WO2009097791A1 - Cartridge of pen-type insulin injector - Google Patents

Abstract

A cartridge of pen-type insulin injector is provided with the medicament or is provided with the medicament and a glass ball (5) in the space defined by the cartridge bottle (1), the capsule (3) and the plunger (2). Said cartridge also contains a large amount of small diameter glass particulates (6), the glass particulates (6) can mix the medicament uniformly and substitute the residua 4.

Description

 Refill of pen type insulin injector

 The invention belongs to the field of medical instruments and relates to a pen-type insulin syringe refill.

Background technique

 At present, the well-known application of the pen-type insulin syringe refill has been used for more than 20 years, and there are still about 20 units of insulin residual liquid, resulting in waste. When the suspended insulin is finally unable to mix, some of the unmixed insulin is erroneously injected or may be injected, posing a safety risk of adverse consequences.

 From the US patent 4850966A published in the United States as early as 1989. 7. 25, the problem of residual liquids has existed from the beginning. This patent is a method for solving the problem that the suspended insulin 3 ml refill originally uses air bubbles to leave space, and the liquid is moved and mixed by shaking the refill, and there are many disadvantages, and a method of placing a glass ball in the refill is proposed. . The method embodiment indicates that no glass balls are placed in the pen core and insulin cannot be mixed for an acceptable period of time. Using a 3 mm diameter glass sphere, the insulin can be mixed by shaking about 10 times. The number of shakings required with two 3 mm diameter glass beads is not reduced, that is, there is no significant effect. The mixing effect experiments were carried out with 1-3 glass balls of 4-6 mm diameter respectively. The result is that the large glass balls have a good mixing effect, and the number of shaking can be less, but the minimum space required for the last mixing. Large, the amount of residual liquid is large. All currently used are a 2. 5 mm diameter glass sphere.

 At present, there are mainly three companies that produce insulin. The pen-type insulin syringes produced by each company have different methods for the safety and residual liquid volume of the refills.

 The Novo and Pen 3 syringes manufactured by Novo Nordisk Pharmaceuticals of Denmark are suitable for suspension and conventional 3 ml (100 units/ml) insulin refills. The front part of the pen injector, as shown in Figure 1, has a small inspection window. In the 17th article of the syringe instruction, what should be done when the refill and the refill are running out? "When the injection is suspended insulin, if When the rubber piston is visible in the small inspection window, do not inject it. The glass ball inside must have enough space to remix the suspended insulin. "In use, when the rubber piston is seen in the small inspection window, the injection pen The stroke is 308 units, and the bolus is 320 units at the end of the trip, with the least amount of residual liquid. If the syringe holder is unscrewed and returned to the push rod at this time, add a 0 mm pad between the push rod and the piston, and start the bolus. It can also discharge about 12 units of insulin liquid. Explain that the liquid is restricted and abandoned.

The correct amount of insulin is very important. In order to keep the patient's blood sugar in an optimal state, the amount of injection is determined each time as needed. When the amount of injection is small, a hyperglycemia state is generated, which affects the therapeutic effect. When the amount of injection is high, it is easy to produce hypoglycemia, and the patient is trembling, sweating, unconsciousness, coma, etc., and even endangering the serious consequences of life. Therefore, the most important thing about using insulin is that it cannot be overdosed. Generally, a single dose of insulin exceeding a few units may cause hypoemia. Sugar reaction. When using suspended insulin, the concentration of the liquid that is not mixed will change, causing a deviation in the insulin content of the actually injected liquid, resulting in adverse consequences.

 In order to reduce the amount of insulin residual liquid, the method used in the injection of suspended insulin in the Novo pen type 3 syringe poses a greater safety risk to the user. When the rubber piston is seen in the small inspection window, the liquid medicine cannot be mixed. The instructions in the book simply remind you not to inject, that is, the user controls and bears the risk of adverse consequences caused by wrong injection. Generally, users often suffer from misuse of unmixed liquids due to factors such as poor eyesight and low attention. In the case where the total remaining amount of the core is more than 30 units, and the amount of injection required is small, the phenomenon of high concentration of insulin injection is highly likely to cause a hypoglycemic dangerous event. Because the more the amount of residual liquid is reduced, the greater the safety risk, although it is possible to reduce the amount of residual liquid by about 12 units in the case of mixing the liquid, in order to control the risk that the user may be wrongly injected, the risk is too large. The liquid medicine is discarded by means of the termination of the push rod stroke. When the rubber piston is not seen in the small inspection window, the liquid can be mixed. At this time, the injection is required according to the required amount, and may stop between 308 and 320 units. Only when the amount is large, the injection can be stopped to 320 units. At this time, there are about 20 units of residual liquid.

