HU227748B1 - Microinfusion device for dosing insuline in the treatment of diabetes - Google Patents

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

Micro-Hyphilis Dispenser for Diabetes Treatment and Price of Dough Juice

ÍX. ,, ^ν5 χ · · ^ ": ·: χ, _s'" RIS ^Wfix Xá & invention for the treatment of diabetes, namely to ensure the aapi iozulioszükséglet inzulinadagolo micro-infusion device.The - ^ '^ késxükík'síWmírzásársr'vrmíb h' process-áweA newpsV ,.

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The object of the present invention was to provide physically and physically more advantageous patients than the prior art

Let's find a cost-saving device for administering insulin.

The device according to the invention, like the known injection pumps, does not require multiple injections of .1X1 per day, yet the costs are incomparably lower than those of inflatables.

r ^ x ·: xxíx S sssSi </> Currently, an Inzui Inpump is extremely expensive, anti is hardly available or unavailable to the majority. The disadvantage of glamor is still. that they need to be replaced every 2 or 4 years, in addition to their cost.

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Surprisingly, the method according to the present invention is a simple porous textile material, e.g. cotton or cloth can be used to ensure continuous dosing and supply of the active ingredient with a removable container.

Dosage delivery systems for the administration of insulin are known in the art. EP 023-9244 A1. For example, a subcutaneous injection kits having a. a leather pad on the outside with a valve soap and a skin on the outside with an aid eg. the bases contain a flexible cannula injectable into the skin and, after insertion of the device, receive the active ingredient from an external device (syringe, infusion pump, etc.), for continuous or repeated subcutaneous administration without the need for further intervention.

WO 93/026728 A1. International Patent Application No. 5,484,011 discloses an infusion device for U&S, which, similarly to the principle described above, can be delivered from a microrjector fixed on the skin of its cannula and connected to it by external force e.g. spring operated interchangeable fluid dispenser 1.

HU 222342 Bis no. U.S. Patent No. 5,123,151 relates to a trauma-corneous drug delivery readset consisting of a reservoir of active ingredient and microforms or micro-edges located at the skin surface thereof, at least as long as the corneal skin layer. The device comes with an electronically controlled pump.

No. 3,964,482. U.S. Pat.

WÖ 20 (19/015389 A2) discloses a miniature subcutaneous delivery patch pump operated by an electrochemical cell.

However, the above-described solutions do not provide a solution according to the present invention which provides a subcutaneous continuous delivery system that operates on the capillary principle and has replaceable active ingredient reservoirs without external resources.

Although the US patent discloses capillary elements (microspins), it exerts its effect by diffusion and does not increase the interchangeability of the hafoil material reservoir.

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The first two solutions mentioned above do not contain the auxiliary energy necessary for the operation of the metering tank and the capillary element.

U.S. Pat. No. 3,964,482 discloses capillary elements, but lacks the porous carrier element and the removable reservoir and is powered by external force.

So it still exists. the need for a oral and simple insulin delivery system that provides patients with insulin that is easy to handle and economically advantageous,

According to the present invention, this novel insulin delivery system is a micro-infusion device for subcutaneous administration of a insulin infusion: composition having a sustained action, characterized in that it comprises a porous textile fiber which can be placed on the skin surface of the body and injected under the skin. comprising a removable container for maintaining a solution of the active substance in the carrier and a fiber containing textile fibers also provided therein, and where the fibers leaving the container are in contact with the fibers in the fixed carrier.

The present invention provides the above advantages.

In the following, detailed description of the preferred embodiments of the invention will be described with reference to the accompanying drawings.

The microinfusion device (1) according to the invention is provided in the fi. . It will be appreciated from Fig. 1 that the microfusion device (1) consists of a removable container (2) containing porous textile fibers and also a fixed support (3) or (4) containing porous textile fibers,

One of the main elements of the present invention is a movable, replaceable (2) infusion container containing Inznim. It allows multiple daily changes as needed, i. When replacing, the joints are always perfect, ie the closure is hermetic, so virtually no infection is possible.

The container (2) of the present invention is made of a suitable material, possibly glass, of a capacity of:

0.1 ml · 10.0 ml, preferably 0.5 ml. Α · ζ: (I) The micro-infusion device can deliver this small amount of insulin continuously and evenly subcutaneously for up to one day.

Due to its size it provides easy and comfortable wearing,

On the other hand, wearing insomnia pumps is a much bigger problem because of their size and fittings.

