Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
  • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
  • A61J1/06—Ampoules or carpules
  • A61J1/062—Carpules
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
  • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
  • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
  • A61J1/06—Ampoules or carpules

Definitions

• the invention relates to ampoules or cartridges for insulin delivery systems.
• Such cartridges are commonly shaped as a glass tube being at one end closed by a piston, which may be pressed into the tube to expel the content of the tube at the other end of the tube.
• This other end is formed as a bottleneck, the outer end of which may be pierced by an injection needle or a catheter through which the content is expelled.
• Glass cartridges as described in the preamble of claim 1 are widely known for various medicament delivery systems. They are especially used for insulin delivery systems, and are usually supplied pre-filled with either 1 ,5 ml of insulin or 3,0 ml of insulin.
• a 1 ,5 ml cartridge usually has an inside diameter around 6,85 mm and a 3,0 ml cartridge usually has an inside diameter around 9,25 mm.
• These known cartridges are pre-filled with insulin having a concentration on 100 International Units (IU) pr. ml.
• a 1 ,5 ml cartridge therefore contains 150 IU and a 3,0 ml cartridge contains 300 IU.
• the typical diabetes patient will require a certain amount of insulin either injected or infused into their body every day. Some patients need as much as 100 IU per day, in which case the 3,0 ml cartridge is recommended.
• the patient loads the cartridge into either an injection system or a pump system and injects or infuses the insulin into their body at a prescribed rate, either through an injection needle or through a catheter inserted into their body. Once the cartridge is empty it is disposed of and a new cartridge is loaded into the delivery system.
• Glass is the most preferred material for cartridges containing insulin, since glass are both chemically and biologically inert so that insulin can be stored within the glass cartridge with- out reactions occurring between the liquid insulin and the glass material. Glass has the additional advantage that it can be thermally sterilized. Glass cartridges are produced from long glass tubes, which are cut up into smaller tubes, one end of which is melted so that a small opening remains. The opposite open end of the tubes is provided with a movable piston, which are usually manufactured from rubber or plastic. Cartridges made from glass however has the disadvantage that the inside diameter is variable due to the manufacturing process. The inside diameter of glass cartridges, varies by 0,1 mm at an average inside diameter of about 10 mm. However, finer tolerances are available by pre sorting the glass cartridges or by tightened monitoring of the glass process. The following table shows the tolerances typically available today:
• the dose accuracy of an insulin delivery system is the subject of the ISO standard 11608-1.
• This standard prescribes that a dose in the range 0 to 20 IU most have an accuracy of +/- 1 IU, i.e. a nominal dose of 20 IU most contain between 19 to 21 IU.
• the ISO standard allows a tolerance of doses smaller than 20 IU to be within +/- 1 IU, while the tolerances of a dose exceeding 20 IU most be within +/- 5 %. The most difficult part of the standard to meet is therefore typically the demand for accuracy on +/- 1 IU for a dose of 20 IU.
• a large diameter combined with a large tolerance provides large variations in the cross section area of the glass cartridge, which will result in large tolerances in the volume delivered by the insulin delivery system. This is however not a major problem when the insulin has a concentration on only 100 IU per ml.
• V H ⁇ - R 2
• One IU of liquid U200 insulin has the volume of 0,005 ml, the front wall of the piston in e.g. a cartridge having a nominal inside diameter of 9,25 mm most therefore be displaced by 0,074 mm in order to expel one IU.
• the volume expelled within these tolerances can be calculated using the following formula:
• V(IU) CS • D ⁇ IC
• V(IU) Volume expressed in IU
• the following table show the expelled volume measured in International Units for a cartridge having a nominal diameter of 9,25 mm and tolerances of +/- 0,06 mm, i.e. an inside diameter between 9,19 mm and 9,31 mm, equaling a cross section area of the volumen of the cartridge between 66,33 mm 2 and 68,08 mm 2 , when the cartridge is used in an insulin delivery system which can move the piston forward with a tolerance of +/- 0,055 mm.
• the forward movement hence being in the range 1 ,433 mm to 1 ,543 mm.
• the mechanical insulin delivery systems available today all have quit a large imprecision due to the mechanical system.
• the leading injection devices has a displacement accuracy around +/- 0,083, meaning that the front wall of the piston can only be moved forward within tolerances of approximately +/- 0,083 mm.
• the maximum allowable inner diameter of the cartridge must, according to the table shown in figure 1 , be smaller than a nominal 7,5 mm cartridge in order to meet the demands set up in the ISO 11608-1 standard.
• Cartridges having an inside diameter larger than 7,5 mm all needs a displacement accuracy smaller than +/- 0,083 mm in order to meet the ISO standard. They are therefore not suitable for use in ordinary insulin pen systems.
• Insulin pumps for pump treatment of diabetes usually have a more precise mechanism than mechanical injection devices due to the presence of a motor mechanism, which is also the case for motor driven injection devices. It is however not necessary with a precise mechanism in insulin pumps due to the presence of a continuous insulin delivery profile.
• cartridges containing liquid U200 insulin and having a diameter from the lower tolerance limit of a nominal 7,5 mm cartridge i.e. 7,45 mm to the upper tolerance limit of a nominal 9,25 mm cartridge i.e. 9,31 can be used both in pumps and in precision injection devices having tolerances within +/- 0,055 mm to +/- 0,083 mm, without dispensing from the requirements of ISO 11608-1.
• a glass cartridge having an inside diameter between 7,45 and 9,31 mm will, when filled with a liquid U200 insulin, be able to fulfil the ISO 11608-1 standard when the cartridge is being used in a precision insulin delivery system having a displacement accuracy of the mechanism advancing the piston within the range from 0,055 mm to 0,083 mm.
• Glass cartridges with an inside diameter in the claimed range can therefore be used both in insulin pump systems and in insulin injection systems.
• the cartridge can be made very slim and with very narrow tolerances, leaving maximum tolerances for the imprecision of the insulin delivery system.
• a glass cartridge having a nominal inside diameter of 7,5 mm needs a length of the stroke zone of approximately 34 mm in order to contain a volume of approximately 1 ,5 ml.
• the total amount of International Unit is 300 IU, which for most patient will be sufficient for three days of treatment.
• the pump is usually connected to the body of the user through a catheter. Due to inflammation of the skin at the site where the catheter is inserted, it is normally recommended to change the catheter and the site approximately every third day. A cartridge containing insulin for minimum three days are therefore to be preferred.
• the overall length of such a car- tridge will be approximately 52 mm.
• a glass cartridge having a nominal inside diameter of 9,25 mm needs a length of the stroke zone of approximately 23 mm in order to contain a volume of approximately 1 ,5 ml, resulting in an overall length of approximately 44 mm.
• Figure 1 Shows a table of the displacement accuracy for different cartridge designs
• FIG. 2 Shows a glass cartridge including needle penetration according to the invention.
• 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.
• the same reference numerals are used for identical or corresponding parts.
• FIG. 1 A table of the displacement accuracy for different cartridge designs is shown in figure 1.
• the displacement accuracy of an insulin delivery system using a cartridge having a nominal diameter of 9,25 mm must be 0,084 mm when the cartridge contains a liquid U100 insulin.
• distal end of the cartridge 1 is meant to refer to the end carrying the conduit 7 through which the insulin is expelled, whereas the term “proximal end” is meant to refer to the opposite end carrying the piston 9.
• a cartridge 1 comprising a cylindrical wall 2 is disclosed in figure 2.
• the cylindrical wall 2 is at the distal end 10 of the cartridge terminated in a neck part ending in a circumferential flange 3 against which a piercable and flexible membrane 4 is held sealingly by a metal cap 5.
• the metal cap 5 At a central part of the membrane 4 the metal cap 5 has an opening 6 through which the membrane 4 is exposed.
• a hollow conduit 7, such as an injection needle or a catheter can be stuck through the membrane 4 to communicate with the inner space of the cartridge 1 in which the liquid insulin is stored between the membrane 4 and a front wall 8 of a piston 9 which fits into the cartridge 1.
• the piston 9 is usually made from a suitable rubber material, such that it is tightly sealed against the inside of the cylindrical wall 2.
• the inside diameter of the glass cartridge is indicated with D in figure 1.
• the cartridge 1 is divided into three different zones.
• the first zone is the connecting zone C, which extends from the distal end 10 of the cartridge 1 to the shoulder 12. Due to the re- quizd diameter of the cylindrical wall 2 of the cartridge 1 on the part of the cylindrical wall 2 lying between the distal end 10 of the cartridge 1 and the shoulder 12, the piston 9 cannot be moved beyond the shoulder 12 and into the neck part area of the cartridge 1. The insulin contained in the neck part of the cartridge 1 can therefore not be pressed out of the cartridge, and will hence be disposed of when the cartridge 1 is discarded.
• the second zone is the stroke zone S, which extends from the shoulder 12 to the front wall 8 of the piston 9. Only the insulin contained in the stroke zone can be utilized for injection or infusion.
• the third zone is the piston zone P, which extends from the proximal end 11 of the cartridge 1 to the front wall 8 of the piston 9. This piston zone P holds the piston 9 and is therefore not available for the insulin contained in the cartridge 1.

