WO2007060156A1

WO2007060156A1 - System of different shaped injection devices

Info

Publication number: WO2007060156A1
Application number: PCT/EP2006/068705
Authority: WO
Inventors: Thomas Dedenroth Miller; Michael Ejstrup Hansen; Jakob Oest Wielandt
Original assignee: Novo Nordisk A/S
Priority date: 2005-11-22
Filing date: 2006-11-21
Publication date: 2007-05-31

Abstract

A system of injection devices for injecting liquid insulin, comprising a first injection device (IA) containing a first type of liquid insulin and a second injection device (IB) containing a second type of liquid insulin. The two injection devices have different outer shapes. In one embodiment, the first injection device is longer than the second injection device and the longest contains the longest working insulin.

Description

System of Different Shaped Injection Devices

THE TECHNICAL FIELD OF THE INVENTION:

The invention relates to a system of injection devices for subcutaneous injections. The system preferably comprises at least two injection devices containing insulin primarily for self- treatment of people suffering from diabetes.

DESCRIPTION OF RELATED ART:

A prior art system is known from WO 2004/069314. This application discloses a system of substantially identical injection devices, each individual injection device comprising a housing accommodating an ampoule containing medicine sufficient for a number of injections and a dose setting mechanism by which a predetermined dose size can be set, and wherein each of the plurality of injection devices has a different predetermined dose size. The difference in the predetermined dose sizes can in one embodiment be based on the drug in the devices having different strength.

People suffering from diabetes are often treated with multiple daily injections in a regimen comprising one or two daily injections of a long acting insulin to cover the basal requirement supplemented by bolus injections of a short or rapid acting insulin to cover requirements related to meals.

A user will therefore often require two different injection devices, one containing the long act- ing insulin and another containing the short or rapid acting insulin. Often these injection devices have different colour indications to inform the user of the kind of insulin contained in the injection device. Orange or yellow is usually the colour used for short or rapid acting insulin whereas green is often used to indicate the long acting insulin types. In addition these injection devices can be provided with tactile means such as a mechanical coding informing the user of the kind of insulin contained in the injection device.

Generally speaking two different types of pen systems are used for the treatment of diabetes. The first type being injection devices with a replaceable cartridge containing the insulin to be injected. Often such cartridges contain 3 ml of insulin, and when this amount has been in- jected a new cartridge is inserted in the same injection device which therefore often is in use for several years. Such injections devices are usually referred to durable injection devices. The other type being injection devices containing a predetermined and non-replaceable amount of insulin, also often 3 ml. The insulin is often contained in a cartridge embedded in the injection device. When the predetermined amount has been injected which in average takes anywhere from a few days to a month, the entire injection device is discarded and a new injection device is used for subsequent injections. Such injection devices are often referred to as disposable of prefilled injection pens.

DE U 201 10 689 discloses a pen-shaped injection device having a cap with a clip for holding the injection device e.g. in a pocket of a shirt. The injection device is contained in a cut-out in a box. Since persons suffering from diabetes often require two injection devices with different types of insulin, the physical shape of the injection device is according to this patent designed such that the right injection device fits into the right box. This is according to the prior art done by having devices with different of length of the clip and boxes with a similar shaped cut-out.

Often insulin itself is known to be used to distinguish between insulin types. Some long- acting insulins are cloudy due to the insulin crystals and thus easy distinguishable from fast- acting insulin that are normally clear. However, new types of long-acting insulin analogues are clear and thus this method to distinguish between insulin types is no longer applicable. This may potentially lead to increased uncertainty about insulin type.

Thus, there is a need for a system of injection devices which has build-in means for informing a user of the type of insulin contained in the injection device. These means should be self- explanatory.

DESCRIPTION OF THE INVENTION:

It is an object of the present invention to provide a system of injection device which discretely by there outer form or shape informs the user of the type of insulin contained in the injection device.

When the only indicia differentiating two otherwise identical injection pens is a colour indication, a user must learn which colour indicates what type of insulin. Usually the colour indica- tion is only located on a minor part of the injection pen such as the injection button. The user must be able to distinct the colours used also when taking the injections in poorly lighted rooms such as public restaurants, restrooms or the like, which can be difficult.

Injection devices usually also carries labels with a text spelling out which type of insulin is contained in the injection device. For durable injection devices the label is usually located on the replaceable cartridge itself.

Further if the indicia are tactile they are usually restricted to a very little, Braille-like indication on the injection button. This requires fine motor skills and dexterity in the finger tips, which is often not the case for persons suffering from late stage diabetes complications

When, on the contrary, the indicia are coupled to the length of the injection device a user can easily distinct the two injection device from each other. The user is thereby able to instantly distinct two injection devices from each other both by vision and by touching the injection de- vice.

