NL2015198B1 - Intravitreal injection device and bevacizumab for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema. - Google Patents

Intravitreal injection device and bevacizumab for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema. Download PDF

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Publication number
NL2015198B1
NL2015198B1 NL2015198A NL2015198A NL2015198B1 NL 2015198 B1 NL2015198 B1 NL 2015198B1 NL 2015198 A NL2015198 A NL 2015198A NL 2015198 A NL2015198 A NL 2015198A NL 2015198 B1 NL2015198 B1 NL 2015198B1
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Prior art keywords
injection
injection device
cylinder
piston
plunger
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NL2015198A
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Dutch (nl)
Inventor
Mechiel Hubert Schellekens Kari
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Mechiel Hubert Schellekens Kari
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Application filed by Mechiel Hubert Schellekens Kari filed Critical Mechiel Hubert Schellekens Kari
Priority to NL2015198A priority Critical patent/NL2015198B1/en
Priority to EP16762893.2A priority patent/EP3324903A1/en
Priority to PCT/NL2016/050540 priority patent/WO2017014630A1/en
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Publication of NL2015198B1 publication Critical patent/NL2015198B1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0026—Ophthalmic product dispenser attachments to facilitate positioning near the eye

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  • Health & Medical Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

The invention relates to an intravitreal injection device, comprising a syringe assembly, comprising a cylinder, a plunger and a needle, a tubular housing configured to receive the syringe assembly, and a positioning element arranged at a distal end of the tubular housing to position the injection device with respect to an eye to be treated. The syringe assembly is movable with respect to the tubular housing in axial direction of the tubular housing between a retracted position, in which the needle is arranged inside the tubular housing and an injection position in which the needle at least partially extends out of the tubular housing. The injection device comprises a first biasing element to bias with a first biasing force the syringe assembly to the retracted position, wherein exerting a pressure on the plunger results in movement of the syringe assembly from the retracted position to the injection position, and subsequently in an injection stroke, in which the plunger moves into the cylinder, and wherein the injection device is configured to automatically return, at the end of the injection stroke, at least the cylinder and needle of the syringe assembly to the retracted position independent from a pressure exerted on the plunger and/or a position of the plunger.

Description

P32446N LOO/MVM
Title: Intravitreal injection device and bevacizumab for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema
The present invention relates to an intravitreal injection device and bevacizumab for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema.
Intravitreal injection devices are used for the injection of medicine into the eye of a patient to be treated. WO 2008/084063, the contents of which are herein incorporated in its entirety by reference, discloses embodiments of an intravitreal injection device in which a syringe assembly is provided in a tubular housing. The syringe assembly can be moved between a retracted position in which the needle of the syringe assembly is completely inside the tubular housing and an injection position in which the needle extends at least partially out of the tubular housing.
In an embodiment of WO 2008/084063, a biasing element is provided to bias the syringe assembly to the retracted position. Before the injection stroke, i.e. the stroke in which the medicine is actually dispensed from the syringe assembly, the syringe assembly is moved against the biasing force of the biasing element to the injection position. When the plunger of the syringe assembly is released the needle returns to the retracted position.
It is an object of the invention to provide an improved intravitreal injection device which allows a more safe and/or reliable use.
The invention provides an intravitreal injection device, comprising: a syringe assembly, comprising a cylinder, a plunger and a needle, a tubular housing configured to receive the syringe assembly, a positioning element arranged at a distal end of the tubular housing to position the injection device with respect to an eye to be treated, wherein the syringe assembly is movable with respect to the tubular housing in axial direction of the tubular housing between a retracted position, in which the needle is arranged inside the tubular housing and an injection position in which the needle at least partially extends out of the tubular housing, characterized in that, the injection device comprises a first biasing element to bias with a first biasing force the syringe assembly to the retracted position, wherein exerting a pressure on the plunger results in movement of the syringe assembly from the retracted position to the injection position, and subsequently in an injection stroke, in which the plunger moves into the cylinder, and wherein the injection device is configured to automatically return, at the end of the injection stroke, at least the cylinder and needle of the syringe assembly to the retracted position independent from a pressure exerted on the plunger and/or a position of the plunger.
The injection device of the invention is configured to automatically move at least the cylinder and needle of the syringe assembly to a retracted position directly at the end of the injection stroke. This means that as soon as the injection stroke is finished, i.e. the desired quantity of liquid medicine has been injected into the eye to be treated, the needle will be automatically pulled out of the eye.
The direct and automatic retraction of the needle has the advantage that the needle remains as short as possible within the eye to be treated. This reduces the chance on injury of the eye due to sudden movements of the injection device with respect to the eye, in particular in a direction non-parallel with the injection direction. Further, the direct and automatic retraction of the needle may decrease the risk of injury of another person such as the person handling the injection device.
