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WO2008001221A2 - Dispositif d'injection simultanée de vaccins multiples - Google Patents

Dispositif d'injection simultanée de vaccins multiples Download PDF

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Publication number
WO2008001221A2
WO2008001221A2 PCT/IB2007/002778 IB2007002778W WO2008001221A2 WO 2008001221 A2 WO2008001221 A2 WO 2008001221A2 IB 2007002778 W IB2007002778 W IB 2007002778W WO 2008001221 A2 WO2008001221 A2 WO 2008001221A2
Authority
WO
WIPO (PCT)
Prior art keywords
delivery device
chamber
fluid
needle unit
chambers
Prior art date
Application number
PCT/IB2007/002778
Other languages
English (en)
Other versions
WO2008001221A3 (fr
Inventor
Michael Broeker
Original Assignee
Novartis Ag
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 Novartis Ag filed Critical Novartis Ag
Publication of WO2008001221A2 publication Critical patent/WO2008001221A2/fr
Publication of WO2008001221A3 publication Critical patent/WO2008001221A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/19—Syringes having more than one chamber, e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/20—Surgical instruments, devices or methods for vaccinating or cleaning the skin previous to the vaccination
    • A61B17/205—Vaccinating by means of needles or other puncturing devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3128—Incorporating one-way valves, e.g. pressure-relief or non-return valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
    • A61M2005/3201—Coaxially assembled needle cannulas placed on top of another, e.g. needles having different diameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/3129—Syringe barrels
    • A61M5/3134—Syringe barrels characterised by constructional features of the distal end, i.e. end closest to the tip of the needle cannula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles

Definitions

  • This invention relates to vaccine delivery devices.
  • the invention concerns such devices having first and second flow-isolated chambers containing separate vaccine components for simultaneous delivery to a patient.
  • Vaccines containing antigens from more than one pathogen within a single dose are known as "multivalent” or “combination” vaccines.
  • Various combination vaccines have been approved for human use in the EU and the USA, including trivalent vaccines for protecting against diphtheria, tetanus and pertussis (“DTP” vaccines) and trivalent vaccines for protecting against measles, mumps and rubella (“MMR” vaccines).
  • Combination vaccines offer patients the advantage of receiving a reduced number of injections, which leads to the clinical advantage of increased compliance (e.g. see chapter 29 of reference 1), particularly for pediatric vaccination. At the same time, however, they can present clinical difficulties.
  • the antigens and other components in the combined formulation can interact, and physical and/or biochemical incompatibility between these components can lead to reduced efficacy in a combined vaccine relative to the separate vaccines (e.g. see reference 2).
  • a compartmentalized syringe system also known as a sequential or bypass syringe, consisting of a single barrel separated by a septum into two compartments.
  • depression of the syringe's plunger forces admixing of the two components, one of which may be a lyophilized powder for reconstitution by an liquid formulation in the other compartment.
  • this type of delivery system permits the simultaneous delivery of vaccines that may be incompatible during storage. Further details are on page 84 of reference 3.
  • a dual chamber bypass of syringe was used in example 2 of reference 4 to deliver a D-T-aP-IPV-Hib/HBsAg vaccine.
  • the invention aims to provide further ways of concurrently delivering antigens from more than one pathogen.
  • vaccine components can be concurrently delivered to a patient from a syringe device while remaining separate from each other until they leave the device.
  • the components do not need to be admixed during manufacture, during storage or within the device itself, but simultaneous administration to a patient can still be achieved.
  • Various dual-chambered delivery devices are known in the art which a first chamber containing a first fluid is isolated from a second chamber containing a second fluid such that the different fluids can be dispensed without mixing until delivery to their intended location.
  • the different fluids have to date comprised, for example, components of fibrin glue material [5], components of a compound to be applied to teeth surfaces [6], an anaesthetic and a pharmaceutical [7] or epoxy cement [8].
  • the invention uses this type of device for delivery of vaccine components or different vaccines.
  • the invention provides a vaccine delivery device comprising: first and second flow-isolated chambers, each having a fluid outlet port; a fluid within the first chamber, comprising a first vaccine component; a fluid within the second chamber, comprising a second vaccine component; and a first plunger received in the first chamber and a second plunger received in the second chamber, each plunger being operative to create a positive pressure sufficient to drive fluid from the respective chamber.
  • the invention provides a vaccine delivery device comprising: a body comprising first and second chambers, each having a fluid outlet port respectively adapted to communicate fluidically with a first lumen and a second lumen, wherein the second chamber includes a seal; a first fluid within the first chamber and a second fluid within the second chamber, wherein the first fluid comprises a first vaccine component and the second fluid comprises a second vaccine component; a plunger received in the first chamber and operative to create a positive pressure sufficient to drive the first fluid from the first chamber; and means to rupture the seal.
  • a device may be packaged (e.g. in the same box) with a leaflet including details of the vaccine to be administered e.g. instructions for administration, details of the antigens within the vaccine, etc.
