiency has been treated for years by administering STH. STH was made possible in 1985 by genetic manipulation, which was originally obtained from cadaveric pituitary glands.
Interferons are produced as tissue hormones by human or animal leukocytes, fibroblasts or T lymphocytes. Interferons are proteins or glycoproteins that have immunostimulatory (e.g., antiviral) or antihormonal effects. Interferons are divided into alpha-interferons, beta-interferons and gamma-interferons. Interferons are available from many manufacturers for indications such as viral diseases (e.g. SARS), cancer, multiple sclerosis, hepatitis b/c, hepatitis c.
Vaccines are compositions produced biologically or by genetic manipulation and comprise, inter alia, various proteins and/or RNA or DNA fragments and/or killed pathogens or attenuated pathogens (e.g. influenza, SARS, poxvirus, measles pathogens, mumps, rubella, polio, pertussis pathogens).
Known types are live vaccines (e.g. vaccinia), live attenuated vaccines containing attenuated viruses or bacteria (e.g. MMR vaccine, yellow fever, polio) and killed vaccines containing inactivated or killed viruses or bacteria or components thereof (e.g. influenza, cholera, bubonic plague, hepatitis a).
Heparins are substances that are used therapeutically to inhibit blood coagulation. Heparins consist in each case of alternating sequences of D-glucosamine and D-glucuronic acid or L-iduronic acid. A chain length consisting of 5 units is sufficient for anticoagulation.
The polysaccharide chains mostly have a molecular weight of 4000 to 40000. In addition to unfractionated heparin, low molecular weight fractionated heparin having a molecular weight of about 5000 is used. Heparins are not absorbed from the gastrointestinal tract but must be administered parenterally. Heparins act by binding to antithrombin III and thereby accelerating the inactivation of activated coagulation factors
Clexel (also known as clexane) is a commercially available pharmaceutical preparation containing the pharmacologically active ingredient enoxaparin sodium. The active ingredient is one of the low molecular weight heparins that has a linear dose-response relationship and consistently has high bioavailability.
Indications for mosaic range from primary prevention of deep vein thrombosis, treatment of deep vein thrombosis with or without pulmonary embolism, treatment of unstable angina and so-called non-Q-wave myocardial infarction, and thrombosis prevention and anticoagulation during hemodialysis.
Examples
Insulin pens consist of a main device with a replaceable pump head. The master device is reusable. It consists of a housing that houses the pump driver, sensor, electronics and power supply (fig. 1; fig. 2; fig. 3). It is also equipped with an interface to external equipment and a start button and a metering button. The pump head is a disposable component and is used only for a very short time (1-3 days). The pump head has an interface with the main device and with the pen needle (fig. 4).
Replaceable pump head
The replaceable pump head consists of a pump chamber (tubing pump) and a flow sensor (impeller meter), which is placed in the housing. The housing has an interface that can be easily separated and reclosed (fig. 5).
In this embodiment, the flow sensor may be divided into two components. Having an impeller in the pump head allows the impeller (test target) to be produced at a reasonable cost. The impeller and pump head are replaced together. The rotation of the wheel is detected with a slotted interrupter firmly integrated in the master (fig. 6). The flow sensor may also be present as one component, in which case it is integrated in the pump head or separate from it.
Catalog of the figure:
FIG. 1: front view of insulin pen (size: about 120 mm. times.45 mm. times.20 mm)
FIG. 2: insulin pen rear view
FIG. 3: individual component of insulin pen
FIG. 4: interface with pump head
FIG. 5: replaceable pump head
FIG. 6: impeller with interrupter
Reference numeral interpretation
1 insulin
2 main body (bottom)
3 replaceable pump head
4 main body (Top surface)
5 cartridge chamber cover
6 Cartridge Chamber
7 Cartridge
8 visual window of cartridge
9 main body connecting piece for receiving replaceable pump head
10 locator between main body and replaceable pump head
11 Motor
12 motor shaft coupling
13 interrupter
14 electronic device with LCD (rear)
15 LCD display device
16 camera battery
17 interface with PC
18 switch
19 Start button
20 dose button
21 replaceable pump head contact area with main body
22 to pump
23 interface with a cartridge
24 interface with a needle
25 needle
26 locator between main body and replaceable pump head
27 replaceable pump head basic parts (outer side)
28 replaceable pump head basic parts (inner side)
29 outer cover of replaceable pump head
30 rotor
31 roller
32 pipeline
33 blade edge
34 flow sensor
35 fluid component