METERING DEVICE FOR DISPENSING MEDICATION FLUID

Abstract

A metering device for dispensing medication fluid includes: a spindle unit, a drive unit for rotationally driving the spindle unit, and a reservoir for the medication fluid. The reservoir has a wall, which defines a cross-sectional area of the reservoir, and a plunger located in the reservoir. The rotational driving of the spindle unit causes a translational motion of the plunger, and therefore displaces medication fluid. Because the product of the cross-sectional area of the reservoir in the unit mm.sup.2 and the spindle pitch in the unit mm/degree is less than 0.13 mm.sup.3/degree and the medication fluid is a liquid insulin having a concentration in a range of U20 to U100, a metering system can be formed that is suitable specifically for the CSII therapy of children and youth, where high discharge accuracy is important for good therapy control.

Claims

1. A metering device (D) for dispensing medication fluid, said metering device (D) comprising: a) a spindle unit (S) having a constant spindle pitch (p); b) a drive unit (M) for rotational driving of the spindle unit (S); c) a reservoir (A) for the medication fluid, wherein the reservoir (A) has a wall (3), which defines a cross-sectional area (Q) of the reservoir (A); and d) a plunger (K) situated in the reservoir (A), wherein the rotational driving of the spindle unit (S) causes a translational movement of the plunger (K) so that the plunger (K) is movable relative to the wall (3) of the reservoir (A) for displacement of the medication fluid, characterized in that the product of the cross-sectional area (Q) of the reservoir (A) in units of mm.sup.2 and the spindle pitch (p) of the spindle unit (S) in units of mm/angular degree is less than 0.13 mm.sup.3/angular degree, and the medication fluid is a liquid insulin in a concentration in a range of U20 to U100.

2. The metering device according to claim 1, characterized in that the medication fluid is a liquid U100 insulin and/or the volume of the reservoir (A) is in the range from 200 to 1000 mm.sup.3.

3. The metering device according to claim 1 or 2, characterized in that the cross-sectional area (Q) of the reservoir (A) is greater than 24 mm.sup.2.

4. The metering device according to any of claims 1 to 3, characterized in that the product of the cross-sectional area (Q) of the reservoir (A) in units of mm.sup.2 and the spindle pitch (p) of the spindle unit (S) in units of mm/angular degree is less than 0.08 mm.sup.3/angular degree, and the cross-sectional area (Q) is greater than 32.2 mm.sup.2.

5. The metering device according to any of claims 1 to 4, characterized in that the spindle pitch (p) is in a range from 0.2 mm/revolution to 1.0 mm/revolution, units converted to a range of 0.00056 mm/angular degree to 0.0028 mm/angular degree.

6. The metering device according to any of claims 1 to 5, characterized in that the drive unit (M) has a motor (15) as the drive element and has a gear (16) driven by the motor (15) with a gear reduction ratio (i) for stepping down the motor angle.

7. The metering device according to claim 6, characterized in that the gear reduction ratio (i) of the gear (16) is in the range of 200 to 2000.

8. The metering device according to any of claims 1 to 7, characterized in that the spindle unit (S) has a spindle nut (2) and a spindle rod (1).

9. The metering device according to claim 8, characterized in that the spindle unit (S) is arranged in the plunger (K) and is drive by an driving rod (19) arranged on the transmission output, wherein the driving rod (19) has an axial stop (22) for supporting the spindle unit (S) in the delivered state.

10. The metering device according to claim 9, characterized in that the spindle rod (1) is fixedly connected to the plunger (K), and the spindle rod (1) is driven by the driving rod (19), wherein an external thread (25) on the spindle rod (1) engages with an internal thread (26) on a twist-proof-locking spindle nut (2), thereby forming a spindle drive (27).

11. The metering device according to claim 10, characterized in that the spindle rod (1) is retracted in a starting state prior to filling the reservoir (A), and the plunger (K) together with the spindle unit (S) can be displaced for filling the reservoir (A) with a pull-up rod (12).

12. The metering device according to claim 10, characterized in that the spindle rod (1) is extracted in a starting state prior to the filling of the reservoir (A), and the wall (3) has an axial stop (21) for the spindle nut (2), preventing any displacement of the spindle nut (2) in the direction of conveyance.

13. The metering device according to claim 12, characterized in that in a reverse rotation of the driving rod (19), the spindle nut (2) is supported on its stop (21) formed on the wall (3).

14. The metering device according to claim 9, characterized in that the spindle rod (1) is driven to rotate by the driving rod (19) wherein the spindle rod (1) has an external thread (25) and engages with an internal thread (26) of a twist-proof-locking spindle nut (2), thereby forming a spindle drive (27), and the spindle nut (2) is fixedly connected to the plunger (K), so that the plunger (K) executes only a translational movement in the delivery of medication fluid.

15. The metering device according to claim 14, characterized in that in a starting state prior to filling the reservoir (A), the spindle nut (2) is in the retracted state and the plunger (K) holding the integrated spindle unit (S) is displaceable in the forward direction and in the opposite direction by means of a pull-up rod (12) for filling the reservoir (A).

16. The metering device according to claim 14, characterized in that the twist-proof-locking spindle nut (2) is extracted in a starting state prior to filling the reservoir (A), and the wall (3) has an axial stop (21) for the spindle rod (1), preventing a displacement of the spindle rod (1) in the direction of delivery.

17. The metering device according to claim 16, characterized in that with a reverse rotation of the driving rod (19), the spindle rod (1) is supported via its stop (21) formed on the wall (3).

