GB2410500A - Seal for a pharmaceutical dispensing device - Google Patents

Seal for a pharmaceutical dispensing device Download PDF

Info

Publication number
GB2410500A
GB2410500A GB0401962A GB0401962A GB2410500A GB 2410500 A GB2410500 A GB 2410500A GB 0401962 A GB0401962 A GB 0401962A GB 0401962 A GB0401962 A GB 0401962A GB 2410500 A GB2410500 A GB 2410500A
Authority
GB
United Kingdom
Prior art keywords
seal
valve
thermoplastic
dispensing device
pharmaceutical
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.)
Granted
Application number
GB0401962A
Other versions
GB2410500B (en
GB0401962D0 (en
Inventor
Dalijit S Ohbi
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.)
Consort Medical Ltd
Original Assignee
Bespak PLC
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 Bespak PLC filed Critical Bespak PLC
Priority to GB0802588A priority Critical patent/GB2445483B/en
Priority to GB0401962A priority patent/GB2410500B/en
Publication of GB0401962D0 publication Critical patent/GB0401962D0/en
Publication of GB2410500A publication Critical patent/GB2410500A/en
Application granted granted Critical
Publication of GB2410500B publication Critical patent/GB2410500B/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L21/00—Compositions of unspecified rubbers
    • 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
    • A61M15/00—Inhalators
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08C—TREATMENT OR CHEMICAL MODIFICATION OF RUBBERS
    • C08C19/00—Chemical modification of rubber
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F299/00—Macromolecular compounds obtained by interreacting polymers involving only carbon-to-carbon unsaturated bond reactions, in the absence of non-macromolecular monomers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/28—Treatment by wave energy or particle radiation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/20—Manufacture of shaped structures of ion-exchange resins
    • C08J5/22—Films, membranes or diaphragms
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/0008—Organic ingredients according to more than one of the "one dot" groups of C08K5/01 - C08K5/59
    • C08K5/0025—Crosslinking or vulcanising agents; including accelerators
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L53/00—Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • C08L67/02—Polyesters derived from dicarboxylic acids and dihydroxy compounds
    • C08L67/025—Polyesters derived from dicarboxylic acids and dihydroxy compounds containing polyether sequences
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K3/00—Materials not provided for elsewhere
    • C09K3/10—Materials in mouldable or extrudable form for sealing or packing joints or covers
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K3/00—Materials not provided for elsewhere
    • C09K3/30—Materials not provided for elsewhere for aerosols
    • 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
    • A61M15/00—Inhalators
    • A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/01—Use of inorganic substances as compounding ingredients characterized by their specific function
    • C08K3/013—Fillers, pigments or reinforcing additives
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L15/00—Compositions of rubber derivatives
    • C08L15/005—Hydrogenated nitrile rubber
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L23/00—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
    • C08L23/02—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers not modified by chemical after-treatment
    • C08L23/04—Homopolymers or copolymers of ethene
    • C08L23/06—Polyethene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L23/00—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
    • C08L23/02—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers not modified by chemical after-treatment
    • C08L23/04—Homopolymers or copolymers of ethene
    • C08L23/08—Copolymers of ethene
    • C08L23/0807—Copolymers of ethene with unsaturated hydrocarbons only containing more than three carbon atoms
    • C08L23/0815—Copolymers of ethene with aliphatic 1-olefins
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L23/00—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
    • C08L23/02—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers not modified by chemical after-treatment
    • C08L23/16—Elastomeric ethene-propene or ethene-propene-diene copolymers, e.g. EPR and EPDM rubbers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L9/00—Compositions of homopolymers or copolymers of conjugated diene hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K3/00—Materials not provided for elsewhere
    • C09K3/10—Materials in mouldable or extrudable form for sealing or packing joints or covers
    • C09K2003/1034—Materials or components characterised by specific properties
    • C09K2003/1053—Elastomeric materials
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2200/00—Chemical nature of materials in mouldable or extrudable form for sealing or packing joints or covers
    • C09K2200/06—Macromolecular organic compounds, e.g. prepolymers

Abstract

A seal, for a valve for a pharmaceutical dispensing device, is formed from a thermoplastic alloy comprising (a) an elastomeric component, such as one or more of ethylene/alkene copolymers, polyisoprene, nitrile rubbers, butyl rubbers, EPDM, EPR; (b) a thermoplastic component, such as one or more of styrene-ethylene-butylene terpolymer, styrene-ethylene-butadiene terpolymer, styrene-propylene-styrene terpolymer, polyether block polyamide, polyether-polyester copolymer; (c) a sensitisor, such as one or more of trially cyanurate, ethylene glycol dimethacrylate, trimethylol propane triacrylate, high vinyl 1,2-polybutadiene. The seal may further comprise additional additives such as fillers, plasticizers, antioxidants, antiozonants, lubricants and pigments.

