WO2011033328A1 - Insulin dosing micro-infusion device useful for the treatment of diabetes - Google Patents

Insulin dosing micro-infusion device useful for the treatment of diabetes Download PDF

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Publication number
WO2011033328A1
WO2011033328A1 PCT/HU2010/000098 HU2010000098W WO2011033328A1 WO 2011033328 A1 WO2011033328 A1 WO 2011033328A1 HU 2010000098 W HU2010000098 W HU 2010000098W WO 2011033328 A1 WO2011033328 A1 WO 2011033328A1
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WO
WIPO (PCT)
Prior art keywords
fibres
micro
infusion device
insulin
reservoir
Prior art date
Application number
PCT/HU2010/000098
Other languages
French (fr)
Inventor
Zoltán PIROS
Original Assignee
Piros Zoltan
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 Piros Zoltan filed Critical Piros Zoltan
Publication of WO2011033328A1 publication Critical patent/WO2011033328A1/en

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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
    • A61M5/141—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor with capillaries for restricting fluid flow
    • 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
    • A61M5/14248—Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body of the skin patch type
    • 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
    • A61M5/158—Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
    • A61M2005/1581—Right-angle needle-type devices

Definitions

  • Insulin dosing micro-infusion device useful for the treatment of diabetes
  • the present invention relates to an insulin-dosing micro-infusion device useful for the treatment of diabetes, i.e. for delivering the daily need of insulin, as well as to the method for the use thereof.
  • the objective of the invention was to provide a device for administering insulin that is more advantageous compared to the known solutions, which is physically more convenient and less expensive for the patients.
  • the device according to the invention similarly to the known insulin pumps - there is no need for several injections a day, at the same time the costs involved are incomparably lower than in case of pumps.
  • the insulin pump is very expensive, which the majority of people can hardly afford or cannot afford at all.
  • Another drawback of the pumps is that in addition to their expensiveness they have to be changed every two or four years.
  • the invented solution provides, by a method based on the principle of capillarity, the continuous administration of the active ingredient through a simple porous textile, e.g. cotton or cloth, and the supply thereof via a replaceable reservoir.
  • a subcutaneous injection set is prepared, which comprises a valve/connecting means on the outer side of its part that can be stuck to the skin, and a flexible cannula to be inserted into the skin by an apparatus, e.g. by a needle on the part to be placed on the skin, and following the placement of the device the solution of the active ingredient is supplied from an outer device (syringe, infusion pump etc.) for continuous or repeated subcutaneous administration, without the need of another insertion.
  • WO 03/026728 Al discloses a transcutaneous infusion device consisting of a microinjector attached to the skin and equipped with a cannula which can be inserted in a similar manner as described above and of a replaceable feeding device connectable thereto, which is operated by an external force, e.g. by spring force.
  • Hungarian patent specification No. HU 222,342 Bl relates to a transcorneal drug-release system comprising an active substance reservoir and micro-pins or micro-blades placed on its side next to the skin, said micro-pins having a length corresponding at least to the thickness of the corneal layer of the skin.
  • the device comprises an electronically controlled pump as well.
  • US Patent Specification No. 3,964,482 describes a drug delivery system for percutaneously administering a drug, comprising a drug reservoir attachable to the skin and a plurality of tubular projections placed on its side to be attached to the skin, and the delivery of the drug is ensured by diffusion or osmotic pressure.
  • this new insulin delivery system is a micro-infusion device for the subcutaneous administration of an insulin injection composition, ensuring sustained activity, comprising a fixed carrier which contains porous textile fibres, imposable on the skin surface of the body, insertable under the skin and containing an element ensuring the tightness of the fibres, and also comprising a replaceable reservoir connected to the carrier, storing the solution of the active substance and ensuring the continuous dosing thereof, wherein the fibres coming out of the reservoir are in contact with the fibres in the fixed carrier.
  • the present invention offers the above benefits.
  • micro-infusion device 1 according to the invention is shown in Figure 6. As it appears from the Figure, the micro-infusion device 1 consists of a replaceable reservoir 2 containing porous textile fibres 1 14 and a fixed carrier 3 or 4 also containing porous textile fibres 1 14.
  • One of the main components of the invention is the mobilizable, replaceable infusion reservoir 2 containing the insulin. It can be replaced even several times a day thus permitting a dosage according to individual needs.
  • the fittings are always perfect, i.e. the sealing is airtight, thereby excluding practically any infection.
  • the reservoir 2 is made of a suitable synthetic material or maybe glass, with a volume capacity of 0.1 ml to 10.0 ml, preferably 0.5 ml.
  • the micro-infusion device 1 is capable of subcutaneously delivering this small amount of insulin into the body continuously and evenly through a whole day.