18. The metering device according to claim 16, characterized in that the spindle rod (1) is designed in two parts, wherein the one part is designed as a spindle rod (1) driven by the driving rod (19) and having an external thread (25), while the second part is designed as a disk (24), wherein an axial force of the spindle rod (1) is accommodated on another radius (29) in operation in reverse, and the disk (24) conducts the axial force on an outer radius (30) to the wall (3) of the reservoir (A).

19. The metering device according to any of claims 1 to 18, characterized in that the wall (3) of the reservoir (A) is cylindrical and surrounded by an outside wall (6) in the axial direction, wherein the reservoir (A) can be fixedly connected to a housing (8) by means of the outside wall (6).

20. The metering device according to claim 19, characterized in that the outside wall (6) of the reservoir (A) can be connected to the housing (8) by means of a bayonet connection (14) and the reservoir (A) in the housing (8) is thereby secured axially, wherein the bayonet connection (14) secures the reservoir (A) axially in the direction of forward movement as well as in the opposite direction.

21. The metering device according to any of claims 10 to 20, characterized in that attempts to provide a twist-proof locking of the spindle nut (2) are accomplished by means of longitudinal grooves.

22. The metering device according to any of claims 10 to 20, characterized in that the spindle nut (2) has radial wings (10) by means of which the spindle nut (2) is supported on an inside wall (11) of the outside wall (6), and the spindle nut (2) is locked in a twist-proof manner.

23. The metering device according to any of claims 1 to 22, characterized in that the metering device (D) is suitable for metering insulin in an insulin pump.

24. Use of a metering device according to any one of the preceding claims as an insulin pump, in particular for children and young people.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Exemplary embodiments of the invention are described below in greater detail on the basis of the drawings, in which:

[0038] FIG. 1a shows a first design range for an metering device according to the invention in comparison with the design ranges of the systems of the first and second generations,

[0039] FIG. 1b shows the diagram shown in FIG. 1a, wherein the design range for forming metering devices has been supplemented with a reduced sensitivity for the diameter error,

[0040] FIG. 1c shows a second design range for a metering device according to the invention in comparison with the design ranges of the systems of the first, second and third generations,

[0041] FIG. 2a shows a first exemplary embodiment of a reservoir having an integrated spindle unit and a pull-up rod in a starting condition in longitudinal section,

[0042] FIG. 2b shows the reservoir which is shown in FIG. 2a and is connected to a drive unit, to form a metering device according to the invention in longitudinal section,

[0043] FIG. 2c shows the reservoir illustrated in FIG. 2a in a view from beneath,

[0044] FIG. 3a shows a second exemplary embodiment of a metering device according to the invention in a starting state before filling in a longitudinal section,

[0045] FIG. 3b shows the metering device illustrated in

[0046] FIG. 3a, in a longitudinal section after filling,

[0047] FIG. 4a shows a reservoir with a spindle rod formed from two parts in a longitudinal section,

[0048] FIG. 4b shows the reservoir illustrated in FIG. 4a in cross section to the longitudinal axis,

[0049] FIG. 5a shows a third exemplary embodiment of a reservoir with an integrated spindle unit and a pull-up rod in a starting state in longitudinal section,

[0050] FIG. 5b shows the reservoir which is illustrated in FIG. 5a and is connected to a drive unit, for forming a metering device according to the invention in longitudinal section,

[0051] FIG. 6a shows a fourth exemplary embodiment of a metering device according to the invention in a starting status in longitudinal section before being filled and

[0052] FIG. 6b shows the metering device illustrated in FIG. 6a in a longitudinal section after being filled.

METHODS FOR IMPLEMENTING THE INVENTION

[0053] The invention has taken as its goal to design a metering device such that extremely small metering amounts can be dispensed accurately and precisely. The basis for optimization of such a system is the law of error propagation according to Gauss which is described here in general in a first step and then is applied to a metering device. On the basis of the conclusions, which follow from this, finally a metering device can be optimized in such a way that it can yield an improved accuracy in dispensing extremely small metering amounts.

[0054] For optimization of the metering device consisting of a drive unit, a spindle unit driven by the drive unit and a reservoir for a medication fluid, wherein the reservoir has a wall and a plunger held in the wall, the law of error propagation according to Gauss is applied. This law is described by the following general equation for a function having three independent variables f(x.sub.1, x.sub.2, x.sub.3):

[00001]$\Delta .Math..Math.f^2={\left(\frac{d.Math..Math.f}{d.Math..Math.x_1}\right)}^2.Math.\Delta .Math..Math.x_1^2+{\left(\frac{d.Math..Math.f}{d.Math..Math.x_2}\right)}^2.Math.\Delta .Math..Math.x_2^2+\left(\frac{\mathrm{df}}{d.Math..Math.x_3}\right).Math.\Delta .Math..Math.x_3^2$

[0055] The error of a function having three variables can thus be calculated by deriving the function according to the respective variables and adding that to their tolerance. The Gaussian approach says that one does not add up the derivations multiplied times their tolerance but instead one adds up their squares. A single error square therefore corresponds to a variance in which the three error variances are added. Finally, to obtain the error tolerance for the entire system, the root of the total error tolerance must be taken:

[00002]$\Delta .Math..Math.f=\sqrt{{\left(\frac{\mathrm{df}}{{\mathrm{dx}}_1}\right)}^2.Math.\Delta .Math..Math.x_1^2+{\left(\frac{d.Math..Math.f}{d.Math..Math.x_2}\right)}^2.Math.\Delta .Math..Math.x_2^2+{\left(\frac{d.Math..Math.f}{d.Math..Math.x_3}\right)}^2.Math.\Delta .Math..Math.x_3^2}$

[0056] The percentage influence of a single factor is obtained by dividing a single variance of a independent factor by the total variance:

[00003]${\mathrm{error}}_i=\frac{{\left(\frac{\mathrm{df}}{{\mathrm{dx}}_i}\right)}^2.Math.\Delta .Math..Math.x_i^2}{{\left(\frac{\mathrm{df}}{{\mathrm{dx}}_1}\right)}^2.Math.\Delta .Math..Math.x_1^2+{\left(\frac{d.Math..Math.f}{d.Math..Math.x_2}\right)}^2.Math.\Delta .Math..Math.x_2^2+{\left(\frac{d.Math..Math.f}{{\mathrm{dx}}_3}\right)}^2.Math.\Delta .Math..Math.x_3^2}$

[0057] The derivations df/dx.sub.i are referred to as sensitivities in mathematics.