Description

24 1 0500 Seal for a Dispensing Apparatus The present invention relates to
a seal material and, in particular, to a thermoplastic alloy, and a method for its production. The seal may be used for dispensing pressurised fluid in the form of an aerosol. The seal is particularly suitable for use in pressurised metered dose aerosol inhaler devices (pMDIs) and in medical check devices suitable for dispensing a pharmaceutical.
The required material properties necessary for good seal performance for pharmaceutical applications include: chemical compatibility (swell), tensile strength, permanent compression set, stress relaxation, elastic modulus, regulatory compliance, low permeability to fluids and gases, low levels of extractables and leachables, and stable properties after extraction.
Accordingly, as well as the requirement for good engineering properties, there is a requirement for sanitary properties, including low levels of extractables and leachables, which might otherwise increase impurities of drug products to unacceptable levels, as well as potentially reacting with the drug product, vehicle or excipients.
The metering valves used in dispensing devices such as pressurised metered dose inhalers are typically constructed from a mixture of metal and/or thermoplastic parts and elastomeric rubber parts. The seal itself typically comprises an elastomer such as a synthetic rubber, for example, nitrite rubber. 2 -
It is known from WO 00/40479 to use a two-phase elastomeric alloy material for a regulating member in an aerosol valve and flow regulator assembly.
The benefits of using "alloyed" or "blended" materials include high elasticity and low hardness. For example, favourable values of elasticity and Shore Hardness (A) can be achieved when a softer elastomeric component is dispersed in a matrix of thermoplastic material.
The production of seals comprising elastomeric materials typically involves steps for the curing/cross linking of natural and synthetic rubbers. Accelerators are compounds which reduce the time required for curing/cross linking of natural and synthetic rubbers. Accelerators may also act to improve the non-permeability characteristics and other physical properties of the rubber.
Peroxides such as dicumyl peroxide can also be used to cure elastomers. However, the curing reaction can be variable and this may affect the material properties; in extreme cases, the material can become brittle. Moreover the products of the reaction have to be removed as they can deteriorate elastomer properties, for example ageing.
Another problem is that peroxides are deactivated by antioxidants. Antioxidants are often required to enhance the ageing properties of the elastomer.
In most pharmaceutical applications it is also necessary to extract or wash the cured elastomer in order to remove surface residues and byproducts resulting from the cure reaction and moulding process. Prolonged extraction - 3 - times have been found to result in a deterioration in material properties.
Products to be dispensed are commonly provided in solution or suspension in an alcohol base, this being particularly common in the dispensing of medicinal compounds for inhalation therapy.
It is an object of the present invention to provide a seal material for a dispensing apparatus which addresses at least some of the problems associated with the prior art.
Accordingly, in a first aspect, the present invention provides a seal for a valve for use in a pharmaceutical dispensing device, which seal is formed from a thermoplastic alloy comprising: (a) an elastomeric component; (b) thermoplastic component; and (c) a sensitisor.
In a second aspect, the present invention provides a seal for a valve for use in a pharmaceutical dispensing device, which seal is formed from a thermoplastic alloy comprising: (i) two or more thermoplastic components; (ii) a sensitisor; and (iii) optionally an elastomeric component.
Thus, in the present invention the seal may comprise an elastomeric component, a thermoplastic component and a sensitisor, or, alternatively, two or more thermoplastics and a sensitisor and optionally an elastomer. 4
The term "thermoplastic alloy", as used herein, is intended to cover a composite product comprising (A) a blend of a thermoplastic component and an elastomeric component, or (B) a blend of two or more thermoplastic components and optionally an elastomeric component. Each of the thermoplastic and elastomeric components may themselves comprise blends.
The term seal as used herein is intended to encompass any sealing member or portion thereof present in a pharmaceutical dispensing device, including, but not limited to, gaskets and seals, whether static or dynamic.
It will be appreciated that the seal may be provided as a separate component or may be formed integrally with the valve, i.e. be co-moulded.
Benefits of using a seal in accordance with the first aspect of the present invention in a pharmaceutical dispensing device include the relatively low levels of leachables and extractables which are present.
Suitable thermoplastics include, but are not limited to TPEs such as, for example, one or more of styrene-ethylene- butylene-styrene terpolymers, styrene-ethylene-butadiene terpolymers, styrene-isoprene-butadiene terpolymers, styrene-propylene-styrene terpolymers, polyether block polyamide, polyether-polyester copolymers and (A - 5 ethylene/alkene copolymer (eg ethylene/octane copolymer), including blends of two or more thereof.