In the conventional sense, infusion formulations should be used in medicine • when the amount of ocular to be administered in the pituitary gland is more than the following ml) which cannot be resolved by injection. In this case, they are administered intravenously to the tendon, which usually exceeds 500 ml,

In the case of the ml-microfossil device (1) of the present invention, the microsol. The theoretical and practical basis for the administration of müligrarntnayi amounts of Insulin is to provide (114) porous textiles, tissues, etc., which are delivered to the skin's bottom. e.g. Insulin is absorbed from the reservoir (2) through the cotton or cotton fiber (s) according to the capillary principle and diffused from there into the bloodstream by means of a fixed carrier.

The other element of the invention is thus a fixed support which is pierced and glued on one side of the body, and on the other side the articula (2) is to be attached.

The two main elements of the invention are joined by the Jeteme porous textile fibers (I 14) which provide the cap.

There are two variants of fixed carriers that can deliver insulin under the skin.

Fig. I shows a solid guide, <RTI ID = 0.0> lance </RTI> which is located in a fixed support (4) of plastic belt (4). e-salt-ish are idelgleneseo ..

Fig. 2 shows a solid metal jean (5) fixedly contained in a fixed support (3), which serves to introduce and tighten the textile fibers (114) into the skin.

Fig. 3 shows a side view of a fixed support for a plastic pipe sawdust (4)

Fig. 4 illustrates a fixed carrier ö) containing a fixed template (5) fixedly.

In the case of the fixed carriers (3) and (4), the solid metal lance (5) specially adapted for this purpose and the solid introduction material (6) are the same as the material for injection or infusion steel used today.

Securing capillaries

This is what the (1 1.4) serves. növésyí. animal or plastic materials of high porosity, spun. Textile fibers can be mixed qualitatively and quantitatively. The desired capillary surface is obtained using fibers of the same thickness and quality (porosity), and fixing the fibers to the same position at the tooth. let's create it. The fabric can thus be a plant, a mural or a synthetic fiber, or a mixture of any proportion and quality. cotton, hemp, flax, etc., animal fiber can do pi. wool. Cotton and woolen cloth are preferred. Plastic fiber can make eg, nylon fiber etc.

Provision of capillary flow

The textile fibers (114) and the capillaries therein are provided with a brush in the microfusion device. continuity. They should be wrinkled and free from crumbling. Furthermore, the fibers should have minimal space for swelling at all times. Ensure continuity when fitting the fixed support (3} or (4) and the removable container (2) when the fibers are in contact.

These conditions are provided by the solutions of the present invention. In Figure 4, the visible skin penetration 2 susceptibility tubes (117) are for the fixed carrier (3,4) and for the fixed carrier (14) are the thickness and size of the window tissue (12.0) and the windows (3). ) in the case of a fixed carrier, the "injury" to the skin caused by the 1.6 mm diameter milk of the penetrating solid spear (5).

The tension of the fibers is also guaranteed by the fabric-friendly plastic tube (120) with a lance <5). In the spherical container (2), the textile fibers are fastened to the opposite side of the sphere along the diameter line.

Providing capillary flow velocity

The rate of administration of the drug (soda) can be controlled by adjusting the size of the capillary joint, the concentration of the solution and the composition of the solvent.

It follows that, depending on the needs of the market, we can implement a more youthful type, as is the case with injections.

The device (I) of the present invention provides a slow, steady, sustained release over several hours and a list of> * * «« Φ V Λ «X * ♦♦ * * * Φφ« χ list. When an individual places a reservoir of insulin (.2) in International Units (IU) appropriate to their daily requirements, he provides insulin for up to 24 hours with regular and conscious meals, and by adjusting the above parameters. when exercising physically.

In case of unexpected events, ie low blood sugar levels (hypoglycemia), the administration of insulin may be interrupted with tears, or high blood glucose levels (in hyperglycemia, a higher dose of the container may be replaced by a container, or even better by injection). this is also the case with the very expensive pantal pads used today.

A. The microarray method is suitable for the transdermal administration of any drug which requires a very small amount of therapeutic effect (eg hormones, etc.),

One such substance is the peptide hormone used in our case, insulin.

Use insulin in the form of a solution because capillary flow is in this form! a.

Ensure capillary flow direction

It is essential that the insulin solution from the reservoir (2) is directed to the subcutaneous tissue fluids, capillaries, at the desired rate and amount. This is ensured by the solvent used. The micro-lysis device 11) developed according to the invention thus consists of two main parts:

(3.1 or (4) "Fixed substrate to be applied to the appropriate surface of the body (stems and glue),

2.Z A container (2) containing an appropriate concentration of the insulin solution and the porous fiber (s) (114) to be mounted on the substrate.