[0058] On the basis of the theoretical principles just described, the Gaussian error propagation law will now be used. As the first step, the variable that is of interest and is to be analyzed is determined. In order to be able to analyze a metering device of the type described here, a relationship must be established between an output variable and independent input variables. For example, the transfer function from the motor angle to the metering amount can be determined for a metering device. If it is assumed that the motor angle is stepped down by a gear reduction ratio, and a spindle unit having a constant pitch is used, then in a first step the stroke of the spindle may be determined as a function of the motor angle:

[00004]$\Delta .Math..Math.h=\frac{\theta }{i}.Math.p$

where Δh is given in mm of the stroke, θ is the motor angle in angular degrees, i is the gear reduction ratio and p is the pitch of the spindle in mm/angular degree. By multiplying the spindle pitch times a cross-sectional area Q of a reservoir in mm.sup.2, the volume delivered is obtained as a function of the motor angle:

[00005]$\Delta .Math..Math.V=\frac{\theta }{i}.Math.p.Math.Q$

[0059] Finally, the volume can be multiplied times a factor for the concentration, so that ultimately the dose administered ΔU can be determined. For example, this factor amounts to 0.1 for U100 insulin, i.e., a volume of 10 mm.sup.3 must be multiplied times a factor of 0.1 to thereby determine the amount of insulin units dispensed in IU. A volume of 10 mm.sup.3 therefore contains a 1 IU of insulin at a concentration U100 insulin; C.sub.insulin is the factor for conversion from 1 volume of insulin to an amount of insulin in units of IU (international units).

[00006]$\Delta .Math..Math.U=\frac{\theta }{i}.Math.p.Math.Q.Math.C_{\mathrm{insulin}}$

[0060] In the following equation, the relationship between the metering amount of insulin and the independent variables is represented, wherein the cross-sectional area Q has been replaced by the corresponding area equation π.Math.D.sub.i.sup.2/4. The figures show only the diameter D.sub.i, from which the cross-sectional area Q can be determined. The Gaussian error propagation law will now be applied to the following function, which describes the relationship between the metering amount of medication fluid dispensed to the motor angle of a metering device:

[00007]$\Delta .Math..Math.U=\frac{\theta }{i}.Math.p.Math.\frac{\pi .Math.D_i^2}{4}.Math.C_{\mathrm{insulin}}$

[0061] The metering amount dispensed ΔU of IU insulin can be derived according to the independent variables. The latter include the pitch p, the equivalent diameter of the reservoir D.sub.i and the motor angle θ. The motor angle error, when considered more broadly, may be any error angle of the drive unit, i.e., an angle error that is caused by the components motor and gear as a result of friction or tolerance errors in the gear wheels, for example. Accordingly, the angle error may be considered as any error in which a predetermined angle of a control unit cannot be converted correctly by the drive unit. At the output of the gear, an angle error for the spindle unit is therefore the result. Due to the derivation of the function according to the independent variables, this yields the sensitivities. The Gaussian error propagation law can be applied when the independent variables are independent of one another and have a normal distribution. It is assumed here that these conditions are met. The three sensitivities are shown below:

[0062] Sensitivity for the equivalent diameter D.sub.i:

[00008]$\frac{d.Math..Math.\Delta .Math..Math.U}{d.Math..Math.D_i}=p.Math.\frac{\pi .Math.D_i}{2}.Math.\theta .Math.\frac{C_{\mathrm{insulin}}}{i}$

[0063] Sensitivity for the pitch p:

[00009]$\frac{d.Math..Math.\Delta .Math..Math.U}{d.Math..Math.p}=\frac{\pi .Math.D_i^2}{4}.Math.\theta .Math.\frac{C_{\mathrm{insulin}}}{i}$

[0064] Sensitivity for the motor angle θ:

[00010]$\frac{d.Math..Math.\Delta .Math..Math.U}{d.Math..Math.\theta }=p.Math.\frac{\pi .Math.D_i^2}{4}.Math.\frac{C_{\mathrm{insulin}}}{i}$

[0065] The result for the motor angle is especially interesting. The sensitivity for the motor angle is proportional to the product of the spindle pitch on the cross-sectional area of the reservoir. In order for a metering error due to inaccurate positioning of the motor to be reducible, the product of the spindle pitch on the cross-sectional area of the reservoir must be minimized. Thus the two factors—spindle pitch and cross-sectional area—must be kept as small as possible. The sensitivities derived by the preceding method can be further simplified by describing the angle θ as a function of the amount of insulin ΔU to be dispensed:

[00011]$\theta =\frac{\Delta .Math..Math.U.Math.i}{p.Math.\left(\frac{\pi .Math.D_i^2}{4}\right).Math.C_{\mathrm{insulin}}}$

[0066] Now this yields the following simplified presentations for the sensitivities, which are new.