And if the longest injection device contains the long acting insulin i.e. the basal insulin and the shortest injection device contains the short (rapid) acting insulin i.e. the bolus or meal time insulin then the user only has to memorize the sentence "long pen for long acting - short pen for short acting" which is highly self explanatory.

Training of newly diagnosed diabetics is important. When training diabetics on how to use more types of insulin for basal/bolus treatment of diabetes, the use of pen length to indicate working mode of insulin, being short acting or long acting, will facilitate easier understanding of insulin working mode, is easy memorable, and thus facilitating easier, faster and safer training. This may be for the benefit of the patient, but also the educator; health care personnel responsible for delivering insulin injections to patients, and/or the people at the pharmacy responsible for handing out correct type of drug.

From an injection pen manufacturer point of view, a correlation of insulin type, length of car- tridge, and length of cartridge holder on the injection pen will provide easy identification features to ensure that wanted type of insulin is assembled with wanted type of pen mechanism to supplement other known identification features as e.g. color coding of mechanical parts.

This is particular suitable for injection devices which has an oblong pen formed shape. If the ampoules or cartridges contain insulin with different strength, the same number of International Units (IU) can be contained in different volumes. If e.g. 300 IU is wanted in one cartridge and the cartridge is filled with insulin having a strength of 100 IU per millilitre of insulin the total volume of the cartridge will be 3 millilitre. If instead the cartridge is filled with insulin having a strength on 200 IU per millilitre then only half the volume i.e. 1 ,5 millilitre is required.

A compact cartridge containing insulin with a strength of 200 IU per millilitre is disclosed in EP 1.424.984. A compact cartridge according to this patent usually has a total length ap- proximately between 44 to 52 millimetres, whereas a 3 ml cartridge as the ones sold by leading insulin producers has a total length of approximately 65 to 70 millimetres i.e. approximately 20 millimetres longer.

A system according to the present invention could in an exemplary embodiment comprise two injection devices which are based on identical or almost identical technologies i.e. injection devices having the same or slightly modified interior dose setting and injection mechanism. It could e.g. be two prefilled injection devices like the Flexpen® from the company Novo Nordisk A/S.

A first injection device containing 3,0 millilitres of long acting insulin in a concentration of 100 IU per millilitre. Such injection device would then contain a total 300 IU of insulin. The same system could further comprise a second injection device containing short acting insulin in a concentration of 200 IU per millilitres. Such injection device would also contain 300 IU of insulin. If the two injection devices were based on the same mechanical dose setting and injec- tion mechanism, the only difference would be the cartridge used. The injection device with the long acting insulin would have the longest cartridge and be the longest injection device whereas the injection device containing short acting insulin would have a shorter cartridge and be significantly shorter.

However instead of having different length of the cartridge, the length differentiation could be obtained through a differentiation of the dose setting and injection mechanics.

Most dose setting and injection mechanics has a threaded piston rod co-operating with a nut where the nut and the piston rod may be rotated relatively to each other. In some injection devices, the dose setting may be obtained by screwing the nut away from a stop to which it is returned during injection by pressing the piston rod forward until the nut member abuts the stop. By other injection devices one of the elements, the nut or the piston rod, is kept inro- tatable and the other is allowed to rotate a set angle depending on the set dose, whereby the piston rod is screwed forward a distance through the nut member.

When injecting insulin the piston rod is moved forward inside the cartridge. The cartridge is provided with a plunger that, when moved forward by the piston rod expels a volume. The volume expelled is the area of the plunger multiplied with the distance the plunger and the piston rod is moved forward. This distance is a result of the rotations of the mechanical sys- tern and the pitch of the thread of the piston rod. If the pitch is little, the piston rod is moved forward at a slower pace than if the pitch is large. Therefore a little pitch is suitable for compact cartridges containing insulin with a strength of 200 IU per ml, since a smaller volume must be expelled in order to expel the same amount of International Units.

In stead of, or in combination with, the difference in length, the difference could also be a difference in diameter since the diameter of the cartridge is also a parameter decisive for the volume expelled. The shorter diameter cartridge could contain short or rapid acting insulin in a strength of 200 IU per millilitre and the cartridge having the largest diameter could contain long acting insulin in a strength of 100 IU per millilitre.

The diameter of the cartridge would also influence the diameter of the injection pen thereby informing the user of the type of insulin contained in the injection pen.

A system of injection devices can include any number of injection devices preceding one. In an exemplary use of the system it would involve two injection devices e.g. prefilled injection devices filled with two different types of insulin. These two injection devices could be used separately in either basal or bolus treatment or combined in a basal/bolus treatment.