  • the instructions may also contain warnings e.g. to keep a solution of adrenaline readily available in case of anaphylactic reaction following vaccination, etc.
  • the devices will be prepared by introducing the first vaccine component into the first chamber and the second vaccine component into the second chamber.
  • the device may comprise first and second syringe units defining the respective first and second chambers and plungers.
  • the syringe units may be detachably coupled to one another via a support member.
  • the support member may comprise C-shaped clamps for snap-fittingly receiving the syringe units.
  • the first and second plungers may be selectively actuatable to eject the two vaccine components in a sequential manner.
  • the first and second plungers are simultaneously actuatable to eject the vaccine components in a simultaneous manner.
  • the first and second plungers may be joined by a harness.
  • the delivery device may comprise a body with a fluid impermeable partition defining the first and second chambers.
  • the partition may extend along the length of the body and the first and second chambers may extend side-by-side within the body. Alternatively, the partition may extend along the length of the body and the first chamber may extend coaxially within the second chamber, or vice- versa.
  • this means may comprise a collapsible roof defining a lower wall of the first chamber and at least one projection which can be urged against the ' seal when contacted by the collapsible roof when under positive pressure created by the plunger in the first chamber.
  • the delivery device may further comprise a needle unit having first and second lumens respectively communicating with the outlet ports of the first and second chambers.
  • the first and second lumens may extend side-by-side within the needle unit.
  • the first and second lumens may extend coaxially within the needle unit.
  • the needle unit may comprise a single needle, the first and second lumens at least partially contained within the needle.
  • the needle unit may comprise first and second needles, the first and second lumens at least partially contained within the respective needle.
  • the body and the needle unit may form a monolithic housing.
  • the needle unit may be removably attached to the body.
  • the needle unit is removably attached, and where comprising first and second needles, the first and second needles may be individually and separately attached to the remainder of the needle unit or directly to the body.
  • a body will typically be made of a glass or plastic material. Where a glass is used, then it is preferred to use a borosilicate glass rather than a soda lime glass.
  • a body is preferably sterilized before a vaccine component is added to it.
  • the devices preferably do not include latex components.
  • Delivery devices of the invention may be marked to show a half-dose volume e.g. to facilitate delivery to children.
  • a device containing a 0.5ml dose may have a mark showing a 0.25ml volume.
  • the mark may, for example, be on one or both of the chambers and/or on one or both of the plungers.
  • the delivery device comprises a support member and further comprises a needle unit
  • the support member may comprise the needle unit;
  • the syringe may have a needle attached to it, or a needle may be supplied separately for assembly and use by an end-user.
  • delivery devices of the present invention do not necessarily come packaged with an associated needle unit, but are suitable to have a needle unit attached to them.
  • Safety needles are preferred. 1-inch 23-gauge, 1 -inch 25-gauge and 5/8-inch 25-gauge needles are typical.
  • the plunger in the or each chamber preferably has a stopper to prevent the plunger from being accidentally removed during aspiration.
  • the chambers may have a latex rubber cap and/or the or each plunger may be latex rubber.
  • Disposable delivery devices contain a single dose of vaccine.
  • the delivery device will generally have a cap to seal the fluid outlet ports prior to attachment of a needle unit, and the cap is preferably made of a rubber, such as a butyl rubber. If the delivery device and needle unit are packaged separately then the needle unit is preferably fitted with a butyl rubber shield.
  • a device may be provided with one or more peel-off label(s) on which, for example, the lot number and expiration date of the contents may be printed, to facilitate record keeping.
  • the vaccine components Devices of the invention have at least two chambers, containing at least two separate liquid components for a vaccine.
  • the two liquid components will include at least one antigen and/or at least one adjuvant.
  • the two components will typically both include at least one antigen, it is also possible for one of the components to be antigen-free e.g. including an adjuvant but no antigen.
  • substantially equal volumes of the two components may be delivered.
  • an excess volume of one component may be used. Where one component is used in excess, the volume ratio preferably exceeds 1.5:1 e.g. >2:1, >2.5:1, >3:1, >5:1, etc.
  • the volumes of the separate components are typically not more than one milliliter, and the preferred volume of each is 0.5 ml or less e.g. ⁇ 0.45ml, ⁇ 0.4ml, ⁇ 0.3ml, ⁇ 0.2ml, etc. Thus the total volume delivered using two components can be ⁇ lml, and may be ⁇ 0.5ml.
  • the individual components located within devices of the invention will each be pharmaceutically acceptable. In addition to antigen and/or adjuvant, they may include components such as pharmaceutical carrier(s) and/or excipient(s). A thorough discussion of such components is available in reference 9.
  • a component may include preservatives such as thiomersal or 2-phenoxyethanol. It is preferred, however, that the components should be substantially free from ⁇ i.e. less than 5 ⁇ g/ml) mercurial material e.g. thiomersal-free. Components containing no mercury are more preferred.
  • a physiological salt such as a sodium salt.
  • Sodium chloride (NaCl) is preferred, which may be present at between 1 and 20 mg/ml.