1. / “Fixed media

When installing "fixed supports", thin metal lances (eg 0.3 rt!! And short (5 or 6 mm maximum) (5) or (6) solid metal lances should be used to ensure that the fi 14) Cotton or Post-Fiber (at an angle of $%%> s to the body surface), perpendicular to the bottom of the skin, should be applied to a maximum depth of IQ tnm to ensure that the fibers are “stretched” while adhering to the skin fix the whole medium,

In the plastic tube process; the "tightness" is provided by the plastic esd (120), so that after the insertion, the auxiliary insert (6), which is used as auxiliary means, can be removed immediately, but also the fixed feeding. glue.

These "fixed media" should be removed every 2-3 days and then replaced with another,

A preferred embodiment of the present invention is illustrated by the accompanying drawings, which, however, are for purposes of purity only and are not limiting.

The construction and size of the solid spear (shown in Fig. 1) is as follows: the spear (6) has a 10-20 mm (stroke) gripper, the solid spear (6) being inserted into the carrier tube (102). part (depends on the height of the carrier), the main) of the solid lance, the inlet section (103) in the skin up to a maximum of mm mm, and the diameter of the (6) solid lance, inlet needle 0.3 mm, the solid lance (6) The tip of (105) is 0.5mm revenge.

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After inserting, the spear is pulled out as an introduction. and removed from the skin.

Fig. 2 shows a divergent hole (106) in a solid lance (5) having an internal width of 0.5 mm, a total width (Li tnm), the enlarged portion of the stem (106) being a solid lance (112). head, its annoyance (2, (1 mnt) _x having a diameter (1.6 mm), 8 sm from the head (1 12) of the spear-stem section (1) to the skin; The other is secured in the carrier The solid metal lance (5) is fixed in the carrier (3) and serves for the introduction and tightening of the textile fibers (114).

As shown in Figure 3, the porous textile fibers (.114} are secured to the inner surface of the semi-rigid substrate by the fastening portion (113) .The other end of the porous textile fibers (114) is secured to the skin-end of the webs .

The conductive or support rail (11) serves to secure the carrier (4) and the spherical container (2) containing the active ingredient solution and the same textile fibers (114).

The substrate (4) is fixed to the skin by a circular adhesive (1 shot) adhesive patch (0 40 »).

The continuous opening (1?) Of the epithelial layer is provided by a tubing having an inside diameter of 1.0 mm, a wall thickness of 0.3 mm, and a length of 2.0 operas, which may be a short intact section of the window-woven (120) plastic tube. , directly. above the window, while in the case of the lance the portion (I 17) of the fixed hemispherical carrier (4) is extended, the height of the hinged fixed carrier (4) (mm) the hinged carrier (4) shoot) Fix to the self-adhesive patch (119).

The skin-penetrating, partially-windowed, fabric-shaped 1120} plastic has a rain-length of up to 10 mtm, which also provides a firm hold on the (114) · fibrous filaments of the active agent penetration breasts,

Figure 4 shows that the dust (? .14}, the textile fibers, is stitched through the hole (106) above the head of the lance (112) and streamed back into the inside of the hemisphere.) The two ends of the fibers are fixed in the same place. The outer diameter of the solid support (3; 9.0 mm) and the inner diameter of the solid support (3) is 6.0 mm. The end of the solid metal lance (5) is secured by the plastic (123} to the hemispherical shape inside the carrier;

2. / A container (2) containing a suitable machine-centered solution of insulin and a cotton or staple fiber (I84}) to be placed on a support (3) or (4),

The concentration of the insulin solution in the reservoir should be adjusted before filling. Insulin concentrations are set in international units (to ME).

The cotton or staple (s), i.e., the desired capillary surface, is solved using the same thickness and quality (porosity) of cotton or staple (sk), and the staples are always fixed in the same places to secure the cotton or staple) the constant annoyance, that is, the elves.

Fig. 5 shows a cross-sectional view of the removable container (2).

The removable (2) spherical container has a diameter of 11.0 rtus ?.

The porous textile fibers exiting the ball (2) are secured by the portion (125).

The sphere (2)? There is a hole (126) which allows the porous textile fibers (114) to escape from the ball (0 1.5 mm) on the opposite side of the porous textile fiber <: (2) secured by the portion (127),

The spherical container (2) contains the active ingredient solution.

Fig. 6 shows an msh-o-infusion device (I) of the invention, the ib elements of which are the removable container (2);

O) or (4) a fixed support and the textile fibers (114).

The skin-penetrating portion of the fixed carrier contains the window-free, tissue-friendly (12) plastic tube containing insulin and the (. 14) textile fibers after removing the dense lance (6) that delivers the skin.

Sterility

Have the preparation of the tinro-infusion device according to the invention been carried out in accordance with well-known potency tests for injection production? seven weeks, maintaining product sterility.