 In the company's disposable one-time insulin pen 30R, the same method is used to reduce the amount of residual liquid. The product manual states that "the amount of liquid remaining in the refill should be at least 12 units to ensure that the liquid can be mixed evenly. If it is less than 12 units, a new injection pen should be used." The pros are both the same. When the syringe is used for conventional insulin, the refills are the same, and the amount of residual liquid of insulin is also the same, and it is obviously necessary to improve them together.

 The excellent pen-injection insulin syringe produced by Eli Lilly and the Dongbao pen-type insulin syringe produced by China Tonghua Dongbao Co., Ltd., the total amount of residual liquid in the refill is about 20 units after injection, due to the injection of suspended insulin. The same refills require a minimum mixing space of approximately 30 units. In the case where the last 12 units of the interval have been unable to remix the insulin, the wrong injection is still caused, resulting in undesirable consequences.

 In summary, the amount of residual liquid is mainly determined by the minimum space required for the last mixing. When the remaining space in the refill is less than 30 units, the glass ball with a diameter of 2.5 mm is almost incapable of moving, and it is not possible to increase the mixing ability by increasing the number of shaking times, and the mixing requirement cannot be achieved. Reducing the amount of residual liquid in this mixing mode increases the safety risk and inconvenience of use. Conventional insulin also produces the same amount of residual liquid in order to match the versatility of the pen. Summary of the invention

 The object of the present invention is to provide a refilling pen which can be combined with the original pen insulin syringe, has high safety, is convenient to use, is simple to implement, and has a high input-output ratio of a pen-type insulin syringe with high safety and low residual liquid amount. And solve the problem that the amount of insulin residual liquid is large after the refill is used, and reduce waste.

The solution proposed by the invention is: a pen-type syringe refill, in the space formed by the refill bottle, the bottle cap and the piston, in the case of a liquid medicine or a glass ball, there is also a substitute for insulin residue Liquid substance. The replacement material is less than the remaining space formed by the refill bottle, the cap and the position of the original piston push rod or the position required to terminate. Substitute substance To make the liquid flow smoothly to the needle. In the suspension type insulin refill, the substitute substance functions to replace or assist in mixing the liquid medicine.

 1. The main method for suspending insulin refills

 In the suspension type insulin refill, the material of the residual liquid can be replaced, and at the same time, it can replace or assist the original glass ball to mix the liquid medicine. In the case of small space and small amount of liquid medicine, a sufficient mixture can be achieved. The effect of the liquid to eliminate or reduce the level of safety risk of uninjected solutions being adversely affected by injection. In order to reduce the amount of residual liquid, the proportion of the remaining space occupied by the substitute substance is as high as possible.

 a. In the remaining space, in the case of residual liquid and a glass pellet, filled with particulate solid substitute material. The substitute material may be a stable spherical solid such as plastic, glass or ceramic. The gap between the spherical solids can make the liquid flow, and can assist the original glass ball to complete the function of mixing the liquid, and replace the residual liquid when the refill is used up. This method can reduce the amount of residual liquid by more than 50%, and the original refill does not have to be changed.