  • Other salts that may be present include potassium chloride, potassium dihydrogen phosphate, disodium phosphate dehydrate, magnesium chloride, calcium chloride, etc.
  • Components may have an osmolality of between 200 m ⁇ sm/kg and 400 m ⁇ sm/kg, preferably between 240-360 m ⁇ sm/kg, and will more preferably fall within the range of 290-310 m ⁇ sm/kg.
  • Components may include one or more buffers.
  • Typical buffers include: a phosphate buffer; a Tris buffer; a borate buffer; a succinate buffer; a histidine buffer; or a citrate buffer. Buffers will typically be included in the 5-2OmM range.
  • the pH of a component will generally be between 5.0 and 8.1, and more typically between 6.0 and 8.0 e.g. between 6.5 and 7.5.
  • the components are preferably sterile.
  • the components are preferably non-pyrogenic e.g. containing ⁇ 1 EU (endotoxin unit, a standard measure) per dose, and preferably ⁇ 0.1 EU per dose.
  • the components are preferably gluten free.
  • Devices of the invention have at least two chambers, and may have more than two e.g.3, 4, 5, etc.
  • the different vaccine components can between them include a wide variety of antigens.
  • Preferred antigens include, but are not limited to: • a diphtheria toxoid ('D').
  • a pertussis antigen which may be whole cell pertussis ('wP') or acellular ('aP').
  • HBV hepatitis B virus
  • 'HAV hepatitis A virus
  • HIV human immunodeficiency virus
  • RSV respiratory syncytial virus
  • SARS human coronavirus an antigen from a respiratory syncytial virus
  • first and second components include, but are not limited to:
  • an antigen in one of the components will generally not also be present in another component, except that an antigen may be found in one component as an unconjugated antigen and in the other as a carrier protein in a conjugate e.g. tetanus toxoid is used both as an antigen for protecting against C.tet ⁇ ni infection and as a carrier protein for H.inflnenz ⁇ e b saccharides.
  • an antigen in one of the components will generally not also be present in another component, except that an antigen may be found in one component as an unconjugated antigen and in the other as a carrier protein in a conjugate e.g. tetanus toxoid is used both as an antigen for protecting against C.tet ⁇ ni infection and as a carrier protein for H.inflnenz ⁇ e b saccharides.
  • the decision to include an antigen in one component rather than another component may be based on various criteria. For instance, if two antigens are known or found to be incompatible when stored together then they would be included in different components. Similarly, if one component includes a non-antigenic substance that is known to be detrimental to a particular antigen then they would be separated from each other. Again, if a first antigen is used with a first adjuvant and a second antigen with a second adjuvant, but the two adjuvants are incompatible, the antigens would be separated.
  • a benefit of the invention is that such incompatibilities can be overcome while maintaining the advantages of concurrent administration. Live vaccines and inactivated vaccines can also be kept separately within the device. Chemically-synthesized antigens (e.g. chemically synthesized bacterial capsular saccharides) may be kept separate from antigens purified from cultured viruses or bacteria.
  • the invention can also be used to administer substances from the same pathogen if those substances may interfere with each other, of if they may assemble after delivery to make an active ingredient.
  • the first component and the second component may include different subunits of a single antigen.
  • the malarial MSP-I antigen cannot be efficiently produced in E.coli as it is ⁇ 190kDa, but its N- and C-termini can be produced separately.
  • these two subunits interfere with each other, but they can be stored and administered separately by using the devices of the invention.
  • Envelope and core proteins of hepatitis C virus may also advantageously be stored separately but administered concurrently.
  • Adjuvants may also advantageously be stored separately but administered concurrently.
  • One or more vaccine components may comprise one or more vaccine adjuvant(s).
  • the adjuvant(s) may be THl adjuvant(s) and/or TH2 adjuvant(s), further discussed below.
  • Adjuvants which may be used in compositions of the invention include, but are not limited to, adjuvants comprising one or more of:
  • an aluminium salt such as a hydroxide (e.g. an oxyhydroxide) or a phosphate (e.g. a hydroxyphosphate), or mixtures thereof.
  • Antigens may be adsorbed to the aluminium salt(s).
  • Calcium salts such as calcium phosphate can also be used.
  • oil-in-water emulsions including squalene-in-water emulsions such as 'MF59'. • saponins.
  • an immunostimulatory oligonucleotide such as one containing a CpG motif (a dinucleotide sequence containing an unmethylated cytosine linked by a phosphate bond to a guanosine). • a double-stranded RNA.
  • the protein is derived from E.coli (E.coli heat labile enterotoxin "LT”), cholera ("CT”), or pertussis ("PT").
  • E.coli heat labile enterotoxin "LT”
  • CT cholera
  • PT pertussis
  • a microparticle i.e. a particle of ⁇ 100nm to ⁇ 150 ⁇ m in diameter, more preferably ⁇ 200nm to ⁇ 30 ⁇ m in diameter, and most preferably ⁇ 500nm to ⁇ 10 ⁇ m in diameter
  • materials that are biodegradable and non-toxic such as a poly(lactide-co-glycolide).