  • compositions for infusion are to be used in therapy when the amount of the solution to be administered parenterally is so high (more than 30 ml), which cannot be performed by injection. In this case the infusion, the amount of which generally exceeds 500 ml, is applied intravenously.
  • the administration of micro- or milligrams of insulin is based on the theory and practice that the insulin is absorbed from the reservoir 2 through the porous textile, fabric etc., e.g. cotton or cloth fibre(s) 1 14 on the basis of the principle of capillarity and then it is delivered by diffusion, with the aid of the fixed carrier, to the blood-stream.
  • the porous textile, fabric etc. e.g. cotton or cloth fibre(s) 1 14 on the basis of the principle of capillarity and then it is delivered by diffusion, with the aid of the fixed carrier, to the blood-stream.
  • the other main component of the invention is therefore the fixed carrier which is to be placed on one side onto a suitable surface of the body (insert and stick) and on the other side the reservoir 2 is to be connected thereto.
  • the two main components of the invention are connected by the porous textile fibres 1 14 ensuring the capillarity and constituting the essence of the invention.
  • the insulin can be delivered under the skin by two variants of the fixed carrier.
  • Figure 1 shows the solid insertion needle, metal lance 6 positioned in the fixed carrier comprising a plastic tube 4, which needle is provisionally positioned in the plastic tube of the fixed carrier 4.
  • Figure 2 shows the solid metal lance 5 immovably positioned in the fixed carrier 3, which serves for inserting the textile fibres into the skin and keeping them tight.
  • Figure 3 shows the side-view of the fixed carrier comprising the plastic tube 4.
  • Figure 4 shows the fixed carrier 3 comprising the solid metal lance 5 immovably.
  • the material of the solid metal lance 5 having a size and form specifically designed for this purpose as well as the material of the solid insertion needle 6 corresponds to the material of the currently used steel needles for injection and infusion.
  • the textile fibres can be combined both in quality and quantity.
  • the surface of the desired capillary is formed by using fibres of identical thickness and quality (porosity) and by fixing the fibres always at the same points.
  • the textile can be vegetable, animal or synthetic fibre or any mixture thereof with arbitrary ratio and quality; the vegetable fibre can be, for example, cotton, hemp, flax, etc., and the animal fibre can be, for example, wool.
  • the cotton and the retirement cloth are preferred.
  • the synthetic fibre can be, for example, nylon fibre etc.
  • the textile fibres 1 14 and the capillaries therein need continuity in the micro-infusion device 1. They have to be free from wrinkles and buttoning. Furthermore, a minimal space is to be provided for swelling of the fibres. When assembling the fixed carrier 3 or 4 and the replaceable reservoir 2, a continuity has to be maintained in contacting the fibres.
  • the suitable space is ensured by the tubes 1 17 on the fixed carriers 3 and 4, said tubes having a length of 2 mm and intruding into the skin, as shown in Figures 3 and 4; and the thickness of the windowed, biocompatible tube 120 and the size of the windows on the fixed carrier 4 as well as the constraininjury" in the skin, caused by the 1.6 mm diameter head of the solid lance 5 intruding into the skin in case of the fixed carrier 3.
  • the tightness of the fibres is guaranteed also by the windowed, biocompatible tube 120 and the lance 5.
  • the textile fibres are fastened to the two opposite sides of the sphere along the line of the diameter.
  • the rate of delivering the (solution of the) active substance can be controlled by adjusting the size of the capillary surface, the concentration of the solution and the composition of the solvent.
  • the device 1 provides a slow, extended dissolution and effect for several hours. If the patient applies a reservoir 2 containing a daily amount of insulin, expressed in the international unit (IU), by adjusting the above parameters the patient can ensure for himself the necessary amount of insulin for 24 hours subject to having regular and conscious meals and physically training his body.
  • IU international unit
  • micro-infusion method is suitable for the transdermal delivery of any other drugs, the therapeutic effect of which can be achieved by a very small quantity (e.g. hormones etc.).
  • Such a substance is the peptide hormone, the insulin, as used herein.
  • the insulin is used in the form of a solution, because the capillary flow can occur in such a form only.
  • the solution of the insulin reaches the tissue fluids under the skin, the capillaries with the required speed and in the required quantity. This can be achieved by the solvent used.
  • micro-infusion device developed according to the invention consists of two main parts, components:
  • the comfortably fixed carrier 3 or 4 which has to be placed on a suitable surface of the body (insert and stick).
  • the reservoir 2 comprising a suitable concentration of the solution of the insulin and porous fibres 1 14, which has to be slid, positioned on the carrier.
  • the placed carriers have to be placed by using thin (e.g. 0.3 mm) and short (max. 15 mm or 20 mm length) solid metal lances 5 or 6 with the aim of delivering the cotton or cloth fibres 1 14 (at 90o angle with the body surface, i.e. perpendicularly) to the bottom of the skin to a maximum depth of 10 mm, thereby ensuring the spatialtightness" of the fibres, while the whole carrier is fixed by sticking the self-adhesive surface to the skin.