The retraction of the needle is independent of the position of the plunger and/or a force being exerted on the plunger. Thus, the movement of the needle to the retracted position cannot be prevented by continued pressure on the plunger. As a result of direct and automatic retraction of the needle into the tubular housing the injection device is very safe and reliable in use.
Further, the automatic retraction of the needle only takes place at the end of the injection stroke. Thus, when the needle is automatically retracted, the user of the injection device is assured that the complete intended dose has been injected by the injection device.
It is remarked that the term syringe assembly does not specifically refer to a separately provided syringe to be placed in the tubular housing, but to a number of parts forming a cylinder, plunger and needle to dispense liquid medicine. The cylinder, plunger, and needle are preferably integrated parts of the injection device in combination with the tubular housing. The plunger extends into the cylinder and defines together a dose space configured to contain a quantity of liquid medicine. The needle is connected to the dose space such that liquid medicine may be dispensed from the dose space through the needle when the plunger is moved into the cylinder.
In an embodiment, the cylinder comprises cylinder extensions and the plunger comprises plunger extensions, wherein the tubular housing comprises inner guiding grooves configured to receive the cylinder extensions and the plunger extensions in order to guide the plunger and cylinder during the movement from the retracted position to the injection position and during the injection stroke.
By guiding the plunger and cylinder in their movement by inner guiding grooves provided in the tubular housing, the order of actions and the associated displacements of the plunger and the cylinder can be predetermined very accurately. This mechanical guiding of the plunger and cylinder in their movements further increase the reliability and safety of the injection device.
It is remarked that the inner guiding grooves may also be applied in an intravitreal injection device to guide the movements of the plunger and the cylinder in an embodiment in which the cylinder and needle of the syringe assembly do not automatically return to the retracted position at the end of the injection stroke.
In an embodiment, the inner guiding grooves comprise longitudinal grooves to receive the cylinder extensions and the plunger extensions in order to guide the axial movement of the syringe assembly from the retracted position to the injection position.
When the syringe assembly is moved from the retracted position to the injection position, an axial movement of the cylinder and the plunger with respect to the tubular housing is required. The movement of the cylinder, plunger and needle from the retracted position to the injection position may be performed as an axial movement, whereby this movement may be guided by longitudinal guiding grooves provided in or on the inner surface of the tubular housing.
In an embodiment, the inner guiding grooves comprise a helical groove configured to receive the plunger extensions, after the syringe assembly has moved in the injection position to guide a screw-like movement of the plunger with respect to the cylinder during the injection stroke.
During the injection stroke, i.e. the movement of the plunger with respect to the cylinder to dispense liquid medicine from the injection device, the movement of the plunger may be a helical movement of at least a part of the plunger. During this helical movement, plunger extensions of the plunger may be arranged in a helical guiding groove to guide this helical movement. The cylinder may remain in a fixed rotational and axial position with respect to the tubular housing such that the helical movement of at least a part of the plunger results in a movement of the plunger into the cylinder to dispense liquid medicine from the syringe assembly.
In an embodiment, the plunger extensions are, at the end of the injection stroke, again arranged in longitudinal grooves of the tubular housing to allow the plunger to move in axial direction from the injection position to the retracted position. At the end of the injection stroke, the plunger extensions may be arranged in longitudinal grooves to allow the plunger, or at least a part thereof to move, together with the cylinder and needle, from the injection position to the retracted position.
In an embodiment, the plunger comprises a proximal plunger part and a distal plunger part, and wherein at the end of the injection stroke the distal plunger part is axially decoupled from the proximal plunger part, such that the first biasing force of the first biasing element can move the distal plunger part, the cylinder and the needle from the injection position to the retracted position independent of a position of the proximal plunger part.
By decoupling the proximal plunger part and the distal plunger part at the end of the injection stroke, the distal plunger part can move independently of the position of the proximal plunger part. As a result, the distal plunger part, the cylinder and the needle can be pushed by the first biasing force from the injection position to the retracted position independent from a pressure exerted on the proximal plunger part and/or a position of the proximal plunger part.
The proximal plunger part is a part of the plunger that is configured to be pushed by the user to inject liquid medicine from the injection device, and may for example comprise a push button and a push rod. The distal plunger part extends into the cylinder, and comprises for example a seal element to sealingly engage the inner side of the cylinder.
In an embodiment, the proximal plunger part comprises an elongate distal end having a non-circular cross-section, and wherein the distal plunger part comprises a proximal recess having a non-circular cross-section, whereby in a first rotational position of the distal plunger part with respect to the proximal plunger part, the distal end cannot move into the proximal recess, and in a second rotational position of the distal plunger part with respect to the proximal plunger part, the distal end can move into the proximal recess.
Non-circular cross-sections of the distal end of the proximal plunger part and a proximal recess of the distal plunger part can advantageously be used to decouple the proximal plunger part and the distal plunger part by rotation of the distal plunger part with respect to the proximal plunger part from the first rotational position to the second rotational position.