[0067] Sensitivity for the equivalent diameter D.sub.i:

[00012]$\frac{d.Math..Math.\Delta .Math..Math.U}{{\mathrm{dD}}_i}=\frac{2.Math.\Delta .Math..Math.U}{D_i}$

[0068] Sensitivity for the pitch p:

[00013]$\frac{d.Math..Math.\Delta .Math..Math.U}{\mathrm{dp}}=\frac{\Delta .Math..Math.U}{p}$

[0069] Sensitivity for the motor angle θ:

[00014]$\frac{d.Math..Math.\Delta .Math..Math.U}{d.Math..Math.\theta }=p.Math.\frac{\pi .Math.D_i^2}{4}.Math.\frac{C_{\mathrm{insulin}}}{i}$

[0070] It must be pointed out here that the sensitivity for the diameter as well as the sensitivity for the spindle pitch cannot be influenced by the insulin concentration C.sub.insulin. This means that dilution of insulin from U100 insulin, for example, to U50 insulin does not lead to an improvement with regard to the dispensing accuracy for the diameter error and the spindle pitch error. This is a new finding. The insulin concentration has only a direct influence on the sensitivity of the motor angle error which can be influenced directly by the insulin concentration so that, for example, the error can be reduced by one-half by using U50 insulin in comparison with U100 insulin. The dispensing accuracy can be improved not only by diluting the concentration of the insulin but according to the sensitivity for the angle error, the dispensing accuracy can be improved significantly beyond an optimized value of the diameter and spindle pitch parameters. This is because the product of the spindle pitch and the area

[00015]$p.Math.\frac{\pi .Math.D_i^2}{4}$

is directly proportional to the sensitivity of the motor angle error, like the insulin concentration. Due to an inventive choice of said multiplication product, a metering device can be created which can dispense extremely small metering amounts in particular with precision so that even insulins in a concentration of U100 can be administered with greater precision than is possible in the state of the art today. Furthermore, the following relationship is apparent from the sensitivities given above. An excessive reduction in the spindle pitch p or the diameter D.sub.i causes an unfortunate increase in the respective sensitivity, which is a disadvantage. For example, if the reservoir diameter D.sub.i is reduced from 10 mm to 5 mm, the corresponding sensitivity is doubled. At the same tolerance for the diameter, this yields larger errors in dispensing. Both the sensitivity for the diameter and the sensitivity for the pitch are indirectly proportional to the diameter and the spindle pitch, respectively. In particular, the systems of the third generation have very small diameters for the metering cylinder, so that there is an unfortunate increase in the corresponding diameter error in dispensing. For the total dispensing error dΔU which takes into account the error square of diameter, spindle pitch and angle error, this therefore yields the following equations:

[00016]$d.Math..Math.\Delta .Math..Math.U^2={\left(\frac{2.Math.\Delta .Math..Math.U}{D_i}\right)}^2.Math.\Delta .Math..Math.D_i^2+{\left(\frac{\Delta .Math..Math.U}{p}\right)}^2.Math.\Delta .Math..Math.p^2+{\left(p.Math.\frac{\pi .Math.D_i^2}{4}.Math.\frac{C_{\mathrm{insulin}}}{i}\right)}^2.Math.\Delta .Math..Math.{\theta }^2$$d.Math..Math.\Delta .Math..Math.U=\sqrt{{\left(\frac{2.Math.\Delta .Math..Math.U}{D_i}\right)}^2.Math.{\mathrm{AD}}_i^2+{\left(\frac{\Delta .Math..Math.U}{p}\right)}^2.Math.\Delta .Math..Math.{p^2\left(p.Math.\frac{\pi .Math.D_i^2}{4}.Math.\frac{C_{\mathrm{insulin}}}{i}\right)}^2.Math.\Delta .Math..Math.{\theta }^2}$

[0071] The results for the procedure described above for the interpretation of a metering device are summarized below. These results are listed in the following Table 3 for a system of the first generation, a system of the second generation and a system of the third generation as well as a system according to the invention. Since U100 insulin is used in insulin pump therapy in general, and this insulin concentration has become established as the gold standard, the following calculations are therefore based on this conventional concentration. In general the findings of the present invention are also applicable to other insulin concentrations such as U40 insulin, for example.

TABLE-US-00003 TABLE 3 Metering amount in IU U100, ΔU 0.0025 0.05 0.1 1 10 First generation pump Metering error± in IU U100, dΔU 0.00499 0.00504 0.00516 0.01394 0.13027 Metering error± in % of metering amount 199.73% 10.07% 5.16% 1.39% 1.30% Reservoir diameter error in % 0.00% 0.68% 2.61% 35.73% 40.92% Spindle pitch error in % 0.00% 0.99% 3.76% 51.45% 58.93% Motor angle error in % 100.00% 98.33% 93.64% 12.83% 0.15% Second generation pump Metering error± in IU U100, dΔU 0.00453 0.00457 0.00471 0.01354 0.12769 Metering error± in % of metering amount 181.16% 9.15% 4.71% 1.35% 1.28% Reservoir diameter error in % 0.00% 0.75% 2.84% 34.27% 38.54% Spindle pitch error in % 0.00% 1.20% 4.52% 54.54% 61.34% Motor angle error in % 100.00% 98.05% 92.65% 11.19% 0.13% Third generation pump Metering error± in IU U100, dΔU 0.00029 0.00125 0.00245 0.02437 0.24369 Metering error± in % of metering amount 11.78% 2.50% 2.45% 2.44% 2.44% Reservoir diameter error in % 3.56% 78.76% 82.01% 83.15% 83.16% Spindle pitch error in % 0.72% 15.95% 16.61% 16.84% 16.84% Motor angle error in % 95.72% 5.30% 1.38% 0.01% 0.00% Invention - MeaPump Juvenile Metering error± in IU U100, dΔU 0.00074 0.00113 0.00186 0.01713 0.17115 Metering error± in % of metering amount 29.55% 2.26% 1.86% 1.71% 1.71% Reservoir diameter error in % 0.22% 37.79% 55.54% 65.74% 65.86% Spindle pitch error in % 0.11% 19.59% 28.79% 34.08% 34.14% Motor angle error in % 99.66% 42.63% 15.66% 0.19% 0.00%