  • the concrettightness is provided by the plastic tube 120, thus following the setting, the insertion needle used as an aid, i.e. the lance 6, can be removed immediately, but fixing is performed by sticking in this case, too.
  • the size and the structure of the solid lance 6 in figure 1 are the following: the lance, insertion needle 6 has a holder 101 of 10-20 mm (the portion 102 of the solid lance, insertion needle 6 in the carrier depends on the height of the carrier),
  • the section 103 of the solid lance, insertion needle 6 in the skin is maximum 10 mm long
  • the diameter of the solid lance, insertion needle 6 is 0.3 mm
  • the head 105 of the solid lance, insertion needle 6 has a length of 0.5 mm.
  • the lance, insertion needle is drawn out, removed from the skin.
  • Figure 2 shows the fibre-holding eye 106 of the solid lance 5, having an inner width of 0.5 mm, total width of 1.1 mm, the widened part of the fibre-holding eye 106 being the head 1 12 of the solid lance, having a length of 2.0 mm and a diameter of 1.6 mm, and a 8-mm section of the handle 1 10 of the lance 5, measured from the head 1 12, being in the skin (together with the eye 106).
  • the remaining part is fixed in the carrier.
  • the solid lance 5 is fastened in the carrier 3 and it serves for delivering the textile fibres 1 14 into the skin and for keeping them tight.
  • the porous textile fibres 1 14 are fastened to the inner surface of the semi- spherical carrier by the fixing element 1 13.
  • the other end of the porous textile fibres 1 14 is fastened to the end of the windowed, biocompatible plastic tube 120 being in the skin.
  • the spherical reservoir 2 containing the carrier 4 and the solution of the active substance as well as the identical textile fibres 1 14 are fixed by the guiding or bearing rail 1 15.
  • the carrier 4 is fixed to the skin surface by a round sticker 1 16, a self-adhesive patch (0 40 mm).
  • the permanent hole in the epidermis is maintained by a tube 1 17, having an inner diameter of 1.0 mm, wall thickness of 0.3 mm and a length of 2.0 mm, which can be a short, intact section of the windowed, biocompatible plastic tube 120, directly above the window, while in case of the lance the relating part 1 17 of the fixed, semi-spherical carrier 4 is extended; the height of the semi-spherical fixed carrier 4 being 6 mm; the semi- spherical fixed carrier 4 being fastened to the self-adhesive patch 1 16 by the element 1 19.
  • the maximum length of the skin penetrating, partially windowed, biocompatible plastic tube 120 is 10 mm; said tube maintains the tightness of the textile fibres 1 14 in addition to serving for the penetration of the active substance.
  • the porous textile fibres 1 14 are thread through the hole 106 above the lance-head 1 12 and taken back to the inside of the semi-sphere.
  • the two ends of the fibres are fixed on the same place.
  • the outer diameter of the semi-spherical fixed carrier 3 is 9.0 mm and the inner diameter thereof is 6.0 mm.
  • the end of the solid metal lance 6 is fastened by the plastic 123 inside the semi-spherical carrier 3.
  • the concentration of the insulin solution has to be adjusted prior to adding it to the reservoir.
  • the concentration of the insulin is adjusted in international units (IU).
  • the surface of the cotton or cloth fibre(s), i.e. the required capillary is achieved by using cotton or cloth fibre(s) of identical thickness and quality (porosity) and by fixing the fibre(s) always on the same places. In this manner the permanent length, i.e. surface of the cotton or cloth fibre(s) can be ensured.
  • Figure 5 shows the sectional drawing of the replaceable reservoir 5.
  • the diameter of the replaceable, spherical carrier 2 is 1 1.0 mm.
  • porous textile fibres 1 14 extending from the sphere 2 are fastened by the element 125.
  • the spherical reservoir 2 contains the solution of the active substance.
  • FIG. 6 shows the micro-infusion device 1 of the invention, the main components of which are the following:
  • the skin-penetrating section of the fixed carrier contains the windowed, biocompatible plastic tube 120 following the removal of the solid lance, insertion needle 6, said lance delivering the insulin and the textile fibres 1 14 into the skin.
  • the micro-infusion device 1 of the invention can be prepared according to the drug safety requirements being well-known for the manufacture of injections, maintaining the sterility of the product.
  • the fixed carrier and the reservoir are packed separately as several reservoirs can be placed or replaced on the same fixed carrier.
  • the invention relates further to the use of the micro-infusion injection device 1 for the administration of insulin.
  • Drugs can exert their effect only if their concentration in the blood remains within the so-called therapeutic window, i.e. it is neither too high, nor too low.
  • ⁇ hydrophilic compounds e.g. dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), dimethyl acetamide (DMA) etc.
  • DMSO dimethyl sulphoxide
  • DMF dimethyl formamide
  • DMA dimethyl acetamide
  • hydrophobic compounds e.g. ethyl acetate, oleic acid etc.
  • surfactants e.g. sodium lauryl sulphate, sorbitan monopalmitate, troiamine, polysorbate 20 etc.
  • miscellaneous compounds e.g. urea, cineol, d-limonenon, lecithin etc.
  • the pH is adjusted, by the slow addition of a solvent or a mixture of solvents and optionally surfactants, preferably of an at least 1 : 1 mixture of troiamine and DMSO to an alkaline domain near 9-10, or a permanent, nearly neutral pH is maintained under slow addition.
  • the nearly neutral pH (6.5-7.0) can be achieved for example by citric acid.
  • the concentration of the insulin is adjusted according to the needs of the patient, which may constitute even a tenfold difference in the case of the individual patients.
  • an insulin solution of 0.45 mixed % is used.