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• Health & Medical Sciences (AREA)
• Hematology (AREA)
• Pharmacology & Pharmacy (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)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• External Artificial Organs (AREA)

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• 2002
  • 2002-08-23 DK DK02758183T patent/DK1424984T3/da active
  • 2002-08-23 KR KR10-2004-7002694A patent/KR20040029015A/ko not_active Application Discontinuation
  • 2002-08-23 JP JP2003522437A patent/JP2005507682A/ja active Pending
  • 2002-08-23 ES ES02758183T patent/ES2247366T3/es not_active Expired - Lifetime
  • 2002-08-23 CA CA002457943A patent/CA2457943A1/en not_active Abandoned
  • 2002-08-23 AT AT02758183T patent/ATE300933T1/de not_active IP Right Cessation
  • 2002-08-23 EP EP02758183A patent/EP1424984B1/en not_active Expired - Lifetime
  • 2002-08-23 PL PL02367865A patent/PL367865A1/xx not_active Application Discontinuation
  • 2002-08-23 DE DE60205390T patent/DE60205390T2/de not_active Expired - Lifetime
  • 2002-08-23 WO PCT/DK2002/000553 patent/WO2003017914A1/en active IP Right Grant
  • 2002-08-23 RU RU2004109579/14A patent/RU2299723C2/ru not_active IP Right Cessation
  • 2002-08-23 CN CNB028165950A patent/CN1264493C/zh not_active Expired - Fee Related
  • 2002-08-23 IL IL15990102A patent/IL159901A0/xx unknown
  • 2002-08-23 AU AU2002325201A patent/AU2002325201B2/en not_active Expired - Fee Related
• 2004
  • 2004-01-16 ZA ZA2004/00344A patent/ZA200400344B/en unknown

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