 b. The substitute is a granular solid and a solid integral with the piston, without the original glass pellets. Fill the remaining space with glass beads. Since the remaining space is fixed, the glass beads with a diameter of less than 2 mm are filled, and the corresponding number is from 10. 30. 100 to hundreds. When a large number of small-diameter glass beads are used, the pen reed moves the glass beads to cause collision and shearing with the drug solution and the suspension to form a forced mixing solution. In particular, in the case where the remaining space is small and the amount of the chemical liquid is small, a good effect of sufficiently mixing can be achieved. The original axial diameter of 2.5 mm glass ball needs more than 3 mm, in order to drive the liquid and the suspended matter to produce a turbulent flow to achieve the mixing effect, so the minimum mixing space required for the original glass ball is relatively large. The amount of residual liquid is large. Since a large number of glass beads can fully satisfy the effect of the mixing solution, the original glass ball can be eliminated. In order to further reduce the amount of residual liquid, it is possible to reduce the residual liquid and the glass micro by adding another substitute which only reduces the effect of the residual liquid, that is, the solid body which is connected or integrated with the piston, which is equivalent to increasing the length of the original piston. The remaining space occupied by the beads is realized. The larger the solid matter, the more the amount of residual liquid is reduced, and the solid matter is limited by the number and diameter of the glass beads which are mixed by the replacement of the original glass sphere. When the mixing requirement is satisfied, the diameter of the glass beads is small, which allows the reduction of the residual space in the axial direction of the residual liquid and the glass beads, and the larger the solid matter. The substitute material is four or more granular solids having a diameter of less than 2.5 mm, such as four glass beads having a diameter of 1.6 mm. More than 10 granular solids, such as 10 glass beads with a diameter of 1.2 mm or 15 glass beads with a diameter of 1 mm, which is equivalent to a glass sphere with a diameter of 2.5 mm, but the mixing effect is better. it is good. The granular solids have a diameter of less than 2 mm. For example, when using glass beads with a diameter of 1 mm or less, the number is about 100 or more. Not only the structure of the refill bottle shoulder and the bottle neck, but also the thickness of the solid material can reach about 2 mm. better result. Since the amount of residual liquid required for glass bead replacement is less, the amount of residual liquid can be reduced by about 80% or more. Because the final mixing time is very small, the effect of full mixing can still be achieved, so the safety risk is completely eliminated.

c. In the remaining space, in the case where there is a residual liquid and a glass ball, the substitute is a liquid bag that is fixed to the refill bottle and has a flow channel. Fixing a liquid flow hole or groove with a shape and a remaining space in the refill bottle Film sealed liquid pouch. When the refill is running out, the glass ball that has been mixed for the last time can still move between a small amount of liquid and a liquid separated by the film. The pouch serves as a supplement to the mixing of the liquid. When the bolus is terminated, the glass sphere is contained in the liquid that is isolated from the membrane. At this time, only a small amount of residual liquid is present in the pores or grooves and the bottle neck of the pouch. Another way is that the substitute is a liquid bladder that is fixed to the piston, and the effect is the same as the piston is advanced to the end of the stroke. This method greatly reduces the amount of residual liquid, and the safety is greatly improved.

 d. A pen-type syringe refill consisting of a refill bottle, a glass ball and a concave plunger. The concave top of the piston and the refill bottle are in a sharp-pointed shape, eliminating a 90° dead angle. In the suspended insulin refill, when the plunger is pushed close to the end of stroke, if the remaining 30 units, the concave plunger changes the shape of the space and increases the axial distance when the overall space is constant. At the same time, the moving distance of the glass ball increases. The radial structure is more round and reasonable, which is beneficial to improve the mixing effect. The small circular arc-angled sealing edge on the top of the concave piston eliminates the original 90° dead angle, making it easier to mix the suspended liquid that may settle here.

 2. Only for regular insulin refills

 In the remaining space, the substitute is a solid member having a liquid flow hole or groove which is fixed to the shape of the refill bottle and which has a shape and a remaining space. When the propelling piston touches the component, it stops, and only a small amount of residual liquid is present in the hole or groove and the bottle neck of the solid member. Another way is that the substitute is a solid piece that is fixed to the piston or integral with the piston in conformity with the shape and the remaining space. As the piston advances at the same time, it touches the shoulder of the refill bottle and stops. This method can reduce the amount of residual liquid by more than 90%.

 Beneficial effect

 The safety is high, the amount of insulin residual liquid is greatly reduced, the use is convenient, the implementation is simple, the input-output ratio is high, and the economic effect is remarkable. In the embodiments of the suspension type insulin refills, which account for more than 90% of the use, the safety is greatly improved, especially the method of containing the glass beads, which basically eliminates the unfavorable effects of the unmixed insulin after being injected. Security risk. The amount of residual fluid is reduced by more than 80% (about 15 units), and the amount of residual insulin refill is reduced by more than 90%. The user does not have to pay too much attention and the measurement is accurate. There is basically no change in the implementation of the insulin filling process. It is only a simple and easy way to change the original glass ball with a diameter of 2.5 mm to a small number of small glass beads or a capsular bag and change the piston. The investment for each refill improvement is only a few cents. The 3 ml (300 units) refills on the market vary in price from 60-100 RMB, saving 5% insulin (15 units) equivalent to 35 yuan. The annual dosage of insulin refills is about several hundred million yuan, and the savings of 5% can reach several billion yuan. Therefore, the input-output ratio is extremely high, and the economic effect is particularly remarkable.