Abstract

The present invention relates to an insulin-dosing micro-infusion device (1) useful for the treatment of diabetes, i.e. for delivering the daily need of insulin, as well as to the method for the use thereof. A micro-infusion device for the subcutaneous administration of an insulin injection composition, ensuring a sustained activity, characterized in that it comprises a fixed carrier (3, 4) or containing porous textile fibres (114), imposable on the skin surface of the body, insertable under the skin and containing an element ensuring the tightness of the fibres, and also comprising a replaceable reservoir (2) containing identical textile fibres, connected to the carrier, storing the solution of the active substance and ensuring the continuous dosing thereof, wherein the fibres coming out of the reservoir are in contact with the fibres in the fixed carrier.

Description

Insulin dosing micro-infusion device useful for the treatment of diabetes
The present invention relates to an insulin-dosing micro-infusion device useful for the treatment of diabetes, i.e. for delivering the daily need of insulin, as well as to the method for the use thereof.
The objective of the invention was to provide a device for administering insulin that is more advantageous compared to the known solutions, which is physically more convenient and less expensive for the patients.
With the device according to the invention - similarly to the known insulin pumps - there is no need for several injections a day, at the same time the costs involved are incomparably lower than in case of pumps. Currently the insulin pump is very expensive, which the majority of people can hardly afford or cannot afford at all. Another drawback of the pumps is that in addition to their expensiveness they have to be changed every two or four years.
Surprisingly, the invented solution provides, by a method based on the principle of capillarity, the continuous administration of the active ingredient through a simple porous textile, e.g. cotton or cloth, and the supply thereof via a replaceable reservoir.
Several delivery systems for administering insulin are known in the art. According to the European Patent Application No. EP 0239244 Al, for instance, a subcutaneous injection set is prepared, which comprises a valve/connecting means on the outer side of its part that can be stuck to the skin, and a flexible cannula to be inserted into the skin by an apparatus, e.g. by a needle on the part to be placed on the skin, and following the placement of the device the solution of the active ingredient is supplied from an outer device (syringe, infusion pump etc.) for continuous or repeated subcutaneous administration, without the need of another insertion.
International patent application No. WO 03/026728 Al discloses a transcutaneous infusion device consisting of a microinjector attached to the skin and equipped with a cannula which can be inserted in a similar manner as described above and of a replaceable feeding device connectable thereto, which is operated by an external force, e.g. by spring force.
Hungarian patent specification No. HU 222,342 Bl relates to a transcorneal drug-release system comprising an active substance reservoir and micro-pins or micro-blades placed on its side next to the skin, said micro-pins having a length corresponding at least to the thickness of the corneal layer of the skin. The device comprises an electronically controlled pump as well.
US Patent Specification No. 3,964,482 describes a drug delivery system for percutaneously administering a drug, comprising a drug reservoir attachable to the skin and a plurality of tubular projections placed on its side to be attached to the skin, and the delivery of the drug is ensured by diffusion or osmotic pressure.
In publication No. WO 2009/015389 A2 a miniaturized patch pump for subcutaneous administration, operated by an electrochemical cell, is disclosed.
Among the above-described solutions, however, no solution can be found, which, according to the invented solution, would represent a subcutaneous continuous delivery system operating without an external resource, based on the principle of capillarity and comprising a replaceable drug reservoir.
Although in the cited US Patent Specification capillary elements (micro-pins) are described, but the system operates by diffusion and the replaceability of the drug reservoir is not mentioned either. In case of the first two cited solutions an auxiliary power is needed for the operation of the dosage reservoir and no capillary element is included.
While US Patent No. 3,964,482 describes capillary elements, the porous element is missing and the replaceable reservoir is operated by an external power.
Accordingly, there still exists the need for a new and simple insulin delivery system by which the insulin can be administered to the patients in an easy to handle and economically advantageous manner.