Suitable elastomeric components include, but are not limited to one or more of natural rubber (polyisoprene), synthetic polyisoprene, nitrite rubber, hydrogenated nitrite rubber, butyl rubbers (isoprene-isobutylene copolymers), halogenated butyl rubbers, ethylene-propylene-diene terpolymers (EPDM) and ethylene-propylene copolymers (EPM), including blends of two or more thereof.
The weight ratio of the thermoplastic component to the elastomeric component is preferably in the range of from 80:30 to 20:80.
Sensitisors for use in the present invention are preferably polyfunctional, poly-unsaturated organic compounds, which have the propensity of forming stable free radicals when exposed to free radicals generated either chemically or by high energy radiation. Preferred sensitisors yield sufficiently long lived free radicals to enable inter-cross inking of polymeric alloy components.
Suitable examples include one or more of triallyl cyanurate, ethylene glycol dimethacrylate, trimethylol propane triacrylate and high vinyl 1,2polybutadiene.
Optionally, a cross-linking agent (also known as a curing agent) may be included to provide or facilitate network formation to result in a threedimensional polymer network structure. An example is a peroxide crosslinking (A agent. The cross-linking agent may act by a free radical mechanism.
The seal advantageously further includes a filler, preferably a mineral filler. Mineral fillers are preferable to carbon black in order to minimise the formation of polynuclear aromatic hydrocarbon compounds. Suitable examples include any of magnesium silicate, aluminium silicate, silica, titanium oxide, zinc oxide, calcium carbonate, magnesium oxide magnesium carbonate, magnesium aluminium silicate, aluminium hydroxide, talc, kaolin and clay, including combinations of two or more thereof.
Preferably, the filler is or comprises one or more of magnesium silicate, talc, calcined clay, nano particle clays, kaolin and/or amino silane coated clay or clay coated with a titanium or zirconate coupling agent.
The seal preferably further includes a process aid, preferably a low molecular weight polyethylene.
The seal may further comprise any of a reinforcement agent, a plasticizer, a binder, a stabilizer, a retarder, a bonding agents, an antioxidant, a lubricant, a pigment, a wax, a resin, an antiozonants, a secondary accelerator or an activator, including combinations of two or more thereof.
Examples of antioxidants are 2:2'-methylene-bis(6-(1-methylcyclohexyl)-para-creosol) and octylated diphenylamine. An advantage of the seal according to the present invention is that it can be essentially free of an antioxidant if desired.
In relation to the first aspect, the present invention also provides a process for the preparation of a seal for a 7 - valve for use in a pharmaceutical dispensing device, the process comprising: (i) forming a composition comprising a mixture of an elastomeric component, a thermoplastic component and a sensitisori (ii) initiating a cross-linking reaction in the mixture to form a thermoplastic alloy comprising cross-linked components; and (iii) either before or after step (ii), forming the composition into a seal.
In relation to the second aspect, the present invention also provides a process for the preparation of a seal for a valve for use in a pharmaceutical dispensing device, the process comprising: (i) forming a composition comprising a mixture of two or more thermoplastic components, a sensitisor and optionally an elastomeric component; (ii) initiating a cross-linking reaction in the mixture to form a thermoplastic alloy comprising cross-linked components; and (iii) either before or after step (ii), forming the composition into a seal.
In the above-described process the step of forming the composition into a seal may involve one or more forming techniques such as compression moulding, injection moulding and/or extrusion.
The initiation of the cross-linking reaction may be achieved by a thermochemical reaction using, for example, a peroxide. Alternatively, or in combination with the thermo - 8 - chemical reaction, high energy radiation is used to effect a cross- linking reaction.
Examples of high energy radiation include electron beam and/or Gamma radiation. Such radiation may be used to expose the polymer alloy to a radiation dose in the range of from 50kGy - 300kGy (kGy = kilo Gray), for example.
The resulting components may optionally be ethanol extracted to reduce the level of leachable species that could migrate into drug mixtures. In this process, the components are loaded into a glass column and washed by refluxing ethanol.
The sensitisor as herein described is preferably provided in liquid form and is preferably miscible with the polymer to provide a homogeneous dispersion. It has been found that the use of such a sensitisor facilitates filler dispersion and can obviate the need for a separate plasticizer. The presence of plasticisers is undesirable in that they tend to leach out of the material. In contrast, the sensitisor as herein described forms or is part of the cross-linked network and therefore does not leach out into the drug media.
In the seal compositions according to the present invention the sensitisor is typically substantially consumed during the cross-linking reaction. This results in a cleaner rubber and the extractables are reduced. Typically, substantially no nitrosamines are generalted during the cross-linking reaction. Most or substantially all of any by - 9 - products resulting from the cross-linking reaction may be volatiles.
The seal according to the present invention may be used in a valve for use in a dispensing device, such as, for example, a nasal, pulmonary or transdermal delivery device.