Preferably, the depth of the proximal recess is about the same or larger than a displacement of the syringe assembly from the retracted position to the injection position, such that as soon as the proximal plunger part is decoupled from the distal plunger part, the proximal plunger part and the distal plunger part can freely move with respect to each other over at least the distance of the displacement of the syringe assembly from the retracted position to the injection position. As a result, the distal plunger part, the cylinder and the needle of the syringe assembly can move to the retracted position independent from a pressure exerted on the plunger and/or a position of the plunger.
Any other decoupling device configured to decouple the proximal plunger part and the distal plunger part at the end of the injection stroke in such a way that the proximal plunger part and the distal plunger part can freely move with respect to each other over a distance of at least the displacement between the retracted position and the injection position can advantageously be used to automatically return, at the end of the injection stroke, at least the cylinder and needle of the syringe assembly to the retracted position independent from a pressure exerted on the plunger and/or a position of the plunger.
In an embodiment, the distal plunger part is moved by the screw-like movement from the first rotational position to the second rotational position.
In this embodiment, the distal plunger part may comprise a rotation element having the proximal recess configured to receive the distal end of the proximal plunger part, and one or more plunger extensions that extend into inner guiding grooves on or in the tubular housing. A retainer element may be provided to hold the proximal plunger part in a fixed rotational position with respect to the tubular housing such that when, during the injection stroke, the rotation element is rotated from the first rotational position to the second rotational position by the plunger extensions that extend into the helical groove, the proximal plunger part remains in the same rotational position. As a consequence, the distal end of the proximal plunger part is aligned at the end of the rotation of the rotation element with the proximal recess such that the distal end may move into the proximal recess with the result that the distal plunger part is decoupled from the proximal plunger part.
In an embodiment, the injection device comprises a removable lock element that prevents that the plunger can be moved into the cylinder. A removable lock element can be provided to ensure that the injection device remains in its initial position, until the lock element is removed. This means that the user can easily see whether the injection device has already been used.
In an embodiment, the injection device comprises a second biasing element exerting a biasing force on the plunger to move into the cylinder as soon as the locking element is removed. In such embodiment, removal of the lock element will automatically result in a movement of the plunger into the cylinder. This will cause that a volume of the dose space defined between the cylinder and the plunger will decrease and that a small amount of liquid medicine will be dispensed from the syringe assembly. This ensures that any air present in the needle may automatically be pumped out of the dose space and/or needle before actual use of the injection device.
In an embodiment, the positioning element comprises a ring shaped element having a curved contact surface to be placed on the eye to be treated. The positioning element preferably comprises a side wall configured to be placed against the eye brow and/or eyelash of a patient to be treated. The outer surface of the side wall may be concavely shaped to improve the holding effect of the side wall.
In an embodiment, the syringe assembly comprises, in particular in a dose space formed by the cylinder and plunger, a dose of bevacizumab of 2 - 20 pi, preferably 5 -15 μΙ.
The invention also relates bevacizumab for use in a method of preventing, treating or delaying macular degeneration, in particular neovascular macular degeneration, or macular diabetic edema, wherein the bevacizumab is administered by an intravitreal injection device as claimed in any of the claims 1-13.
The intravitreal injection device of the invention is in particular suitable to administer in a single shot of a suitable amount of liquid medicine to a patient.
In an embodiment the loaded dose of bevacizumab in the intravitreal injection device is preferably 2-20 μΙ, more preferably 5 -15 μΙ. According to an embodiment, bevacizumab is injected once in a single shot by the intravitreal injection device with a dose of about 5-15 μΙ, preferably 10 μ I to prevent, treat or delay macular degeneration, in particular neovascular macular degeneration, or macular diabetic edema.
An embodiment of the invention will now be described, by way of example only, with reference to the accompanying schematic drawings in which:
Figures 1 and 2 show side views of an injection device for intravitreal injection;
Figures 3 and 4 show longitudinal cross sections of the injection device of Figures 1 and 2;
Figures 5 and 6 show side views of the plunger and cylinder in exploded view; and
Figures 7a-7e show subsequent steps during use of the injection device of Figure 1; and
Figures 8a-8e show schematically the guiding of cylinder and plunger during the steps of Figures 7a-7e.
Figures 1 and 2 show side views of an injection device for intravitreal injection, generally indicated by reference numeral 1. The injection device 1 is in particular suitable for dispensing small amounts of liquid medicine.
The injection device 1 comprises a tubular housing 2, a positioning element 3 and a syringe assembly 4 arranged in the tubular housing 2. It is remarked that the term syringe assembly does not specifically refer to a separately provided syringe to be placed in the tubular housing 2, but to a number of parts forming a cylinder, plunger and needle to dispense liquid medicine. In the embodiment, shown in Figures 1 and 2 the cylinder, plunger and needle are integrated parts of the injection device 1.