  • a cytokine such as an interleukin.
  • Devices of the invention are suitable for administration of vaccines to human or animal patients, and the invention provides a method of raising an immune response in a patient, comprising the step of administering a composition from a delivery device of the invention to the patient.
  • the immune response raised by these methods and uses will generally include an antibody response, preferably a protective antibody response. Methods for assessing antibody responses, neutralising capability, protection, etc. after vaccination are well known in the art.
  • compositions can be administered from a delivery device of the invention in various ways.
  • the most preferred immunisation route is by intramuscular injection (e.g. into the arm or leg), but other available routes include subcutaneous injection, intradermal, transcutaneous, transdermal, etc.
  • Vaccines may be used to treat both children and adults.
  • the patient may be less than 1 year old, 1-5 years old, 5-15 years old, 15-55 years old, or at least 55 years old.
  • Typical patients for receiving the vaccines are the elderly (e.g. >50 years old, preferably >65 years), the young (e.g. ⁇ 5 years old), hospitalised patients, healthcare workers, armed service and military personnel, pregnant women, the chronically ill, immunodef ⁇ cient patients, and people travelling abroad.
  • the vaccines are not suitable solely for these groups, however, and may be used more generally in a population.
  • Treatment can be by a single dose schedule or a multiple dose schedule. Multiple doses may be used in a primary immunisation schedule and/or in a booster immunisation schedule. In a multiple dose schedule the various doses may be given by the same or different routes e.g. a parenteral prime and mucosal boost, a mucosal prime and parenteral boost, etc. Administration of more than one dose is useful in immunologically naive patients. Multiple doses will typically be administered at least 1 week apart (e.g. about 2 weeks, about 3 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 12 weeks, about 16 weeks, etc.).
  • composition comprising
  • X may consist exclusively of X or may include something additional e.g. X + Y.
  • a process comprising a step of mixing two or more components does not require any specific order of mixing.
  • components can be mixed in any order.
  • two components can be combined with each other, and then the combination may be combined with the third component, etc.
  • animal (and particularly bovine) materials are used in the culture of cells, they should be obtained from sources that are free from transmissible spongiform encaphalopathies (TSEs), and in particular free from bovine spongiform encephalopathy (BSE). Overall, it is preferred to culture cells in the total absence of animal-derived materials.
  • a compound is administered to the body as part of a composition then that compound may alternatively be replaced by a suitable prodrug.
  • cell substrate is used, it is preferably one that has been approved for use in human vaccine production e.g. as in Ph Eur general chapter 5.2.3.
  • FIGS. IA and " I B schematically illustrate delivery devices of a type disclosed in reference 5. A similar device is disclosed in reference 8, although differing in detail at its delivery end.
  • FlG. IA relates to a first embodiment, in which a syringe body is divided into first and second chambers by a longitudinal partition.
  • FIG. IB relates to a second embodiment, in which first and second syringe units are received in a needle unit.
  • FIG. 2 illustrates, in perspective, a delivery device of a type disclosed in reference 6, in which two syringes are detachably coupled by a clip assembly.
  • FIGS. 3 A and 3B illustrate, in respective plan and perspective views, the clip assembly of FIG. 2;
  • FIGS. 4, 4A, 5, 5A and 5B illustrate delivery devices of a type disclosed in reference 7.
  • FIGS. 4 and 4A relate to a first embodiment, in which a needle unit includes coaxial lumens leading from respective first and second chambers.
  • FIGS. 5, 5A and 5B relate to a second embodiment, in which a needle unit includes parallel, adjacent lumens leading from respective first and second chambers.
  • any known form of dual-chambered delivery device 10; 10'; 100; 200; 200' can be used, provided that the first chamber 12a contains a fluid comprising a first vaccine component and the second chamber 12b contains a fluid comprising a second vaccine component.
  • the delivery device 10; 10'; 100 generally comprises first and second flow- isolated chambers 12a, 12b, a first plunger 14a received in the first chamber and a second plunger 14b received in the second chamber, and a needle unit 16.
  • the first and second flow-isolated chambers 12a, 12b each have a fluid outlet port.
  • a first lumen 18a and a second lumen 18b are each in fluid communication with the respective fluid outlet port and at least partially contained within the needle unit 16.
  • Each plunger 14a, 14b is operative to create a positive pressure sufficient to drive fluid from the respective chamber 12a, 12b, through the respective lumen 18a, 18b and out of a distal port 20 of the needle unit 16.
  • the flow-isolated chambers 12a, 12b are dimensioned and shaped to correspond to a respective piston 15a, 15b of the plungers 14a, 14b.
  • the first and second chambers 12a, 12b may be defined by a fluid-impermeable partition 24 extending longitudinally within a syringe body 26, as shown in FIG. IA.
  • the partition 24 can extend beyond the distal end 28 of the syringe body 26 and be dimensioned so that when the needle unit 16 is mounted on a distal stretch of the partition 24, the latter forms the two lumens 18a, 18b.