Preferred uses of the seal are in a pressurised metered dose aerosol inhaler device and in a medical check device suitable for dispensing a pharmaceutical.
The term pharmaceutical as used herein is intended to encompass any pharmaceutical, compound, composition, medicament, agent or product which can be delivered or administered to a human being or animal, for example pharmaceuticals, drugs, biological and medicinal products.
Examples include antiallergics, analgesics, bronchodilators, antihistamines, therapeutic proteins and peptides, antitussives, anginal preparations, antibiotics, anti- inflammatory preparations, hormones, or sulfonamides, such as, for example, a vasoconstrictive amine, an enzyme, an alkaloid, or a steroid, including combinations of two or more thereof. In particular, examples include isoproterenol [alpha-(isopropylaminomethyl) protocatechuyl alcohol], phenylephrine, phenylpropanolamine, glucagon, adrenochrome, trypsin, epinephrine, ephedrine, narcotine, codeine, atropine, heparin, morphine, dihydromorphinone, ergotamine, scopolamine, methapyrilene, cyanocobalamin, terbutaline, rimiterol, salbutamol, flunisolide, colchicine, pirbuterol, beclomethasone, orciprenaline, fentanyl, and diamorphine, streptomycin, penicillin, procaine penicillin, tetracycline, chlorotetracycline and hydroxytetracycline, adrenocorticotropic hormone and adrenocortical hormones, such as cortisone, hydrocortisone, hydrocortisone acetate and prednisolone, insulin, cromolyn sodium, and mometasone, including combinations of two or more thereof.
The pharmaceutical may be used as either the free base or as one or more salts conventional in the art, such as, for example, acetate, benzenesulphonate, benzoate, bircarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, fluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulphate, mucate, napsylate, nitrate, pamoate, (embonate), pantothenate, phosphate, diphosphate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulphate, tannate, tartrate, and triethiodide, including combinations of two or more thereof. Cationic salts may also be used, for example the alkali metals, e.g. Na and K, and ammonium salts and salts of amines known in the art to be pharmaceutically acceptable, for example glycine, ethylene diamine, choline, diethanolamine, triethanolamine, octadecylamine, diethylamine, triethylamine, 1-amino-2-propanol-amino-2(hydroxymethyl)propane-1,3-diol, and 1-(3,4- dihydroxyphenyl)-2 isopropylaminoethanol.
The pharmaceutical will typically be one which is suitable for inhalation and may be provided in any suitable form for this purpose, for example as a powder or as a solution or suspension in a solvent or carrier liquid, for
example ethanol.
The pharmaceutical may, for example, be one which is suitable for the treatment of asthma. Examples include salbutamol, beclomethasone, salmeterol, fluticasone, formoterol, terbutaline, sodium chromoglycate, budesonide and flunisolide, and physiologically acceptable salts (for example salbutamol sulphate, salmeterol xinafoate, fluticasone propionate, beclomethasone dipropionate, and terbutaline sulphate), solvates and esters, including combinations of two or more thereof. Individual isomers such as, for example, R-salbutamol, may also be used. As will be appreciated, the pharmaceutical may comprise of one or more active ingredients, an example of which is flutiform, and may optionally be provided together with a suitable carrier, for example a liquid carrier. One or more surfactants may be included if desired.
According to a second aspect, the present invention also provides a pharmaceutical dispensing device having a valve as herein described. The pharmaceutical dispensing device may be, for example, a nasal, pulmonary or transdermal delivery device. Preferred devices are a pharmaceutical metered dose aerosol inhaler device and a medical check device.
The present invention also provides a dispensing apparatus for dispensing pressurized fluid comprising a valve body defining a chamber, a valve member extending movably through the chamber and through at least one annular seal co-operating with the valve member and the body to - 12 regulate the discharge of fluid, wherein the or at least one of the seals is as herein described with reference to the first aspect of the invention.
Such a device may be used for dispensing medicine, pharmaceuticals, biological agents, drugs and/or products in solution or suspension as herein described.
In a preferred embodiment, the dispensing apparatus comprises a pressurized dispensing container having a valve body provided with two annular valve seals through which a valve member is axially slidable, the seals being disposed at inlet and outlet apertures of a valve chamber so that the valve functions as a metering valve.
The dispensing apparatus as herein described may comprise a pressurized dispensing container operatively connected to the valve body and containing the fluid to be dispensed and a hydrofluorocarbon propellant comprising propellant type 134a or 227. The designation of propellant types referred to in the present application is as specified in British Standard BS4580:1970 "Specification for number designations of organic refrigerants". Accordingly, propellant 134a is: 1, 1,1,2tetrafluoroethane CH2F-CF3 and propellant 227 is: 1,1,1,2,3,3,3 heptafluoropropane CF3-CHF CF3.
The fluid to be dispensed typically comprises a liquid or particulate product as a solution or suspension in a carrier liquid. The carrier liquid preferably comprises an alcohol such as ethanol. One or more surfactants may be present. - 13