The positioning element 3 is configured to be placed on an eye to be treated in order to reliably and quickly inject an amount of medicine into the eye. The positioning element 3 is a ring shaped element arranged at the distal end of the tubular housing 2 and comprises a curved contact surface to be placed around the cornea of the eye to be treated.
The positioning element 3 comprises an extended side wall 5 configured to be placed against the eyebrow and/or eyelash of a patient to be treated. The outer surface 6 of the side wall is concavely shaped to receive at least partially of the eyelid eye lash and/or eye brow of a patient therein.
The injection device 1 further comprises a removable lock element 7. This lock element 7 has to be removed before the injection device 1 can be used to inject a medicine into the eye of a patient.
The lock element 7 may also serve as a tamper-evident, i.e. as long as the lock element is present, the injection device 2 has not been used.
Figures 3 and 4 show longitudinal cross sections A-A and B-B of the injection device 1. The syringe assembly 4 comprises a plunger 8, a cylinder 9 and a needle 10. The plunger 8 comprises a proximal plunger part 8a and a distal plunger part 8b. The proximal plunger part 8a comprises a push rod 11 and a push button 12. The distal plunger part 8b comprises a rotation element 13 and a seal element 14 extending into the cylinder 9. The cylinder 9 and the seal element 14 define a dose space 15 for accommodating a dose of medicine.
The dose space 15 comprises a small amount of liquid medicine, for example 2-20 μΙ, such as about 10 μΙ. At the distal end of the dose space 15, the needle 10 is provided. The rotation element comprises a proximal recess 24.
The syringe assembly 4 is movable in the tubular housing 2 in its longitudinal direction between a retracted position as shown in Figures 3 and 4 and an injection position. In the retracted position, the needle 10 is completely in the tubular housing 2. In the injection position, the needle 10 extends partially out of the tubular housing 2 so that it can pierce into an eye to be treated.
Figure 3 shows that the tubular housing 2 comprises a first pair of diametrically opposed longitudinal guiding grooves 16 to guide an axial movement of the cylinder 9 and the plunger 8 in the tubular housing 2. The cylinder 9 comprises two diametrically opposed cylinder extensions 17 and the rotation element 13 comprises two diametrically opposed plunger extensions 18 that extend into the longitudinal guiding grooves 16.
Figure 4 shows one of a second pair of diametrically opposed longitudinal guiding grooves 19. The second pair of guiding grooves 19 is configured to receive the plunger extensions 18 after the rotation element 13 is rotated from a first rotational position, as shown in Figures 3 and 4, to a second rotational position as will be described hereinafter. A helical groove is provided between each of the first longitudinal grooves 16 and the second longitudinal grooves 19 to guide the rotation element 13 during rotation from the first rotational position to the second rotational position.
The first pair of longitudinal guiding grooves 16 and the second pair of longitudinal guiding grooves 19 are, for example, arranged at an angle of about 30 degrees with respect to each other about the longitudinal axis of the tubular housing 2. A first biasing element 20 is provided to bias the syringe assembly 4 to the retracted position. A second biasing element 21 is provided between a retainer 22 and the rotation element 13 to push the plunger 8 into the cylinder 9 as soon as the lock element 7 is pulled out of the tubular housing 2. This movement of the plunger 8 into the cylinder 9 directly after removal of the lock element 7 ensures that any air in the needle 10 is pushed out of the needle by medicine that is pushed out of the dose space 15.
The first biasing element 20 and the second biasing element 21 of the shown embodiment are helical springs, but the biasing elements may also be formed by any other suitable element. The cylinder 9 comprises two upwardly extending arms 23 to support the retainer 22 in a fixed rotational position with respect to the cylinder 9.
The parts of the syringe assembly 4 are shown in more detail in the exploded views of Figures 5 and 6. The exploded view of Figure 5 corresponds with the cross section view of Figure 3, and the exploded view of Figure 6 corresponds with the cross section view of Figure 4.
By comparison of the distal end of the push rod 11 in Figures 5 and 6, it can be seen that the cross section of this distal end is non-circular. Similarly, it can be seen by comparison of Figures 3 and 4 that the cross section of the proximal recess 24 is noncircular. The cross section of the distal end of the push rod 11 and the cross section of the proximal recess 24 are selected such that in one or more rotational positions of the distal end of the push rod 11 with respect to the proximal recess 24, the distal end cannot move into the proximal recess 24, while in one or more other rotational positions of the distal end of the push rod 11 with respect to the proximal recess 24, the distal end can move into the proximal recess 24.
The retainer 22 comprises a non-circular opening through which the push rod 11 extends. The push rod 11 therefore cannot rotate with respect to the retainer 22 and as a result with respect to the cylinder 9.
As explained above, the rotation element 13 may rotate with respect to the cylinder 9 between a first rotation position and a second rotational position.