  • the needle unit 16 can be provided with a respective partition 30 forming the lumens 18a, 18b and having a means for attaching the partitions 24, 30 of the syringe body 26 and the needle unit 16 together.
  • Attachment of the two partitions 24, 30 can be realised by a variety of systems which, among others, may include a keyed surface formed on one of the opposing ends of the partitions and a complementary shaped projection formed on the other end and received in a slot or simply having opposing surfaces of the partitions extend complementary to and in contact with one another.
  • the pair of flow-isolated lumens 18a, 18b extend along the entire length of the needle unit 16 and exit via the distal port 20. Accordingly, each of different fluids runs along a path isolated from other path until it exits through the distal port 20, typically into a patient.
  • the pair of flow-isolated lumens 18a, 18b may extend along only a major part of the length of the needle unit 16 before opening into a downstream region 22 of the needle unit in which the different fluids mix prior to exiting via the distal port 20.
  • This is illustrated in FIGS. IA and IB by a distal portion of the lumen separating partition being shown in phantom.
  • the syringe body 26 and the needle unit 16 of the delivery device 10 may be two separate components detachably coupled to one another in a leak-free manner.
  • the needle's proximal end 32 has a cross section widening towards a distal end 28 of the syringe body 12 and, preferably, provided with a conical shape, which is instrumental in accelerating fluid flow as fluid runs from the syringe body 12 into the needle unit 16.
  • Numerous techniques can be utilised for coupling the components together.
  • either the distal end 28 of the. syringe' body 12 can be provided with an outer or inner thread mating a respective thread on an opposing surface of the proximal end 32 of the needle unit 16.
  • the needle unit 16 and the syringe body 12 can be attached in a snap-in manner wherein the mating ends of these components are dimensioned to tightly fit one another in response to an external force applied to the components. Regardless of the way the components are coupled, the needle unit 16 and the syringe body 12 have to be detachably assembled in a fluid-proof manner to prevent a leak of fluids proximal to the outlet port 20.
  • the delivery device 10 can be formed as a monolithic body having a proximal part formed as the syringe body 12 and distal part functioning as the needle unit 16.
  • a proximal part formed as the syringe body 12
  • distal part functioning as the needle unit 16.
  • administering fluids is not as convenient as it would be with a multi-part structure because of the difficulty of reaching a desired location within a human or animal body associated with the flexibility of the delivery device 10.
  • a multi-part delivery device can be more flexible than the monolithic body.
  • the chambers 12a, 12b may be defined by discrete syringe units 40, 42 (FIGS. IB and 2), the syringe units being coupled to form a unitary delivery device 10'; 100.
  • a support member achieves coupling of the syringe units 40, 42.
  • the support member comprises the needle unit 16.
  • the proximal end 32 of the needle unit 16 is formed with a conical flange 34 having nests 36, each if which is configured to receive a distal end of a respective syringe unit 40, 42.
  • the nests 36 are configured to sealingly engage the distal ends of the syringe units, but shaped so as to allow slight displacement of the received unit to establish a desired position convenient for a user.
  • the syringe units 40, 42 are spaced from another upon attachment with the needle unit 16 to allow the user to position one of his/her fingers between the syringe units.
  • Fluid communication between each of the syringe units 40, 42 and a respective lumen 18a, 18b is provided by fluid conveying channels 50 which can be formed either on the distal end of the syringe units 40, 42 or on the proximal end of the lumens 18a, 18b.
  • the support member comprises a clip assembly generally designated at 140, which has an elongated, generally flat central member 142 that is interposed between the two syringe units 40, 42 so as to space them from one another in a parallel fashion.
  • the clip assembly 140 is further comprised of a first collar means on one side of the central member 142 for attachment to one of the syringe units 40.
  • a second collar means is similarly formed on an opposite side of the elongated central member 142 for attachment to the other syringe unit 42.
  • Each of the first and second collar means are comprised of two resilient C-shaped clamps that can be removably snapped onto a syringe unit 40, 42 to securely hold the syringe units 40, 42 in the manner described. As shown best in FIGS.
  • the elongated central member 142 has C-shaped clamps 146 and 148 formed on one side of the central member 142 and C-shaped clamps 150 and 152 formed on the opposite side of the central member 142.
  • the width of each clamp 146, 148, 150, and 152, as schematically indicated at 156, is large enough so that each of the clamps can be snapped onto the cylindrical syringe units 40, 42.
  • the entire clip assembly generally designated at 140 is preferably constructed as a unitary, moulded plastic piece which has sufficient resilience or memory so that the clip assembly can be snapped onto and off of standard syringe units, thus permitting interchangeability of the syringe units 40, 42 as to either side of the clip assembly 140.
  • the syringe units 40, 42 may comprise standard syringes.
  • Each syringe unit 40, 42 has a standard luer connector 128 at the delivery end of a syringe barrel 122.
  • the luer connectors 128 may be standard threaded female luer connectors. Attached at the delivery end of each syringe barrel 122 at the luer connectors 128 are delivery tips generally designated at 130.
  • Each delivery tip 130 is comprised of a hub 132 which has a corresponding male luer connector for barrel 122.