DEFINITIONS:

An "injection pen" is typically an injection apparatus having an oblong or elongated shape somewhat like a pen for writing. Although such pens usually have a tubular cross-section, they could easily have a different cross-section such as triangular, rectangular or square or any variation around these geometries. As used herein, the term "drug" is meant to encompass any drug-containing flowable medicine capable of being passed through a delivery means such as a hollow needle in a controlled manner, such as a liquid, solution, gel or fine suspension. Representative drugs includes pharmaceuticals such as peptides, proteins (e.g. insulin, insulin analogues and C- peptide), and hormones, biologically derived or active agents, hormonal and gene based agents, nutritional formulas and other substances in both solid (dispensed) or liquid form.

Correspondingly, the term "subcutaneous" injection is meant to encompass any method of transcutaneous delivery to a subject.

Further the term "injection needle" defines a piercing member adapted to penetrate the skin of a subject for the purpose of delivering or removing a liquid.

The wording "outer shape" or "outer form" is throughout the present application used to indi- cate the outer appearance of the injection device such as the length or the cross-section.

The wording "active area" of a cartridge is meant to refer to the area of a cartridge within which the plunger or piston can move. A cartridge usually has a narrow area at the distal end into which area the plunger can not move due to the narrow diameter of that section.

"Cartridge" is the term used to describe the container containing the insulin. Cartridges are usually made from glass but could also moulded from any suitable polymer. A cartridge or ampoule is preferably sealed at one end by a pierceable membrane which can be pierced e.g. by an injection needle. The opposite end is closed by a plunger or piston made from rubber or a suitable polymer. The plunger or piston can be slidable moved inside the cartridge. The space between the pierceable membrane and the movable plunger holds the insulin which is pressed out as the plunger decreased the volume of the space holding the insulin.

"Technology platform" is meant to mean the basic structure upon which the injection devices in the system are based. In order to be based on the same technology platform, the injection devices of the system must work by the same mechanical principles i.e. the individual constructional components of each injection device must be the same and interact in the same way. The only difference is the physical appearance and especially the physical size of the various mechanical components. Technology platform products share underlying structures or basic architectures that are common across a group of products or that will be the basis of a series of products commercialized over a number of years. Several products may be derived from a common technol- ogy platform. Members of a product family normally have many common parts and assemblies.

All references, including publications, patent applications, and patents, cited herein are incorporated by reference in their entirety and to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

All headings and sub-headings are used herein for convenience only and should not be constructed as limiting the invention in any way. The use of any and all examples, or exemplary language (e.g. such as) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. The citation and incorporation of patent documents herein is done for convenience only and does not reflect any view of the validity, patentability, and/or enforceability of such patent documents.

This invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law.

BRIEF DESCRIPTION OF THE DRAWINGS:

The invention will be explained more fully below in connection with a preferred embodiment and with reference to the drawings in which:

Figure 1 Shows a system comprising to injection pens having a difference in length.

Figure 2 Shows the interior of one of the injection pens in the system.

The figures are schematic and simplified for clarity, and they just show details, which are essential to the understanding of the invention, while other details are left out. Throughout, the same reference numerals are used for identical or corresponding parts. DETAILED DESCRIPTION OF EMBODIMENT:

When in the following terms as "upper" and "lower", "right" and "left", "horizontal" and "verti- cal", "clockwise" and "counter clockwise" or similar relative expressions are used, these only refer to the appended figures and not to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as there relative dimensions are intended to serve illustrative purposes only.

In that context it may be convenient to define that the term "distal end" in the appended figures is meant to refer to the end of the injection device carrying the injection needle whereas the term "proximal end" is meant to refer to the opposite end pointing away from the injection needle.

Figure 1 discloses a number of injection pens. The injection pen disclosed in figure 1A comprises a standard cartridge 1 containing 3,0 ml of insulin with a strength of 100 IU per mil IiIi- tre, thus containing a total of 300 IU. The injection pen disclosed in figure 1 B comprises a more compact cartridge 100 but contains the same dose setting and injection mechanics as in figure 1 A. The injection pen disclosed in figure 1 B contains 1 ,5 ml of insulin with a strength of 200 IU per millilitre, thus also containing a total of 300 IU.

Such compact cartridge is described in details in EP 1.424.984.

The cartridge 1 is at its proximal end provided with a rubber piston 10 which is acted upon by a piston rod 20. The piston rod 20 has an external thread 21 which mates the internal thread 31 of the nut member 30. The nut member 30 is secured to the cartridge holder which is part of the housing 40.

The piston rod 20 further has a keyed surface 22 mating the internal keyed surface 52 of the piston rod guide 50 such that the piston rod 20 is rotated when the piston rod guide 50 is rotated.