In the first rotational position of the rotation element 13, the push rod 11 is positioned with respect to the rotation element 13, as shown in Figures 3 and 4, in such a way that the distal end of the push rod 11 cannot move into the proximal recess 24. However, in the second rotational position of the push rod 11 with respect to the rotation element 13, the cross section of the distal end of the push rod 11 is aligned with the cross section of the proximal recess such that the distal end of the push rod 11 may move into the proximal recess 24 of the rotation element 13. As a result, the proximal plunger part 8a is decoupled from distal plunger part 8b in this second rotational position of the rotation element 13.
It is remarked that the cylinder 9 comprises two helical slots 25 to allow the plunger extensions 18 to move through the helical guiding groove during the rotation of the rotation element 13 from the first rotational position to the second rotational position.
The steps of injecting a fluid with the injection device 1 will now be described with reference to Figures 7a-7e.
Figure 7a shows the injection device 1 before use. The dose space 15 is filled with a small amount of about 10 μΙ -about 15 μΙ of liquid medicine, in particular bevacizumab. This liquid medicine is intended to be injected into an eye to be treated for neovascular macular degeneration or macular diabetic edema. In the state shown in Figure 7a, the plunger 8 and the cylinder 9 cannot be moved with respect to the tubular housing 2 and each other due to the presence of the lock element 7. The lock element 7 in particular prevents that the second biasing element 21 can press the plunger 8 into the cylinder 9.
As a first step, the lock element 7 is removed from the tubular housing 2. By removing the lock element 7, the plunger 8 is moved by the second biasing means 21 over a first distance into the cylinder, whereby the volume of the dose space 15 is decreased. As a result, liquid medicine is pressed into the needle 10 and air present in the needle 10 is driven out of the needle 10 so that the dose space 15 and the needle 10 are only filled with liquid medicine.
In this movement of the plunger 8, the plunger 8 is guided by the first pair of guiding grooves 16 through which the plunger extensions 18 move in axial direction. The relative movement of the plunger 8 with respect to the cylinder 9 ends when the plunger extensions 18 abut against the cylinder extensions 17.
Figure 7b shows the injection device 1 after removal of the lock element 7 and the subsequent automatic movement of the plunger 8 with respect to the cylinder 9.
In a next step, the positioning element 3 can be located in a proper position on the eye to be treated, whereby the ring shaped positioning element 3 is placed around the cornea.
The extended side wall 5 ensures that the eye lid and eye brow of the eye to be treated are kept away from the inner opening of the positioning element 3.
When the positioning element 3 is properly positioned on the eye to be treated, the syringe assembly 4, i.e. plunger 8 and cylinder 9, can be moved from the retracted position in which the needle 10 is completely in the tubular housing 2 to the injection position in which the needle 10 extends from the tubular housing 2.
The movement of the syringe assembly 4 from the retracted position to the injection position is established by pushing on the push button 12, whereby the first biasing element 20 is compressed. During this movement, the needle 10 will be pushed through the flexible element 26 and at the end of the movement the needle 10 will extend for about 5 mm out of the flexible element 26 and into the eye to be treated.
Both the plunger 8 and the cylinder 9 will move in axial direction without rotation with respect to the tubular housing 2, as the cylinder extensions 17 and the plunger extensions 18 will move through the first longitudinal grooves 16. The syringe assembly 4 can be moved with respect to the tubular housing 2 in distal direction of the injection device 1 until the cylinder extensions 17 reach the distal ends of the first longitudinal guiding grooves 16. It is remarked that during the axial movement of the syringe assembly 4 with respect to the tubular housing 2, the plunger 8 will not move with respect to the cylinder 9 as the plunger extensions 18 already abut against the cylinder extensions 17.
Figure 7c shows the injection device 1 after the movement of the syringe assembly 4 from the retracted position to the injection position. The plunger extensions 18 are now positioned at the beginning of the helical groove connecting one of the first longitudinal guiding grooves 16 with one of the second longitudinal guiding grooves 19. When the user continues to exert pressure on the push button 12, the cylinder 9 cannot be moved further in distal direction, since the cylinder extensions 17 have reached the distal ends of the longitudinal guiding grooves 16. But the plunger extensions 18 can now follow the helical guiding groove by rotation of the rotation element 13.
Thus, when the user continues to push on the plunger 8, the rotation element 13 will make a rotational movement from the first rotational position to the second rotational position in which the plunger extensions 18 follow the helical guiding groove. This rotational movement also moves the plunger 8 into the cylinder 9 therewith decreasing the volume of the dosage space 15 and injecting fluid medicine from the needle 10 into the eye of the patient.
This movement of the plunger 8 into the cylinder 9 in which the injection device 1 actually injects fluid medicine into the eye of the patient is also referred to as the injection stroke.
At the end of the injection stroke the plunger extension 18 is arranged in the second longitudinal guiding groove 19, as shown in Figure 7d.