  • each syringe barrel 122 Attached to the hub 132 of each delivery tip is an elongated, tapered flexible delivery tube 134 through which the fluid contents of each chamber 12a, 12b is dispensed as will be hereinafter more fully described.
  • the other end of each syringe barrel 122 is equipped with a circular support disc 126 which provides a surface against which the fingers of a user can be pushed when exerting pressure on the plunger 14a, 14b.
  • the proximal end of plunger 14a, 14b has a circular push flange 138 so that by pushing on the flange 138 while at the same time pressing with the fingers on support disc 126, the plunger 14a, 14b can be pushed into the syringe barrel 122 in a standard fashion. This, in turn, will effect delivery of the fluid contents of the syringe barrel 122 at the distal end 136 of each flexible, elongated delivery tube 134.
  • the clip assembly 140 is designed to hold the two syringes units 40, 42 parallel to one another, but at the same time as close together as possible.
  • the two syringes units 40, 42 will be slightly longitudinally offset because they are held so closely together.
  • the support discs 126 of the two syringe units 40, 42 will slightly overlap one another in order to permit the two syringe units 40, 42 to be held together as closely as possible.
  • a spacer means is preferably included for longitudinally offsetting one syringe from the other to permit or accommodate the overlapping relationship of the discs 126.
  • the spacer means is comprised of a shoulder 154 which is formed on the C-shaped clamp 150. This shoulder 154 thus holds the support disc 126 of one of the syringe units 40, 42 in a manner so that it can overlap the other support disc 126.
  • the resilient C-shaped clamps which are formed on the opposite sides of elongated central member 142 are longitudinally spaced from one another by a distance such that the clamps 146 and 150 will abut the support discs 126 of each syringe barrel 122, whereas the C-shaped clamps 148 and 152 will abut the luer connectors 128 at the opposite ends of the syringe barrels 122.
  • the C-shaped clamps 146 and 148 as well as the C-shaped clamps 150 and 152 on the other side of the elongated central member 142 serve to lock the syringe barrels against any longitudinal movement relative to one another or relative to the elongated central member 142.
  • syringe units 40, 42 held parallel to one another, but they are also locked into a slightly offset longitudinal relationship. This is advantageous because it permits the overall delivery device 100 to have a small width which therefore permits the delivery system to be more easily held and actuated when expelling fluid and pushing on the plungers 124.
  • the double syringe delivery device 100 can also optionally comprise a retainer means for joining the flexible delivery tubes 134 together at their distal ends 136, as well as a cap means tethered to the retainer means for selectively capping the distal ends 136 of the delivery tubes 134.
  • the retainer means is illustrated as comprising a retainer block 143 that has passageways formed therethrough for receiving the distal ends 136 of each flexible delivery tube 134.
  • the retainer block is flared and the internal passageways are similarly provided with flared openings to permit easier access and entry of the delivery tubes 134 into the passageways. Since the retainer block 143 only secures the extreme distal ends 136 of the flexible delivery tubes 134, the flexible delivery tubes 134 are otherwise permitted to be bendable for ease in accessing any desired delivery point.
  • the tethered cap means is illustrated in the drawings as comprising strap or tether 139 which is joined to the retainer block 143 at one end and which is joined at the other end to a removable cap 137 having two openings 131 which fit over the distal ends 136 of the delivery tubes 134.
  • cap 137, strap or tether 139 and retainer block 143 are all preferably moulded as a single unitary piece.
  • the delivery device 10 includes a harness 60 which couples the plungers 14a, 14b for synchronous actuation 32.
  • Another harness 60 is illustrated in the example of FIG. 2, coupling the individual syringe units 40, 42 at the proximal ends of their respective plungers, 14a, 14b.
  • the plungers 14a, 14b of the example of FIG. IB can also be envisaged for the plungers 14a, 14b of the example of FIG. IB to be coupled by a harness for synchronous actuation and hence simultaneous ejection of the different fluids from the outlet port 20.
  • the harness 60 can be removably attached to proximal ends of the plungers 14a, 14b, which, thus, can also be actuated separately to deliver the fluids in a sequential manner upon dismounting the harness 60.
  • each plunger 14a, 14b may have a hollow interior portion into which posts protruding from the harness 60 are received.
  • the delivery device 200; 200' generally comprises a syringe body 226, first and second flow-isolated chambers 212a, 212b and a needle unit 216.
  • Each of the first and second flow-isolated chambers 212a, 212b has a respective fluid outlet port 217a, 217b.
  • a first lumen 218a and a second lumen 218b are each in fluid communication with the respective fluid outlet port 217a, 217b and at least partially contained within the needle unit 216.
  • a plunger 214 is received in the first chamber 212a and operative to create a positive pressure sufficient to drive fluid from the first chamber 212a.
  • annular collapsible roof 270 At the distal end 228 of the syringe body 226 is an annular collapsible roof 270.
  • the annular collapsible roof 270 is attached to the syringe body 226 by a flexible section 272 providing a hinge for the annular collapsible roof 270 and a pliable annular seal 274.