The outer shape of the piston rod guide 50 fits with the internal shape of the connector tube 60. The connector tube 60 can be coupled to the dose dial 70 by engagement of the teeth 61 on the connector tube 60 with corresponding slits 71 on the dose dial 70. The connector tube 60 is coupled to the dose dial 70 when a user exerts pressure on the injection button 80.

In order to set the size of the dose to be injected, the user rotates the dose dial 70 which screws out from the housing 40 in the thread connection 42, 72 provided between the dose dial 70 and the housing 40. The size of the dose can be viewed in the window 41. As the dose dial 70 screws out, the connector tube 60 follows the axial movement of the combined rotational/axial movement of the dose dial 70. The connector tube 60 is prevented from rotating by the engagement with the piston rod guide 50 which is connected to the housing through a one-way coupling 33, 53 comprising a ratchet 53 and a toothed ring 33.

When the correct dose is set, the user expels the set dose by pushing back the injection button 80. This movement makes the dose dial 70 rotate down in the thread connection 42, 72 between the dose dial 70 and the housing 40. Since the connector tube 60 is now locked to the dose dial 70 through the engagement between the teeth 61 and the corresponding slits 71 and is free to rotate in the one-way coupling 33, 53, the connector tube 60 rotates with the dose dial 70. This rotation is transformed to the piston rod guide 50 and on to the piston rod 20 which is screwed forward in the internal thread 31 of the nut member 30.

A more detailed description of such injection pen is given in US 6.004.297. The injection pen could further be equipped with an End-of-Content ring 90 as detailed described in EP 1.250.167

Figures 1 B and 2B illustrates the same kind of injection pen, however in order to make the injection pen shorter, the cartridge 100 has been shortened. Since the total volume of a cartridge 1 , 100, 200 is determined by the formula:

V = π x R² x L,

the length (L) only needs to be half the length of the before mentioned standard cartridge 1 when the volume (V) is decreased from 3,0 ml to 1 ,5 ml and the radius (R) are kept constant.

The pitch between the threaded piston rod 20 and the interior thread 31 of the nut member 30 is decisive for the distance the piston rod 20 travels when rotated. The forward travel of the piston rod 20 multiplied with the area of the plunger 10 determines the volume to be expelled.

In figure 1 A and 2A, the pitch is approximately 1 :3 whereas the pitch of the injection pen shown in figure 1 B and 2B is around 1 :1 ,5. All other mechanical components of the dose setting and injection mechanism are the same. The active area, i.e. the area through which the rubber piston 10 can move, of the more compact cartridge 100 has only half the length of the active area of the standard cartridge 1.

If the standard cartridge 1 is filled with long acting insulin in a concentration of 100 IU per mil- lilitre and the compact cartridge 100 is filled with short acting insulin in a concentration of 200 IU per millilitre then the longest injection pen is filled with long acting insulin and the shortest injection pen is filled with short acting insulin.

An even shorter injection pen is disclosed in figure 1 C and 2C. Here the length of the dose dial has been shortened and the distance the dose dial 270 can be screwed out from the housing 240 has been decreased. The maximum number of IU a user can set is fewer than in the injection pens disclosed in the figures 1 A, 2A and 1 B, 2B.

The shorter dose setting and injection mechanism combined with the compact cartridge 100, 200 results in a very short and compact injection pen.

Some preferred embodiments have been shown in the foregoing, but it should be stressed that the invention is not limited to these, but may be embodied in other ways within the sub- ject matter defined in the following claims. The figures e.g. discloses the injection device of the present invention in the form of an oblong pen-shaped object, however, this particular shape is in no way limiting for the present invention as defined in the claims.

Claims

Claims:

1. A system of at least two pen-shaped injection devices for injecting liquid insulin, compris- ing;

a first and a second injection device of different length, wherein;

the first injection device is shorter than the second injection device and contains short time acting insulin, and

the second injection device is longer than the first injection device and contains long time acting insulin.

2. A system of injection devices according to claim 1 , wherein the at least two injection devices contains the same amount of International Units (IU) of insulin.

3. A system of injection devices according to claims 1 or 2, wherein the injection devices in the system is based on the same technology platform.

4. A system of injection devices according to claims 3, wherein the first injection device containing short acting insulin has a cartridge (1 ) that is shorter than the cartridge (100, 200) of the second injection device containing long acting insulin.

5. A system of injection devices according to claim 3 or 4, wherein the at least two injection devices comprises a threaded piston rod (20, 120, 220) that are moved forward into a cartridge (1 , 100, 200) secured in the at least two injection devices in order to expel the insulin contained in the cartridge (1 , 100, 200).

6. A system of injection devices according to claim 5, wherein the threaded piston rod (20, 120, 220) in the first injection device has a pitch different from the pitch of the piston rod (20, 120, 220) in the second injection device.

7. An injection device for injecting liquid insulin, which injection device is useable in a system according to any of the preceding claims.