Claims (25)

  1. CLAIMS: 1. A seal for a valve for use in a pharmaceutical dispensing
    device, which seal is formed from a thermoplastic alloy comprising: (a) an elastomeric component; (b) a thermoplastic component; and (c) a sensitisor.
  2. 2. A seal for a valve for use in a pharmaceutical dispensing device, which seal is formed from a thermoplastic alloy comprising: (i) two or more thermoplastic components; (ii) a sensitisor; and (iii) optionally an elastomeric component.
  3. 3. A seal as claimed in claim 1 or claim 2, wherein the elastomeric component comprises one or more of ethylene/alkene copolymers, polyisoprene, nitrite rubber, hydrogenated nitrite rubber, butyl rubbers, halogenated butyl rubbers, EPDM and EPR.
  4. 4. A seal as claimed in any one of the preceding claims, wherein the thermoplastic component comprises one or more of styrene-ethylene-butylene terpolymer, styrene- ethylene-butadiene terpolymer, styrene-propylene-styrene terpolymer, polyether block polyamide and polyether- polyester copolymer.
  5. 5. A seal as claimed in any one of the preceding claims, wherein the sensitisor comprises one or more of triallyl cyanurate, ethylene glycol dimethacrylate, trimethylol propane triacrylate and high vinyl 1,2polybutadiene.
  6. 6. A seal as claimed in any one of the preceding claims, wherein the seal is formed from a thermoplastic alloy which further comprises acrosslinking agent.
  7. 7. A seal as claimed in any one of the preceding claims, wherein the weight ratio of the thermoplastic to the elastomeric component is in the range of from 80:20 to 20:80.
  8. 8. A seal as claimed in any one of the preceding claims, wherein the seal further includes a mineral filler
  9. 9. A seal as claimed in claim 8, wherein the mineral filler is selected from one or more of clays, calcined clays, nano particle clays, talcs and amino silane coated clay.
  10. 10. A seal as claimed in any one of the preceding claims, wherein the seal further includes a process aid, preferably a low molecular weight polyethylene.
  11. 11. A seal as claimed in any one of the preceding claims, further comprising one or more of a reinforcement agent, a plasticizer, a binder, a stabilizer, a retarder, a bonding agents, an antioxidant, a lubricant, a pigment, a wax, a resin, an antiozonants, a secondary accelerator or an activator. ()
  12. 12. A valve for use in a pharmaceutical dispensing device having a seal as defined in any one of claims 1 to 11.
  13. 13. A pharmaceutical dispensing device having a valve as claimed in claim 12.
  14. 14. A pharmaceutical dispensing device as claimed in claim 13 which is a pharmaceutical metered dose aerosol inhaler device.
  15. 15. A dispensing apparatus for dispensing pressurised fluid comprising a valve body defining a chamber, a valve member extending movably through the chamber and through at least one annular seal co-operating with the valve member and the body to regulate the discharge of fluid, wherein the or at least one of the seals is as defined in any one of claims 1 to 11.
  16. 16. A dispensing apparatus which comprises a pressurised dispensing container having a valve body provided with two annular valve seals through which a valve member is axially slidable, said seals being disposed at inlet and outlet apertures of a valve chamber so that the valve functions as a metering valve, wherein at least one of the annular valve seals is as defined in any one of claims 1 to 11.
  17. 17. A dispensing apparatus as claimed in claim 15 or claim 16, comprising a pressurized dispensing container operatively connected to the valve body and containing the \ - 16 fluid to be dispensed and a hydrofluorocarbon propellant comprising propellant type 134a or 227.
  18. 18. A dispensing apparatus as claimed in any one of claims 15 to 15, wherein the fluid to be dispensed comprises a liquid or particulate product as a solution or suspension in a carrier liquid comprising alcohol.
  19. 19. A dispensing apparatus as claimed in claim 18, wherein the alcohol comprises ethanol.
  20. 20. A process for the preparation of a seal for a valve for use in a pharmaceutical dispensing device, the process comprising: (i) forming a composition comprising a mixture of an elastomeric component, a thermoplastic component and a sensitisor; (ii) initiating a cross-linking reaction in the mixture to form a thermoplastic alloy comprising cross-linked components; and (iii) either before or after step (ii), forming the composition into a seal.
  21. 21. A process for the preparation of a seal for a valve for use in a pharmaceutical dispensing device, the process comprising: A. forming a composition comprising a mixture of two or more thermoplastic components, a sensitisor and optionally an elastomeric component; B. initiating a cross-linking reaction in the mixture to form a thermoplastic alloy comprising cross-linked components; and C. either before or after step B, forming the composition into a seal.
  22. 22. A process as claimed in claim 20 or claim 21, wherein a thermochemical reaction is used to initiate the cross-linking reaction.
  23. 23. A process as claimed in claim 22, wherein the thermo-chemical reaction relies on a peroxide cross-linking agent.
  24. 24. A process as claimed in any one of claims 20 to 23, wherein high energy radiation is used to initiate the cross-linking reaction.
  25. 25. A process as claimed in claim 24, wherein the high energy radiation comprises a source of one or both of an electron beam and Gamma radiation.
GB0401962A 2004-01-29 2004-01-29 Seal for a dispensing apparatus Expired - Lifetime GB2410500B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
GB0802588A GB2445483B (en) 2004-01-29 2004-01-29 Seal for a dispensing apparatus
GB0401962A GB2410500B (en) 2004-01-29 2004-01-29 Seal for a dispensing apparatus