[0072] Table 4 also lists the tolerances used for the calculation. The error square of the independent factors and the total errors in units of IU insulin have been summarized in Table 4. The tolerance for the spindle pitch is ±1% of the pitch. The tolerance for the diameter is ±0.05 mm for all diameters. The tolerances used corresponds to today's production tolerances.

TABLE-US-00004 TABLE 4 Metering amount in IU U100, ΔU 0.0025 0.05 0.1 1 10 Value Tol.± Error.sup.2 Error.sup.2 Error.sup.2 Error.sup.2 Error.sup.2 First generation pump Gear reduction ratio 906 Reservoir diameter in mm 12.00 0.05 4.34.sup.−10 1.74.sup.−07 6.94.sup.−07 6.94.sup.−05 6.94.sup.−03 Pitch in mm/revolution 1.20 0.012 6.25.sup.−10 2.50.sup.−07 1.00.sup.−06 1.00.sup.−04 1.00.sup.−02 Motor angle in angular degree 120 2.49.sup.−05 2.49.sup.−05 2.49.sup.−05 2.49.sup.−05 2.49.sup.−05 Insulin concentration U100 0.10 Error in IU total, dΔU 0.00499 0.00504 0.00516 0.01394 0.13027 Second generation pump Gear reduction ratio 920 Reservoir diameter in mm 12.62 0.05 3.93.sup.−10 1.57.sup.−07 6.28.sup.−07 6.28.sup.−05 6.28.sup.−03 Pitch in mm/revolution 1.00 0.010 6.25.sup.−10 2.50.sup.−07 1.00.sup.−06 1.00.sup.−04 1.00.sup.−02 Motor angle in angular degree 120 2.05.sup.−05 2.05.sup.−05 2.05.sup.−05 2.05.sup.−05 2.05.sup.−05 Insulin concentration U100 0.10 Error in IU total, dΔU 0.00453 0.00457 0.00471 0.01354 0.12769 Third generation pump Gear reduction ratio 920 Reservoir diameter in mm 4.50 0.05 3.09.sup.−09 1.23.sup.−06 4.94.sup.−06 4.94.sup.−04 4.94.sup.−02 Pitch in mm/revolution 0.5 0.005 6.25.sup.−10 2.50.sup.−07 1.00.sup.−06 1.00.sup.−04 1.00.sup.−02 Motor angle in angular degree 120 8.30.sup.−08 8.30.sup.−08 8.30.sup.−08 8.30.sup.−08 8.30.sup.−08 Insulin concentration U100 0.10 Error in IU total, dΔU 0.00029 0.00125 0.00245 0.02437 0.24369 Inventive MeaPump Juvenile Gear reduction ratio 920 Reservoir diameter in mm 7.20 0.05 1.21.sup.−09 4.82.sup.−07 1.93.sup.−06 1.93.sup.−04 1.93.sup.−02 Pitch in mm/revolution 0.5 0.005 6.25.sup.−10 2.50.sup.−07 1.00.sup.−06 1.00.sup.−04 1.00.sup.−02 Motor angle in angular degree 120 5.44.sup.−07 5.44.sup.−07 5.44.sup.−07 5.44.sup.−07 5.44.sup.−07 Insulin concentration U100 0.10 Error in IU total, dΔU 0.00074 0.00113 0.00186 0.01713 0.17115

[0073] Extension conclusions can be drawn from the preceding calculations and results. The metering devices of the first and second generations have the least error for large dispensing amounts because of the lowest sensitivities for the diameter and the spindle pitch. The third-generation system has the largest error for the large dispensing amounts. The third-generation system has the greatest sensitivity for the diameter. In dispensing large dosage amounts, therefore third-generation systems have a large dispensing error. The sensitivity for the spindle pitch is proportional to the inversion of the pitch. A reduction in the spindle pitch at the same tolerance therefore leads to an increase in the corresponding error square. Miniaturization of the parameters, as may be the case in particular with the third-generation systems, increases the sensitivity. At the same tolerances, the error squares of the diameter and spindle pitch show an unfavorable increase for third-generation systems. However, third-generation systems have the best dispensing accuracy for the smallest metering increment of 0.0025 IU. At a dispensing rate of 0.05 IU/h which is relevant for CSII treatment of children and young people, however, the metering device according to the invention has a better accuracy in comparison with the third-generation systems as well as in comparison with the first and second-generation systems. The metering device according to the invention has similar or better dispensing accuracies in the range of the smallest metering amounts in comparison with a system of the third generation. In the range of large metering amounts, it has only a marginally worse performance in comparison with the first and second-generation systems. The metering device according to the invention can dispense extremely small metering amounts accurately and, in doing so, achieves or even exceeds the performance of the third-generation systems. However, the metering device according to the invention also has an error at large metering amounts which is insignificantly greater than that of the first- and second-generation systems. At moderate rates, the system according to the invention turns out much better than the systems known from the prior art. At a metering rate of 0.1 IU/h, the system according to the invention can deliver the total metering amount with an accuracy of ±1.86% after a dispensing interval of 1 hour. A system of the first generation or second generation achieves an error tolerance of only ±5.16% or ±4.71%, respectively, whereas the third-generation system has an error of ±2.45%. Moreover, it must be pointed out here that for a dose of 0.05 IU/h, the error for the system according to the invention amounts to 2.26% after 1 hours. For a first-generation system, this error amounts to 10.07%, which is substantial. In order for the system of the first generation to have a comparable error, the insulin must be diluted in 1/5 ratio, i.e., U20 insulin must be used. This comparison shows how much a metering device according to the invention, in which the product p.Math.π.Math.D.sub.i.sup.2/4=p.Math.Q, which is formed from the spindle pitch and the reservoir area, is selected to be optimal, is capable of improving the dispensing accuracy in comparison with the prior art. The following table compares the reservoir area Q and the spindle pitch p for the systems of the first and second generations, one system of the third generation and a system according to the invention (MeaPump Juvenile). The product of the cross-sectional area and the pitch can be formed from these parameters. Likewise the sensitivity of the diameter which is proportional to the inverse of the diameter is also shown.