 DRAWINGS

 Figure 1 is a schematic view of the small inspection window of the Novo Pen syringe

 2 is a schematic view of Embodiment 1

Figure 3 is a schematic view of Embodiment 2 4 is a schematic view of Embodiment 3

 Figure 5 is a schematic view of Embodiment 4

 Figure 6 is a schematic view of Embodiment 5

 Figure 7 is a schematic view of Embodiment 6

 Figure 8 is a schematic view of Embodiment 7

 Figure 9 is a schematic view of Embodiment 8

 Figure 10 is a schematic view of Embodiment 8

 Figure 11 is a schematic view of Embodiment 9

 Figure 12 is a schematic view of Embodiment 10.

 Figure 13 is a schematic view of the embodiment 10

 Figure 14 is a schematic view of Embodiment 11

 Figure 1. Refill bottle, 2. Original piston, 3. Bottle cap, 4. Residual liquid, 5. Raw glass pellet, 6. Granular solid material, 7. Disc, 8. Integral piston, 9. Liquid Pouch, 10. Piston integrated pouch, 11. Inner sealing piston integrated pouch, 12. Perforated solid piece

 13. Grooved solid parts, 14. convex solid parts, 15. convex type piston integrated parts, 16. grooved piston integrated parts, 17. concave piston

 detailed description

 Example 1

 5毫米。 In the original insulin refill in Figure 2, the remaining space of the refill bottle 1 , the bottle cap 3 and the original piston 2 of the push stroke end position, there is insulin residual liquid 4 and a diameter of 2.5 mm In the case of the original glass pellet 5, the particulate solid material 6 is filled, and the substitute material may be a spherical material having a stable diameter such as plastic, glass, or ceramic having a diameter of less than 2.5 mm. For example, 10 glass balls with a diameter of 2.5 mm can replace about 6 units of liquid medicine, and 30 glass balls with a diameter of 1.5 mm have certain effects. When the particulate solid material is a plastic, the specific gravity is small, and the effect of replacing the insulin residue is mainly used when it is used up.

 Example 2

 In Fig. 3, since the substitute uses a material having a high specific gravity such as glass or ceramic, and can completely replace the raw glass pellet for mixing, the glass pellet is eliminated. In this case, the alternatives are glass beads with low price and good performance. For example, 400 glass beads having a diameter of 0.8-1 mm or 600 diameters of 0. 6-0. 8 mm can replace about 12 units of liquid medicine.

 Example 3

In Fig. 4, in order to further reduce the amount of residual liquid, a new replacement wafer 7 is added, and is integrated with the piston to achieve the purpose of reducing the remaining space occupied by the chemical liquid and the glass microbeads. By adjusting the thickness of the wafer and the glass beads, the remaining space occupied by the liquid medicine and the glass beads can be controlled, and the manner in which the push rod stroke ends or the glass beads are terminated can be controlled. because The remaining amount is corresponding to the syringe label display and clearer, and the disc can be made of eye-catching white or green. Under the conditions defined by the original pen insulin syringe, after experiment, the distance between the wafer and the shoulder of the bottle is about 1 mm, the thickness of the wafer is about 2 mm, and the diameter of the glass microbead is less than 1 mm, which is better.

 Experimental purpose: minimum mixing space and effect

 6毫米玻璃珠珠550 550. The glass beads 100, the diameter of 0. 6-0. 8 mm glass beads 300, the diameter of 0. 4-0. 6 mm glass beads 550 2,0. 4mm. 4mm glass beads 2600, filled with the mixed suspension after standing for 24 hours, after a few shakes, a good mixing is achieved. The plunger is pushed to make the remaining liquids 35, 30, 25, 20, and 15 units, and after each standing for 24 hours, the mixture is shaken several times to achieve a good mixing effect. After the termination of the bolus, 200 diameter 0. 8-1 mm glass beads are equivalent to about 6 units of liquid medicine, and the residual liquid amount is about 6 units.