  • the annular collapsible roof 270 defines a partition between the first chamber 212a and the second chamber 212b. Thus, the second chamber 212b is lodged within the distal end 228 of the syringe body 226 under the collapsible roof
  • the second chamber 212b is an annular thin walled plastic reservoir which sealingly contains the second vaccine component within a thin wall 213.
  • the annular collapsible roof 270 is deflected distally so as to compress sharp plastic projections 276 into the thin wall 213 of the reservoir, thus rupturing the seal.
  • the second vaccine component is thus released from the chamber 212b. After its release from the second chamber 212b, liquid flows through the lumen 218b into the needle unit 216, and out of the outlet port 220. At the same time, the first vaccine component flows through the lumen 218a and out of the outlet port 220.
  • the flow path of the second component includes passage through annular filter 278, which prevents plastic material from the ruptured reservoir passing.
  • annular filter 278 prevents plastic material from the ruptured reservoir passing.
  • Such a flow path for the second component is preferred because flow back into the syringe body 226 is inhibited by the annular collapsible roof 270 with its continuous hinge 272 and the pliable annular seal 274.
  • the liquid passes through an annular one way valve consisting of a flexibly hinged plastic seal 280 which is open when fluid pressure is applied as a result of the liquid being released from the second chamber 212b.
  • the hinged plastic seal 280 closes the one way valve when the ambient pressure on the opposite side of the hinged plastic seal 280 from the second chamber 212b is greater than that produced by the annular collapsible roof 270 compressing the reservoir. Such closing of the one way valve by hinged plastic seal 280 prevents fluids from backing up into the second chamber 212b.
  • the lumens 218a, 218b are arranged concentrically within the needle unit 216.
  • the needle unit 216 hence comprises an inner cylindrical wall 282 and a concentric outer cylindrical wall
  • the outer cylindrical wall 284 comprises a porous needle which has pores 286 around (See FIG.
  • pores 286 are closely and substantially uniformly spaced on the exterior wall of needle unit 216 so as to provide for uniform infusion of liquid from second chamber 212b into the patient along the entire length of the needle unit 216 which is inserted, and not just the end 220. It will be appreciated that it is not essential for the needle unit 216 to include such pores 286.
  • the delivery device 200' is the same as the delivery device 200 illustrated in FIGS. 4 and 4A, except that the second chamber 212b is not an annular reservoir and the lumens 218a, 218b extend in a parallel, side-by-side relationship within the needle unit 216.
  • the needle unit 216 thus comprises a first needle 290 and a second needle 292, each containing, at least partially, the respective first and second lumens 218a, 218b.
  • the first and second needles may be coupled by a longitudinal joint 294.
  • the second needle 292 may include pores 286 for the purpose described above in respect of the example of FIGS. 4 and 4A.
  • the distal end 296 of the second needle may extend in front of the distal end 298 of the first needle 290 by about 1.59 to 3.18 mm.
  • the needle unit 216 and the syringe body 226 may comprise a monolithic housing.
  • the needle unit 216 may be detachably connected to the syringe body 226.
  • the needle unit 216 can comprise a single injection needle having at least part of the first and second lumens defined therein, or could comprise a first needle and a second needle, the first and second lumens being at least partially contained within the respective needle.
  • the two needles may extend in a side-by-side adjacent manner, as in the example of
  • FIG. 5 may have a space therebetween.
  • the two needles may or may not be parallel.
  • the separation (from centre to centre of the respective needles at their distal ends) may be between about lmm and about 5mm.
  • the volume of each of the first and second chambers 212a, 212b is approximately 0.25ml.
  • the syringe body 26; 226 or the syringe units 40, 42 may be comprised of plastic material, although glass is a more typical material. Where a glass is used, it is preferred to use a borosilicate glass rather than a soda lime glass. It will be appreciated that alternative delivery devices can be envisaged by combining features as appropriate from each of the foregoing examples.
  • the partition 24 extends longitudinally along the length of the syringe body 12 (and optionally beyond the distal end thereof) thus defining the first and second chambers 12a, 12b as extending side-by-side within the syringe body 12.
  • the partition 24 to define the first chamber to extend coaxially within the second chamber, or vice- versa.

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  • Health & Medical Sciences (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

L'invention concerne un dispositif (10 ; 10'; 100 ; 200 ; 200') d'injection de vaccins comportant un dispositif d'injection standard à deux compartiments dans lequel un des deux compartiments (12a ; 212a) contient une première composante de vaccin et l'autre compartiment (12b, 212b) contient une deuxième composante de vaccin. Selon l'invention, ces composantes peuvent être injectées simultanément dans un patient avec un seul dispositif de seringue tout en restant séparées jusqu'à leur sortie du dispositif.