[0074] Table 5 shows that the products formed form the spindle pitch and the area are much smaller for the system according to the invention and the third-generation system than those for the first- and second-generation systems. However, the sensitivity for the dispensing error of the diameter which is proportional to the inverse of the diameter (1/D.sub.i), is largest for the third-generation system at 0.222. As described above, the result is that a large dispensing error must be expected with large metering amounts.

TABLE-US-00005 TABLE 5 Pitch p in Area Q mm.sup.2/angular Product in mm.sup.2 degree p*Q 1/D.sub.i First generation Roche Accuchek Spirit 113.10 0.0034 0.377 0.083 Roche D-Tron 67.20 0.0034 0.224 0.108 Minimed, Paradigm Veo 113.10 0.0028 0.314 0.083 Animas, Ping, 2020 95.03 0.0028 0.264 0.091 Deltec, Cozmo 113.10 0.0028 0.314 0.083 Second generation Insulet, Omnipod 125.00 0.0011 0.139 0.079 MeaPump Adult 125.00 0.0028 0.347 0.079 Third generation System of third generation 15.90 0.0014 0.022 0.222 System according to invention MeaPump Juvenile (invention) 40.72 0.0014 0.057 0.139

[0075] The metering device according to the invention is capable of dispensing small metering amounts with a very high precision, wherein the error of the motor angle is minimized for small metering amounts. Likewise, the metering device according to the invention is capable of dispensing large amounts of medication fluid with a very high precision. In the case of large metering amounts, the percentage error of the motor angle tends toward zero (the absolute value remains constant), while the error of the diameter due to diameter tolerance and the error of the spindle pitch due to pitch tolerances are significant here. The system according to the invention can thus dispense extremely small metering amounts with a much greater accuracy than in the prior art consisting of systems of the first and second generations.

[0076] The results of Table 5 above have been plotted graphically in FIG. 1a where the pitch of the spindle is plotted on the x axis and the cross-sectional area Q is plotted on the y axis. The respective systems of the first generation and the second generation have been combined in graphical quadrants, wherein the respective cross-sectional areas are given in mm.sup.2. It is claimed according to the invention that the product formed form the cross-sectional area and the pitch should be less than 0.13 mm.sup.3/angular degree. The limiting line for this condition can thus be determined with the following equation:

[00017]$Q=\frac{0.13.Math.\left(\frac{{\mathrm{mm}}^3}{\mathrm{angular}.Math..Math.\mathrm{degree}}\right).Math.360.Math.\left(\frac{\mathrm{angular}.Math..Math.\mathrm{degree}}{\mathrm{revolution}}\right)}{p\left(\mathrm{mm}/\mathrm{revolution}\right)}$

[0077] The average product of the spindle pitch and the cross-sectional area amounts to 0.30 mm.sup.3/angular degree for systems of the first generation. The metering device according to the invention has an equivalent dilution of the concentration of more than 50% with a product of the spindle pitch and the cross-sectional area amounting to less than 0.13=.sup.3/angular degree. This means that first-generation systems must use an insulin concentration lower than U50 to achieve at least the same dispensing accuracy as that of the metering device according to the invention. The lower limit according to claim 3 amounts to 24 mm.sup.2, which corresponds to an equivalent diameter of 5.5 mm. The lower limit ensures that the sensitivity for the diameter does not exceed a maximum value and therefore accurate dispensing of large metering amounts can be ensured, whereas the upper limit for the claimed design range ensures that small and extremely small metering amounts can be dispensed accurately. The range claimed in FIG. 1b has good properties with regard to dispensing accuracy over the entire metering range. This range is especially suitable for CSII treatment of children and young people with type 1 diabetes, for whom undiluted U100 insulin can be used. FIG. 1c shows another restricted range of the invention. In this range, it is possible to create metering devices having a further improvement in dispensing accuracy. The range shown in FIG. 1c has a cross-sectional area greater than 32.2 mm.sup.2, which corresponds to a diameter of 6.4 mm for the reservoir. The product of the cross-sectional area and the pitch is represented by the upper limiting line. This limit satisfies the equation Q.Math.p=0.08 mm.sup.3/angular degree. FIG. 1c also shows the third-generation device. The third-generation systems have a new design with a reservoir and a separate metering cylinder. These systems are shown here only for the sake of thoroughness. Only the systems of the first and second generation as well as the embodiment according to the invention belong to the same category, in which the reservoir itself has a movable plunger for dispensing medication fluid. Metering devices of the first and second generation as well as the invention could be considered as injection pumps, for which a plunger of a reservoir is displaced by a drive unit and medication fluid is delivered in this way.