According to the invention this new insulin delivery system is a micro-infusion device for the subcutaneous administration of an insulin injection composition, ensuring sustained activity, comprising a fixed carrier which contains porous textile fibres, imposable on the skin surface of the body, insertable under the skin and containing an element ensuring the tightness of the fibres, and also comprising a replaceable reservoir connected to the carrier, storing the solution of the active substance and ensuring the continuous dosing thereof, wherein the fibres coming out of the reservoir are in contact with the fibres in the fixed carrier.
The present invention offers the above benefits.
In the following we disclose the invention by providing a detailed description of the preferred embodiments thereof and making reference to the enclosed figures.
The micro-infusion device 1 according to the invention is shown in Figure 6. As it appears from the Figure, the micro-infusion device 1 consists of a replaceable reservoir 2 containing porous textile fibres 1 14 and a fixed carrier 3 or 4 also containing porous textile fibres 1 14.
One of the main components of the invention is the mobilizable, replaceable infusion reservoir 2 containing the insulin. It can be replaced even several times a day thus permitting a dosage according to individual needs. When replaced, the fittings are always perfect, i.e. the sealing is airtight, thereby excluding practically any infection.
The reservoir 2 according to the invention is made of a suitable synthetic material or maybe glass, with a volume capacity of 0.1 ml to 10.0 ml, preferably 0.5 ml. The micro-infusion device 1 is capable of subcutaneously delivering this small amount of insulin into the body continuously and evenly through a whole day.
Owing to its size it is easy and comfortable to wear.
Compared to this, wearing insulin pumps constitutes a significantly bigger problem due to their size and accessories.
Conventionally compositions for infusion are to be used in therapy when the amount of the solution to be administered parenterally is so high (more than 30 ml), which cannot be performed by injection. In this case the infusion, the amount of which generally exceeds 500 ml, is applied intravenously.
In case of the micro-infusion device 1 according to the invention the administration of micro- or milligrams of insulin is based on the theory and practice that the insulin is absorbed from the reservoir 2 through the porous textile, fabric etc., e.g. cotton or cloth fibre(s) 1 14 on the basis of the principle of capillarity and then it is delivered by diffusion, with the aid of the fixed carrier, to the blood-stream.
The other main component of the invention is therefore the fixed carrier which is to be placed on one side onto a suitable surface of the body (insert and stick) and on the other side the reservoir 2 is to be connected thereto. The two main components of the invention are connected by the porous textile fibres 1 14 ensuring the capillarity and constituting the essence of the invention.
The insulin can be delivered under the skin by two variants of the fixed carrier.
Figure 1 shows the solid insertion needle, metal lance 6 positioned in the fixed carrier comprising a plastic tube 4, which needle is provisionally positioned in the plastic tube of the fixed carrier 4.
Figure 2 shows the solid metal lance 5 immovably positioned in the fixed carrier 3, which serves for inserting the textile fibres into the skin and keeping them tight.
Figure 3 shows the side-view of the fixed carrier comprising the plastic tube 4.
Figure 4 shows the fixed carrier 3 comprising the solid metal lance 5 immovably.
In case of the fixed carriers 3 and 4 the material of the solid metal lance 5 having a size and form specifically designed for this purpose as well as the material of the solid insertion needle 6 corresponds to the material of the currently used steel needles for injection and infusion.
Formation of capillaries
This purpose is achieved by vegetable, animal or synthetic, high-porosity twisted fibres. The textile fibres can be combined both in quality and quantity. The surface of the desired capillary is formed by using fibres of identical thickness and quality (porosity) and by fixing the fibres always at the same points. Accordingly, the textile can be vegetable, animal or synthetic fibre or any mixture thereof with arbitrary ratio and quality; the vegetable fibre can be, for example, cotton, hemp, flax, etc., and the animal fibre can be, for example, wool. The cotton and the wollen cloth are preferred. The synthetic fibre can be, for example, nylon fibre etc.
Maintenance of capillary flow
The textile fibres 1 14 and the capillaries therein need continuity in the micro-infusion device 1. They have to be free from wrinkles and buttoning. Furthermore, a minimal space is to be provided for swelling of the fibres. When assembling the fixed carrier 3 or 4 and the replaceable reservoir 2, a continuity has to be maintained in contacting the fibres.
These tasks are solved by the solutions of the invention: The suitable space is ensured by the tubes 1 17 on the fixed carriers 3 and 4, said tubes having a length of 2 mm and intruding into the skin, as shown in Figures 3 and 4; and the thickness of the windowed, biocompatible tube 120 and the size of the windows on the fixed carrier 4 as well as the„injury" in the skin, caused by the 1.6 mm diameter head of the solid lance 5 intruding into the skin in case of the fixed carrier 3.