 Example 4

 In Figure 5 the integral piston 8 replaces the original piston and wafer. The overall piston is simple to manufacture, low in cost and more suitable for filling process requirements. In order to make the remaining amount correspond to the syringe marking display and clearer, a bold indication can be added to the overall piston.

 Example 5

 In the remaining space of Fig. 6, in the case where a residual liquid and a glass pellet are present, a liquid capsule 9 sealed by a film having a liquid flow path fixed in a shape and a remaining space is fixed to the refill bottle. The film of the liquid pouch can be made of a stable elastic material. The pouch can be made into an olive type with a small neck on a specific molding die. The liquid is sealed by flipping and closed, and pushed into the bottle neck to be fixed. The amount of fluid in the capsule is about 0.2 ml, and should meet the requirements of medical standards and does not affect the use of insulin.

 Example 6

 In Fig. 7, a simple piston integrated bag 10 is mounted in the refill. The bladder film has a rubber ring over the piston to seal the liquid and seal the piston and the refill bottle.

 Example 7

 In Fig. 8, the inner core of the refill is provided with an inner sealing piston integral bag 11, which is fixed on the inner wall of the concave piston by an elastic ring with an apron to seal the liquid. This diagram is the state of the last work.

 Example 8

 In the manner suitable for the conventional insulin refill in Fig. 9, in the remaining space, the perforated solid member 12 fixed in a shape and the remaining space on the refill bottle, or the grooved solid member 13 in Fig. 10, The solid member may be made of a material such as rubber or plastic, and is fixed to the refill bottle by elasticity or other means.

 Example 9

In Fig. 11, a convex solid member 14 whose shape coincides with the remaining space is attached to the piston, and as the piston advances at the same time, the shoulder of the refill bottle is stopped. The neck is slightly smaller in diameter or has a groove to allow liquid to circulate. The piece can be made of a rubber material. Example 10

 The convex piston unitary member 15 having a shape and the remaining space in Fig. 12 and the grooved convex piston body member 16 in Fig. 13 can be made of a rubber material, which is simple in manufacture and lower in cost.

 Example 11

 In the pen holder for the suspension type drug solution composed of the refill bottle 1, the original glass pellet 5 and the concave piston 17, as shown in Fig. 13, the depth and shape of the concave piston recess are determined experimentally. The concave tip of the concave piston is in contact with the bottle seal. The oblique angle is about 1. 5 mm high and the curved bevel is about 60°. The beveled tip has a slightly larger diameter and is elastically brought into close contact with the wall of the refill bottle to prevent lifting. The material of the concave piston can be made of a raw rubber material. As the mixing effect is increased, the minimum mixing space is reduced to less than 25 units, the safety is improved, the amount of residual liquid is reduced, the implementation is simple, and the economic effect is good.

Claims

Rights request A pen-type syringe refill having a liquid medicine or a glass ball in a space formed by a refill bottle, a bottle cap and a piston, characterized by: an alternative substance.  2. A refill according to claim 1 wherein: the replacement material is less than the remaining space formed by the refill bottle, the cap and the original piston end position.  3. A refill according to claims 1 and 2, characterized in that the substitute substance is more than four particulate solids having a diameter of less than 2.5 mm.  The refill according to claim 3, wherein the number of the particulate solids is 10 or more. 5. A refill according to claim 3 wherein the particulate solid has a diameter of less than 2 mm. 6. A refill according to claims 1, 2, 3, characterized in that the substitute is a granular solid and a solid integral with the piston, without glass beads.  7. The refill according to claims 1, 2, and 3, characterized in that: the substitute is a liquid pouch which is fixed to the refill bottle and has a flow passage, and has a glass ball.  8. A refill according to claims 1, 2, 3, characterized in that the substitute is a liquid pouch secured to the piston.  9. The refill according to claim 1, 2, 3, wherein: the substitute is a solid member fixed to the refill bottle and having a shape conforming to the remaining space, and having a flow hole or a groove.  10. A refill according to claims 1, 2, 3, wherein: the substitute is a solid member that conforms to the remaining space and is integral with the piston.  11. A pen injector refill consisting of a refill bottle, a glass ball and a piston, characterized in that: the top of the piston is concave.  12. The pen injector refill according to claim 11, wherein: the concave top of the piston is in a sharply pointed shape in contact with the refill bottle.