It is advisable to carry out the borehole of the fixed carrier and container: it is possible to carry out a berth as several tanks can be installed and replaced on the same fixed carrier.

The invention also relates to the use of a (1) -necrosisphosphonose injection device for the administration of insulin.

Chemical methods to aid drug absorption

Medicines can only work when they are in bed if their blood levels are so called. within the therapeutic window, that is, neither needle high nor bowl low,

Absorption chemicals, solvents.

Hydrophilic compounds (e.g., dimethyl sulfoxide (DMSO), dbnstiMónnamld (DMF), dimethylacetal.d. (DMA), etc.).

»-Hydrophobic compounds (eg ethyl acetate, oleic acid, etc.)» - surfactants (e.g., α-sodium lauryl sulfate, sorhitan monopalnate, trolarine, polysorbate 20, etc.) ♦ various compounds (eg carbamld, innol) , d-lhnonenos, lecithin, etc.)

A. Solvents or chemicals may be co-incubated as desired.

Enhanced Cellular Effect of Cellulose Injection Solution from Cell. the dosage forms for the bulk administration with the pH or solvent and optionally with surfactants. preferably trromoline and. dtaso with a mixture of at least 1: 1 for approx. The pH is adjusted to about 9-10, or is maintained at near neutral pH only by slow addition. The near neutral (6.5-7.0) pH is e.g. citric acid.

Insulin is reversibly inactivated above pH 7.5. If ρϊ-ϊ-i is reduced again to neutral p-H, the effect of insulin will reappear. In the body, the solution is diluted and mixed with your tissue and blood, and the pH of the solution is slowly restored to neutral so that the insulin can work again.

Confidence of concentration is adjusted according to the needs of the patient, which can be up to ten times the difference: it can mean for each patient. Preferably a 0.45% w / w solution of inlinlin is used.

Further details of the invention are illustrated by the following non-limiting examples:

EXAMPLES * * ♦ ♦ * ♦ X X Λ ♦ «« « * * ♦ »» X * * * ** ♦ «« «« * - ♦ ♦ V «« * X * ♦ ♦♦ ií χ » Solution composition: Example 1 charge methylsulfox id (DMSO) 2.0 tnl action lure » 2.0 nt! distilled water for injection 1.0 nti insulin 100 IU (0.0045 g) pH 9-10 Example 2 dimethylsulfoxide (DMS0) 2.0 tnl treiamin 2.0 ml citric acid monohydrate 0.95 g distilled water for injection 1.0 ml insulin 100 IU (0.9045 g)

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Claims (8)

i. Microinfusion device for subcutaneous administration of insulin injection preparation {{), comprising a fixed carrier (114) containing porous textile fibers, which can be applied to the skin surface and injected under the skin (3). Or (4) and a removable container (2) containing a solution of the active ingredient (4) and the same textile fibers (114), connected to the carrier (3,4), to provide a solution for liquid application, and where the fibers (114) are in contact with the fibers (114) in the carrier (3) or (4). The micronization device (I) according to claim I, characterized in that the fixed support (3) is? Part (4) is provided with a specific concentration of the active ingredient in a replaceable infusion container (2) containing a solution and a porous fabric (114), wherein: the capillary flow of the injection solution is provided to the bottom of the skin. The microinhibitory device (;) according to claim 1, characterized in that, in addition to the known self-adhesive patch (I horse) for securing the device to the skin surface, the fixed support (3) is a solid support for porous textile fibers (114). at the end it contains a metal spear (5) having a hole (horse) for threading the fibers. Microfluidic device (1) according to claim 1, characterized in that the fixed support (4) comprises an open plastic tube (120) on the two opposite sides of which the porous textile fibers are held tight. Microinfusion device (I) according to claim 4, characterized in that a dense lance (6) can be inserted into the plastic tube (120) to facilitate the delivery of the fixed support (3) to the skin. An xaikrotic cooking device (1) according to any one of claims 1 to 5, characterized in that the porous fabric comprises spun yarns of vegetable, animal or plastic origin or mixtures thereof, preferably spun yarns or cotton yarns. Device according to any one of claims 1 to 1, characterized in that the insulin is contained in solvents and optionally surfactants which provide capillary flow. 8, 1-7. Device according to any one of claims 1 to 3, characterized in that it provides a sustained action of the injection solution in the container (2). with a slow and steady dose, the pH of the solution, with a mixture of solvent and optionally surfactant, preferably at least 1: 1 in the ratio of trolamia-OMSO, is within the log range of 9 to 10 or only slow and with a steady dose, a near neutral pH is achieved.