The tightness of the fibres is guaranteed also by the windowed, biocompatible tube 120 and the lance 5. In the spherical reservoir 2 the textile fibres are fastened to the two opposite sides of the sphere along the line of the diameter.
Controlling the rate of the capillary flow
The rate of delivering the (solution of the) active substance can be controlled by adjusting the size of the capillary surface, the concentration of the solution and the composition of the solvent.
Consequently, several variants can be prepared according to the needs of the market, similarly as in the case of injections.
The device 1 according to the invention provides a slow, extended dissolution and effect for several hours. If the patient applies a reservoir 2 containing a daily amount of insulin, expressed in the international unit (IU), by adjusting the above parameters the patient can ensure for himself the necessary amount of insulin for 24 hours subject to having regular and conscious meals and physically training his body.
If unexpected events occur, i.e. in case of a low blood sugar level (hypoglycaemia) the administration, delivery of insulin can be easily interrupted, and vice versa, in case of a high blood sugar level (hyperglycaemia) the applied reservoir can be changed for a reservoir for higher doses or it is even more expedient to apply a subcutaneous injection. This is the same with the currently used very expensive insulin pumps.
The micro-infusion method is suitable for the transdermal delivery of any other drugs, the therapeutic effect of which can be achieved by a very small quantity (e.g. hormones etc.).
Such a substance is the peptide hormone, the insulin, as used herein.
The insulin is used in the form of a solution, because the capillary flow can occur in such a form only.
Controlling the direction of the capillary flow
It is essential that from the reservoir 2 the solution of the insulin reaches the tissue fluids under the skin, the capillaries with the required speed and in the required quantity. This can be achieved by the solvent used.
Therefore, the micro-infusion device developed according to the invention consists of two main parts, components:
1 ) The„fixed carrier" 3 or 4, which has to be placed on a suitable surface of the body (insert and stick).
2) The reservoir 2 comprising a suitable concentration of the solution of the insulin and porous fibres 1 14, which has to be slid, positioned on the carrier.
1.„Fixed carrier"
The„fixed carriers" have to be placed by using thin (e.g. 0.3 mm) and short (max. 15 mm or 20 mm length) solid metal lances 5 or 6 with the aim of delivering the cotton or cloth fibres 1 14 (at 90o angle with the body surface, i.e. perpendicularly) to the bottom of the skin to a maximum depth of 10 mm, thereby ensuring the „tightness" of the fibres, while the whole carrier is fixed by sticking the self-adhesive surface to the skin.
When using the plastic tube, the„tightness" is provided by the plastic tube 120, thus following the setting, the insertion needle used as an aid, i.e. the lance 6, can be removed immediately, but fixing is performed by sticking in this case, too.
It is necessary to remove these„fixed carriers" every 2-3 days and to insert a new one to another place. One preferred embodiment of the invention is demonstrated by the enclosed figures, which, however, serve for illustration purposes only, without limiting the scope of the invention.
The size and the structure of the solid lance 6 in figure 1 are the following: the lance, insertion needle 6 has a holder 101 of 10-20 mm (the portion 102 of the solid lance, insertion needle 6 in the carrier depends on the height of the carrier),
the section 103 of the solid lance, insertion needle 6 in the skin is maximum 10 mm long,
the diameter of the solid lance, insertion needle 6 is 0.3 mm,
the head 105 of the solid lance, insertion needle 6 has a length of 0.5 mm.
Following the insertion, the lance, insertion needle is drawn out, removed from the skin.
Figure 2 shows the fibre-holding eye 106 of the solid lance 5, having an inner width of 0.5 mm, total width of 1.1 mm, the widened part of the fibre-holding eye 106 being the head 1 12 of the solid lance, having a length of 2.0 mm and a diameter of 1.6 mm, and a 8-mm section of the handle 1 10 of the lance 5, measured from the head 1 12, being in the skin (together with the eye 106). The remaining part is fixed in the carrier. The solid lance 5 is fastened in the carrier 3 and it serves for delivering the textile fibres 1 14 into the skin and for keeping them tight.
As it can be seen in figure 3, the porous textile fibres 1 14 are fastened to the inner surface of the semi- spherical carrier by the fixing element 1 13. The other end of the porous textile fibres 1 14 is fastened to the end of the windowed, biocompatible plastic tube 120 being in the skin.
The spherical reservoir 2 containing the carrier 4 and the solution of the active substance as well as the identical textile fibres 1 14 are fixed by the guiding or bearing rail 1 15.