During rotation of the rotation element 13 from the first rotational position to the second rotational position, the push rod 11 is held by the retainer 22 in the same rotational position with respect to the tubular housing 1. As a result, the cross section of the distal end of the push rod 11 is, at the end of the rotation of the rotation element 13, aligned with the associated cross section of the proximal recess 24 of the rotation element 13 such that the distal end of the push rod 11 can move into the proximal recess 24 (compare Figures 7c and 7d). As a consequence, the proximal plunger part 8a, i.e. the push rod 11 and push button, is decoupled from the distal plunger part 8b, i.e. the rotation element 13 and the seal element 14. The depth of the proximal recess 24 substantially corresponds with the displacement of the syringe assembly 4 between the retracted position and the injection position. As a result, the first biasing element 20 can automatically push the distal plunger part 8b, the cylinder 9 and the needle 10 from the injection position to the retracted position, while the distal end of the push rod enters the proximal recess 24.
This movement from the injection position to the retracted position automatically takes place independent of the position of the proximal plunger part 8a and independent of a force being exerted on the push button 12. In this way, the needle 10 is directly and automatically retracted from the eye at the end of the injection stroke, but only when a predetermined end of the injection stroke has been reached.
Figure 7e shows the injection device 1 after the distal plunger part 8b, the cylinder 9 and the needle 10 from the injection position to the retracted position. It can be seen that the distal end of the push rod 11 has been moved into the proximal recess 24 of the rotation element 13. The needle 10 is retracted into the tubular housing 2 and cannot be moved anymore outside the tubular housing 2.
Figures 8a-8e show schematically the movement of one of the cylinder extensions 17 and one of the plunger extensions 18 through one of the first longitudinal guiding grooves 16, a helical groove, indicated by reference numeral 27, and one of the second longitudinal guiding grooves 19. It is remarked that the position of the cylinder extension 17 and the plunger extensions 18 in Figures 8a-8e correspond with the state of the injection device 1 shown in Figures 7a-7e, respectively.
In Figure 8a the position of the cylinder extension 17 and the plunger extension 18 in the longitudinal guiding groove 16 before removal of the lock element 7 is shown. As soon as the lock element 7 is removed, the second biasing element 21 will push the plunger extension 18 in an axial movement towards the cylinder extension 17 until the plunger extension 18 abuts against the cylinder extension 17.
This position, corresponding to the state shown in Figure 7b, is shown in Figure 8b. When pressure is exerted on the plunger 8, the cylinder extension 17 and the plunger extension 18 will move together in an axial movement through the longitudinal guiding groove 16 until the cylinder extension 17 abuts against the distal end of the longitudinal guiding groove 16, as shown in Figure 8c. During this movement the syringe assembly is moved from the retracted position to the injection position. The plunger extension 18 is now arranged at the beginning of the helical guiding groove 27.
When pressure on the plunger 8 is continued the plunger extension 18 will move through the helical guiding groove 27, while the rotation element 13 makes a screw-like movement, i.e. a combination of a rotating and axial movement. In this movement, the injection stroke, the plunger 8 is moved into the cylinder 9 to inject fluid medicine into the eye of a patient. At the end of the injection stroke the plunger extension 18 is arranged in the second longitudinal guiding groove 19, and due to the rotation of the rotation element 13 from the first rotational position to the second rotational position, the proximal plunger part 8a is decoupled from the distal plunger part 8b.
Since the first biasing element 20 pushes against the cylinder 9, the distal plunger part 8b, the cylinder 9 and the needle 10 will automatically move from the injection position to the retracted position. During this movement, the cylinder extension 17 moves through the first longitudinal guiding groove 16 and the plunger extension 18 moves through the second longitudinal guiding groove 19.
Figure 8e shows the cylinder extension 17 and the plunger extension 18 at the end of this movement.

