EP1424984B1 - A cartridge for liquid insulin - Google Patents

A cartridge for liquid insulin Download PDF

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Publication number
EP1424984B1
EP1424984B1 EP02758183A EP02758183A EP1424984B1 EP 1424984 B1 EP1424984 B1 EP 1424984B1 EP 02758183 A EP02758183 A EP 02758183A EP 02758183 A EP02758183 A EP 02758183A EP 1424984 B1 EP1424984 B1 EP 1424984B1
Authority
EP
European Patent Office
Prior art keywords
cartridge
insulin
glass
zone
piston
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP02758183A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP1424984A1 (en
Inventor
Lars Thougaard Kristensen
Steffen Hansen
Lars Peter Klitmose
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novo Nordisk AS
Original Assignee
Novo Nordisk AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Novo Nordisk AS filed Critical Novo Nordisk AS
Publication of EP1424984A1 publication Critical patent/EP1424984A1/en
Application granted granted Critical
Publication of EP1424984B1 publication Critical patent/EP1424984B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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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
    • 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

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 see e.g. EP-A-745 369. 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 without 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 have 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.
  • 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: Inside diameter 7 7,5 8 9,25 10 11 12 Tolerances +/- 0,05 0,05 0,06 0,06 0,08 0,09 0,1
  • 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.
  • the displacement accuracy is calculated for different dimensions of glass cartridges.
  • the two first columns show the different dimensions and tolerances of the inner diameter of various cartridges.
  • the nominal and maximal cross section areas of the cartridges are calculated in column 3 and 4.
  • Column 5 recites the insulin concentration.
  • 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 must therefore be displaced by 0,074 mm in order to expel one IU.
  • the front wall of the piston most be moved a distance equal to 20 times 0,074 mm i.e. 1,488 mm +/- 0,055 mm (from 1,433 to 1,543 mm) in order to deliver a dose of 20 IU within a tolerance of +/-1 IU.
  • V(IU) CS ⁇ D ⁇ IC
  • 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 When operating in the lower range of the inside diameters specified in claim 1 it is ensured that, such as disclosed in claim 2, 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 Intemational 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 cartridge 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.
  • 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 reduced 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.

Landscapes

  • 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)
EP02758183A 2001-08-31 2002-08-23 A cartridge for liquid insulin Expired - Lifetime EP1424984B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DK200101282 2001-08-31
DKPA200101282 2001-08-31
PCT/DK2002/000553 WO2003017914A1 (en) 2001-08-31 2002-08-23 A cartridge for liquid insulin

Publications (2)

Publication Number Publication Date
EP1424984A1 EP1424984A1 (en) 2004-06-09
EP1424984B1 true EP1424984B1 (en) 2005-08-03

Family

ID=8160689

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02758183A Expired - Lifetime EP1424984B1 (en) 2001-08-31 2002-08-23 A cartridge for liquid insulin

Country Status (15)

Country Link
EP (1) EP1424984B1 (da)
JP (1) JP2005507682A (da)
KR (1) KR20040029015A (da)
CN (1) CN1264493C (da)
AT (1) ATE300933T1 (da)
AU (1) AU2002325201B2 (da)
CA (1) CA2457943A1 (da)
DE (1) DE60205390T2 (da)
DK (1) DK1424984T3 (da)
ES (1) ES2247366T3 (da)
IL (1) IL159901A0 (da)
PL (1) PL367865A1 (da)
RU (1) RU2299723C2 (da)
WO (1) WO2003017914A1 (da)
ZA (1) ZA200400344B (da)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008055689A1 (en) * 2006-11-10 2008-05-15 Roche Diagnostics Gmbh Container for receiving medical liquids
US9603995B2 (en) 2013-03-15 2017-03-28 Tandem Diabetes Care. Inc. Device and method for setting therapeutic parameters for an infusion device
US10773027B2 (en) 2015-03-23 2020-09-15 Sanofi-Aventis Deutschland Gmbh Injection Device

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3468173D1 (en) * 1983-09-07 1988-02-04 Disetronic Ag Portable infusion apparatus
DE3606163A1 (de) * 1986-02-26 1987-08-27 Hoechst Ag Vorrichtung zur applikation von arzneimittelsuspensionen
DK503386D0 (da) * 1986-10-20 1986-10-20 Novo Industri As Peptidpraeparater
US5334162A (en) * 1993-03-15 1994-08-02 Eli Lilly And Company Cartridge assembly for a lyophilized compound forming a disposable portion of an injector pen and method for same
ZA941881B (en) * 1993-04-02 1995-09-18 Lilly Co Eli Manifold medication injection apparatus and method
GB9511169D0 (en) * 1995-06-02 1995-07-26 Lilly Co Eli Containers for liquid medicaments
US6146361A (en) * 1996-09-26 2000-11-14 Becton Dickinson And Company Medication delivery pen having a 31 gauge needle
AU3247999A (en) * 1998-03-06 1999-09-20 Novo Nordisk A/S Coating system providing low friction
AU4492800A (en) * 1999-04-30 2000-12-12 Eli Lilly And Company Cartridge assembly for medicament suspensions

Also Published As

Publication number Publication date
EP1424984A1 (en) 2004-06-09
CN1547459A (zh) 2004-11-17
PL367865A1 (en) 2005-03-07
ATE300933T1 (de) 2005-08-15
ZA200400344B (en) 2005-03-30
IL159901A0 (en) 2004-06-20
DE60205390T2 (de) 2006-04-20
RU2299723C2 (ru) 2007-05-27
CN1264493C (zh) 2006-07-19
DE60205390D1 (de) 2005-09-08
AU2002325201B2 (en) 2007-11-01
DK1424984T3 (da) 2005-11-14
RU2004109579A (ru) 2005-03-20
ES2247366T3 (es) 2006-03-01
WO2003017914A1 (en) 2003-03-06
JP2005507682A (ja) 2005-03-24
KR20040029015A (ko) 2004-04-03
CA2457943A1 (en) 2003-03-06

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