The carrier 4 is fixed to the skin surface by a round sticker 1 16, a self-adhesive patch (0 40 mm). The permanent hole in the epidermis is maintained by a tube 1 17, having an inner diameter of 1.0 mm, wall thickness of 0.3 mm and a length of 2.0 mm, which can be a short, intact section of the windowed, biocompatible plastic tube 120, directly above the window, while in case of the lance the relating part 1 17 of the fixed, semi-spherical carrier 4 is extended; the height of the semi-spherical fixed carrier 4 being 6 mm; the semi- spherical fixed carrier 4 being fastened to the self-adhesive patch 1 16 by the element 1 19.
The maximum length of the skin penetrating, partially windowed, biocompatible plastic tube 120 is 10 mm; said tube maintains the tightness of the textile fibres 1 14 in addition to serving for the penetration of the active substance.
As it can be seen in figure 4, the porous textile fibres 1 14 are thread through the hole 106 above the lance-head 1 12 and taken back to the inside of the semi-sphere. The two ends of the fibres are fixed on the same place. The outer diameter of the semi-spherical fixed carrier 3 is 9.0 mm and the inner diameter thereof is 6.0 mm. The end of the solid metal lance 6 is fastened by the plastic 123 inside the semi-spherical carrier 3.
2) The reservoir 2 containing the solution of the insulin in a suitable concentration and the cotton or cloth fibre(s) 114, which is to be placed on the carrier 3 or 4
The concentration of the insulin solution has to be adjusted prior to adding it to the reservoir. The concentration of the insulin is adjusted in international units (IU).
The surface of the cotton or cloth fibre(s), i.e. the required capillary is achieved by using cotton or cloth fibre(s) of identical thickness and quality (porosity) and by fixing the fibre(s) always on the same places. In this manner the permanent length, i.e. surface of the cotton or cloth fibre(s) can be ensured.
Figure 5 shows the sectional drawing of the replaceable reservoir 5.
The diameter of the replaceable, spherical carrier 2 is 1 1.0 mm.
The porous textile fibres 1 14 extending from the sphere 2 are fastened by the element 125.
On the sphere 2 there is a hole 126 making it possible that the porous textile fibres 1 14 can get out of the sphere (0 1.5 mm); on the opposite side the porous textile fibres 1 14 are fastened to the wall of the sphere 2 by the element 127.
The spherical reservoir 2 contains the solution of the active substance.
Figure 6 shows the micro-infusion device 1 of the invention, the main components of which are the following:
replaceable reservoir 2,
fixed carrier 3 or 4,
and textile fibres 1 14. The skin-penetrating section of the fixed carrier contains the windowed, biocompatible plastic tube 120 following the removal of the solid lance, insertion needle 6, said lance delivering the insulin and the textile fibres 1 14 into the skin.
Sterility
The micro-infusion device 1 of the invention can be prepared according to the drug safety requirements being well-known for the manufacture of injections, maintaining the sterility of the product.
Expediently the fixed carrier and the reservoir are packed separately as several reservoirs can be placed or replaced on the same fixed carrier.
The invention relates further to the use of the micro-infusion injection device 1 for the administration of insulin.
Chemical methods enhancing the absorption of the drug
Drugs can exert their effect only if their concentration in the blood remains within the so-called therapeutic window, i.e. it is neither too high, nor too low.
Chemicals and solutions enhancing absorption
· hydrophilic compounds (e.g. dimethyl sulphoxide (DMSO), dimethyl formamide (DMF), dimethyl acetamide (DMA) etc.)
• hydrophobic compounds (e.g. ethyl acetate, oleic acid etc.)
• surfactants (e.g. sodium lauryl sulphate, sorbitan monopalmitate, troiamine, polysorbate 20 etc.)
· miscellaneous compounds (e.g. urea, cineol, d-limonenon, lecithin etc.)
The above solvents and chemicals can be freely combined.
In order to increase the extended release of the injection solution, the pH is adjusted, by the slow addition of a solvent or a mixture of solvents and optionally surfactants, preferably of an at least 1 : 1 mixture of troiamine and DMSO to an alkaline domain near 9-10, or a permanent, nearly neutral pH is maintained under slow addition. The nearly neutral pH (6.5-7.0) can be achieved for example by citric acid.
Under pH 7.5 the insulin reversibly becomes inactivated. When the pH is reduced to neutral pH, the effect of the insulin is exerted again. In the body the solution, combining with the body fluids and the blood, becomes diluted, and the pH value of 9- 10 of the solution is slowly restored to the neutral value, thereby making it possible for the insulin to exert its effect.
The concentration of the insulin is adjusted according to the needs of the patient, which may constitute even a tenfold difference in the case of the individual patients. Preferably an insulin solution of 0.45 mixed % is used.
The invention is further illustrated with the following non-limiting examples:
EXAMPLES
Composition of the solutions:
Example 1
Dimethyl sulphoxide (DMSO) 2.0 ml
troiamine 2.0 ml
distilled water for injection 1.0 ml
insulin 100 NE (0.0045 g) pH = 9- 10
Example 2
Dimethyl suiphoxide (DMSO)
trolamine 2.0 ml citric acid monohydrate
distilled water for injection 1.0 ml insulin 100 NE (0.0045 g) pH = 6.7-7.0