[0078] FIG. 2a shows a reservoir A which has an integrated spindle unit S. The spindle unit S consists of a spindle rod 1 and a spindle nut 2, wherein the spindle nut 2 is movable in the embodiment shown here. The reservoir A has an inside wall 3, along which a plunger K is guided. The plunger K itself is connected directly to the spindle nut 2. Seals 4, which are designed here in the form of O-rings 5, are provided between the inside wall 3 and the plunger K. In addition to the inside wall 3, which has an inside diameter of 7.2 mm here, the reservoir A also has an outside wall 6. Inside wall 3 and outside wall 6 are fixedly connected to one another. The outside wall 6 also has locking cams 7, by means of which the reservoir A can be connected to a fixed housing 8. Therefore, in the forward movement of the spindle nut 2 and/or the plunger K, the spindle nut cannot move rotationally, i.e., it forms a twist-proof lock. In the exemplary embodiment of FIGS. 2a and 2b shown here, the spindle nut is designed in the form of a radial wing 10. The radial wing 10 is shown in a view from beneath in FIG. 2c. The outside wall 6 is designed with an oval shape. The wings 10 protruding radially outward are supported on an inside wall 11 of the outside wall 6 and thus prevent a rotational movement of the spindle nut 2. In the starting condition shown in FIG. 2a, the spindle nut 2 is shown in its retracted position, wherein the spindle rod 2 may be connected to a pull-up rod 12. To fill the reservoir A with insulin, the user first connects the reservoir to a storage container by means of an adapter. The reservoir A itself has a connecting needle 13 by means of which the fluidic connection to the reservoir A is established by means of the adapter. In a first handling step, the user pushes the plunger K in the forward direction and thereby displaces the air in the reservoir A into the supply container. In another handling step, there is a plunger movement in the opposite direction, wherein insulin can then flow overflow from the supply container into the reservoir A. FIG. 2b shows a metering device D according to the invention. The reservoir A having the integrated spindle unit S is connected to a drive unit M after being filled, so that the metering device D is formed. By means of a bayonet connection 14, the reservoir A is connected to a fixed housing 8. A motor 15 of the drive unit M drives an driving rod 19, so that it can rotate by means of a gear 16, wherein a planetary gear 17 and a deflecting gear 18 are present here. The total gear reduction ratio i consists of the gear reduction ratio of the planetary gear 17 and the gear reduction ratio of the deflecting gear 18 in the form of a spur gear. The motor has Hall sensors for the positioning, these sensors having a motor increment of 60 angular degrees of the motor angle. The exemplary embodiment shown in FIG. 2b has a gear reduction ratio i of 920, a spindle pitch p of 0.5 mm/revolution and a diameter D.sub.i of 7.2 mm. This yields the data according to the invention, as depicted in Table 5, according to which the product of the cross-sectional area and the pitch amounts to 0.057 mm.sup.3/angular degree, and the sensitivity for the diameter is proportional to 0.139 mm.sup.−1. The driving rod 19, which is driven to rotate engages in a profiled elongated hole 20 which is formed on the spindle rod 1. In rotation of the driving rod 19, it entrains the spindle rod 1. The spindle nut 2 which is secured in a twist-proof manner strikes the spindle rod 1 and thus moves in the axial direction of advance. Due to the displacement of the plunger K, medication fluid is dispensed to the user. The fluid path downstream from the connecting needle 13 is not shown in FIG. 2b. In general, the fluid path has a fluidic connection from the connecting needle 13 to the subcutaneous tissue of a user. A cannula leading into the subcutaneous tissue can ensure the connection of the user to the metering device. The double-walled design of the reservoir A shown in FIGS. 2a to 2c has various advantages. First the outside wall 6 in an oval shape can secure the twist-proof locking of the spindle nut 2. Furthermore, the outside wall 6 protects the actual reservoir A from impacts and the like. Pressure on the outside wall 6 does not result in any compression of the reservoir cylinder in the interior. Such a double-walled reservoir A does not require a fixed housing, such as that provided in metering devices of the first generation, for example, in order to protect the ampoules.

[0079] The example in FIGS. 2a to 2c can also be embodied with an alternative twist-proof lock. The twist-proof lock may involve a tongue-and-groove connection between the inside wall and the spindle nut. In this variant, the inside wall is lengthened toward the drive unit. A pull-up rod is suitable for filling in this variant.