Claims (15)

1. Intravitreale injectie-inrichting, omvattende: een injectiesamenstel, omvattende een cilinder, een zuiger en een naald, een buisvormige behuizing ingericht om het injectiesamenstel te ontvangen, een positioneringselement dat is aangebracht aan een distaai uiteinde van de buisvormige behuizing om de injectie-inrichting te positioneren ten opzichte van een te behandelen oog, waarbij het injectiesamenstel in axiale richting van de buisvormige behuizing beweegbaar is ten opzichte van de buisvormige behuizing tussen een teruggetrokken positie, waarin de naald zich in de buisvormige behuizing bevindt, en een injectiepositie, waarin de naald zich ten minste gedeeltelijk uitstrekt buiten de buisvormige behuizing, met het kenmerk, dat de injectie-inrichting een eerste voorspanelement heeft om met een eerste voorspankracht het injectiesamenstel voor te spannen naar de teruggetrokken positie, waarbij het uitoefenen van een druk op de zuiger resulteert in beweging van het injectiesamenstel van de teruggetrokken positie naar de injectiepositie en vervolgens in een injectieslag, waarin de zuiger de cilinder in beweegt, en dat de injectie-inrichting is ingericht om ten minste de cilinder en de naald van het injectiesamenstel automatisch, aan het einde van de injectieslag, terug te brengen naar de teruggetrokken positie onafhankelijk van de druk die wordt uitgeoefend op de zuiger en/of een positie van de zuiger.An intravitreal injection device comprising: an injection assembly comprising a cylinder, a piston and a needle, a tubular housing adapted to receive the injection assembly, a positioning element disposed at a distal end of the tubular housing around the injection device to be positioned with respect to an eye to be treated, wherein the injection assembly is movable in axial direction of the tubular housing relative to the tubular housing between a retracted position in which the needle is located in the tubular housing and an injection position in which the needle extending at least partially outside the tubular housing, characterized in that the injection device has a first biasing element to bias the injection assembly to the retracted position with a first biasing force, the application of a pressure to the piston resulting in movement of the injection assembly of the retracted position to the injection position and then into an injection stroke, in which the piston moves into the cylinder, and that the injection device is adapted to automatically return at least the cylinder and the needle of the injection assembly at the end of the injection stroke to the retracted position independently of the pressure exerted on the piston and / or a position of the piston. 2. Injectie-inrichting volgens conclusie 1, waarbij de cilinder cilinderextensies omvat en de zuiger zuigerextensies omvat, en waarbij de buisvormige behuizing inwendige geleidingsgroeven omvat die zijn ingericht om de cilinderextensies en de zuigerextensies te ontvangen om de zuiger en de cilinder te geleiden tijdens de beweging van de teruggetrokken positie naar de injectiepositie en tijdens de injectieslag.The injection device of claim 1, wherein the cylinder includes cylinder extensions and the piston includes piston extensions, and wherein the tubular housing includes internal guide grooves adapted to receive the cylinder extensions and piston extensions to guide the piston and cylinder during movement from the retracted position to the injection position and during the injection stroke. 3. Injectie-inrichting volgens conclusie 2, waarbij de inwendige geleidingsgroeven langsgroeven omvatten om de cilinderextensies en de zuigerextensies te ontvangen om de axiale beweging van het injectiesamenstel van de teruggetrokken positie naar de injectiepositie te geleiden.The injection device of claim 2, wherein the internal guide grooves include longitudinal grooves to receive the cylinder extensions and the piston extensions to guide the axial movement of the injection assembly from the retracted position to the injection position. 4. Injectie-inrichting volgens conclusie 2 of 3, waarbij de inwendige geleidingsgroeven een spiraalvormige groef omvatten die is ingericht om de zuigerextensies te ontvangen, nadat het injectiesamenstel is bewogen naar de injectiepositie, om een schroefachtige verplaatsing van de zuiger ten opzichte van de cilinder te geleiden tijdens de injectieslag.The injection device of claim 2 or 3, wherein the internal guide grooves comprise a spiral groove adapted to receive the piston extensions, after the injection assembly has been moved to the injection position, to cause a screw-like displacement of the piston relative to the cylinder. during the injection stroke. 5. Injectie-inrichting volgens een van de conclusies 2-4, waarbij aan het einde van de injectieslag de zuigerextensies weer zijn aangebracht in langsgroeven van de buisvormige behuizing om het mogelijk te maken de zuiger in de axiale richting van de injectiepositie naar de teruggetrokken positie te laten bewegen.The injection device of any one of claims 2-4, wherein at the end of the injection stroke the piston extensions are again provided in longitudinal grooves of the tubular housing to allow the piston in the axial direction from the injection position to the retracted position to move. 6. Injectie-inrichting volgens een van de voorgaande conclusies, waarbij de zuiger een proximaal zuigergedeelte en een distaai zuigergedeelte omvat, en waarbij aan het einde van de injectieslag het distale zuigergedeelte in axiale richting ontkoppeld wordt van het proximale zuigergedeelte, zodanig dat de eerste voorspankracht van het eerste voorspanelement het distale zuigergedeelte, de cilinder en de naald van de injectiepositie naar de teruggetrokken positie kan bewegen onafhankelijk van een druk die wordt uitgeoefend op het proximale zuigergedeelte en/of een positie van het proximale zuigergedeelte.An injection device according to any of the preceding claims, wherein the piston comprises a proximal piston portion and a distal piston portion, and wherein at the end of the injection stroke the distal piston portion is disengaged axially from the proximal piston portion such that the first biasing force of the first biasing element, the distal piston portion, the cylinder, and the needle can move from the injection position to the retracted position regardless of a pressure exerted on the proximal piston portion and / or a position of the proximal piston portion. 