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB0401962A GB2410500B (en) 2004-01-29 2004-01-29 Seal for a dispensing apparatus

Publications (3)

Publication Number Publication Date
GB0401962D0 GB0401962D0 (en) 2004-03-03
GB2410500A true GB2410500A (en) 2005-08-03
GB2410500B GB2410500B (en) 2008-05-21

Family

ID=31971675

Family Applications (1)

Application Number Title Priority Date Filing Date
GB0401962A Expired - Lifetime GB2410500B (en) 2004-01-29 2004-01-29 Seal for a dispensing apparatus

Country Status (1)

Country Link
GB (1) GB2410500B (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008029111A1 (en) * 2006-09-04 2008-03-13 Consort Medical Plc Seal for a dispensing apparatus
FR2910950A1 (en) * 2006-12-28 2008-07-04 Valois Sas Valve or pump seal for a fluid distribution device comprises an elastomer and a basic mineral filler
WO2008087352A2 (en) * 2006-12-28 2008-07-24 Valois Sas Pump or valve seal
WO2009129909A1 (en) * 2008-04-25 2009-10-29 Byk-Chemie Gmbh Dispersion of waxes and inorganic nanoparticles and use thereof
GB2475885A (en) * 2009-12-03 2011-06-08 Consort Medical Plc Seal for a Dispensing Apparatus
US8129474B2 (en) 2005-03-04 2012-03-06 Consort Medical Plc Seal for a dispensing apparatus
WO2014081746A1 (en) 2012-11-23 2014-05-30 3M Innovative Properties Company Metered dose dispensing valve
CN109608736A (en) * 2018-12-06 2019-04-12 铜陵新创流体科技有限公司 A kind of pipe used in mine sealing gasket for valve piece preparation method
CN113025002A (en) * 2021-02-01 2021-06-25 浙江工业大学 Degradable foaming material and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2108943A (en) * 1981-10-02 1983-05-25 Terumo Corp Medical container stopper
WO1995003984A1 (en) * 1993-07-28 1995-02-09 Minnesota Mining And Manufacturing Company Seals for use in an aerosol delivery device
US5714545A (en) * 1995-07-19 1998-02-03 Yukong Limited Thermoplastic elastomeric composition and process for preparing the same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2108943A (en) * 1981-10-02 1983-05-25 Terumo Corp Medical container stopper
WO1995003984A1 (en) * 1993-07-28 1995-02-09 Minnesota Mining And Manufacturing Company Seals for use in an aerosol delivery device
US5714545A (en) * 1995-07-19 1998-02-03 Yukong Limited Thermoplastic elastomeric composition and process for preparing the same

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8129474B2 (en) 2005-03-04 2012-03-06 Consort Medical Plc Seal for a dispensing apparatus