[0080] Another exemplary embodiment is depicted in FIGS. 3a and 3b. This exemplary embodiment has a design similar to that in the embodiment of FIGS. 2a to 2c because, here again, a spindle rod 1 is driven to rotate and a twist-proof-locking spindle nut 2 executes a linear movement. In a starting state before filling in FIG. 3a, the spindle nut and the plunger K connected to it are in an upper position. Due to a reverse rotation of the spindle nut 2, the spindle nut 2 moves in reverse and draws insulin out of a storage container and into the reservoir A and thereby fills the reservoir A. The exemplary embodiment in FIGS. 3a and 3b therefore has the advantage that the filling need not be carried out by hand but instead can be done automatically by the metering device. In order for this to be possible, the spindle rod 1 must be supportable during the reverse movement of the plunger K. This support is advantageously provided on the inside wall 3. The wall 3 therefore has a stop 21 for the spindle rod 1. In the reverse rotation of the spindle rod 1, it is supported on the wall 3. After the filling, the drive unit changes its direction of rotation. By rotating the spindle rod 1 in the forward direction, the spindle rod 1 moves against a stop 22 formed on the driving rod 19. In the forward direction the spindle rod 1 is thus supported on the driving rod 19. In filling the reservoir A however the spindle rod 1 is supported on the inside wall 3 of the reservoir A. The twist-proof locking of the spindle nut 2 may take place by means of longitudinal grooves and cams between the inside wall and the spindle nut 2. The exemplary embodiment in FIGS. 3a and 3b therefore has the advantage that the reservoir A of the drive unit M can be filled itself so this can spare the user the tedious job of filling. Furthermore the support of the spindle rod S on the inside wall 3 during filling can be very advantageous because this makes it possible to ensure that no axial forces are acting on the driving rod 19 during the filling and that the drive unit M is being guides. Only the bayonet connection 14, which is provided for such forces is claimed for the forces that act during filling and the following dispensing of the medication fluid. Filling by way of the drive unit M is additionally advantageous in that a control unit can calculate the filling volume on the basis of the reverse motor steps. It is therefore possible to fill the reservoir A with a certain volume precisely as intended by the user. After the filling, the spindle rod 1 runs up against the stop 22 formed on the driving rod 19. Beneath the driving rod 19 there is a force sensor 23 which can monitor an axial force acting on the spindle unit S during conveyance. The force senor 23 primarily has the task of detecting occlusions. It can likewise detect that the spindle rod 1 has run up against the stop 22 formed on the driving rod 19.

[0081] FIG. 4a shows a reservoir A similar to the design shown in FIGS. 3a and 3b. The reservoir A in FIG. 4a differs in that the spindle rod 1 is designed in two parts here. In addition to the spindle rod 1, FIG. 4a also shows a stop disk 24, which is fixedly connected to the inside wall 3. The stop disk 24 has a stop 28 for the spindle rod 1, wherein the active radius 29 for support of the spindle rod on the stop disk 24 can be reduced. The torque loss generated between the spindle rod 1 and its axial stop 28 can thus be greatly reduced. The reservoir A illustrated in FIG. 4a thus has the advantage that the torque losses occurring in operation in reverse can be reduced by providing the support between the spindle rod 1 and its stop 28 formed on the stop disk on a smaller radius 29. The axial force is transferred from an outer radius 30 to the inside wall 3 by way of the stop disk. The stop disk 24 is connected to the inside wall 3 in a rotationally fixed and axially secured manner. FIG. 4b shows a view across the longitudinal axis in which the two-piece design of the spindle rod 1 is readily visible.

[0082] FIGS. 5a and 5b show another exemplary embodiment of the convenient filling method. In this example, the plunger K is connected to the spindle rod 1. The spindle nut 2 is locked in a twist-proof manner and can be supported during a forward motion on a stop 22 formed on the driving rod 19. The spindle rod 1 in turn has an elongated hole 20, in which the driving rod 19 can engage. In contrast with the embodiments discussed previously, the spindle rod 1 here executes a rotation created by the driving rod 19 as well as a linear movement provoked by the twist-proof locking of the spindle nut 2. The spindle nut 2 may be connected to a pull-up; rod 12 in order to perform the filling of the reservoir A in a convenient manner. In this case, a radial wing 10 is in turn suitable as an element for the twist-proof locking, which can be supported on the inside wall 11.

[0083] FIGS. 6a and 6b show another exemplary embodiment which is provided for automatic filling. The spindle nut 2, which is locked in a twist-proof position, is supported on the inside wall 3 on the stop 21 of the reservoir during filling. For example, profiling is used for the twist-proof locking between the spindle nut 2 and the inside wall 3. Simple tongue-and-groove connections between the components are also conceivable and should prevent rotation of the spindle nut 2. Axial displacement of the spindle nut 2 is prevented by the stop 21 during reverse rotation, and in the opposite direction the spindle nut 2 strikes against its axial stop 22 formed on the driving rod 19.

[0084] In the exemplary embodiments, the spindle rod 1 has an external thread 25 and the spindle nut 22 has an internal thread 26. The external thread and internal thread together thus form a spindle drive 27. It should be pointed out that a reversal of the spindle nut 2 and spindle rod 1 is also conceivable. This means that the spindle nut 2 is rotated instead of the spindle rod 1 being driven to rotation. In this case, the spindle rod 1 must be designed with the twist-proof locking, wherein the approaches discussed previously may be used for the twist-proof locking.

LIST OF REFERENCE NUMERALS

[0085] D Metering device [0086] S Spindle unit [0087] M Drive unit [0088] A Reservoir [0089] K Plunger [0090] Q Cross-sectional area of reservoir [0091] D.sub.i Equivalent diameter of reservoir [0092] p Spindle pitch [0093] i Gear reduction ratio [0094] Ci Insulin concentration [0095] 1 Spindle rod [0096] 2 Spindle nut [0097] 3 Inside wall [0098] 4 Sealing [0099] 5 O-ring [0100] 6 Outside wall [0101] 7 Locking cam [0102] 8 Housing [0103] 9 Twist-proof lock [0104] 10 Wing [0105] 11 Inside wall [0106] 12 Pull-up rod [0107] 13 Connecting needle [0108] 14 Bayonet connection [0109] 15 Motor [0110] 16 Gear [0111] 17 Planetary gear [0112] 18 Deflecting gear [0113] 19 Driving rod [0114] 20 Elongated hole [0115] 21 Stop for support on inside wall [0116] 22 Stop for support on driving rod [0117] 23 Force sensor [0118] 24 Stop disk [0119] 25 External thread [0120] 26 Internal thread [0121] 27 Spindle drive [0122] 28 Stop for support on stop disk [0123] 29 Inside radius [0124] 30 Outside radius