PCT/IB2007/002778 2006-06-21 2007-06-21 Dispositif d'injection simultanée de vaccins multiples WO2008001221A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP06253192.6 2006-06-21
EP06253192 2006-06-21
EP06255141.1 2006-10-05
EP06255141 2006-10-05

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WO2008001221A2 true WO2008001221A2 (fr) 2008-01-03
WO2008001221A3 WO2008001221A3 (fr) 2008-04-17

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010009563A1 (fr) * 2008-07-21 2010-01-28 Medmix Systems Ag Ensemble distributeur avec seringues séparées et support de seringues
WO2010136896A1 (fr) 2009-05-29 2010-12-02 Novartis Ag Dosages d'hémagglutinines de virus de la grippe
WO2013088367A1 (fr) 2011-12-12 2013-06-20 Novartis Ag Analyse pour hémagglutinines du virus de la grippe
WO2013088086A1 (fr) * 2011-12-15 2013-06-20 Universite Paris Diderot - Paris 7 Ensemble d'injection a chambre implantable
WO2013188931A1 (fr) * 2012-06-20 2013-12-27 Vermeylen Jan Gustaaf M Récipient rempli d'un anesthésique local et procédé de préparation d'un mélange constitué d'un anesthésique local et d'un second liquide
EP3435889A4 (fr) * 2016-04-27 2020-01-01 Vanderbilt University Système et méthode de recherche de fuites après une anastomose
JP2020156923A (ja) * 2019-03-27 2020-10-01 テルモ株式会社 シリンジ接続具
JP2021109006A (ja) * 2020-01-14 2021-08-02 持田製薬株式会社 注入装置

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DE419869C (de) * 1924-10-23 1925-10-12 Robert Roehr Dr Schweinerotlauf-Impfbesteck
EP0104791A2 (fr) * 1982-09-10 1984-04-04 Avvari Rangaswamy Seringue analgésique
DE3903315A1 (de) * 1988-02-10 1989-08-24 Albert Martin Spritze
US5290259A (en) * 1993-02-18 1994-03-01 Ultradent Products, Inc. Double syringe delivery system
WO2000056381A1 (fr) * 1999-03-25 2000-09-28 D'antonio Consultants International, Inc. Systeme d'injection hypodermique
US20040092864A1 (en) * 2002-05-10 2004-05-13 Boehm Frank H. Dual chamber syringe and dual lumen needle

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE419869C (de) * 1924-10-23 1925-10-12 Robert Roehr Dr Schweinerotlauf-Impfbesteck
EP0104791A2 (fr) * 1982-09-10 1984-04-04 Avvari Rangaswamy Seringue analgésique
DE3903315A1 (de) * 1988-02-10 1989-08-24 Albert Martin Spritze
US5290259A (en) * 1993-02-18 1994-03-01 Ultradent Products, Inc. Double syringe delivery system
WO2000056381A1 (fr) * 1999-03-25 2000-09-28 D'antonio Consultants International, Inc. Systeme d'injection hypodermique
US20040092864A1 (en) * 2002-05-10 2004-05-13 Boehm Frank H. Dual chamber syringe and dual lumen needle

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010009563A1 (fr) * 2008-07-21 2010-01-28 Medmix Systems Ag Ensemble distributeur avec seringues séparées et support de seringues
CH699191A1 (de) * 2008-07-21 2010-01-29 Medmix Systems Ag Austraganordnung mit Einzelspritzen und Spritzenhalter.
CN102099068A (zh) * 2008-07-21 2011-06-15 药物混合系统股份公司 带有分开的注射器和注射器保持器的分配组件
JP2011528585A (ja) * 2008-07-21 2011-11-24 メッドミックス システムズ アーゲー シリンジホルダ及び個別に設けられたシリンジを有する計量分配アセンブリ
US8240511B2 (en) 2008-07-21 2012-08-14 Medmix Systems Ag Dispensing assembly with separate syringes and syringe holder
WO2010136896A1 (fr) 2009-05-29 2010-12-02 Novartis Ag Dosages d'hémagglutinines de virus de la grippe
WO2013088367A1 (fr) 2011-12-12 2013-06-20 Novartis Ag Analyse pour hémagglutinines du virus de la grippe
EP3023790A1 (fr) 2011-12-12 2016-05-25 Novartis AG Dosage pour hémagglutinines du virus de la grippe
WO2013088086A1 (fr) * 2011-12-15 2013-06-20 Universite Paris Diderot - Paris 7 Ensemble d'injection a chambre implantable
FR2984171A1 (fr) * 2011-12-15 2013-06-21 Univ Paris Diderot Paris 7 Ensemble d'injection a chambre implantable
WO2013188931A1 (fr) * 2012-06-20 2013-12-27 Vermeylen Jan Gustaaf M Récipient rempli d'un anesthésique local et procédé de préparation d'un mélange constitué d'un anesthésique local et d'un second liquide
EP3435889A4 (fr) * 2016-04-27 2020-01-01 Vanderbilt University Système et méthode de recherche de fuites après une anastomose
JP2020156923A (ja) * 2019-03-27 2020-10-01 テルモ株式会社 シリンジ接続具
JP2021109006A (ja) * 2020-01-14 2021-08-02 持田製薬株式会社 注入装置

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