WO2008029111A1 (en) * 2006-09-04 2008-03-13 Consort Medical Plc Seal for a dispensing apparatus
US8110633B2 (en) 2006-09-04 2012-02-07 Consort Medical Plc Seal for a dispensing apparatus
US8063130B2 (en) 2006-12-28 2011-11-22 Valois Sas Pump or valve seal
WO2008087352A3 (en) * 2006-12-28 2009-03-12 Valois Sas Pump or valve seal
WO2008087352A2 (en) * 2006-12-28 2008-07-24 Valois Sas Pump or valve seal
FR2910950A1 (en) * 2006-12-28 2008-07-04 Valois Sas Valve or pump seal for a fluid distribution device comprises an elastomer and a basic mineral filler
WO2009129909A1 (en) * 2008-04-25 2009-10-29 Byk-Chemie Gmbh Dispersion of waxes and inorganic nanoparticles and use thereof
GB2475885A (en) * 2009-12-03 2011-06-08 Consort Medical Plc Seal for a Dispensing Apparatus
GB2475885B (en) * 2009-12-03 2015-04-29 Consort Medical Plc Seal for a dispensing apparatus
WO2014081746A1 (en) 2012-11-23 2014-05-30 3M Innovative Properties Company Metered dose dispensing valve
CN109608736A (en) * 2018-12-06 2019-04-12 铜陵新创流体科技有限公司 A kind of pipe used in mine sealing gasket for valve piece preparation method
CN113025002A (en) * 2021-02-01 2021-06-25 浙江工业大学 Degradable foaming material and preparation method thereof
CN113025002B (en) * 2021-02-01 2022-08-23 浙江工业大学 Degradable foaming material and preparation method thereof

Also Published As

Publication number Publication date
GB2410500B (en) 2008-05-21
GB0401962D0 (en) 2004-03-03

Similar Documents

Publication Publication Date Title
EP2069450B1 (en) Seal for a dispensing apparatus
US20120266871A1 (en) Seal for a dispensing apparatus
EP1861143B1 (en) Pharmaceutical dispensing apparatus with seal
WO2005010413A2 (en) Two component molded valve stems
US7736712B2 (en) Seal material for a dispensing apparatus
GB2410500A (en) Seal for a pharmaceutical dispensing device
JP2024052867A (en) Pressurized Dispensing Container
WO2017021698A1 (en) Seal for a dispensing apparatus
AU2005316813A1 (en) Elastomer seals for use in medicinal aerosol devices
US20050092679A1 (en) Method of cleaning or purifying a polymer
GB2445483A (en) Seal for a pharmaceutical dispensing device
AU2005245248A1 (en) Medicinal aerosol formulation products with improved chemical stability
RU2800100C1 (en) Distribution container under pressure
US20060131346A1 (en) Two component molded valve stems
GB2415699A (en) Seal material for a dispensing apparatus

Legal Events

Date Code Title Description
PE20 Patent expired after termination of 20 years

Expiry date: 20240128