7. Injectie-inrichting volgens conclusie 6, waarbij het proximale zuigergedeelte een langwerpig distaai uiteinde met een niet-cirkelvormige dwarsdoorsnede heeft, en waarbij het distale zuigergedeelte een proximale uitsparing met een niet-cirkelvormige dwarsdoorsnede heeft, waarbij in een eerste rotatiepositie van het proximale zuigergedeelte ten opzichte van het distale zuigergedeelte, het distale uiteinde niet de proximale uitsparing in kan bewegen, en in een tweede rotatiepositie van het proximale zuigergedeelte ten opzichte van het distale zuigergedeelte, het distale uiteinde de proximale uitsparing in kan bewegen.The injection device of claim 6, wherein the proximal piston portion has an elongated distal end with a non-circular cross-section, and wherein the distal piston portion has a proximal recess with a non-circular cross-section, wherein in a first rotational position of the proximal piston portion relative to the distal piston portion, the distal end cannot move into the proximal recess, and in a second rotational position of the proximal piston portion relative to the distal piston portion, the distal end can move into the proximal recess. 8. Injectie-inrichting volgens conclusies 4 en 7, waarbij het distale zuigergedeelte door de schroefachtige verplaatsing wordt bewogen van de eerste rotatiepositie naar de tweede rotatiepositie.An injection device according to claims 4 and 7, wherein the distal piston portion is moved from the first rotation position to the second rotation position by the screw-like displacement. 9. Injectie-inrichting volgens een van de voorgaande conclusies, waarbij de injectie-inrichting een verwijderbaar vergrendelelement omvat dat voorkomt dat de zuiger de cilinder in kan worden bewogen.An injection device according to any one of the preceding claims, wherein the injection device comprises a removable locking element that prevents the piston from being moved into the cylinder. 10. Injectie-inrichting volgens conclusie 9, waarbij de injectie-inrichting een tweede voorspanelement heeft voor het uitoefenen van een voorspankracht op de zuiger, om deze de cilinder in te bewegen zodra het vergrendelelement is verwijderd.The injection device of claim 9, wherein the injection device has a second biasing element for exerting a biasing force on the piston to move it into the cylinder as soon as the locking element is removed. 11. Injectie-inrichting volgens een van de voorgaande conclusies, waarbij het positioneringselement een ringvormig element omvat met een gekromd contactvlak dat op het te behandelen oog wordt geplaatst.An injection device according to any one of the preceding claims, wherein the positioning element comprises an annular element with a curved contact surface which is placed on the eye to be treated. 12. Injectie-inrichting volgens een van de voorgaande conclusies, waarbij het positioneringselement een zijwand omvat die is ingericht om tegen een wenkbrauw en/of wimper van een te behandelen patiënt te worden geplaatst, waarbij de zijwand bij voorkeur concaaf is.12. Injection device according to one of the preceding claims, wherein the positioning element comprises a side wall which is adapted to be placed against an eyebrow and / or eyelash of a patient to be treated, the side wall preferably being concave. 13. Injectie-inrichting volgens een van de voorgaande conclusies, waarbij het injectiesamenstel een dosis bevacizumab van 2-20 pl, bij voorkeur 5-15 μΙ omvat.An injection device according to any one of the preceding claims, wherein the injection assembly comprises a dose of bevacizumab of 2-20 µl, preferably 5-15 μΙ. 14. Bevacizumab voor gebruik in een werkwijze voor het voorkomen, behandelen of vertragen van macula degeneratie, met name neovasculaire maculadegeneratie of diabetisch maculair oedeem, waarbij de bevacizumab wordt afgegeven door een intravitreale injectie-inrichting volgens een van de voorgaande conclusies.Bevacizumab for use in a method for preventing, treating or delaying macular degeneration, in particular neovascular macular degeneration or diabetic macular edema, wherein the bevacizumab is delivered by an intravitreal injection device according to any of the preceding claims. 15. Bevacizumab voor gebruik volgens conclusie 14, waarbij een geladen dosis bevacizumab in de intravitreale injectie-inrichting bij voorkeur 2-20 μΙ is, met meer voorkeur 5-15 μΙ.Bevacizumab for use according to claim 14, wherein a charged dose of bevacizumab in the intravitreal injection device is preferably 2-20 μΙ, more preferably 5-15 μΙ.
NL2015198A 2015-07-21 2015-07-21 Intravitreal injection device and bevacizumab for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema. NL2015198B1 (en)

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NL2015198A NL2015198B1 (en) 2015-07-21 2015-07-21 Intravitreal injection device and bevacizumab for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema.
EP16762893.2A EP3324903A1 (en) 2015-07-21 2016-07-20 Intravitreal injection device and bevacizumab, ranibuzimab, bevacuzimab, aflibercept or triamcinolone for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema
PCT/NL2016/050540 WO2017014630A1 (en) 2015-07-21 2016-07-20 Intravitreal injection device and bevacizumab, ranibuzimab, bevacuzimab, aflibercept or triamcinolone for use in a method of preventing, treating or delaying macular degeneration or macular diabetic edema

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