Claims

Claims
1. A micro-infusion device ( 1) for the subcutaneous administration of an insulin injection composition, ensuring a sustained activity, characterized in that it comprises a fixed carrier (3) or (4) containing porous textile fibres ( 1 14), imposable on the skin surface of the body, insertable under the skin and containing an element ensuring the tightness of the fibres, and also comprising a replaceable reservoir (2) containing identical textile fibres (1 14), connected to the carrier (3, 4), storing the solution of the active substance and ensuring the continuous dosing thereof, wherein the fibres ( 1 14) coming out of the reservoir (2) are in contact with the fibres ( 1 14) in the fixed carrier (3) or (4).
2. A micro-infusion device (1) as claimed in Claim 1 , characterized in that on the fixed carrier (3) or (4) there is a replaceable infusion reservoir (2) containing the given concentration of the active substance and the porous textile (1 14), where the capillary flow of the injection solution is ensured to the bottom of the skin.
3. A micro-infusion device (1) as claimed in Claim 1, characterized in that in addition to the known self-adhesive patch (1 16) securing the fixing of the device to the skin surface, the fixed carrier (3) contains a solid metal lance (5) ensuring the tightness of the porous textile fibres ( 1 14) and having an eye (106) for drawing the fibres.
4. A micro-infusion device (1) as claimed in Claim 1 , characterized in that the fixed carrier (4) contains a plastic tube (120) having an opening (120) on the opposite sides, by which the tightness of the porous textile fibres (1 14) is ensured.
5. A micro-infusion device ( 1) as claimed in Claim 4, characterized in that a solid lance (6) can be inserted into the plastic tube ( 120) for promoting the insertion of the fixed carrier (3) into the skin.
6. A micro-infusion device (1) as claimed in any of Claims 1 to 5, characterized in that it comprises twisted vegetable, animal or synthetic fibres or a mixture thereof, preferably twisted cloth or cotton fibres.
7. A micro-infusion device ( 1) as claimed in any of Claims 1 to 6, characterized in that it comprises the insulin in the mixture of solvents maintaining the capillary flow and optionally surfactants.
8. A micro-infusion device ( 1) as claimed in any of Claims 1 to 7, characterized in that for ensuring the sustained activity of the injection solution in the reservoir (2), the pH of the solution is adjusted, by the slow and even addition of a solvent and optionally a surfactant, preferably of an at least 1 : 1 mixture of trolamine and DMSO, to an alkaline domain near 9- 10; or a permanent, nearly neutral pH is maintained by slow, even addition.
9. Method for using the device as claimed in Claim 1, characterized in administering insulin with the device ( 1 ) as claimed in any of Claims 1 to 8.
PCT/HU2010/000098 2009-09-21 2010-09-15 Insulin dosing micro-infusion device useful for the treatment of diabetes WO2011033328A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU0900596A HU227748B1 (en) 2009-09-21 2009-09-21 Microinfusion device for dosing insuline in the treatment of diabetes
HUP0900596 2009-09-21

Publications (1)

Publication Number Publication Date
WO2011033328A1 true WO2011033328A1 (en) 2011-03-24

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WO (1) WO2011033328A1 (en)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3964482A (en) 1971-05-17 1976-06-22 Alza Corporation Drug delivery device
US4159720A (en) * 1977-11-28 1979-07-03 Burton Andrew F Infusion of liquids into tissue
EP0239244A1 (en) 1986-02-25 1987-09-30 Pacesetter Infusion Ltd. Subcutaneous injection set
WO2003026728A1 (en) 2001-09-27 2003-04-03 Unomedical A/S Injector device for placing a subcutaneous infusion set
HU222342B1 (en) 1995-07-14 2003-06-28 Boehringer Ingelheim Kg Transcorneal drug-release system
WO2006127905A2 (en) * 2005-05-24 2006-11-30 Chrono Therapeutics, Inc. Portable drug delivery device
WO2009015389A2 (en) 2007-07-26 2009-01-29 Entra Pharmaceuticals Inc. Skin-patch pump comprising a changing-volume electrochemical actuator

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3964482A (en) 1971-05-17 1976-06-22 Alza Corporation Drug delivery device
US4159720A (en) * 1977-11-28 1979-07-03 Burton Andrew F Infusion of liquids into tissue
EP0239244A1 (en) 1986-02-25 1987-09-30 Pacesetter Infusion Ltd. Subcutaneous injection set
HU222342B1 (en) 1995-07-14 2003-06-28 Boehringer Ingelheim Kg Transcorneal drug-release system
WO2003026728A1 (en) 2001-09-27 2003-04-03 Unomedical A/S Injector device for placing a subcutaneous infusion set
WO2006127905A2 (en) * 2005-05-24 2006-11-30 Chrono Therapeutics, Inc. Portable drug delivery device
WO2009015389A2 (en) 2007-07-26 2009-01-29 Entra Pharmaceuticals Inc. Skin-patch pump comprising a changing-volume electrochemical actuator

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HU227748B1 (en) 2012-02-28
HUP0900596A2 (en) 2011-05-30

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